PAGENO="0001"
FDA ISSUES
~,S(o ~
HEARINGS
BEFORE THE
STIBOOMIMTTTEE ON
IIIEALTH AND TIIIE ENVIRONMIENT
OF THE
COMIMITTEE ON ENERGY AN]) COM1\[ERCE
HOUSE OF REPRESENTATIVES
NINETY-NINTH CONGRESS
FIRST SESSION
RISKS AND BENEFITS OF RAW MILK
FEBRUARY 13, 1985
EMERGENCY REYE'S SYNDROME PREVENTION ACT OF 1985
MARCH 15, 1985
ORPHAN DRUG ACT REAUTHORIZATION
MARCH 20, 1985
Serial No. 99-26
Printed for the use of the Committee on Energy and Commerce
U.S. GOVERNMENT PRINTING OFFICE
52-2660 WASHINGTON : 1985
PAGENO="0002"
COMMITTEE ON ENERGY AND COMMERCE
JOHN D. DINGELL, Michigan, Chairman
JAMES H. SCHEUER, New York
HENRY A. WAXMAN, California
TIMOTHY E. WIRTH, Colorado
PHILIP R. SHARP, Indiana
JAMES J. FLORIO, New Jersey
EDWARD J. MARKEY, Massachusetts
THOMAS A. LUKEN, Ohio
DOUG WALGREN, Pennsylvania
BARBARA A. MIKULSKI, Maryland
AL SWITT, Washington
MICKEY LELAND, Texas
RICHARD C. SHELBY, Alabama
CARDISS COLLINS, Illinois
MIKE SYNAR, Oklahoma
W.J. "BILLY" TAUZIN, Louisiana
RON WYDEN, Oregon
RALPH M. HALL, Texas
DENNIS E. ECKART, Ohio
WAYNE DOWDY, Mississippi
BILL RICHARDSON, New Mexico
JIM SLATTERY, Kansas
GERRY SIKORSKI, Minnesota
JOHN BRYANT, Texas
JIM BATES, California
WM. MICHAEL KITZMILLER, Staff Director
SHARON E. DAVIS, Chief Clerk/Administrative Assistant
DONALD A. WA~rr, Printing Editor
ARNOLD I. HAVENS, Minority Counsel
SUBCOMMITTEE ON HEALTH AND THE ENVIRONMENT
HENRY A. WAXMAN, California, Chairman
JAMES H. SCHEUER, New York EDWARD R. MADIGAN, Illinois
DOUG WALGREN, Pennsylvania WILLIAM E. DANNEMEYER, California
RICHARD C. SHELBY, Alabama BOB WHITTAKER, Kansas
RON WYDEN, Oregon THOMAS J. TAUKE, Iowa
GERRY SIKORSKI, Minnesota DON RITTER, Pennsylvania
TIMOTHY E. WIRTH, Colorado THOMAS J. BLILEY, JR., Virginia
JAMES J. FLORIO, New Jersey HOWARD C. NIELSON, Utah
THOMAS A. LUKEN, Ohio MICHAEL BILIRAKIS, Florida
BARBARA A. MIKULSKI, Maryland FRED J. ECKERT, New York
MICKEY LELAND, Texas JAMES T. BROYHILL, North Carolina
CARDISS, COLLINS, Illinois (Ex Officio)
BILL RICHARDSON, New Mexico
JIM BATES, California
JOHN D. DINGELL, Michigan
(Ex Officio)
KAREN NELSON, Staff Director
E. RIPLEY FORBES, Special Assistant
WILLIAM V. CORE, Counsel
MICHAEL J. MASON, Associate Minority Counsel
EDWIN H. AuliN, Associate Minority Counsel
JAMES T. BROYHILL, North Carolina
NORMAN F. LENT, New York
EDWARD R. MADIGAN, Illinois
CARLOS J. MOORHEAD, California
MATTHEW J. RINALDO, New Jersey
WILLIAM E. DANNEMEYER, California
BOB WHITTAKER, Kansas
THOMAS J. TAUKE, Iowa
DON RITTER, Pennsylvania
DAN COATS, Indiana
THOMAS J. BLILEY, JR., Virginia
JACK FIELDS, Texas
MICHAEL G. OXLEY, Ohio
HOWARD C. NIELSON, Utah
MICHAEL BILIRAKIS, Florida
DAN SCHAEFER, Colorado
FRED J. ECKERT, New York
(H)
PAGENO="0003"
CONTENTS
RISKS AND BENEFITS OF RAW MILK
Page
Hearing held on February 13, 1985 1
Testimony of:
Adams, John, director, Milk Regulatory and Animal Health Affairs, Na-
tional Milk Producers Federation 138
Bolton, John, M.D., on behalf of American Academy of Pediatrics 18
Chin, James, M.D., chief, Infectious Disease Section, California Depart-
ment of Health Services 152
Fierer, Joshua, M.D., professor of medicine and pathology, University of
California, San Diego School of Medicine, and director of microbiology
at the VA Medicial Center, San Diego 24
Fleiss, Paul M., M.D., secretary-treasurer, American Association of Medi-
cal Milk Commissions 32
Gooch, Sandy, owner, Mrs. Gooch's Natural Foods Ranch Market 241
Hesser, Pat and William 4
Novell, Raymond A., counsel, Alta-Dena Certified Dairy 224
Okamura, Larry 3
Orsborn, John, DVM, chief, Veterinarian Laboratory Services, California
Department of Food and Agriculture 152
Potter, Morris E., DVM, veterinary epidemiologist, Center for Infectious
Diseases, Centers for Disease Control 161
Smith, Patton, DVM, assistant director, California Department of Food
and Agriculture 209
Stueve, Harold J., owner-partner, Alta-Dena Certified Dairy 224
Telford, Paul 9
Thomas, R. Dean, president, Delst Chemical & Research, Inc 171
Material submitted for the record by:
American Medical Association 266
Binz, Evelyn B 273
Danish Creamery Association 265
Delst Chemical & Research, Inc., letter dated February 14, 1985, from
Dean Thomas to Chairman Waxman re further clarification to ques-
tions asked during the hearing 223
Health and the Environment Subcommittee:
Letter, dated February 12, 1985, from S. Benson Werner to Chairman
Waxman re false and misleading propaganda distributed by Alta
Dena Dairy 127
Two sets of standards from American Association of Medical Milk
Commissions, revised 1976 and 1984, also a letter dated February
15, 1985, from Paul Fleiss to Chairman Waxman 49
EMERGENCY REYE'S SYNDROME PREVENTION ACT OF 1985
Hearing held on March 15 275
Text of H.R. 1381 277
Testimony of:
Chayet, Neil L., legal counsel, Committee on the Care of Children 540
Cope, James D., president, the Proprietary Asociation 518
Dickson, R. Bruce, counsel, Aspirin Foundation of America 462
Dumigan, George and Diane, New Haven, CT 307
Freudenberger, John E. and Terry, president, National Reye's Syndrome
Foundation 286
Happle, Jimmy and Gail, Florence, SC 306
(III)
PAGENO="0004"
lv
Page
Testimony of-Continued
Jennison, Dr. M. Harry, executive director, American Academy of Pediat-
rics 316
Metzenbaum, Howard H., a U.S. Senator from the State of Ohio 281
Michels, Dan, Director, Office of Compliance, Public Health Service, De-
partment of Health and Human Services 326
Pruitt, Albert, M.D., FAAP, chairman, Committee on Drugs, American
Academy of Pediatrics 319
Taubin, Joel M., M.D., vice president, National Reye's Syndrome Founda-
tion 285
White, Joseph M., M.D., president, Aspirin Foundation of America 462
Wolfe, Sidney, M., M.D., director, Public Citizen Health Research Group... 316
Young, Frank E., M.D., Ph.D., Commissioner, Food and Drug Administra-
tion, Public Health Service, Department of Health and Human Services 326
Material submitted for the record by:
American Advertising Federation 672
American Aspirin Association:
Dickson, Bruce, letter dated April 10, 1985, enclosing requested mate-
rials 464
Reye Syndrome awareness research final report 465
Voluntary precautionary program progress report 454
American Association of Advertising Agencies, Inc 679
American Newspaper Publishers Association 683
American Pharmaceutical Association 659
American Reye's Syndrome Association 651
Association of National Advertisers, Inc 689
Chayet, Neil L., letter dated March 28, 1985 644
Health and Human Services Department:
Aspirin Foundation of America 364
Estrogenic drugs-patient package inserts 346
Heckler, Hon. Margaret, statement 377
Industry initiatives other than Aspirin Foundation on Reye Syn-
drome Warnings 383
Letter, dated March 8, 1985, entitled Dear Drug Establishment Regis-
trant 373
Letter, dated April 11, 1985, from Frank Young to Chairman
Waxman re response to January 11, 1985 letter to Secretary Heck-
ler 365
Retail survey-Reye Syndrome warning statement posters 372
Reye Syndrome public education materials 418
Reye Syndrome PSA 364
Magazine Publishers Association 683
National Association of Broadcasters 693
National Association of Chain Drug Stores, Inc 669
National Association of Truck Stop Operators 649
Outdoor Advertising Association of America, Inc 702
Wignhoff, Edwin D 704
ORPHAN DRUG ACT REAUTHORIZATION
Hearing held on March 20, 1985 709
Testimony of:
Baird, William, president, American Narcolepsy Association 749
Finkel, Marion, M.D., Director, Office of Orphan Products Development,
Food and Drug Administration, Public Health Service, Department of
Health and Human Services 710
Martin, Larry H., president, Florida Medical Device Association and gen-
eral counsel, Neuromed, Inc 764
Meyers, Abbey S., chairperson, government-industry liaison committee,
director, family and professional services, Tourette Syndrome Associa-
tion
Scarlett, Tom, general counsel, Food and Drug Administration, Public
Health Service, Department of Health and Human Services 710
Shaw, Dilip P., Ph.D., vice president, Regulatory Affairs, Lyphomed, Inc ... 747
Simon, John W., on behalf of American Academy of Ophthalmology 752
Thoene, Jess G., M.D., president-elect, National Organization for Rare
Disorders
PAGENO="0005"
V
Testimony of-Continued Page
Young, Frank E., M.D., Ph.D, Commissioner, Food and Drug Adminis-
tration, Public Health Service, Department of Health and Human
Services 710
Material submitted for the record by:
American Pharmaceutical Association 776
Health and Human Services Department, letter, dated March 21, 1985,
from Henry Dausch to Chairman Waxman re additional materials in
response to questions during the hearing 726
PMA Commission on Drugs for Rare Diseases 780
PAGENO="0006"
PAGENO="0007"
RISKS AND BENEFITS OF RAW MILK
WEDNESDAY, FEBRUARY 13, 1985
HOUSE OF REPRESENTATIVES,
COMMITTEE ON ENERGY AND COMMERCE,
SUBCOMMITTEE ON HEALTH AND THE ENVIRONMENT,
Los Angeles, CA.
The Subcommittee met, pursuant to notice, at 9:35 a.m., in the
Moss Auditorium, room A2-342 of the Marion Davies Children's
Clinic, University of California, Los Angeles, CA, Hon. Henry A.
Waxman (chairman) presiding.
Mr. WAXMAN. I would like to call the meeting to order.
Welcome to all of our guests for this discussion of the question of
raw unpasteurized milk. We convene this morning's session to re-
ceive testimony on the health effects of raw, unpasteurized milk.
There is a lot of advertising about the benefits of raw milk. It is
said to be the safest, purest milk one can buy. The advertisements
and testimonials seem persuasive. Who would not want to do what
is best for one's health and that of one's family?
But now there is growing concern among some public health ex-
perts about an association between contaminated raw milk and a
variety of life-threatening illnesses. Many medical experts tell us
that some raw milk consumers have been exposed to dangerous
levels of bacteria with names such as salmonella, campylobacter,
and brucella. State regulations may not adequately protect the
public from the risk of contaminated raw milk.
If this situation is true, there is cause for alarm.
In view of the reports of illness and death associated with con-
taminated raw milk, the Federal Food and Drug Administration is
currently considering a proposal to ban raw milk sales. This com-
mittee has legislative and oversight jurisdiction over the FDA and
is interested in a full and complete discussion of this issue.
I am particularly interested in knowing how raw milk could
become contaminated. Are existing State and industry quality con-
trol procedures adequate to prevent bacterial contamination?
Second, do consumers who drink raw milk have a good under-
standing of not only the claimed benefits, but also the possible
risks? Further, are there any groups for whom contaminated raw
milk presents a particular risk?
Our witnesses this morning represent both sides of this often
controversial and emotional issue. Our roster of witnesses includes
a representative from the Nation's largest raw milk producer,
health officials and physicians with direct experience in assessing
(1)
PAGENO="0008"
2
the risks and benefits of drinking raw milk, and ordinary citizens
who have experienced personal tragedies with this product.
Before we call our first witness panel, I would like to recognize a
distinguished Member of Congress also from the Southern Califor-
nia area, Congressman Dannemeyer, for some opening comments
he may wish to make.
Mr. DANNEMEYER. Thank you, Mr. Waxman.
Ladies and gentlemen, it is my understanding that the principal
reason for this hearing being held is that in the continuing contro-
versy over the availability of certified raw milk in California in
these United States, certain people in the public health world are
claiming that the continued availability should be stopped because
allegedly salmonella is sometimes found in certified raw milk.
That is the claim, that it is unfit for human consumption because
on occasion it contains salmonella.
I would like to publicly congratulate officials of the Department
of Public Health of the State of California and of the County of Los
Angeles because it is my understanding that they are prepared to
say this morning on the public record that they are going to de-
clare war on salmonella in California and in the United States if
they can get that action taken. That is to say, in their view, salmo-
nella in any food available to a consumer in California, is so inimi-
cal to the health of such a person that it is public policy that we
should stop this availability of any food product that contains sal-
monella.
I commend them for this judgment and wish them well in their
effàrts to eliminate salmonella from the table of consumers in our
State.
This will mean, my friends, that the following foods, consistent
with this war on salmonella, will be eliminated by edict of the
State Department of Public Health of California: pork, turkey, po-
tatoes, tacos, beef, water, ice cream, milk, goat, chicken, cake,
Mexican food, mayonnaise, and egg nog.
Those are the food products from the records of the Centers for
Disease Control in Atlanta, GA that were implicated by way of con-
sumption of food products that manifested illness in humans caus-
ing salmonella food poisoning.
In 1979, the following products produced the same result: pork,
turkey, hospitals, chicken, green beans, beef, eggs, canned soda,
baked goods, hollandaise sauce, crab meat, egg noodles, casserole,
watermelon, meat, stuffed shells with cheese, ice cream, raw milk.
In 1980, turkey, beef, bakery products, eggs, ham, Chinese food,
chicken salad, pork, ice cream, fruits and vegetables, egg nog,
potato salad, milk, salad sauce, and Mexican food.
In 1981, chicken, pork, egg nog, shell fish, milk, ice cream, baked
foods, turkey, beef, cheese, and Mexican food.
The records for 1982 and 1983 and 1984 were not available for
this hearing today. When they are available, we will likewise make
reference to them.
Of the cases that the CDC has reported-that is attributable to
the food, part of an outbreak, in the 4 years to which I have made
reference, 1978, 1979, 1980, and 1981-11,255 cases were made. Of
those associated with milk were 65-roughly 0.5 of 1 percent. In
other words, of all the cases reported to CDC in that 4-year span,
PAGENO="0009"
3
0.5 of 1 percent are related to milk from salmonella food poisoning.
The others came from the food products I have indicated.
So I think it is commendable that the health authorities of Cali-
fornia in pursuit of this declaration of war which is being an-
nounced today, to my understanding, to eliminate salmonella from
the tables of consumers in California, you know, we are going to
have to just get by in our eating with less foods than are presently
available, but that is all the price we have to pay in terms of reach-
ing this world where our public health officials say we can no
longer tolerate the presence of food products containing salmonella.
It is interesting to note that of the association of food products
with milk, in 1978, pasteurized milk-I repeat, pasteurized milk-
was responsible for 25 cases of salmonella food poisoning.
In 1978, 7 cases of raw milk; in 1979, 8; 1980, 7; 1981, 26, a half a
percent out of the total of 11,255. So when the public health offi-
cials testify today, I look forward to them stating today their decla-
ration of war on salmonella so we Californians can live in a salmo-
nella-free environment in order to protect the public health.
I would also expect since we are banning water from the use of
consumers in California that the public health officials will recom-
mend that we establish an army of inspectors that will station
themselves in residential neighborhoods of California for the pur-
pose of making sure that the domestic water supply does not find
its way into the drinking habits of the consumers of our State.
I believe it is reasonable to suggest that we will be able to use
the domestic water supply for plumbing purposes, that is, for toi-
lets and for bathing, but certainly we do not want to permit water
from the domestic supply to be available for consumption for drink-
ing because history shows that this is a source of salmonella food
poisoning and in the pursuit of our war against salmonella we
should not tolerate continued availability of domestic water sup-
plies for the citizens of our State.
Thank you, Mr. Chairman. I look forward to today's testimony.
Mr. WAXMAN. Thank you, Mr. Dannemeyer.
Our first witnesses this morning are individuals who have had a
personal experience with an illness associated with unpasteurized
raw milk. I want to express the committee's appreciation for their
willingness to come forward and tell about what must be intensely
personal events in their lives. I would ask Mr. Larry Okamura, Mr.
Paul Telford and Mr. and Mrs. Hesser to come forward and take
chairs at the table.
Let me thank each of you for coming to present your testimony.
We are looking forward to hearing what you have to say and would
like you to summarize what you have in your statements, what you
think is important for us to know in a period of time that would
give you the ability to tell us what happened, but not take long be-
cause we have many witnesses today.
STATEMENTS OF LARRY OKAMURA, PAT AND WILLIAM HESSER,
AND PAUL TELFORD
Mr. OKAMURA. Thank you, Mr. Chairman.
It was back in May that my daughter went on a field trip to
Alta-Dena Dairy with her school class. They gave her raw milk, ice
PAGENO="0010"
4
cream, and kefir. She consumed the raw milk and the ice cream.
We were not told she would be given anything on this outing. This
was on a Thursday.
It was roughly Sunday when we were told in passing that she
had been given these products and that Sunday night she looked
strange, just not herself. On Monday, my wife called me at work
and told me she woke up with a 103-degree-plus temperature and
she called the doctor and she said we should bring her in that
afternoon. After I came home, we took her to the doctor and he as-
sumed that it was some sort of stomach flu or food poisoning. On
Tuesday-that Monday evening, she started diarrhea and on Tues-
day she had at least 34 movements. That is when our pediatrician
said he wanted to keep an eye on her. He wanted to see her daily
until this cleared up.
We told him that she had consumed raw milk. He then asked for
a stool sample which he had taken to some lab and they tested it
for salmonella and whatever. The salmonella came back negative,
but it came back positive on the campylobacter of which he said
was very dangerous in her condition.
She kept the diarrhea going, I guess, until Friday, but it contin-
ually got decreasingly less but the only reason my daughter was
not hospitalized was the fact that she was cooperative for the fact
that we had kept feeding her two or three quarters of Gatorade,
plus other liquids and in that 3½-day period, she lost over 2½
pounds. Our pediatrician said that the campylobacter only came
from the raw milk because he got in touch with Public Health.
They told him that this is the direct derivative of raw milk.
I don't believe that other people should be submitted to some-
thing like this.
Mr. WAXMAN. Thank you very much.
We will ask each of the witnesses to talk first and then ask ques-
tions.
Mr. and Mrs. Hesser.
STATEMENT OF WILLIAM AND PAT HESSER
Mrs. HESSER. Thank you.
My personal experience with salmonella is I was drinking the
raw milk for about 10 years on and off throughout the 10 years,
during which time I had diarrhea and nausea and not knowing
what it came from.
In April of 1984, I got extremely sick and I had all of the symp-
toms of salmonella, not knowing what it was.
I was pregnant carrying twins that were very healthy at the
time. Through my suffering, they did suffer and they died. Two
weeks after-we knew they were dead for 2 weeks. We gave birth-
I gave birth to them and they were stillborn at the time. They were
autopsied and found to have had the infection of salmonella. They
died from the mother's infection which is what the autopsy says,
and that was salmonella dublin.
The milk in our refrigerator was tested and it had salmonella
dublin. It was all confirmed. Everything was just tested and
proven.
PAGENO="0011"
5
The suffering on my own part, I know, was severe, and as for the
children, I know they suffered. They were born here at UCLA and
in talking with nurses and doctors, it was the concern of how much
suffering they went through and they did.
Mr. HESSER. During my wife's illness, she suffered severe abdomi-
nal cramps in addition to severe back pain and chest pain and be-
cause she was carrying twins, it was believed that she was having
trouble, carrying them high, and that that was causing breathing
difficulty.
During her 2½ week illness, she would intermittently be sick,
every other day, violently sick, and on the other day, she would be
moderately ill. She experienced vomiting, nausea, extreme pain in
her back particularly and chest, and stomach. She was not able to
sleep most of this time nor eat. The concern was she would dehy-
drate in carrying the twins and also the need for nourishment and
protein was a problem.
So our concern was to get nourishment into her and we contin-
ued to give her additional raw milk products which we were using
at the time, which was probably the worst thing she could have
continued to consume because it had salmonella dublin in it.
The suffering was very severe on my wife's part. The emotional
suffering that both my wife and I endured and continue to endure
since that time has been severe.
We believed as consumers and felt we were well informed and
well read, that the benefits of raw milk were substantial and that
raw milk was good for our health. We believed every time there
was a recall, what the dairies involved would say strictly, that the
recall was a matter of harassment by the State and, therefore, we
did continue toconsume raw milk products.
We do believe because of the readings we have done since then,
medically and scientific readings, that there is a serious concern re-
garding salmonella dublin in particular in raw milk and we do
urge that there would be consideration for the banning of sales of
raw milk.
Thank you.
[The statement of Mr. and Mrs. Hesser follows:]
PAGENO="0012"
6
William and Patricia Hesser
February 11, 1985
Rep. Henry A. Waxman
U.S. House of R?presentativeS
Subcommittee on Health and the Environment
8425 W. 3rd Street
Los Angeles, CA 90048
RE: Personal statement submitted to the Subcommittee on
Health and the Environment for their hearing on the
risks and benefits of unpasteurized milk.
Dear Rep. Waxman:
I, William Hesser, began using certified raw milk products
in 1972 when I moved to Southern California. My interest
in nutrition and natural foods started in 1970 when I read
Adelle Davis' Let's Eat Right To Keep Fit and was intro-
duced to Prevention magazine. Raw milk products were un-
available in the state where I lived in 1970, so I was
happy to be able to~purchase raw milk products when I
moved to California.
I believed raw milk,products were nutritionally superior
to pasteurized milk. I believed pasteurization destroyed
essential enzymes, vitamins, minerals, and, in conjunction
with homogenization, altered the fat content of *the milk.
Health-food industry literature urged the importance of
using certified raw milk products to beassured of its
safety. Pro raw milk literature said that "certified"
meant the milk was safe, pure, and nutritious because the
cows were free from disease and were kept in a clean en-
vironment.
My wife Patricia began using certified raw milk products
prior to our marriage and we continued using them until
1983. In the summer of 1982 Patricia became pregnant.
In the course of prenatal care we found that Patricia was
carrying twins. Patricia's health was good and her preg-
nancy was uneventful for the most part. Patricia became
physically ill in late March of 1983. Patricia's symptoms
included severe abdominal, chest, and back pains, diff i-
culty in breathing, nausea, diarrhea, vomiting, loss of
appetite, and difficulty sleeping because of pain and
general discomfort. Patricia's illness continued until
PAGENO="0013"
7
April 15, 1983 when Patricia became concerned at the lack
of fetal movements. An ultrasound test revealed fetal
demise of the twins. Two and one-half weeks later, on
May 4, Patricia delivered stillborn twins at UCLA Medical
Center. During labor Patricia experienced a high fever.
Blood tests revealed she had a Salmonella infection in
her bloodstream. We were told this infection was "life
threatening." Antibiotics were given until the infection
subsided. Autopsies of the twins revealed the cause of
death to be Salmonella Dublin infection which was trans-
mitted from Patricia to the twins.
A recall of certain certified raw milk products was ordered
by the California Department of Health Services during the
above-mentioned timeframe. The recalled products' lot num-
bers matched those of milk in our refrigerator. Testing
of our milk by the Pasadena Health Department and Califor-'
nia Department of Health Services in Berkeley revealed the
milk to be contaminated with Salmonella Dublin--the sane
bacteria which killed the twins.
It is impossible to adequately express the emotional pain,
trauma, and distress which these events placed upon us!
The dairy where we purchased our certified raw milk pro-
ducts is the leading producer/distributor of raw milk in
the USA. This dairy denies that its milk is ever con-
taminated with Salmonella bacteria. Furthermore, they
deny that Salmonella is a harmful bacteria, nor has ever
caused human illness or death. These claims are made de-
spite the fact that over 22 state-ordered recalls of con-
taminated, disease-ridden milk have occured since 1978.
The dairy's claim is that the recalls are the result of
governnent harassment of the raw milk industry. Numerous
lawsuits against this dairy have been filed. The dairy's
unfortunate, calloused attitude gives the raw milk consumer
the impression that certified raw milk products are safe
for human consumption, and are the target of harassment.
It is our concern that other people will drink contamin-
ated raw milk products, become ill, and die. Untold
suffering can be prevented! Warning labels, such as appear
on cigarette packages, are the minimum which should be done
to alert raw milk consumers -to the. potential hazards of
raw milk. However, it is not unreasonable to discontinue
the sale of raw milk for purposes of human consumption.
A wealth of medical and scientific evidence is available
to show the hazards of raw milk products, whether certified
or not. Salmonella Dublin, in particular, is almost ex-
clusively contracted from drinking raw milk. Other vir-
ulent bacteria thrives in raw milk as well.
PAGENO="0014"
8
Another measure should be taken on the federal level. The
FDA annually subsidizes dairies for the nonproduction of
milk so that milk prices can remain stable. The California
dairy mentioned in this statement was the recipient of
three million dollars in 1983 for nonproduction of milk
which the dairy then sold as raw milk. The FDA should
establish regulations forbidding that subsidized milk can
be sold as raw milk products.
The government has an obligation to introduce and pass
legislation forbidding the sale of raw milk products.
Medical authorities and scientists have an obligation to
warn the public of the hazards of raw milk. Those whose
lives have been affected by contaminated raw milk products
have an obligation to speak out as able. Dairies, especially
raw milk dairies, have the greatest responsibility! They
must accept responsibility for their products. They must
recognize the hazards of raw milk and adequately warn the
public of the risks as well as the purported benefits of
raw milk.
Sincerely,
William Hesser and Patricia Hesser
, Californi4
PAGENO="0015"
9
Mr. WAXMAN. Thank you very much, Mr. and Mrs. Hesser.
Mr. Telford.
STATEMENT OF PAUL TELFORD
Mr. TELFORD. Thank you, Mr. Chairman.
My father died July 26, 1982, in the Glendale Adventist Hospital.
He had been admitted July 21 suffering from diarrhea and weak-
ness and fever. Blood cultures revealed the presence of salmonella
dublin and Listeria monocytogenes. The cause of death as listed by
the coroner's death certifIcate, was purulent meningitis as a result
of the Listeria. A brain swab showed Listeria monocytogenes type
4.
My father was extremely healthy all his life and was working
just shortly before the time of this and at that time he had, in
June, been admitted to Glendale Adventist Hospital for detection
of cancer in the upper lung, the right lung area. He was discharged
on June 14 after about a week in the hospital, and continued out-
patient radiation and chemotherapy. He was able to drive himself
back and forth for these treatments and was progressing very well.
We had good reason to have high hopes for his recovery from the
cancer.
Due to the radiation therapy, he began to develop soreness in his
throat and it made it very difficult for him to eat anything of a
solid nature and so he went to a liquid diet.
Part of the products that he partook of were WaEe-On, Meritene,
and Ensure, which are commercially prepared products. They are
dietary products commercially available. He also took these with
milk.
He was concerned that he had enough calorie nutritional intake
to keep up his strength, so he decided to purchase certified raw
milk. It was readily available to him. Alta-Dena's outlet was just a
few blocks from my parents' home so he would stop and purchase
it on the way home from treatment.
On the last period, the last time that raw milk was purchased at
Alta-Dena's outlet, was July 16. On Monday, July 19, he had diar-
rhea and was very weak. On Tuesday, we thought that it was prob-
ably due to his inability to eat and we decided to admit him to the
hospital on Wednesday, and I was to pick him up, but at 5 a.m. in
the morning, he was feeling so poorly that my mother called an
ambulance and he was admitted to Glendale Adventist with fever
and extreme chills.
My father's demise was very quick. He was in the hospital until
July 26. He was not able to communicate with us after about 3
days in the hospital. He had fevers at times exceeding 104 degrees.
After my father's deaths there was a great deal of media atten-
tion to producers and distributors of raw milk, particularly the
Alta-Dena Dairy as a result of Alta-Dena's lawsuit against the
State of California, which, to my understanding, Alta-Dena later
dropped.
These producers and distributors of raw milk in the State have
made tremendous gains in their continuing effort to be relieved of
government testing of their product. They have been able to do this
PAGENO="0016"
10
essentially because of their ability to hire lobbyists and to contrib-
ute to campaign funds of legislators.
Their latest effort was SB565 which would appoint a commission,
the majority of which would come from the producers themselves,
who would be entrusted with protecting the public health from the
harmful bacteria this product can contain. Although this bill
passed the legislature, Governor Deukmejian did not sign it.
How can anyone expect an industry to police itself whose largest
producer, Harold Stueve, owner of Alta-Dena, is quoted as saying,
"The Lord gives us everything in its wholeness, and that's the way
He meant us to keep it"; a man whose single great passion is said
to be "the production and sale of raw milk"; who vehemently
denies that any harm could come to anyone drinking his milk?
I think Louis Pasteur would roll over in his grave as pasteuriza-
tion has generally been regarded as one of the most important
public health measures ever undertaken.
Mr. Stueve and his industry have been able to continue this de-
ception on the American public because of the elusive nature of the
bacteria and its being found in other foods. However, in my fa-
ther's case, there is no other food intake to which they can shift
the blame. This fact and the occurrence of the two bacteria togeth-
er, salmonella dublin and Listeria monocytogenes, which occur
almost exclusively in barn yard situations, make it difficult to be-
lieve in the innocence of raw milk and its producers and distribu-
tors.
How long can you, our elected representatives, listen to the
clever deception of this industry? How long can you turn a deaf ear
to those public agencies whose duty it is to protect us? Can you, in
all honesty, let an industry who tries so hard to remove itself from
liability, when people become ill and die, police itself?
Please provide for more Government supervision and testing. At
least require a warning label to be placed on this product which
describes its potential lethal consequences to those whose resist-
ance has been lowered in any way. Allow the American public the
opportunity to at least make an informed choice.
I thank you for this opportunity to share my family's experience
with you. I wish that my father and countless thousands who have
been or will be affected by the consumption of raw milk could do
the same.
[The statement of Mr. Telford follows:]
PAGENO="0017"
11
STATEMENT OF PAUL A. TELFORD
My father, Paul B. Telford, died July 26, 1982 in Glendale,
California. He had been admitted to Glendale Adventist
Hospital on July 21, 1982 suffering from diarrhea, weakness
and fever. Blood cultures revealed the presence of
Salmonella dublin and Listeria monocytoqemes. The cause of
death as listed by the Coroner's death certificate was
purulent neningitis. A brain swab taken by the coroner
showed Listeria monocytogenes type 4.
My father was 66 years old and had been extremely strong and
healthy all his life with no significant illnesses or
accidents and was never hospitalized. He met a demanding
work schedule as building engineer for Yamaha International
in Buena Park, California. He lived with my mother in the
Brookside Mobile Home Park in El Monte, California. He
was admitted to Glendale Adventist Hospital on June 6, 1982
after chest x-rays revealed some abnormalities. A biopsy
resulted in a diagnosis of small cell carcinoma of the upper
right bronchial area. He was discharged June 14, 1982 and
returned five days a week for radiation therapy. He also was
undergoing chemotherapy. He was however, able to drive him-
self from his home to the hospital and back, thirty miles round
trip, and was progressing very well. He began developing a
soreness in his throat in July which progressively worsened
to the point that swallowing was so painfull that he went
to a liquid diet of the commercially prepared products
Wate-on, Meritene and Ensure. He mixed some of these with
milk. He was concerened that he would have enough calorie
and nutritional intake to keep up his stength. This led him
to purchase Alta-Dena Certified Raw Milk thinking it to be
higher in calories and nutrients and being unaware of any
potential health risks. It was also convenient since Alta-Dena
had a drive thru location a few blocks from my parents home.
He purchased three one-half gallon containers over a week to
ten day period, the last being July 16, 1982. On Monday,
July 19, 1982 he had diarrhea and was quite weak. Tuesday,
July 20, 1982 thinking that his condition was due to his being
unable to eat properly we decided to admit him to the hospital
on Wednesday, July 21, 1982. I was to pick him up but his
discomfort was so great early Wednesday morning that my mother
called an ambulance at 5:00 am. He was admitted to Glendale
Adventist Hospital experiencing periods of fever and extreme
chills. Thursday afternoon, July 22, 1982 his temperature
continued to increase despite efforts to keep it down
medication, sponge baths and ice packs ).
(1)
PAGENO="0018"
12
Friday, July 23, 1982 he was no longer able to speak to us
in the afternoon, his temperature ranged as high as 104 degrees.
Saturday, July 24, 1982 with fever raging and his temperature
exceeding 104 degrees he was unable to respond to us in any way.
He went through periods when he did not breathe causing my
mother and those of us present a great deal of anxiety. We now
had real fears that he would not survive. Sunday, July 25,
1982 his condition was unchanged. Monday, July 26, 1982 at
approximately 5:00 am my father died. My mother has not been
the same since and has been hospitalized twice the last time
for a stroke which has left her with some paralisis.
Over the next several weeks there was a great deal of "media"
attention to producers and distributors of raw milk especially
Alta-Dena Dairy. Part of this due to Alta-Dena's law suit
against the State of California because of various agencies
efforts to protect- the public. Alta-Dena later dropped the
suit.
These producers and distributors in the past few years have
made tremendous gains in California in their continuing
effort to be relieved of government testing. This they have
been able to do because of their ability to hire lobbiests
Alta-Dena Dairy has gross revenues exceeding $100 million
and contribute large sums to legislators. Their latest effort
was SB565 which would appoint a commission, the majority of
which would come from the producers themselves, who would be
entrusted with protecting the public from the harmfull
bacteria this product can contain. Although this bill passed
through the legislature, thankfully, Governor Deukmejian did
not sign it.
How can anyone expect an industry to police itself whose
largest producer Harold Stueve, owner of Alta-Dena, is quoted
as saying, " The Lord gives us everything in its wholeness,
and that's the way He meant us to keep it". A man whose
single great passion is said to be " the production and sale
of raw milk ". Who vehemently denies that any harm could come
to anyone drinking his milk. Louis Pasteur would roll over
in his grave. Pasteurization is generally regarded as one
of the most important public healthmeasures ever undertaken.
Mr. Stueve and his industry have been able to continue this
deception of the American public because of the elusive
nature -of the bacteria and its also being found in other
foods. However, in my fathers case, there is no other food
intake to which they can shift the blame. This fact and
the occurrence of the two bacteria together, Salmonella dublin
and Listeria monocytogenes, which occurs almost exclusively
in barn yard situations make it difficult to believe in the
innocence of raw milk and its producers and distributors.
How long can you, our elected representatives, listen to the
clever deception of this industry. How long can you turn a
deaf ear to those public agencies whose duty it is to protect
us. Can you, in all honesty, let an industry who tries so hard
to remove itself from liability when people become ill and die
police itself.
Please provide for more government supervision and testing.
Require a warning label to be placed on this product which
discribes its potential lethal consequences to those whose
resistance has been lowered in any way. Allow the American
public the opportunity to at least make an informed choice.
I thank you for this opportunity to share my families experience
with you. How I wish that my father and the countless thousands
who have been or will be affected by the consumption of raw
milk could do the same.
PAGENO="0019"
13
Mr. WAxIsi*i.~. Thank you very much, Mr. Telford.
We thank you all for sharing your personal and tragic experi-
ences with us. In each case, you attribute the raw milk that you or
your family member consumed to be the source for the medical
problems.
Mr. and Mrs. Hesser, as I understand your testimony, the autop-
sy of the twins showed that there was salmonella?
Mrs. HESSER. Yes, it did.
Mr. WAxMAN. And when the milk in your refrigerator was
tested, there was an indication that that had also been infected?
Mrs. HESSER. Yes.
Mr. WAXMAN. I think you mentioned you had consumed other
products; you had been consuming this product for years before,
and that you had other natural products that you had or still may
consume. Was there any particular reason why you decided to
drink raw milk?
Mrs. HESSER. The general health benefit that it proposed to have.
It obviously didn't have as much as I thought.
Mr. WAxMAN. You thought it would be better for your health to
drink raw milk and have natural foods?
Mrs. HESSER. Yes.
Mr. WA.xr N. Did you ever hear of any problems or potential
risks from raw milk?
Mrs. HESSER. I had heard of the occasional recalls that had been
made and I also believed the papers which stated both sides very
clearly, and Alta-Dena's side was "We are being ha~rassed."
Mr. WAx1 N. The milk you were drinking was labeled "certified
raw milk", I believe?
Mrs. HESSER. Yes.
Mr. WAxi~N. What did you think "certified" meant?
Mrs. HESSER. Personally, I thought it meant it was checked, and
it was safe for consumption and there would be no problem. Fur-
thermore, with the recalls themselves, I felt when it was recalled,
it meant they were not having a bad product on the shelf~ I felt
that it was obviously taken off and that people did not have the
opportunity to buy it.
Mr. WAx N. I see, and did you know that there was a recall
before you drank the milk or was this something you discovered
afterwards?
Mrs. HE8SER. It was always afterwards.
Mr. WAXMAN. Would you have been drinking raw milk if you be-
lieved there to be a potential health risk?
Mrs. HESSER. No.
Mr. WAx1~~t~. If there had been a warning label on the milk, do
you think that would have influenced you?
Mrs. HESSER. I don't really know.
Mr. WAx~. All right.
Did you have any other problems that were associated with
drinking raw milk?
Mrs. HE5SER. Like I said, from the past-when I came to Califor-
nia and started drinking the raw milk because it was available, I
did have occasional diarrhea and nausea and things like that that I
assumed were my stomach upset, never connecting the two.
PAGENO="0020"
14
Mr. WAXMAN. So after you learned more about the problems
with raw milk, you thought back to those other occasions and
thought there might have been a connection?
Mrs. HESSER. Yes, and since I stopped drinking it, I don't have
that problem on occasion.
Mr. WAXMAN. Now Mr. Telford, your father was going through
chemotherapy and radiation therapy?
Mr. TELFORD. Yes.
Mr. WAXMAN. Did the doctors explain to you afterward that be-
cause he was going through chemotherapy and radiation, that he
was more vulnerable to infection than otherwise would be ~he
case?
Mr. TELFORD. That is correct.
Mr. WAXMAN. Did he consume raw milk over a long period of
time? Was this a regular habit of his?
Mr. TELFORD. No. He had just started consuming it again. My
father grew up on a farm as many people his age would have done,
he was 66 years old, and so as a youth, he consumed raw milk
probably almost exclusively from the dairy cattle on their own
farm.
So my father's experience with raw milk as a youth was prob-
ably excellent and he just felt that it would be a good source of nu-
trients and calories that he needed.
Mr. WAXMAN. I am wondering if he thought that because he had
been ill that raw milk would be especially healthful for him to take
at that time and what might have happened was because his body
was more vulnerable to an infection, that might not otherwise have
infected him at all, became much more serious?
Mr. TELFORD. Certainly the family would have been a great deal
more concerned had there been some type of a warning. Then we
could have at least had asked his doctors whether they thought it
was a good idea that he be ingesting raw milk. They were aware of
the fact that he wasn't eating and they had suggested the commer-
cially prepared products for him to try and use, but I can't say for
sure if my father alone would have been discouraged from taking
the milk if a warning label were there, but certainly my mother
and others of us in the family would have at least looked into it.
You don't see a warning label and then disregard it particularly
when someone's health is in jeopardy.
Mr. WAXMAN. Your father took the raw milk voluntarily and
Mrs. Hesser took it voluntarily with the expectations that the kind
of thing that happened wouldn't have happened, but, Mr. Oka-
mura, your daughter was how old?
Mr. OKAMURA. Five or six. Her birthday is in May.
Mr. WAXMAN. So one doesn't think of children at five or six
making informed, voluntary decisions-even though it may be vol-
untary-to eat something that will affect her health. Did you know
she was going to be taking this?
Mr. OKAMURA. We were not told there would be any food prod-
ucts served, but we knew about the trip.
Mr. WAXMAN. You didn't imagine there would be any problem
with the food products, did you?
Mr. OKAMURA. No, I never did.
PAGENO="0021"
15
Mr. WAx1~i,~. If they had said she was going on the tour and,
"We will give her raw milk," would you have said, "No"?
Mr. OKAMURA. I believe so, because we don't use raw milk in our
household. We never have.
Mr. WAxi~&r~. She went with a class?
Mr. OKAMURA. With her class.
Mr. WAXMAN. Did other children become ill?
Mr. OKAMURA. Yes. Nine others in her class of thirty were out
that same Monday that she came down with it.
Mr. WAx~&N. Thirty kids went on the trip, and nine became ill?
Mr. OKAMURA. Right. Nine were not in school. I am assuming
there were others in her class that were sick, plus the parents of
the children that went on the field trip came down with some posi-
tive reaction, also.
Mr. WAxi~w~. Did they eat any other foods that might have
caused the problem? How do you know for sure it was raw milk?
Mr. OKAMURA. It was just her class that came down with any
kind of illness in the whole of the school, because Public Health
came in and took a random stool sample from all the children in
school. I don't know what was the number, but in her class, they
took a stool sample from everyone and there were close to half the
class was a positive reaction of the campylobacter.
The only other thing they ate that was different from their
normal diet-on that Friday was what they call McDonald's day
and whatever part of the school that wants, they can have McDon-
ald's hamburgers. Like I say, the balance of the school had no signs
of the campylobacter. It was just her class.
Mr. WAXMAN. Everybody had hamburgers, but not everybody
had the milk, is that what you are saying?
Mr. OKAMURA. Right. Only her class of 30 went on the field trip.
Mr. WAXMAN. But everybody had hamburgers at school?
Mr. OKAMURA. Right.
Mr. WAx1~N. Only the kids in her class became ill, then?
Mr. OKAMURA. Right.
Mr. WAx~&N. Thank you very much.
Mr. Dannemeyer.
Mr. DANNEMEYER. Thank you, Mr. Chairman.
Mr. Okamura, the field trip was on a Friday?
Mr. OKAMURA. No. The field trip was on a Thursday.
Mr. DANNEMEYER. And was your daughter's class the only one
that went on the field trip?
Mr. OKAMURA. Yes, it was.
Mr. DANNEMEYER. And did all the children in the class drink
milk at the Alta-Dena Dairy?
Mr. OKAMU1ti~,. They were all given-whether they consumed it
or not, I have no idea.
Mr. DANNEMEYER. When did your daughter first evidence signs
of illness that you describe? On Sunday, did you say?
Mr. OIWvIUKA. Sunday evening.
Mr. DANNEMEYER. Sunday evening?
Mr. OKAMURA. She just looked a little strange Sunday evening.
It is one of those things that a parent sees in their child, you
know. She just didn't act like herself.
PAGENO="0022"
16
Mr. DANNEMEYER. How about the other children? Did you find
out when they began to manifest these signs of illness?
Mr. OKAMURA. The other children in her class?
Mr. DANNEMEYER. Yes.
Mr. OKAMURA. We didn't know about the others until Public
Health informed us.
Mr. DANNEMEYER. How about any of those other children that
had hamburgers on Friday? Did any of them complain of any ill-
ness at all that you are aware of?
Mr. OKAMURA. No. Like I said, the balance of the school was of-
fered the opportunity to get McDonald's hamburgers of which I am
assuming at least 65 percent buy the hamburgers, and it was only
her class that came down with the positive reaction.
Mr. DANNEMEYER. Thank you.
Mr. Hesser and Mrs. Hesser, during the pregnancy that you de-
scribed, were you taking insulin at the time?
Mrs. HESSER. No, I wasn't.
Mr. DANNEMEYER. Did the doctor prescribe insulin for you? Did
he suggest you should take it?
Mrs. HESSER. One did.
Mr. DANNEMEYER. You declined to take it; is that right?
Mrs. HESSER. Yes, that is true.
Mr. DANNEMEYER. How long had you been using Alta-Dena's cer-
tified raw milk products? Since .1974?
Mr. HESSER. 1974, yes.
Mr. DANNEMEYER. How often did you consume them?
Mrs. HESSER. Every day.
Mr. DANNEMEYER. Both you and your husband?
Mrs. HESSER. Oh, yes, absolutely.
Mr. DANNEMEYER. And did you, Mr. Hesser, experience any of
the symptoms similar to your wife?
Mr. HESSER. I did not become ill. For 2 months during the time
my wife was pregnant, I was experiencing slight stomach upset and
diarrhea. A stool culture showed I did not have salmonella at the
time my wife did.
At that time, I was working two jobs though, my full-time job
during the day, and I had a part-time job in the evening. I would
eat most of my meals out. I would catch dinner on the way to my
second job and by the time I got home, it would be 11 o'clock and I
would probably not eat at that time. So I was not eating at home
normally as I would have been.
Mr. DANNEMEYER. In any event, your wife said she consumed
Alta-Dena's certified raw milk from 1974 onward. I would assume
you would be consuming it in the home as well; is that right?
Mr. HESSER. Yes, throughout the seventies and into the eighties.
Mr. DANNEMEYER. I take it in that large part of that interval,
you were not manifesting symptoms of illness yourself is that
right?
Mr. HESSER. Not that I felt I needed to be treated for, no.
Mr. DANNEMEYER. Thank you.
Mr. Telford, how long had your father been suffering this menin-
gitis, I think, you described, or the cancer that you described? How
long had he been--
PAGENO="0023"
17
Mr. TELFORD. The meningitis is a result of the Listeria monocyto-
genes, and that manifested itself in the last week of his life.
He had been diagnosed on June 6, 1982, as having cancer.
Mr. DANNEMEYER. June 6, 1982?
Mr. TELFORD. That is correct.
Mr. DANNEMEYER. And prior to that time, was he in good health?
Mr. TELFORD. Yes.
Mr. DANNEMEYER. And I take it he began what? What type of
treatment did he begin after the diagnosis in June 1982?
Mr. TELFORD. Well, he went into the hospital. A biopsy was per-
formed on the seventh, I believe, to determine what he had. The
result was that they diagnosed a small cell carcinoma. He then
began radiation treatment and one chemotherapy treatment in the
hospital. He was released on June 14 and then returned 5 days a
week to the hospital from the 14th until he returned to the hospi-
tal in July, 1 day a week-sorry; 5 days a week for his radiation
treatment, and I think a weekly chemotherapy treatment.
Mr. DANNEMEYER. And did I understand correctly that you first
purchased-when did he first purchase Alta-Dena's certified milk?
Mr. TELFORD. It would be hard for me to tell you exactly, but I
would say it was the first part of July, probably, as he developed
the throat soreness. That was the first time that he purchased
Alta-Dena's raw milk.
Mr. DANNEMEYER. Where was the cancer in his body, in his
throat?
Mr. TELFORD. Upper right lung.
Mr. DANNEMEYER. And do you know how many times your father
purchased the milk before he passed away?
Mr. TELFORD. At least three. There were three containers in the
house.
Mr. DANNEMEYER. Were these containers tested for what they
may contain after his death or at any time?
Mr. TELFORD. Two were empty and one was partially consumed
and one of them tested positive.
Mr. DANNEMEYER. For what?
Mr. TELFORD. For salmonella dublin.
Mr. DANNEMEYER. I see.
Mr. TELFORD. That doesn't necessarily mean anything as far as I
understand, however.
Mr. DANNEMEYER. Well, we will let the scientists worry about
that, I guess.
Mr. TELFORD. Right.
Mr. DANNEMEYER. Thank you, Mr. Chairman.
Mr. WAxM~. I want to thank each of you for being with us
today and helping us look at this issue from your own personal ex-
periences.
Our next witnesses represent physicians with personal experi-
ences in assessing the risks of illness associated with raw milk.
John Bolton is a pediatrician representing the American Acade-
my of Pediatrics. Joshua Fierer is a physician and expert in the
transmission of infectious diseases. Paul M. Fleiss is a physician in
Los Angeles and secretary-treasurer of the American Association of
Medical Milk Commissions.
I would like to ask you gentlemen to please come forward.
PAGENO="0024"
18
Mr. WAXMAN. We would like to welcome the three of you to this
hearing. We know that you have prepared statements and, without
objection, we will put the prepared statements in the record just as
you have presented them to us.
We would like to ask you, if you would, to summarize those state-
ments so we can have time for questions and answers.
Dr. Bolton, would you start.
STATEMENTS OF JOHN BOLTON, M.D., ON BEHALF OF AMERICAN
ACADEMY OF PEDIATRICS; JOSHUA FIERER, M.D., PROFESSOR
OF MEDICINE AND PATHOLOGY, UNIVERSITY OF CALIFORNIA,
SAN DIEGO SCHOOL OF MEDICINE, AND DIRECTOR OF MICRO-
BIOLOGY AT THE VA MEDICAL CENTER IN SAN DIEGO; AND
PAUL M. FLEISS, M.D., SECRETARY-TREASURER, AMERICAN AS-
SOCIATION OF MEDICAL MILK COMMISSIONS
Dr. BOLTON. Thank you, sir.
The first comment I would like to make is that my prepared
statement on the table over here is the one submitted in Septem-
ber. I have submitted an updated statement which apparently is
still in Mr. Waxman's office and didn't get brought over, so that
will be supplied to the committee later.
Dr. BOLTON. I am John Bolton, a board-certified pediatrician
practicing in San Francisco, and I am designated as the representa-
tive of the American Academy of Pediatrics on the topic of raw
milk.
My background includes 2 years as a medical epidemiologist with
the Centers for Disease Control in Atlanta, GA, and I am currently
on the faculty of the University of California in San Francisco as
an assistant clinical professor of pediatrics.
The data from the CDC have shown numerous instances around
the country where salmonella and campylobacter have been linked
to raw milk usage. For example, since 1977, more than 192 isolates
have occurred in certified raw milk in California.
This milk is transported across State lines by distributors. There
are many organisms linked to raw milk use, but the two most seri-
ous are salmonella and campylobacter. Campylobacter causes high
fever and bloody diarrhea, similar to the usual salmonella infec-
tion. Salmonella dublin, on the other hand, is not one of the usual
salmonellae. This is a relatively new strain in this country having
come in in the late sixties or so when it started to infect the herds.
This is a very, very lethal bacterium.
Seventy-five percent or more of the isolates of this germ come
from outside the human gastrointestinal tract-this would be from
brain, joint fluid or spinal fluid. Less than 5 percent of the usual
Salmonellae are found outside the intestinal tract. For your run-of-
the-mill salmonella, we are talking about a 5-percent hospitaliza-
tion rate. For salmonella dublin, we see an 80-percent hospitaliza-
tion rate.
With salmonella, again the run-of-the-mill type, there is a death
rate of 1 percent or less; salmonella dublin, 24 to 26 percent.
It is an extremely virulent organism. It picks on the very young
and the very old and weak. This has been pointed out here today in
PAGENO="0025"
19
the testimony by the Hessers, by people like Megan Day, a little
girl up in the East Bay now living in southern California.
Her mother thought it was right to give her infant raw milk;
gave her raw milk, shortly after which Megan developed a brain
abscess with salmonella dublin. Her brain was operated on two dif-
ferent times to drain this abscess. This child today has cerebral
palsy, mental retardation, has a seizure disorder, epilepsy-all of
this courtesy of salmonella dublin.
Again, this is not the run-of-the-mill salmonella. Salmonella,
some people say, is ubiquitous-everywhere. But it is not every-
where. Salmonella is everywhere you find faecal matter. It is asso-
ciated with the gastrointestinal tract of animals. Any place you
find salmonella, you know there has been faecal contamination.
As Mr. Dannemeyer pointed out, there have been outbreaks all
over the country with various foodstuffs but the assumption in all
these, if you check the CDC documents and look, is that most likely
there was faecal contamination.
There is one exception to this, one exception only that I know of,
where salmonella does not have its origin or hometown in the GI
tract of some insect or turtle or animal or whatever. That is in raw
milk and in cattle.
Salmonella dublin is a host-adapted organism. This means it
doesn't live in you, doesn't live in us and colonize us, doesn't like to
live in pigs, goats, and sheep and other animals. It is host-adapted
to cattle and it is very sneaky in one special respect; that is, it can
be carried in a nonsick animal and carried outside the intestinal
tract where, instead of being shed in the stool, in the faeces as
most salmonella are, it is shed intermittently in the milk. This is
why the raw milk problem is so great, that no matter how much
you clean the cattle, no matter how you scrub them or anything, if
you have a shedder cow in a herd that is intermittently dropping
these organisms in the milk, you have a great chance that people
are going to get this milk and be contaminated or infected with it.
No, there is a similar thing. You may have heard in your public
health classes in high school and things like this, about typhoid,
but what do we have, a bunch of four-legged typhoid Mary's? I
don't know. Something happens to these cattle. It is like the ty-
phoid Mary story, a woman who carried the typhoid germ in her
gallbladder. By the way, typhoid is another salmonella, not as bad
as salmonella dublin. Mary would go around and cook for people
and she was loved by all, they loved her, but a large percentage of
the people she cooked for died of salmonella. But here we have a
cow with no malice to anyone, who doesn't have a fever or any-
thing, and intermittently drops this organism in the milk. It would
be great if there were some way that we could say that you could
assure that raw milk on the marketplace was safe for consumption,
but because of this simple fact, the fact of milk-shedding cattle, no
matter how clean the dairy is, no matter how much you scrub the
cattle, you have the risk of this bug coming through.
You say, does it come through? This has been found in certified
raw milk by 14 or 15 different agencies, including the State of Ari-
zona, the State of Nevada, the State of California, 8 or 10 different
counties in California, and the U.S. Food and Drug Administration.
PAGENO="0026"
20
As a matter of fact, on two different occasions, the FDA picked
up certified raw milk samples transported to Nevada, took 20 or 30
samples, cultured them to see if the salmonella was in there, and
they found each time a range of between 10- and 20-percent con-
tamination, meaning a consumer might be able to drink the raw
milk and get away with it, but then again, you may have a chance
that the organism is there in the milk.
This is a product advertised as perfect food for infants. It is ad-
vertised as a food for invalids.
Every reputable health organization that I know of has come out
and said this is not safe for infants. It is not safe for the elderly or
people with any kind of debilatating diseases.
Even the proponents' witnesses that have come forward to give
testimony regarding this, the raw milk proponents-Dr. John
Douglas from here in Los Angeles-was a witness at the FDA hear-
ings back in November in Washington and reading from his tran-
script: "The disadvantage of certified raw milk is there is occasion-
al contamination with pathogenic bacteria."
David Snydman, hospital epidemiologist, New England Medical
Center at Tufts, brought out by the proponents to testify before the
California Legislature, from a statement in his letter, if you read
his letter: "It is my impression that there may be an increased risk
of salmonella infection from ingesting raw milk."
I could go on with this, further statements from Dr. Joseph
Fleiss where he makes similar statements that there is a causal re-
lationship there.
So, to sum it up, I wish there were some way to make it safe. I
don't think there is.
Thank you.
I would show your committee one thing I have just recently ob-
tained. It is a copy of the warning sign being posted in San Francis-
co now by ordinance that says you cannot sell raw milk in San
Francisco without posting a warning sign to let people know that it
should not be fed to the very old, very young, people with malig-
nancy or immune deficiencies, and it is not pasteurized and may
contain organisms that cause human disease.
I don't know whether it will do any good, but it is a step.
[The prepared statement of Dr. Bolton referred to follows:]
PAGENO="0027"
21
STATEMENT OF JOHN BOLTON, M.D.
My name is John Bolton. I am a Board Certified Pediatrician practicing in San
Francisco, California. I am the designated representative of the American
Academy of Pediatrics on the topic of raw milk. My background includes two
years as a medical epidemiologist with the Centers for Disease Control in
Atlanta, Georgia, and I am currently on the faculty of the University of
California Medical Center in San Francisco as an assistant clinical professor in
pediatrics.*
The major goals of the American Academy of Pediatrics have always been the goals
that would lead to the betterment of child health practices throughout the
world. Our committees are actively working on guidelines for immunization,
nutritional practices, child safety practices, and in many other fields which
---`impact- on children.
One of our recent concerns has been the growing popularity of raw milk as a sup-
-, posed 11health food." Our organization has reviewed both the nutritional proper-
ties and the safety records of raw milk and has found that the risks outweigh
the benefits. That is to say, there are no benefits of raw milk that would out-
weigh the extreme risk of infection that sometimes follows feeding raw milk pro-
ducts to Infants, children with malignancies, and children with problems
Involving the immune system.
Data from the Centers for Disease Control have shown numerous incidents around
the country where infections with Salmonella and Campylobacter have been linked
to raw milk usage. Since 1977, 192 isolates of Salmonella have been made in
certified raw milk marketed in California. This milk is also transported across
state lines by distributors. The most recent finding on September 28th of this
year involved 4,000 gallons of certified raw milk which was distributed to con-
sumers and retail outlets. It is obvious that many other instances of con-
tamination may have gone undetected.
There are many organisms that have been linked to raw milk usage, but the two
most commonly noted at this time are Campylobacter and Salmonella dublin.
Campylobacter causes high fever and bloody diarrhea, a disease indistinguishable
from the usual Salmonella infection. Unfortunately, Salmonella dublin is not
one of the usual Salmonellae. More that 75 percent of the human isolates of
this organism have come from sites outside the gastro intestinal tract including
* blood, brain and cerebro-spinal- fluid. This is a "host adapted" organism which
is found almost exclusively in cattle, except for the times when it infects man
with devastating results.
When we consider that "usual" Salmonella infection, statistics from the United
States and elsewhere reveal a 5 percent hospitalization rate and a death rate of
less than 1 percent. Contrast these figures with S. dublin infections where
more than 80 percent require hospitalization and approximately 25 percent die.
The 1983 line listing of Salmonella dublin victims in California
also indicates those who were raw milk drinkers. Significantly, out
PAGENO="0028"
22
of 123 cases, 51 drank raw milk, and 1414 were customers of the same dairy. If
you examine the comment column on the right you will note that the list of pre-
existing diseases reads like the index to a pathology textbook: cancer, leuke-
mia, lymphoma, cirrhosis, lupus, AIDS, etc.
This points out one of the most tragic aspects of this problem. Seriously ill
patients purchase a so-called "health food" only to be exposed to S. dublin.
This product Is even advertised as a "basic food for invalids." (~xh4b1+-2)
The proponents of raw milk sometimes bring up the fact that prison volunteers
had to ingest up to 100,000 organisms in order to be infected with Salmonella.
Since that study was done, it has been shown that some strains of Salmonella are
so potent that it takes only a few organisms to produce illness. It is unlikely
that there will be human experiments with Salmonella dublin, given its high case
fatality rate.
What about the milk itself, this milk that has been shown to be contaminated
many times? Is there some property of milk that makes it a better rehicle for
production of salmonellosis when it is contaminated?
This is well exolained in a letter from Dr. William Foege, formerly
Director of the Centers for Disease Control: "Milk contaminated with
Salmonellae is particularly hazardous because the high fat content of milk pro-
tects the pathogens from gastric acid, and its fluid nature shortens the gastric
transit time ... We can conceive of no practical way raw milk can assuredly be
safely marketed ... Unpasteurized (raw) milk is inherently unsafe. The Center
for Disease Control supports pasteurization of milk and other dairy products."
This is a product that is advertised as a "perfect food for
infants." Could anything be further from the truth? While we are on the sub-
ject of advertising, certified raw milk Is advertised in national magazines as
"always pure ... wholesome ... healthful." The advocates have claimed that con-
sumers know the risk they take in drinking raw milk. Our experience is other-
wise. The parents of sick children ask us, "Why was there no warning that this
might kill my child?".
Although some people clearly ignore warning labels, shouldn't the consumer at
least have a fighting chanqe, a chance to know that he is about to consume a
product repeatedly contaminated with potentially lethal bacteria?
As far a~ the claim by producers that certified raw milk is made safe by the
practice of spraying the udders of the cattle with an antiseptic solution and
then using two clean towels to wipe off, I would ask you the following question:
Would you allow a surgeon to operate on you who said he did not need sterile
rubber gloves since his hands would be sprayed with an antiseptic solution and
then wiped off with two clean towels?
This analogy is Important even though it may sound strained. It is not possible
to prevent contamination of raw milk since potentially harmful bacteria still
PAGENO="0029"
23
reside on the udders and inside some of the cattle as well. Cattle referred to
as mammary shedders have been identified by the California State Department of
Food and Agriculture. The industry attitude toward this problem has been to
refuse to surrender such cattle for study even though requested by the
- Department of Food and Agriculture.
Another ploy of the industry is to point to other foods such as poultry which
are frequently contaminated with Salmonellae, but not cultured as a routine
~praotice. What they fail to, point out is that these foods are intended to be
cooked before consumption. Heat destroys Salmonellae. Pasturization, heat
treatment of milk, is the only way to assure safe milk supplies.
I would leave you with the following facts:
1. Certified raw milk has been found contaminated by more than 111 separate
county, state and federal agencies.
2. Salmonella dublin, a host adapted organism for cattle, has been the most
* frequent contaminants.
3. The antibiotogram "fingerprints" of the bacterium have shown a match between
one certified raw milk dairy and the organisms found in the cases who drank
that milk. -
11. Approximately 50 percent of the 19811 California Salmonella dublin cases were
customers of the same dairy.
* 5. The CDC has reported numerous instances around the country where
Campylobacter and ~almonella infections, both sporadic cases and outbreaks,
have been linked to raw milk usage.
6. The 1982 FDA investigation of' one major producer of certified raw milk
showed numerous errors in lab techniques and Salmonellae on plates read as
* "negative" by the dairy's lab. *
7. Culture of this milk on two other occasions by the FDA revealed 10-20 per-
cent of the samples contained Salmonellae.
Thank you for your time and attention. I am available to answer any questions,
PAGENO="0030"
24
Mr. WAXMAN. Thank you very much.
Dr. Fierer.
STATEMENT OF JOSHUA FIERER, M.D.
Dr. FIERER. Thank you for having me at this hearing. I am a
physician who specializes in infectious diseases and professor of
medicine and pathology at the University of California's San Diego
School of Medicine, and Director of Microbiology at the VA Medi-
cal Center in San Diego.
I have written over 30 scientific articles about medical microbi-
ology and infectious diseases and am associate editor of one of the
two leading textbooks on infectious diseases published in the
United States.
I am here to tell you about my own personal experiences treating
a dozen patients with salmonella dublin infections in the past 3½
years.
I realize that salmonella dublin is not the only organism associ-
ated with raw milk. However, it is more closely associated with
raw milk than other salmonellas and even campylobacters, prob-
ably because, as Dr. Bolton said, this is host adapted to bovine and
is not found generally throughout the food chain.
The other reason I want to concentrate on salmonella dublin is
because it causes very serious infections in people, as you have
heard from some of the previous testimony.
Most salmonella infections are self-limited; they are illnesses
characterized by fever and diarrhea that usually last 3 or 4 days
and usually there is no serious morbidity. Most of the infections, in
fact, go undiagnosed.
Salmonella dublin infections are different and I will use my own
clinical experience to illustrate this difference.
First, in the United States at least, salmonella dublin affects pri-
marily people at the extremes of life, infants and the elderly, and
patients who have serious underlying diseases which compromise
their immune responses.
Second, when the infection occurs, it usually is a systemic infec-
tion, not a gastrointestinal illness, but one characterized by blood-
stream invasion and metastolic infections, abscesses, outside of the
GI tract.
We recently had a patient at University Hospital in San Diego
that illustrates these properties of this organism very vividly. She
is a woman in her midtwenties who had kidney failure and who
required hemodialysis. She and her roommate drank certified raw
milk for months and had no symptoms of infection, no ill-effects at
all that either of them noticed. She was admitted to the hospital
for her kidney transplantation and within 3 days of having the
transplant-and immunosuppression while still in the hospital-
she developed a high fever, 103 degrees, shaking chills. Blood cul-
tures were done and salmonella dublin grew out.
She ended up with an abscess of her cervical vertebrae and had
about a 4-week hospitalization for treatment of that.
This case illustrates the important points that I want to make
about salmonella dublin: that is, a relatively healthy person, even
somebody with chronic renal failure, can be exposed to salmonella
PAGENO="0031"
25
dublin and not become ill. However, in the face of immunosuppres-
sion asymptomatic infection turns into a potentially lethal one and
this can happen very quickly.
When salmonella dublin causes illness in an adult, it doesn't
present as gastroenteritis-this woman had no diarrhea-but it
presents itself as asepticemia. As a result of the invasion of the
bloodstream, patients can die or suffer serious infections of their
heart, blood vessels, brains, lungs, or bones. These infections are
difficult to treat, partly because many salmonella dublin are resist-
ant to the antibiotics we ordinarily use to treat salmonella infec-
tions.
Three of my 12 patients have died, 2 directly as a result of the
salmonella dublin infection.
The ability of salmonella dublin to invade the bloodstream distin-
guishes it from most other salmonella. Since 1980, in my hospital,
we have had 10 cases of salmonella septicemia-bacteria that iso-
lated from blood cultures-and 7 of these were due to salmonella
dublin.
That is 70 percent of all the salmonella bacteriemias were due to
dublin.
That was true even though salmonella dublin represented less
than 10 percent of all salmonella infections diagnosed in San Diego
during that time period. That, I think, is illustrative of the particu-
lar virulence of this organism.
As I interpret information from the U.S. Department of Agricul-
ture, salmonella dublin infections are now epidemic in the cattle
herds of America, having spread through the West and Midwest.
This bovine epidemic is now being reflected in humans with in-
creasing numbers of salmonella dublin infections reported in the
United States in each of the last 4 years.
Raw milk is not the only source of these infections, but it is the
single most common source and it is the source that can be effec-
tively controlled with known technology-that is, pasteurization.
Therefore, I would urge both State and Federal Governments to
protect the public, protect the public health, and to require pas-
teurization.
Thank you.
[Dr. Fierer's prepared statement follows:]
PAGENO="0032"
26
Testimony of Joshua Fierer, M.D.
Concerning Infection Hazard of Raw Milk
U.S. House of Representatives Subcommittee
on Health and Environment
Introduction
My testimony will be concerned with the clinical manifestions of
Salmonella dublin infections in adults. Although S. dublin is not the
only serotype of Salmonella that has been transmitted by raw milk, it is
preeminently important in the context of this hearing for two reasons: 1)
S. dublin is host adapted to bovines and is rarely found anywhere else in.
the~fôod chain. Therefore, nearly all human infections with S. dublin are
acquired either by direct contact with bovines (veterinarians and farmers),
from eating raw beef, or from drinking raw milk. Consequently S. dublin
infections can serve as a indicator of milk-borne salmonellosis. In
contrast, other types of Salmonella are widely distributed in the food
chain, so that even if a patient with salmonellosis drinks raw milk, it is
difficult to incriminate that vehicle as the source of the infection in
the absence of an epidemic; 2) 5. dublin infections in people are unusually
severe. There has been an attemptb~ raw milk advocates to minimize the
seriousness of salmonellosis. This review of S. dublin infection will
provide evidence that S. dublin is capable of cau~Ti~j1ife threatening
infections and must be considered a serious risk to raw milk drinkers who
have predisposing illnesses.
Backg round:
Salmonella is a genus of bacteria that was discovered 100 years ago.
From the very beginning this genus was recognized to be pathogenic for
humans and animals. That is, Salmonella are capable of producing illness
in otherwise healthy individuals under natural conditions of infection.
Salmonella dublin (S. dublin) is one of nearly 1000 serotypes of
salmonella.i~iff~rs from other serotypes of Salmonella in several ways:
1. 5. dublin is host adapted. The vast majority of
SalmoneIIä~ serotypes can infect all animals. A few sero-
types are host adapted which means they are found naturally
in only a single animal species; Salmonella ~ the cause
of typhoid fever, is host adapted to humans and S. dublin,
in an analogous way, is host adapted to bovines. Serotypes
such as S. enteritidis, which are not host adapted, are
frequently ~ dUnt.ii~e in our diet so, they are the most
common causes of Salmonella gastroenteritiS. One reason that
S. dublin infections are uncommon in people is that our
exposure is so limited.
2. S. dublin is metabolically different from other
Sa1m~neIIh serotypes. For instance, S. dublin requires the
vitamin nicotinic acid (niacin) for growth. This vitamin is
abundant in cows.
3. The human disease caused by S. dublin is not
primarily gastroenteritis, which is~i~rincipa1
illness caused by non-host adapted Salmonella. Instead,
this organism invades the body through the intestine,
producing very serious illness (see below).
PAGENO="0033"
27
The Clinical Manifestations of S. dublin Infection:
This discussion is based on my own experience with 12 S. dublin
cases, and an unpublished series of cases from 1983 that was collected
by the California Department of Health Services. All the cases were
diagnosed in California and represent sporadic (non-epidemic) cases.
The findings are summarized on tables 1 and 2.
In general, the adult patients who were infected with S. dublin
were "susceptible hosts." That is, they had some illness or physiological
impairment that lowered their resistance. About one-third of the cases
occurred in people over 60 years old, many of whom (15/55) were 70 or
over., Some of these elderly people had no other known risk factors for
infection, other than age. Treatments that decreased or eliminated
gastric acid also predisposed to infection. This included people who
had gastrectomies for ulcers and people who were taking antacids.
Gastric acid is an important natural defense against all ingested
pathogens. Pregnant women were also susceptible to infection. It is
known that late in pregnancy the immune system is supp~essed, possibly
due to hormonal changes, and pregnant women are more susceptible to
other infections, such as tuberculosis. Most of the other patients had
other illnesses or treatments known to suppress the immune response,
such as leukemia, cancer, AIDS, organ transplants, and corticosteroid
use. Only 21% of the patients had no known underlying illness and they
tended to have mild disease, often only diarrhea.
Table 1
Characteristics of Patients Who Developed
S. dublin Infections
Series
V.A.M.C. California
San Diego
1979-1984 1983
(% Positive) (% Positive)
i~ge >60 58 30
Underlying Illness* 90 75
Cancer or leukemia 25 19
Liver disease o 5
Transplant o 5
Acquired Immuno- 17 5
deficiency (AIDS)
Stomach disorders 33 5
Corticosteroids 25 14
Pregnant o 7
None s 23
:c~mbers of Patients** 12 43
5Patients may have had more than one underlying illness~
*~These 43 cases were abstracted from 123 that were reported in 1983.
They are all the adults who had consumed raw milk or other raw dairy
products.
52-266 0-85-2
PAGENO="0034"
28
Table 2
Clinical Manifestations S. dublin Infection
V.A.M.C. California
San Diego 1983
(% positive) (% positive)
Hospitalized 90 84
Death 25 19
Bacteremia 90 58
(Positive blood
culture)
Extra-intestinal 42 26
infection
Diarrhea 17 33
The manifestations of S. dublin infection in these patients were
dramatically different frommost salmonellae infections. Nearly 90% of
the patients were sick enough to require hospitalization. In two
thirds of the cases, S. dublin invaded the blood stream usually causing
a serious infection outside of the intestine. Examples of those
extra-intestinal infections included: meningitis, endocarditis
(infected heart valve), abscesses, and aortitis (infected aorta).
About 20% of the patients died, directly or indirectly as a result of
the infection.
These findings distinguish S. dublin infection from nearly all
other forms of salmonellosis. The usual illness caused by other
Salmonella consists of diarrhea and fever that last about 72 hours.
Rarely do adult patients require hospitalization, and only young
infants have a high mortality rate. Only 10% of salmonellosis cases
have associated bacteremia.
What accounts for the dramatic difference between S. dublin and
other organisms? There are two possible explanations that are not
mutually exclusive. One is that S. dublin is more virulent for people
than are other strains. There is precedent for this in that S.
choleraesuis, a Salmonella that is host adapted to pigs, is
exceptionally virulent and invasive in people. The second explanation
is that the people who got infected are so impaired that they cannot
defend themselves against this or any other Salmonella. There is
indirect evidence to support this. In Scotland there was a large
epidemic of S. dublin due to drinking contaminated raw milk. In this
rural setting, nearly all the illness occurred in previously healthy
people andthere were no deaths and no complications. This suggests
that if healthy people are infected by S. dublin, they can limit their
illness to gastroenteritis. However, I do not think the vulnerability
of the host is the entire explanation for the behavior of S. dublin in
California. Since 1980 there have been 10 cases of Salmoi~ella
bacteremia at the V.A.M.C., in San Diego and 7 were due to S. dublin.
Thus, S. dublin was represented far out of proportion. to the overall
incidei~ce of S. dublin infection in San Diego County.
PAGENO="0035"
29
Conclus ions
In California, S. dublin infections have been very serious. They
occurred in susceptible people who usually become very ill and some-
times died as a result of the infection. The irony is that many of
these people began drinking raw milk because they had some chronic
illness and thought the raw milk was a "health food" that would benefit
them. They had no warning, no way of knowing that the milk might be
contaminated with potentially lethal bacteria. I think these people
should be protected from this hazard. At the very least, they should
be warned of the potential hazard so that they can make an informed
choice as to what kind of milk they drink. At best, raw milk will be
removed from sale.
PAGENO="0036"
30
INFANTS AS A SOURCE OF In 12 of the 48 households where animals were kept, Sal-
SALMONELLA the "baby type". Only once was the infant milk formula
found to be positive and in 9 cases the animal feed.
CONTA1~4I1~4ATION In ~% of the households Salmonella could be isolated
from various surfaces. In 92% of these cases the type was
M. VAN SCHOTHORST the same as that of the baby. These surfaces included those
of the baby's bath, the bottle and nipple, playpen, dish
cloth, rubbish bin, etc. The kitchen sink was found to be
contaminated in 42% of the households, in 97% of these
In the Netherlands, about 10,000 Salmonella strains are cases the "baby type" was isolated.
isolated yearly from humans. Circa 9% of these originate The number of samples examined and the number of
from infants, It is assumed that in most cases sainsonellosis samples found positive are presented in Table 2 as well as
of older children and adults is caused by consumption of the number of samples from which the "baby type" was iso-
contaminated foods. It is not likely that food is the cause of lated.
the infection as long as the baby is being breast or bottle When the columns indicating the total number of posi.
fed. Also after weaning the infant is mostly fed with Salmo- tives and the number of samples with the "baby types" are
nella free food, suth as canned food, biscuits and freshly compared, it is evident that in most cases the Salmonella
prepared, adequately heated meals. isolated from the various samples was of the same type as
Since little is known about how a baby catches salmonel- that found in the faeces of the baby. It is possible to think
losis, an attempt was made to try and obtain information of various sources of these household contaminations.
on the methods of food preparation and hygiene habits in a Animals are frequently regarded as an important res-
household with a case of infant salmondllosis. Such ervoir of Salmonella but it is highly improbable that ani-
households were visited and farces of the baby and also of mals or animal feed have contaminated the kitchen sink
other inhabitants, pet animals, relevant foods, swabs from and other surfaces. Also in those households where no pets
kitchen sink etc. were examined for the presence of were present, a high percentage of the kitchen sinks were
salmonellae. Furthermore, by talking to the family, an idea found to be contamined with the "baby type".
of the hygiene awareness of the family was obtained. Human carriers could be the source of the "baby type"
During the course of these studies, although it became but only in 36% of the homes such carriers were actually
* apparent that the causes of infant salmonellosis were diffi- found. Although animal and human excreters cannot be
cult to identiI~', a new source of contamination of a house- excluded as the origin of the infection of the baby, it is
hold was discovered. This paper deals mainly with the 1st- much more likely that the babies were the source of the
ter aspect. household contamination.
The studies were carried out in the Netherlands in the This assumption is substantiated by the results of the
National Institute of Public Health (Bilthoven) and the quantitative examination of faeces of some of the babies.
mtdical center in Rotterdam. These results revealed that during various periods of time,
During a period of one year 74 households were visited high numbers of Salmonella may be present in the faecal
by public health nurses, one or more weeks after a case of material. It should be mentioned here that often the babies
infant sa.lmonellosis was diagnosed and confirmed. were fully recovered after only a few days of illness and
The samples of faeces, foods and swabs were examined their farces looked completely normal.
according to the EEC standard method using buffered pep- When a mother is attending to baby's toilet, it is clear
tone water for pre-enrichment during 16 to 20 hours at that a hundredth of a gram of faecal material may easily
37"C, tetrathionate brilliant green bile broth for enrichment adhere to the fingers. When this baby is excreting a million
at 43uC for 48 hours, and brilliant green agar as selective salmonellae per gram, a thousand can thus remain on the
agar. hands of the mother. Via the mother's hands other mem-
A surprisingly great variety of different Salmonella scm bers of the family, animals, foods and surfaces may become
and phage types were found, namely 15 serotypes, 4 phage contaminated and the infant may even become reinfected.
types of Salmonella panama and 16 phage types of Salnso- This assumption is strongly supported by the finding
nella typhimurium. in 74% of the households, however, the that only 0.6% of the family members were infected with
Salmonella type isolated from the other people, surfaces, another Salmonella type (a percentage that is more or less
etc. was the same as excreted by the baby (the "baby type"). normal for carriership) while 17% were infected with the
The most important Salmonella findings in the various "baby type".
households are presented in Table 1. In 31 of the 74 house- This risk of contamination may occur over long periods
holds where farces of the family was collected, at least one of time as can be learned from Figure 1 and Table 3. In the
of the family members was excreting Salmonella, and in 27 figure two excretion patterns are illustrated, both indicating
of the households (36%) they were excreting the "baby that several months after illness, quite a high number of sal-
type". monellae may still be present in the faeces. In Table 3, the
TABLE t Salmonella isolations in 75 households. TABLE 2 Salmonella in household-samples.
Number of households Number of samples
With With
Examined Positive "balpy~ype~ Examined Positive "baby type~
Human faeces 74 31 27 Human faeces 232 44 39
Animal faeces 48 12 11 Animal faeces 84 15 14
Baby food 49 1 1 Baby fisod 65 1 1
Animal feed 31 9 5 Animal feed 63 9 5
Kitchen sink 73 31 30 Kitchen sink 140 39 -- 36
PAGENO="0037"
31
TABLE 3 Time of salmonella excretion.
-~ >9 months
4 babies
>7 months
8 babies
> 5 months
14 babies
>3 months
22 babies
Eeamiaed: 25 babies
lag N
~5moxths
FIGURE 1 Salmonella exaction pattern of two babies.
periods during which 25 non-selected babies were excreting
Salmonella is presented. It is disquieting to fond that almost
90% of these babies were excreting Salmonella for more
than 3 months.
In conclusion it is clear that babies who had at one time
Salmonellosis may continue to be an important source of
salmonellae in a household. However, many cases of Sal-
monellosis go undetected, therefore it can be stated that to
limit the spread of salrnonellae in households, on any
occasion, mothers should wash their hands very carefully
after attending to the baby's toilet and adhere more closely
than normal to the basic rules of food hygiene.
REFERENCE
I. VAN SCHOTHORSTM., Htt/SMANJ. axdVANOtM.,N,tT.G,e,xk
197n, 822, 1121-1125.
Ae&*catdgeretThuarnrtrJ5,aappea,elie Pexxd~egi#f:beXx:h txeea,ie~.,t
H)ge*eS)ep,~~en - ~ 31-32, 1981'. a,,Ireu,egarf~O8. Tb. G.!d-
Q 6mnuth,
BOVINE MILK ANTIBODIES
IN THE TREATMENT OF
ENTERIC INFECTIONS AND
THEIR ABILITY TO
ELIMINATE VIRULENCE
FACTORS FROM PATHOGENIC
E. COLI
J.-J. PAHUD, H. HILPERT, K. SCHWARZ, H. AMSTER AND M. SMILEY
Diarrhoeal diseases as a group, are known to be the
major single killer in several areas of the world. Infectious
diarrhoea itself remains an essential problem in pediatrics,
as dehydration and electrolyte losses in premature and new-
born infants, frequently have a fatal outcome. The gut asso-
dated lymphoid organs are not yet fully developed in the
newborn child, who is particularly vulnerable to enteropa-
r.hogenic microorganisms. Maternal antibodies transmitted
to the human foetus in utero consist mostly of 7S IgG, but
do not include any IgA [1-2]. These antibodies remainpri-
manly in the child's blood, and the limited amounts of lgG
transferred to the intestinal mucosa are unstable in the
secretions and demonstrate only weak activity against the
enreropathogens. Mother's milk plays an essential role in
compensating this deficiency by transmitting protective fac-
tors to the infant's digestive tract, induding immunoglobu-
lins (mostly secretory IgA), lactoferrin, lysozyme, lympho-
cytes and macrophages. It is now well established that
breast-fed infants show a significantly higher resistance
against bacterial and viral infections, compared to infants
fed with adapted cow's milk [3-5).
In the formulation of artificial infant milk, priority is
usually given to the nutritional value and safety of the pre-
paration, but little attention is paid to the sheer absence of
immunobiological factors. Passive oral immunization using
milk immunoglobulins from specifically vaccinated cows
was first proposed by Petersen and Campbell [6). These
authors dalmed that the intestinal resorption of milk anti-
bodies was sufficient to induce general humoral immunity.
Current evidence tends to disprove the transmissiunper Os
of significant immunity to the circulation of the newborn
infant [2]. However, as an alternative to mother's milk, oral
administration of bovine milk antibodies may contribute to
the local immunity of the infant's gut against human ente-
ropathogens. Several aspects of this concept previously
under discussion will be briefly reviewed, namely the speci-
ficity of bovine milk antibodies, their stability during tech-
nological processing, antibacterial activity, resistance against
difestion efficiency in clinical trials and absence of toxicity
The antibody specificity of cow's milk was actively
induced with a polyvalent vaccine incorporating the entero-
pathogenic E. coli (EPEC) serotypes most frequently
encountered in infantile gastroenteritis. After skimmin
colostral milk and precipitating casein, the imniunoglo u-
lins were concentrated from lactoserum by ultrafiltration.
Diafiltration was applied to remove lactose and mineral
salts. Sterilization was performed by filtration and drying
by lyophilisation, in order to avoid denaturation by heat
treatment. The antibody activity was fully retained through-
out the entire industrial processing.
The immunobiological activity of the antibody prepara-
tions was demonstrated on v:oni by passive hemagglntina-
ton, bacterial agglutination and bacterial growth inhibition.
0
PAGENO="0038"
32
Mr. WAXMAN. Thank you very much, Dr. Fierer.
STATEMENT OF PAUL M. FLEISS, M.D., M.P.H.
Dr. FLEISS. Thank you. I am Dr. Paul M. Fleiss. I am a board cer-
tified pediatrician in the private practice of pediatrics in Holly-
wood. I am assistant clinical professor at the University of South-
ern California School of Medicine. I am a lecturer at the UCLA
School of Public Health. I am on the staff of Children's Hospital,
Los Angeles, Cedars-Sinai Medical Center, and several other hospi-
tals in the Los Angeles area. I am also on the professional advisory
board of La Leche League International. That is an organization that
you might be familiar with. It is involved with support of mothers
breast feeding their infants.
I am also the chairman of the Los Angeles County Milk Commis-
sion. The Los Angeles County Milk Commission is composed of four
physicians, one veterinarian, and one public member.
But it is our job to ensure that raw milk meets the standards.
Our job is to certify, and our standards are set by our commission
and the American Association of Medical Milk Commissions.
We check milk, raw milk daily for the total number of bacteria,
and number of coliform bacteria.
We check for salmonella on a once-a-week basis from raw milk
that is sold.
It is my belief that this raw certified milk is a healthy, safe prod-
uct to consume.
I would like to-I would say that I would like to comment on my
colleagues' statements but I am not going to do that. Also the
people that had the very unfortunate experiences, I would like to
comment on those but I will not do that at this time. I would like
to review what exactly pasteurization is. It is the heat treatment of
milk. It in no way guarantees the safety of milk. Pasteurization
will kill approximately 90 percent of the bacteria that are found in
milk. There have been many milk-borne epidemics that have been
caused by pasteurized milk.
So I would like to make that clear. Pasteurization was not a
process invented for milk. It was begun for wine and beer more
than 100 years ago. It was used on milk because there was a time
in the beginning of the century when there were milk-borne epide-
mics which were quite common. There was TB and brucellosis,
spread by milk. And it was a very important public health measure
at that time. Milk-borne epidemics had to be stopped, and pasteuri-
zation was effective in putting an end to milk-borne epidemics of
TB and brucellosis.
But this is not the turn of the century. This is 1985 that we have
now a great deal of change that has taken place in dairy technolo-
gy. We might say it is not the same to practice medicine in 1900 as
it is in 1985.
Modern dairy technology has allowed us to produce milk that is
free from contamination. You~an take healthy cows, check the
cows. You have very sterile equipment. You have milkers that are
checked for disease, trained especially in sanitation methods. You
can have the whole process being overlooked by a sanitarian, regis-
PAGENO="0039"
33
tered sanitarian. And you can have a process where the milk is
checked for bacteria.
You have a process that can allow raw milk to be sold that is
safe from contamination, whereas, pasteurization alone is not
enough to guarantee that milk is going to be safe.
In a lot of cases we have dairies that can use sloppy milking
techniques and techniques that are outdated and pasteurize their
milk; and the pasteurization is rather an excuse for good sanita-
tion, and this should never be.
I have visited dairies all over the world. I can tell you that in
some places they, like in England and I visited dairies in Scotland,
those using equipment that has been essentially outdated in the
United States for the last 40 years. I saw milk being delivered in
horse-drawn carts, unrefrigerated carts. We don't have those condi-
tions here in the United States.
It is possible to produce milk that is free from contamination.
One point I would like to make, some dairies do not only pasteur-
ize milk, they are sterilizing the milk. There are standards that are
set for the minimum pasteurization but in a study we did that was
done by Dr. Anderson at Cal State, Los Angeles, it was found that
a study of bacteria contents of pasteurized milk, there were patho-
gens in pasteurized milk such as proteus and other known causes
of human disease in samples of pasteurized milk. But we found
some samples of milk where there were no bacteria, which means
that the dairies were not only pasteurizing their milk, they were
sterilizing it, submitting it to temperatures that were well beyond
the standards for pasteurization.
Some people might say this is, might be a good thing to do be-
cause you have sterilized the milk but actually what you have done
is changed a good deal of the nutrients. We not only have a prob-
lem in the United States with infectious disease, but we have a
problem of nutrition. And we have a problem where milk is one of
the major sources of human nutrition. It has been estimated that
milk and milk products make up 25 percent of the diet of Ameri-
cans. Now if we are going to substantially decrease the nutrients of
one of the major products of our diets, we will have more people
that are susceptible to infectious diseases.
Of course, the average consumption in the United States is about
6 ounces of milk per capita. There are quite a few people who don't
drink milk at all, and some drink a great deal.
Where there have been epidemics of salmonella dublin in other
parts of the world and indeed the person with the most experience
with salmonella dublin is Dr. Sharp, who reported on his findings
in the British Medical Journal, and he did not have the experience
that has been found in the United States that it was a particular
virulent organism. His statement was that illness from salmonella
dublin more likely results from the impairment of the host than
from invasiveness of the organism.
The heat treatment of milk does a lot of things to it. Now, you
don't have to be a biochemist and measure what the heat treat-
ment does to milk. You can just go and look at the pasteurization
tanks and after milk has been pasteurized there is a residue that
has to be scaped from the sides of the tanks as this represents cal-
cium and casein deposited on the sides of the tank in pasteuriza-
PAGENO="0040"
34
tion. So, we don't have to ask for studies to tell us that milk that is
heat treated has less protein in it. It has less available calcium.
And heat treatment of milk destroys some of the immunoglobulins
found in milk. Some of these immunoglobulins have been found to
be effective in human disease.
Heat treatment of milk does destroy the enzymes present in
milk. There are enzymes in milk such as lactase, which splits lac-
tose. This is a concern for people that have lactose intolerance, and
a good deal of the adult population has lactose intolerance. There
are many reports of-from consumers saying they can tolerate raw
milk, and they cannot tolerate pasteurized milk.
This has been stated to me many, many times. Of course, this
might be due to the presence of the lactase enzyme that is present
in raw milk. There is also lipase in raw milk. This is why some-
times raw milk in storage can deteriorate because of the liberation
of free fatty acids. This has an advantage for people possibly with
fat absorption problems.
There are also vitamins and minerals. You might say 25 percent
of the vitamin contents on average are changed or altered by the
heat treatment of milk. Many consumers of raw milk have stated
to me that they were very sickly before they began consumption of
raw milk, and they have-that they owe their good health to avail-
ability of raw milk in Los Angeles County.
I would like to say my experience, I came about my opinions
mostly from my experience of dealing with patients. When I first
started in private practice of pediatrics I would advise people not to
drink raw milk or raw certified milk. But it wasn't long before I
was in practice. Since I was in Hollywood, I have a very large
number of patients who depend on raw certified milk. They would
come, they came to me and said they were drinking the milk. I can
remember advising people they should never do this. But enough
people came in with nice robust healthy babies that I began to ask
them more about that. They told me where they were buying the
milk. I called up the dairy. I talked to the veterinarians. Then, of
course, I visited the dairy and I saw the process for myself. I
became more and more convinced that what I had been taught in
my public health courses in medical school had been outdated by
modern dairy technology.
I would like to say that there are a lot of critics of raw milk who
have never visited the dairy and don't have any experience with
the way it is produced.
I would say that it was patients and consumers-and there are
many of these, and at times the dairy produces 18,000 gallons of
milk a day. If you think the average person drinks approximately 6
ounces of milk a day, you don't have to be a biostatistician or epi-
demiologist to know there are a lot of milk drinkers out there, per-
haps 100,000 to 200,000 people per day. Then if you end up with-I
don't have the figures in front of me. But a few scattered cases of
salmonella you see the incident relatively low.
Of course, as far as I know, there has never been a cluster, what
epidemiologists term a cluster of disease attributed to the consump-
tion of raw certified milk.
[Dr. Fleiss' prepared statement follows:]
PAGENO="0041"
35.
STATEMENT OF PAUL M. FLEISS, M.D., M.P.H.
PEDIATRICS, PEDIATRIC NUTRITION
Dairy technology has advanced a great deal since the early
1900's. While pasteurization was once the only way to prevent
the spread of milk-borne diseases such as tuberculosis and
brucellosis, their procedure is not now enough to guarantee the
safety of dairy products. Milk must be produced under the most
stringent of standards and under constant supervision to ensure
its sanitation. Once milk is produced with modern advances in
technology and strict regulations such as those of the
A.A.M.M.C., pasteurization is not necessary and obsolete. Raw
milk should be available to the consumer for the following
reasons:
1. Fre~edom of choice. Many people prefer to eat their
food unheated. This should be obvious by observing the
popularity of Japanese sushi bars in the U.S. Also many people
ingest raw oysters, beef liver and steak on a regular basis.
Food intake histories on a random basis have revealed that people
eat a wide variety of food products, heated and unheated.
2. ~1~aste. Unheated milk does not taste the same as
pasteurized milk. One does not have to be a physician or
scientist to make this observation.
3. Nutritional benefits. Major nutrients are decreased
10-50% by the heat treatment of food(l). This would not be
significant except that milk products comprise 25% of the
American diet and for some few individuals this could mean the
PAGENO="0042"
36
difference between health and a deficiency state.
4. ~ This begins prior to the milk
reaching the stomach. The lipase found in milk splits off free
fatty acids and is responsible for the rancid flavor of unheated
milk as it ages. The presence of enzymes (lipases) is the reason
*why ice cream made from raw milk cannot be stored. The lactase
present ,in milk breaks up some lactose into glucose and
galactose. Both glucose and galactose are sweeter than lactose.
This is why raw milk often tests sweeter than pasteurized milk
and why many people with lactose intolerance report that they are
able to tolerate raw milk and not pasteurized milk.
5. Antibo~lies. These have been found in raw milk and they
have been effective against enteric infections.
6. Processing. Many dairies are not pasteurizing their
milk but are sterilizing the product. Milk is now being
subjected to very high temperatures in order to reduce the
bacteria found because of poor dairy practices causing obvious
contamination. Many new substances, especially altered antigens,
formed from heat treatment, and the health effects of such
treatment are unknown but to some people present additional
health hazards(2).
7. Safety. Milk produced under the standards of the
American Association of MedicalMilk Commissions has not been
associated with any clustered outbreak of disease. On the other
hand, outbreaks of disease have been traced to pasteurized milk.
Milk, raw or heated, may be a source of vital nutrients and
of disease as well. There is a need for unbiased scientific
investigation into the ramifications of changing this food.
After all, the raw unheated product is the oldest known food of
baby mammals and mankind. Since the studies of raw versus
pasteurized milk are all suspect, what is needed is for an
unbiased group to scientifically design a study of weanling
laboratory animals raised exclusively on pasteurized or
unpasteurized milk. Only then will we have the data necessary to
weigh risk versus benefit in this matter.
PAGENO="0043"
37
CERTIFIED RAW MILK: IS IT WORTH SAVING?
Milk of animals has been used as human food since before--the beginning
of recorded history.' In the United States the unqualified term, milk, is usually
considered to refer to cow's milk, since virtually all milk destined for human
consumption is from the cow. Although similar constituents are pres~nt in the milk
of all mammals, the proportions of constituents vary greatly among each individual
mammal. The milk of each species is unique and is a complete food for its young
for a definable period of time after birth.2
Human milk, raw and direct from mother's breast, is without question
the food of choice for humans for the first six months of life. There have been
many reports of antiviral and antthacterial properties of human milk being destroyed
3,4,5,6,7
by heat treatment, and calcium and fat absorption are decreased by heating
human milk.8 Raw human milk has mitogenic activity which heated formula does not.9
Further, animal experiments have repeatedly demonstrated that newborn animals survive
best with raw colostrum milk.2
On the other hand, pasteurization of milk has been one of the significant
public health events of the last 80 years. It virtually stopped milk-borne epidemics
- and partially solved the problem of milk spoilage. It has been responsible for the
milk industry growing from virtual obscurity to a giant of t~e food industry. (The
pediatrician, Henry Koplik, M.D. [of Koplik spots fame) was one o the early advocates
and promoters of the heat treating of milk for infants.7) The growth of large cities
at the turn of the century made pasteurization a necessity as milk was produced under
unsanitary conthtions, handled without medical supervision of workers and transported
without refrigeration before being consumed. Pasteurization is not -sterilization,
but it can destroy 90% of the bacteria present in milk. Still, bacterial opores and
thermoduric bacteria may survive pasteurization, and although thene organi ems usually
PAGENO="0044"
U
do not cause disease, they may produce intestinal gas under anerobic conditions in
the colon.
Raw milk, by comparison, is milk that has not been heated. Thirty-one
states in the United States allow raw milk to be sold. There is no medical super-
vision of the producer or the bottler (if it is bottled). Raw milk is usually
marketed directly from the farm to the consumer and has been assc*iated with
disease outbreaks in humans.1°
Certified Raw Milk (CR11), not to be confused with Raw Milk or pasteurized
Milk, is produced by dairies operated in accordance with the Methods and Standards
adopted by the American Association of Medical Milk Commissions ~`\AMMC) and under
the direct supervision of a local Milk Commission. `Certified Raw Milk is a basic
product and must be pure, clean, fresh, nutritious milk in its natural state, not
having been heated and without the addition of coloring agents or preservatives"
is the definition of Methods and Standards of the A.A.M.M.C.11 CR11 bears the
certification of a county milk commission. In Los Angeles County, the los Angeles
County Milk Commission consists of six members residing in the county, presently
comprising four physicians, one veterinarian and one public member11 appointed by
the Board of Supervisors for a term of four years.
Standards for CR11 state that the milk must be tested daily by an inde-
pendent bacterialogical laboratory. Allowed total bacterial count is less then
10,000 per ml and total coliforms less than 10 per ~i.l2 Cows in the dairy herd
are checked regularly for tuberculosis, ~rucella and Salmonella. All employees
areTgiven regular physical examinations, and all equipment used in producing
CR14 is checked by a sanitationist employed by the milk commission.
Alta Dena Dairy, the only producer of CRM in the State of California
at the present time, has 8,300 cows in their Certified herd that produce 20,000
gallons of CRM each day. This means that approximately 160,000 Cal1fOrnIu"~
drink CR11 every day, and there are probably une mill ion users of CkM, represent jog
PAGENO="0045"
39
about 5% of the State's population.
Alta Dena Dairy also produces Pasteurized Milk. (CRM represents about
20% of their total milk sales.) The dairy has a reputation for being a model for
the industry. Consumers, dairymen and interested physicians may tour the dairy on
any day. Cows producing CRM are washed carefully before each milking and then
milked by electric vacuum milkers, taking milk to coolers without touching air or
human hands. All equipment is kept clean, and surfaces coming in contact with the
milk are sterilized before and after each run of milk.
Consumers of CRM obviously believe strongly in the product as the demand
has continually grown in recent years despite recommendations of some medical
authorities. Some of the reasons consumers give for demanding CRM are:
(1) Pasteurization, although it eliminates harmful bacteria from milk,
does not eliminate dirt, and pasteurization promotes carelessness in milk production
sanitation.
(2) CRM has a superior taste and tends to stay fresh longer.
(3) Vitamins are destroyed by heat: pasteurization reduces vitamin
content of milk by 10 to 40%.
(4) Minerals are not as available for absorption after pasteorizat ion.
(5) Fat absorption decreases after pasteurization.
(6) Pasteurization destroys enzymes present in silk.
(7) Protein is partially denatured by pasteurization.
(8) Homogenization is a factor in heart disease as Bovine Xanthine
Oxidase then can be absorbed in a form which damages arteries.
(9) Pasteurized Milk Protein is more likely to be allergenic than
unheated milk.
(10) Experimental animals fed unheated milk were much healthier thaii
those fed pasteurized milk.
PAGENO="0046"
40
Discussion
Milk, an important source of nutrients in the lanerican diet, his been
recognized as a vehicle of infection for over one hundred years. infection `miy
occur in two ways. One is from direct infection from the cow; the other is by
infection of the milk during its passage from cow to consumer. Even though the
consumer should feel secure that milk is nutritious and free from diseise carrying
organisms, neither pasteurization nor certification can absolutely guarantee the
absence of pathogens in milk when it is consumed. Uncertified, however, is far
more likely to contain disease carrying organisms.
There are many reasons why consumers may desire to ingest unheated milk;
some may be valid, but some are not, as milk is only one source of nutrients in the
diet. These consumers are willing to accept the small risk of infection associated
with drinking CRM. Indeed, CRM buyers have expressed rage that some medical people
attack CEM while tacitly condoning vastly more dangerous substances, i.e., tobacco,
marijuana and alcohol.
And although no proof exists that adult humans and their offspring should
drink cow's milk, many consumers will find raw milk to drink if CRM is not avinlablc:
this could become a severe Public Health problem. We therefore ;uspect phynic)ins,
consumers and Public Health officials should support the market~';y of CRM since
there is such a large public demand for this reasonably safe and nutritious product.
PAGENO="0047"
41
REFERFNCES
1. Whittier, E.O.: Encyclopedia Britannica, 1968, Vol. 15, pp 446
2. Jelliffe, D.B.; Jelliffe, E.F.P.: Human Milk in the Modern World,
Oxford University Press, 1978
3. Bjerksten, Bengt; Berman, L.G.; Dc Chateau, P.: Collecting and Banking
Human Milk: To Heat or Not to Heat, British Medical Journal, 2d1:765,
1980
4. Matthews, T.H.J.; Lawrence, N.E.; Nair, C.D.G.; Tyrell, D.A.J.: Antiviral
Activity in Milk of Possible Clinical Importance, Lancet, Dec. 25, 1976,
1387-1389
5. Ford, J.E.; Law, B.A.; Marshall, V.M.E.; Reiter, B.: Influence of Heat
Treatment of Human Milk on Some of its Protective Constituents, The Journal
of Pediatrics, Vol. 90, No. 1, pp 29-35, Jan. 1977
6. Raptopoulou-bigx, M.; Marwick, K.; McClelland, D.13.L.: Antimicrobial Proteins
in Sterilized Human Milk, British Medical Journal, 1977, 1, 12-14
7. Hall, C.; Trout, C.: Milk Pasteurization, Avi Publishing Co., 1968
8. Williamson, S.; Finulane, E.; Ellis, H.; and Cansu, I.R.: Effect of Heat
Treatment of Human Milk on Absorption of Nitrogen, Fat, Calcium and Phosphorus
by Preterm Infants, Archives of Disease in Childhood, ]97fl, 53, 555-563
9. Klagsburn, N.; Neumann, J. and Tapper, D.: The Mitogenic Activity of human
Breast Milk, Journal of Surgical Research, 26, 417-422, 1979
10. California Morbidity, April 10, 1981, No. 13
11. Food and Agricultural Code, Div. 15, Article 7, p 466
12. TJe American Association of Medical Milk Commission, Inc.: Methods and
Standards for the Production of Certified Milk, Revised 1981
PAGENO="0048"
42
Mr. WAXMAN. Thank you very much, Dr. Fleiss.
Dr. Fleiss, your testimony was at odds with what we just heard
from Dr. Fierer and Dr. Bolton. If I understand correctly, Dr. Fleiss
questions the infectious nature of salmonella, first of all, whether
it is as virulent as Dr. Fierer would claim and; second, whether it
is in raw certified milk and; third, he claims sometimes it is in pas-
teurized milk and that pasteurization isn't a certain enough way of
eliminating infection. And, fourth, that pasteurization can lead to
less nutrition in milk.
Dr. Fierer, Dr. Bolton, would you respond to those points, if I
stated them correctly, and I think I have.
Dr. FIERER. Is it a correct statement?
Dr. FLEISS. Yes; that was a very good summary. The only thing I
would like to add is that pasteurization is not enough to guarantee
the safety of the milk. We need strict standards of sanitation. Then
what you have is strict standards of sanitation and then pasteuriza-
tion is no longer necessary.
Mr. WAXMAN. Let me just isolate it because otherwise my ques-
tion is so broad we will get the testimony repeated.
Let's take some of these more narrowly. Dr. Fierer, do you be-
lieve pasteurization is a sufficient process to prevent any infection
and, two, do you believe that the way the raw milk is handled
without pasteurization is a way to ensure that there is not going to
be infection communicated to people?
Dr. FIERER. I am not-I am a physician, not an expert in milk
handling. But obviously pasteurization is not sterilization. It is not
an attempt to kill all microorganisms in the milk. If you contami-
nate the milk heavily enough with whatever organisms, then pas-
teurization will not completely eliminate the hazard from the milk.
One hopes that the dairy industry doesn't do that. On the other
hand, what we are hearing is an attempt to substitute sanitation
for pasteurization. The issue is will that ever be completely effec-
tive. From talking with veterinarians who specialize in bovine in-
fections, I can tell you that this infection, salmonella dublin infec-
tion, can remain latent in the cattle. The cattle, when stressed, re-
activate the infection-calving is such stress-and in these circum-
stances the organism circulates in the blood, and appears in the
milk excreted directly. There is no way that amount of sanitation
can prevent that.
Mr. WAXMAN. In other words, if I went to Alta-Dena Dairy and
found them to be very sanitary in how they handled the cows and
the milk and then went through the procedures in how they try to
take special precautions to be sanitary, I--
Dr. FIERER. Terrific, but it doesn't eliminate the problem.
Mr. WAXMAN. Why doesn't it eliminate the problem?
Dr. FIERER. Because of the direct shedding into the milk. If Alta-
Dena wasn't as careful as they are-and I believe that, that they
are extraordinarily careful in the way they produce their milk-we
would have epidemics as they have had in Scotland over the years.
There, when the milk is heavily contaminated through gross fecal
contamination then everybody gets ill who drinks it.
Mr. WAXMAN. If they used sanitary methods they probably elimi-
nated a lot of potential.
Dr. FIERER. Absolutely.
PAGENO="0049"
43
Mr. WAXMAN. But as careful as they might possibly be, it is your
opinion that because of the fecal discharge by the cow there is still
going to be some transmission of infection?
Dr. FIERER. Because of the milk discharge.
Mr. WAXMAN. The milk discharge.
Dr. FIERER. Milk discharge, that is right.
Mr. WAXMAN. Dr. Fleiss, what do you say to that?
Dr. FLEI5s. I think that this question of shedding is not a uni-
formly accepted process. Theoretically it is possible but also theo-
retically this means that the bacteria cross from the blood to the
milk. This is not a usual kind of procedure that happens in the
process of milk being formed.
So, shedding is really in theory. It is not really established fact.
I think again, if sanitation isn't good, well, pasteurization isn't a
guarantee either.
There are numerous studies that have shown that there have
been disease-causing bacteria in pasteurized milk samples.
Mr. WAXMAN. Do you deny there are disease-causing bacteria in
raw milk?
Dr. FLEIs5. Well, there may be.
Mr. WAXMAN. Do you think there is never any disease-carrying
bacteria in raw milk?
Dr. FLEI55. No; I can't guarantee that. I think the possibility is
always there.
Mr. WAXMAN. Is the possibility equal if the milk is pasteurized
on the one hand or raw on the other?
Dr. FLEIS5. My personal belief is that it is probably greater, there
is more chance of disease-causing bacteria being present in pasteur-
ized milk because I do not believe that the majority of the dairy
industry sticks to the strict sanitary conditions that the producer of
raw certified milk does.
Mr. WAXMAN. Dr. Fleiss, your views are so at variance with the
other two witnesses, but also with the American Academy of Pedi-
atrics, A.M.A., American Public Health Association, all those
groups are on record opposed to the use of raw milk because they
believe it is a risk to the public health.
Dr. FLEI55. Yes.
Mr. WAXMAN. In light of their views, what special expertise or
data do you have or how do you explain why they have such an
overwhelming consensus of those groups saying there is a greater
chance of infection from raw milk, and your contradicting them?
Dr. FLEI55. I would like to say that historically they are correct,
but they are perhaps 40 or 50 years behind the times. I think that
we had a time when milk-borne disease was a real threat to our
health, when TB and brucellosis were extremely rampant and we
needed some guarantee. At that time pasteurization was a miracle.
It was like the advent of penicillin or other modern major ad-
vances. But now we have come further than that. I think that with
time there has been a lag in the appreciation of nutritional bene-
fits by all of those organizations that you have mentioned.
I think the American Medical Association, American Academy of
Pediatrics, American Veterinarian Association, they have all been
a little-they have been lagging behind in their appreciation of
what nutrition means to Americans.
PAGENO="0050"
44
Mr. WAXMAN. Let me ask you this question. How do you handle
the suggestion that there are some groups of people that are more
vulnerable to infections, such as babies, people who are suffering
from some disease, or the elderly? Do you dismiss that or do you
think that that is more likely a group to be affected?
Dr. FLEISS. Oh, no, as I stated, pregnancy, the very young infant,
debilitated, the cancer patient, the patient that is under chemo-
therapy, the patient that has had radiation therapy-these are spe-
cial groups of patients. They are very vulnerable to disease-causing
organisms. They should, of course, be treated as such.
I think when a patient does have a debilitating disease or cancer
or is being treated by immunosuppressive drugs, that they should
be warned about the potential for infection, potential for infection
both from food, from water, and from other persons. Certainly
these people are at risk for infections from-their physicians
should warn them to stay away from sick people, for instance. But
that doesn't always happen.
Mr. WAXMAN. If you recognize there are some groups that are at
higher risk of infections, do you think we ought to look with special
care when there are products such as raw milk that are targeted
for those markets, the children, elderly-the very people who want
to make sure that they are getting the best health care because
they happen to be sick already?
Dr. FLEI55. I don't think that raw certified milk is targeted for
sick individuals. I think that you will find that healthy people are
consuming raw certified milk--
Mr. WAXMAN. Let me interrupt you and place in the record a
publication put out by Alta-Dena Certified Dairy. They say "It is
the safest, purest, most wholesome milk you can buy. Its easy di-
gestibility makes it the ideal formula-milk for babies . . . and for
the same reason, a basic food for invalids."
Aren't we talking about two high-risk groups that are more sus-
ceptible to infection yet Alta-Dena is suggesting they ought to
drink raw milk?
[The publication referred to follows:]
PAGENO="0051"
45
1'1\~.
54_ `C
What is Certified Milk and Why should you buy it in preference to other
milk?
Certified Milk is the highest grade milk that skill and care can produce
or money can buy. It is produced according to the rigid standards and con-
trols of the American Association of Medical Milk Commissions. Its produc-
tion is supervised by the local Milk Commissions.
It is the safest, purest, most wholesome milk you can buy. Its easy
digestibility makes it the ideal formula-milk for babies.. and for the same
reason, a basic food for invalids. Healthy youngsters and adults, too, enjoy
the fine rich flavor, of this purest of milks.
IS THERE PROOF OF CERTIFIED MILK'S SUPERIORITY?
The world's finest milk has the lowest Bacterial Count allowed in milk-
Certified Milk must test less than 10,000 bacteria per mililiter. The State &
County regulations permit 50,000 bacteria per mililiter before pasteuriza-
tion, and 1 5,000 bacteria per mililiter after pasteurization. Certified Milk
must have less than 10 coliform per mil-whereas milk before pasteuriza-
tion may be as high as 750 coliform per mil-so it may readily be seen that
Certified Milk virtually is The Perfect Milk.
PAGENO="0052"
46
Is Certified Milk economical?
Yes. Quoting W. E. Krauss, noted authority of the Ohio Agriculture Ex-
periment Station, "In a Suitable menu designed to meet the daily needs
according to the accepted nutritional yardstick, MILK CONTRIBUTED RELA-
TIVELY MORE FOOD VALUE FOR LESS MONEY than did the other foods
comprising the meal." The added safety and purity of Certified Milk makes
it a definite factor in food value and economy.
What are the rigid and exacting standards under which Certified Milk is
produced?
Many special elemenls enter into the careful production of Certified
Milk involving (1) the selected milk producing herd . . . (2) the special
employees connected with every step of production and processing . . . and
(3) the unique facilities ar~d modern equipment used.
How does the herd producing Certified Milk differ from others?
A Certified Herd is composed of only carefully selected cows. They
are chosen for the select certified herd" because they have passed with
flying colors the most rigid and exacting tests. They are subjected to reg-
ular examinations by a veterinarian who checks for every known cow infec-
tion. Their product is checked daily by laboratory technicians and their
health records must have been perfect since they were calves. Each cow
is fed scientifically balanced rations to insure the consistent quality and
flavor of her milk. Alta-Dena Dairy, owned and operated by Stueve Brothers,
produce all their milk in order to give you the highest quality milk available.
We believe in order to keep cows healthy, proper feeding is essential and
since the soil is depleting in minerals we add them to our feed. It is proven
that the mineral feeding to the cows shows through in the milk. We feed
green alfalfa during the summer and dry alfalfa during the winter.
A ration is fed to milking cows consisting of barley, oats, milo, almond
hulls, bran, beet pulp, orange pulp, milo mill feed, cotton seed hulls, soy
PAGENO="0053"
47
meal, copra, cotton seed meal, molasses, kelp, corn fermentation solubles,
salt, yeast and trace minerals.
Under what rigid sanitary conditions is Certified milk produced?
All cows are washed very carefully before each milking, and then milked
by Electric vacuum milkers, taking milk over to coolers, without touching
air or human hands.
Certified buildings are constructed to provide the best possible sanitary
features; adequate light, mechanical ventilation and flooring. All equipment
is kept scrupulously clean, in perfect repair, and all surfaces coming in con-
tact with the milk are sterilized before and after each run of milk. The highest
standards are required to provide the public with the purest, most whole-
some milk possible.
What are some of the Standards that must be met by employees connected
with the production of Certified Milk?
Physicians give regular examinations to every person employed in the
dairy or in any capacity connected with the production, bottling or distribu-
tion of Certified Milk. A new employee must pass a rigid examination and
must present a satisfactory past health record . . . in addition to his regularly
scheduled examinations.
How are these standards and protections actively practiced?
In addition to the above mentioned requirements, physicians visit the
farms periodically for a thorough inspection of the working media and to
insure you top quality Certified Milk.
All persons handling Certified Milk must wear clean, white suits and
caps that may be worn for no other purpose.
These are only a few of the precautions taken to assure consumers
that Certified Milk is the cleanest, purest, most wholesome milk possible.
Alta-Dena Dairy has a complete laboratory which is controlled by a
licensed bacteriologist where we are able to run tests on all of our products
and maintain consistent quality control at all times.
PAGENO="0054"
48
Dr. Fi~iss. I don't know anything about that particular brochure.
I think that there are groups throughout our population that con-
sume--
Mr. WAXMAN. I have just been told this document I just read to
you has the seal of the American Association of Medical Milk Com-
missions, and you are an official of that organization. Is that cor-
rect?
Dr. FLEISS. Yes.
Mr. WAXMAN. With babies, do you think that raw milk is more
easily digestible and therefore the ideal formula milk for babies?
Dr. Fr~iss. No. Babies should be breast fed. I think that this is a
very, very important point. I think that raw milk is inappropriate
for very young babies. I also think that formula as it is now pro-
duced is inappropriate for babies. I will make my point. I have
heard strong opinion on that. If you want to talk about that, I have
many examples of why infant formula is--
Mr. WAXMAN. I gather that is an area where the three of you
would concur, Dr. Bolton, Dr. Fierer?
Dr. FIERER. Yes.
Dr. BOLTON. Yes.
Dr. FLEISS. One thing about infant formula, there was recently
found in one of the most common infant formulas, found to be high
in trichloroethylene, an organic solvent.
Mr. WAXMAN. I will interrupt you because--
Dr. FLEISS. I just want to say--
Mr. WAXMAN. It is a little off the subject. I agree with you, from
all I have heard as well.
Dr. FLEISS. OK.
Mr. WAXMAN. I am sure the other two witnesses would agree.
Let me ask you one last question. You are the secretary-treasur-
er of the American Association of Medical Milk Commissions. The
certified milk standards of the AAMMC were recently reYised.
Were these changes intended to strengthen them or weaken the
quality control procedures required to manufacture certified raw
milk? Isn't it true the revised standards no longer require that cer-
tified raw milk be free from salmonella organisms?
Dr. Fu~ass. I am not aware of that. I don't know that. I think
that as it is stated in the beginning of the standards for the
AAMMC it says the goal is to produce the most nutritious free
from disease-causing organisms milk that is possible.
Mr. WAXMAN. I want to put into the record at this time both sets
of the AAMMC standards which would indicate that the latest re-
visions specifically delete the requirement that certified raw milk
be free from salmonella organisms. And I want you to have a
chance to look at that. If you want to submit a reply or explanation
for this, we would be pleased to receive it and put it in the record.
[The information referred to follows:]
PAGENO="0055"
49
AMERICAN ASSOCIATION OF MEDICAL MILK COMMISSIONS, INC.
Paul M. Fleiss, M.D., MPH., F.A.A.P.
Secretary
1824 North Hillhurst Avenue
Los Angeles, California 90027
(213) 6641977
February 15, 1985
Congressman Henry Waxman
2418 Rayburn House Office Bldg.
Washington, D.C. 20515
Honorable Waxman:
This letter is in reference to your questions regarding the test-
ing of raw certified milk.
Without specifying every potential bacteria, THE METHODS AND
STANDARDS FOR THE PRODUCTION OF CERTIFIED MILK established a
criterion which far exceeds that required of pasteurized milk
(even after pasteurization).
Page 6, Title 5 specifies what laboratory standards must be fol-
lowed in testing certified milk. Page 2, Title 2, Sec. 1, para-
graph 3 states, "... these ... standards ... shall be regarded
as minimal and may be augmented by the requirements of local
milk commissions."
Finally, the Appendix (page 20) states, "The ultimate aim of
the procedures shall be to provide a product in which the original
nutritive qualities, flavor and appearance have been preserved
and to ensure that no harmful organisms or substances are present
to adversely affect the consumer."
Salmonella is not specified because to do so would require that
other bacteria be listed as well. In my opinion, these standards
more fully ensure the quality of the finished product.
Sin72(
PAUL M. FL ISS, M.D.
Secretary and Treasurer
PMF:cjr
enclosure
PAGENO="0056"
50
1~IethO(1S afl(I Standar(ls
for the Production of
Robert Tjqjtçnger, Jr., M.D.
President Of
`lifE AMERICAN ASSOCIATION OF
MEDICAL MILK COMMISSIONS, INC.
1136 East (;reei~ Street
Pasadena, California 91101
L. Allen MeDonough, M.D.
Chairman of Council of AAMMC
1036 Lindbergh Drive, N.E.
Atlanta, Georgia 30324
National Head1uarters
P. 0. Box 554
Alpharetta, Georgia 3020!
~1'~H~fl 1Gl~-
J. L. flopping, Jr., D.V.M.
Ar~a Codt.~ 404!*t'
Revised
1976
PAGENO="0057"
51
CONTENTS
TITLE 1
HISTORICAL INTRODUCTION 1
TITLE 2
DEFINITION OFCERTIFIEDMILK 2
1. Definition 2
2. Certified Milk, the Basic Product 3
3. (:~-t~fkd Milk, Pasteurized 3
4. C~tj lied Cream, Certified Half and half,
and Certified Fat-free (Skim) Milk :3
5. Special Certi fled Milks 4
a. Certified Milk with Vitamin D Added 4
li. Certified Milk - Homogenized 4
c. Certified Fat-free (Skim) Milk with
Vitamins A and D Added 4
d. l,ow Sodium Certified Milk 5
e. ( ~t-rti lied Acidophilus Milk
f. other Prod nets Made liv Culturing or
(.:liiirtiitig Certified Milk or Cream . . . 5
6. I ~alwli ng special Certi lied Milk 5
7. Certified (;~at's Milk 5
TITLE 3
NUTRITIONAL VALUE AND FLAVOR OF
MILK 6
TITLE 4
MEDICAL MILK COMMISSIONS 7
I. ( )rgan ization 7
2. l)u ties of \kdieal Milk Corn r1ii~ions . . . 7
a. 0 )flieers and supervisors of \lediral
Milk (:o,iitiik.ioi~. 7
li. \lethods of ( :~rti heat ion 8
e_ Report () I \leilieal \ lilk ( ominissions 9
~l. .\d~ frti~.ing 9
TITLE 5
LABORATORYSTANDARDS 9
- ~1J l~''~"''~ inil Rep()rt~ 9
2. lLLrterU)loglcal \ lethod5 and ~tandard5 - - 9
3. ll~~~d and ( :heui ieal ~ lethods and
10
~1. ~`((liin4nt iln(1 I' l~vor lests 11
5. I )eteetion of \lver5)bial I uhi hitants
( \n I ihiotir..) II
TITLE 6
BUILDINGS AND EQUIPMENT II
~iiptrVisioii and Report I I
2. (;iriiral II
a. Location of Building. II
li. Surroundings of Buildings II
(. Lx trrmi natii m of LI ies and other
lNtS 12
PAGENO="0058"
52
d. Exclusion of Rats and Vermin . t2
e. Water Supply 12
f. Drinking Fountai~or Cups 12
g. Toilets..... . 12
h. Homes, Dormitories, Boarding Houses. 13
i. Visitors 13
j. Pollution 13
3. Cow Barns .`. 13
:4. Milking Barn or Room and Equipment ~.. 13
a Construction and Condition 11
b. Cleanliness 14
5. Milk Receiving Rooms 15
6. Dairy Building 15
a.. Construction and Condition 15
b. Rooms Required 15
* c.Use 16
7. Dairy Building Equipment and Bottles. . 16
a. Necessary Equipment 16
b. Construction 1 6
* è. Condition. 1.6
d. cleaning and Sanitizing. . ... 17
TITLE 7
VETERINARY SUPERVISION . 19
1. Supervision and Reports 19
2. Herd Management 19
a. Identification of Cows 19
b. Herd Records 19
c. Milking and Calving Period 19
d. Pastures and Yards 19
e. Feeding 20
f. Bedding 20
3. Disease Control 20
a. Isolation of the Herd 20
b. Admission to the Herd 20
c. Tuberculosis 21
d. Brucellosis . 21
e. Salmonella 22
f. Withdrawals From the Milking String 22
g. Mastitis and Abnormal Milk 22
h. Notification of Veterinarian 23
i. Disposition of Dead Animals 23
TITLE 8
MILKING, PROCESSING, DISTRIBUTION.... 23
1. Supervision and Reports 23
2. General 23
a. l'~mployees Clothing 23
h. Things to lie Avoided by 1~mpIoyees 23
3. Milking 24
a. Protection from Contamination . . . . 24
b. I'reparation aml Handling of Cows. . . 24
e. Milkers' Ilands
4. Milk I landling dud Processing 25
a. Collecting aud Filtering 25
b. Cooling 25
PAGENO="0059"
* .53
*
I rocessing, Bottlingand Sealing .. . . . 25
d. Labeling 27
5. Iransportation and Distribution 27
a. Equipment 27
b. Temperature 27
c. Delivery Time Limit 27
d. Bottles from Quarantined Homes . .,. 28
6. Preservation of Vitamins and Good
Flavor 28
TITLE9
PERSONNEL, MEDICAL SUPERVISION 28
I. supervision and Reports .28
2. Duties of the Physician 28
a. Medical Examinations 28
h. Medical Inspect ion 29
c. Special Examinations 29
3. Duties of Owner or Superintendent. . . . 30
4. Duties of Employees 30
5. Management of Communicable
Infections 30
6. Records of Employees . . . 30
APPENDIX
APPROVED LABORATORYMETHODS 32
1. total Bacterial Counis. . . 32
2. The I)etermi,thtion of Coliform
Organisms ~ 32
3. Heat-Resistant Bacteria in Milk 32
4. Examination for I lemoly tic Streptococci 33
5. Suggested Routine Bacteriological
Procedure 37
6~ Diagnosis and Control of Mastitis 37
7. Sanitizing Methods and Materials 38
8. Determination of Curd Tension of Milk
(American I)airy Science Association) . . 39
9. litration of Ascorbic Acid in Milk
(New Jersey Agricultural College) 41
10. Tests for Brucella Agglutinins in Milk. . . 42
a. Titration of Agglutinins in Whey . . . . 42
b. The Ring Test for Whole Milk 44
I I . I )eteetion of microbial I nhibitants
(:~ntihiotics) 44
PAGENO="0060"
54
METHODS AND STANDARDS
for the Production of
Certified Milk
TITLE 1
Historical Introduction
Certified Milk had its origin in the medical profes-
sion. In 1893 Dr. Henry L. Colt of Newark, N. J.,
formulated a plan by means of which he and his col-
leagues might obtain for infant feeding a supply of
clean, safe, pure, nutritious milk, the best which the
knowledge of the time could produce. In accordance
with this plan the Medical Society of Essex County,
N. j., appointed a Med teal Milk Commission which en-
tered into contract with a dairyman (Stephen Fran-
CISCO of Caldwcll, N. J.) willing and able to produce
this iiiilk which was to be "certified" by the Commis-
sion and labeled with the copyrighted and trade-
marked iiaine ``Certified Milk." 0th er medical socie-
ties soon followed the example of the Essex County
Medical Society and by 1909 there were 58 local
Medical Milk Coininis~ions, functioning in different
parts of the country ; each formulating its own metli-
ods and standards but showing a remarkable similarity
in fIIIl(lallletItal requirements.
In 1907 most of these local COfllflhiSSiOflS were or-
ganii.ed into the American Association of Medical
Milk Co,ii,,iiMsions~ 1 iir .. which had br its ohject~
the adoption of iiiii form methods and standards for
the production of Certified \lilk and the extension of
the inuvenietit throughout the country. Four standing
commi (tees were appointe(l: Medical Examination of
Employees; Chemical Standards; Bacteriological
Standards; and Veterinary Inspections and Protection
Against Tuberculosis. The personnel of these corn-
tnittees, giving their ServiCes without pay for many
years for the development of methods and standards
is cause for Pri(1C I)octors \V. 11. Park, M. J. Rose-
nau, I). L. Edsall, L. L. Van Slyke. henry Dwight
(:hapiii, Rowland C. Freeman, M. P. Ravenel, Francis
11. Slack, A. R. \Vard, Leonard Pearson and others.
These eo,nnnttees submitted reports which were a-
(lopted by the associations and in 1909 were published
in the form of "a Manual of the Working Methods
an(1 Standards for. the use of the Medical Milk torn-
iii is.sion.
Since that time the Methods and Standards have
been revised from year to year at the annual conven-
PAGENO="0061"
55
tion~ of the American Association of Medical Milk
Commissions in accordance with advancing scientific
knowledge. :
Certified Milk has retained a position of leadership
in the dairy industry which has exerted an itifluence
far greater than v~Iume of its sales may indicate~'It
is the object of this Association to retain this leader-
ship and it is the belief of its members that regardless
of what subsequent treatment may be given to milk,
improvements of the product as to safety. and nutri-
tional factors, can best be accomplished at the source
of production. it is the belief of the Association that
Certified Milk is the highest grade of milk obtainable.
Recognition of the standing of the Association is to be
found in the laws, of many states and municipalities
which require that Certified Milk shall be produced
in accordance with the Methods and Standards as `cur-
rently published by the American Association of Med-
ical Milk Commissions (or words to that effect) and
by a similar definition which occurs in the United
States Public Health Service Milk Ordinance.
TITLE 2
Definition of Certified Milk
Sec. 1.
Certified Milk is produced by dairies operated in
accordance with time Metlu)ds an (1 Standards ~1(h)1)tC(l
by the American Association of Medical Milk Corn-
missions, Inc., and under the direct supervision of
local Medical Milk Commissions or other agencies
recognized and approved by the American Association
of Medical Milk Commissions, Inc. herein the terni
Medical Milk Commission may be understood to apply
to any such recognized and approved agency.
Only milk produced in accordance with the Meth-
ods and Standards and by approved dairies shall be
* labelcd CERTIFIED MILK and shall bear the copy-
righted seal of the American Association of Medical
Milk Commissions, Inc.
The requirements in these Methods and Standards
for the Production of Certified Milk shall be regarded
as minimal and may be augmented by the require-
ments of local Medical Milk Commissions. Any
deviation from these Methods and Standards for the
purpose of meeting local requirements or conditions,
but without lowering fundamental standards, may be
sanctioned but must be' acceptable to the Committee
on Methods and Standards in conformity with the
constitution and by-laws of the American Association.
of Medical Milk Commissions, Inc.
PAGENO="0062"
56
Sec. 2.Certified Milk (Unheated) - The Basic Product
Certified Milk, so labeled without (1ualification, is
a basic pro(lUct 811(1 must tie pure, cleati, fresh, nu-
tritious milk in its natural state, not having been
heated and without the ad(htion of coloring matter,
or preservatives, nothing having beeti added and
nothing taketi away. Unless otherwise labeled it is to
be cow's milk. It must be the product of healthy
animals and pro(luced and handled strictly in con-
forinity with these Methods and Standards, and must
meet bacteriological standards as specified in title 5,
Sec. 2. It shall be free front objectionable odor and
flavor. Any modification or processing of Certified
Milk shall be plainly indicated on the label as herein-
after specified or as iiiay be approved by the Com-
mittee on Methods and Standards, during intervals
between annual meetings of the Association, and
subject to approval by the Council.
Sec. 3. Certified Milk (Heated) - Pasteurized
Certified Milk produced in accordance with these
Methods and Standards may be subsequently pasteur-
ize(l and labeled Certified Milk-pasteurized, it shall
he pasteurized and bottled through equipment not for
the handling of any other grade of milk or milk pro-
duct except that, upon recommendation of the Milk
Coinniission and after (tue consideration of each appli-
cation, the Committee on' Methods and Standards may
grant 1)crniii~sion for the milk to be pasteurized and
bottled through freshly cleaned and sanitized equip-
nient which may thereafter be used for other grades
of milk. (Sec Title 2, Sec. 7). Whether proccessed
or not every precaution shall be taken to insure that
CertifiedMilk is not contaminated by any other milk
and that it is as represented on the label. In any case
tIme location, the processing and the milk-handling
~1imipnmtemmt, tIme methods use~l, and the standards main-
taimied shall be subject to the~ontrol of the Milk
Commission, 811(1 is their responsibility.
Sec. 4. Certified Cream,..Certified Half and Half, and
Certified Fat-free (Skim) Milk
Alt requirements covering the production, handling
and standards of Certified Milk, except those refer-
ring to butterfat, shall also ~ipply to Certified Cream
and Certifi(~d'Fat-Free (Skim) Milk. The percentage
of butterfat in Certified Cream shall either be stated
on the labels or conform to established local custom
amid legal requirements.
Certified half and half shall be made from Certi-
fied Milk amid Certified Creammi. The percentage of
PAGENO="0063"
57
butterfat in Certified Half and half shall be either
stated on the label or conform to established loca!
customs or lcgal requirements.
Certified Fat.free.(Skirn) Milk is defined as skim
milk produced by centrifugal separation of Certi Iled
Milk to comply with individual state laws.
Sec. 5. Special Certified Milks
The productionof milk with special am~ niitrit~onal
properties, may be sold as Certified Milk pro~/iding the
fluid Whole milk, skim milk orcrca,n used s Certified
and meets all the requirements of Methods and Stand-
ards. The Methods and Standards for these products
shall be in accordance with existing license agreements
and must be approved by the local health authorities,
Committee on Methods and Standards and Medical
Milk Commissions.
a. Certified Vitamin P Milk - Vitamin D Certified
Milk is defined as whole Certified Milk rendered anti-
rachitic by the! addition of a concentrate and shall
be of sufficient vitamin D potency to show by bio-
logical assay a content of at least 400 IJ.S.P. units per
quart. it is suggested that each Medical Milk Cpm-
mission shall make or have made such teats as will
insure the maintenance at all times of the potency re-
quired for Vitamin D Certified Milk produced under
its certification, i.e., at least two biological assays per
year. One of the two biological assays should he made
in December or January and the other six months
later. Producers of Vitamin D Certified Milk shall
keep complete records covering the production of this
product. These records are to be kept on file at the
farm and with the Milk Commission. Any concentrate
of Vitamin D used for thc production of Vitamin I)
Certified Milk shall be a brand declared suitable for
such purposes by. local, state or municipal h~alt1i
agencies.
* b. Certified Milk-Homogenized - Certified Milk-
Homogenized may be produced and labeled with the
approval of the Medical Milk Commission and the
Committee on Methods and Standards of the Ameri-
can Association of Medical Milk Commissions. it also
may be labeled "Certified Milk-homogenized, soft
curd" provided it maintains a curd tension below
15 grams.
c. Fat-free (Skim) Milk with Vitamins A and D
Added. - Certified Fat-free (Skim) Milk with vita-
mins A and D added may be produced and labeled
with the approval of the Medical Milk Commission
and the Committee on Methods and Standards of the
A.A.M.M.C. The vitamin D content of this milk shall
PAGENO="0064"
58
(()nform with the specilications of Title 2, St~c. 5a.
The vitamin A content shall be State(l on the label of
the cap of each hot tie, as agree(l upon by the local
Medical Milk Commissions. `Ibm' vitamin concentrates
used shall be a brand declared suitable for such pur-
~ by local, state or municipal health agencies.
d. Certified Low Sodium Milk. - A milk which is
prothiced and handled in accordance with these Meth-
0(15 and Standards and treated so that its sodium
content is reduced to less than 50 milligrams of
so(Iium per quart, or contains less than 5 mg. sodium
per 100 gins, or less than 12 mg. sodium per 8 oz.
glass.
e. Certified Acidophilus Milk. - A milk which is
produced and handled in accordance with these Meth-
ods aiim1 Sta n(iar(ls. The mimilk is inoculated with a pure
culture of Lactobacillus Aci(Iophilus, and contains
large tin tubers of therapeutically valuable, viable
I ac!obacillmis Aci(lophilus cells.
f. Other products made by culturing or churning
Certified Milk or Cream. - Other products made b
mmml Luring or churning Certified milk or cream may be
labeled ``Made front Ccrti lied Milk" or ``Made from
( ert i iie(l creamit `.
Sec. 6. Labeling Special Certified Milks
LaI)cls br Special Certified Milks shall bear the
Seal of time' American Association of Medical Milk
Commission's. The wording for such labels shall be
submitted to and approved by the Committee on
Methods and Standards of the American Association
of Medical Milk Conimnissions.SUdi prO(luCtS must be
made tinder the Supi~rvision of the local Medical
Milk Conimission.
Sec. 7. Certified Goat's Milk
Certified Coat's ~lilk is hereby defined to be the
lacteal secretion obtained by the complete milking of
one or morç healthy goats properly fed and kept,
excluding that obtained within fifteen days before and
five days after kidding, or such longer period as may
be necessary to render the milk practically colostrum
free; which contains not less than 10.7% of milk
solids, and miot more than 89.3% of watery fluids, or
less than 2.8% of milk faL The bacterial count for
raw goat's milk shall not be more than 10,000
colonies SPC per ml and not more than 500 colonies
per ml after pasteurization. The coliform requirement
shall be less than 10 per ml on the raw milk and not
more than 1 ~ ml after pasteurization.
PAGENO="0065"
59
TITLE 3
Nutritional Value and Flavor of Milk
Two important influences in maintaining the
highest nutritional value and also the best flavor in
milk, are, (1) the feeding of the cows, and (2) th~ care
with which the milk is handled and processed. Both of
these involve considerable detailed ktowlcdge, and
application, but there are two key vitamins towards
which special attention can be directed. Vitamin A
serves very well as a good measure of the quality of
the feeding program. Vitamin A in milk is very
definitely influenced by the ration of the cow, and if
feeds are produced so that they have a high vitamin
A content, they will also tend to be high in other
factors which may influence the quality of the milk.
Likewise, the ascorbic acid (vitamin C) content of the
milk can serve as a measure of the effectiveness of
proper care in': handling and processing so far as
nutritional valüe.is concerned.
The forage crop feeds, hay, silage, and pastures sup-
ply most of the vitamins and other nutrients which
influence the quality of the milk, and also help to
maintain normal health in the cows. The production
of good forage crop feeds requires: proper soil fer-
tility, adapted varieties of crops, harvesting at the best
stage of growth, and for stored feeds, good preserva-
tion and storage. The natural Vitamin A content of
milk will vary from season to season due to. ration
changes unless care is taken to see to it that cows get
an adequate daily intake of Vitamin A or its pre-
cursor, carotene. Only' pasture or green chopped
forages can be depended upon to furnish Vitamin A
activity as carotene, for much of the Vitamin A
activity of harvested forages is lost during the first six
months of storage. Thus it is necessary that lactating
cows be furnished supplemental Vitamin A daily in
their diets to insure healthy cows and milk that is.
high in Vitamin A.
The chief factors in the handling and processing of
* milk. which affeèt its nutritional value are (I) Free-
dom from contamination, (2) Oxygen content of the
milk, (3) Length of time between production and use,
(4) Heat' treatment, (5) Exposure to light Here again
Certified Milk producers should apply the results of
* the extensive studies which have been reported in
this field. The test for ascorbic acid described in the
Appendix provides a means of checking results along
this line, *
The flavor of milk is closely associated with its
52-266 O-85---3
PAGENO="0066"
60
nutritional value. The methods outlined for producing
milk of high nutritional value arc also important for
producing the best milk flavor.
All rations fed to lactating cows shall be supple-
mented with trace minerals in accordance with the
latest recommendations of the National Research
Council.
TITLE 4
Organization and Duties of
Medical Milk Conimissions
Sec. 1. Organization
A Medical Milk Commission may be appointed
(1) by a recognized Medical Society, (2) by public
health officials, (3) by the council of the A.A.M.M.C.
which may itself serve as a Medical Milk Commission,.
or (4) as provided for by law in the community where
the milk is to be marketed.
Before such a Commission shall be recognized
under the terms of these Methods and Standards, it
must be approved by vote of the Council of the
American Association pf Medical Milk Commissions,
Inc., and formal notification of such approval be
issued by the President and Secretary of the above
association. The Council of the Association may
rescind such approval at any time for cause and after
hearing.
Sec. 2. Duties of Medical Milk Commissions
a. Officers and Supervisors of Medical Milk Com-
missions. - In addition to electing a President, Secre-
tary and Treasurer, the Commission shall appoint the
following Supervisors to enforce the Methods and
Standards: A Physician, a Veterinarian, a Laboratory
l)irector and a Sanitarian, who may or may not be
members of the Commission. The Physician and the
Veterinarian must be duly licensed practitioners. The
Commission may delegate the duties of cnspection
and enforcement to other Commissions certifying
the same farms or dairies, or with the approval of
the Committee on Methods and Standards of the
American Association of Medical Milk Commissions,
Inc., to State or Municipal Authorities. The Labors-
tory Director must possess adequate chemical and
bacteriological knowledge, and skill, and must have.
access to the necessary laboratory facilities. At the
discretion of the Commission the work of the Labora-
tory Director may be divided among two or more
properly qualified persons. The terms of employment
PAGENO="0067"
61
ol the above men tionel Sn pervm)rs an (I I he means of
(Ic fra yislg the cx uses of I heir W( )rk shi all he del er-
mined by the Coninuss~on. these Supervisors shall be
required to render to the Coinnussion and farms
monthly reports of their inspections an (1 exa mi
tions afl(I COpies. of these reports may be sent to
every member of the Commission. All records of the
Commission shall he opcmm to inspection at any) time
by the Secretary of the American Association of
Medical Milk Commissions, tue., or his daly author-
ized representative.
The above mentioned Supervisors of the Commis-
sion shall perform time (In ties' hereinafter specified.
b. Methods of Certification. - After the Commis-
sioui has applied for and received a certificate oî recog-
nition and approval signed by the Prcsi(Ient and the
Secretary of the American Association of Medical
Milk Commissions, Inc., it may receive application for
certification from dairymen who desire to undertake
the production of Certi fled Milk. i)airyincn produc-
ing Certified Milk are hereinafter referred to as Pro-
ducers. Uponreccipt of application for certification
the Commission shall institute an investigation by
its members and/or Supervisors to (letcrnline whether
or not the applicant has proper interest, intentions,
personnel, livestock and equipment for the successful
production of Certified Milk. If the result of such, an
investigation is favorable, time Commission uuiay (e1-
ti fy the milk and shall enter into an agreement with
the Producer to produ(~ Certified Milk under the
Methods and Standards. The Secretary of the Ameri-
can Association of Medical Milk Conuniissions, Inc.,
shall immediately be notified of such action, so that
permits may be issued for licensed mann factnrcrs to
supply the producer with approved Containers and
closures and formal ack nowiedgment of certification
may be issued.
In this procedure it is understood that (1) certifica-
tion is the responsibility of the Medical Milk Com-
mission, (2) the Commission's certi Iieation shall eon-
:`~ tinue as long as its standards and requirements are
maintained but (3) certification of a Producer may be
suspended at any time after due hearing by either the
Commission or by the Council of the American As-
sociation of Medical Milk Commissions, Inc., for fail-
ure to operate in accordance with Methods and
Standards or to meet financial obligations to the
Commission orto the American Association of Medi-
cal Milk Commissions, Inc., (4) full financial responsi-
bility and liability for failure to meet the required
standards for Certified Milk shall rest with the Pro-
PAGENO="0068"
62
(lucers, (5) all money collected by the Medical Milk
Commission from Certified Milk Producers shall be
USe(l solely for the expt~nsi~~ of the Commission.
c. Report of Medical Milk Commissions. - Every
Medical Milk Commission shall rendet a quarterly re-
port to the office of the Association, and also shall
render special reports whenever requested to do so
by the Secretary.
Medical Milk Commissions shall promptly report
to the Secretary of the Association any outbreak or
epidemic of communicable disease suspected or
knowii to be milk-borne in the communities where
Certified Milk is produced or distributed so that the
Association may be of all possible service.
d. Advertising. - All advertising (including ex-
hibits, billboards, posters, newspaper copy, printed
matter and radio broadcasts) sponsored or promoted
by the Certified Milk Producers' Association of
America, inc., shall be subject to the approval of the
Committee on Research and/or the Council of the
American Associa ti on of Medical Milk Coni missio us,
* Inc.
All advertising, as specified above, sponsored or
promoted by individual Certified Milk Producers shall
be subject to the approval of their respective Medical
Milk Commissions.
TITLE 5
Laboratory Standards for
Certified Milk
Sec. 1. Supervision and Reports
The maintenance of laboratory standards for Cer-
tified Milk shall be under the supervision of the Lab-
oratory Director of the Commission who shall be held
responsible for the inspections and tests specified in
Title 5. He shall promptly render monthly reports
to the Commission and farms and shall immediately
notify them if high bacterial counts or other question-
able conditions are found.
Sec. 2. Bacteriological Methods and Standards
Routine bacteriological examinations shall be made
at least once each week or more frequently as the
Commission may direct. ~At least 50 er cent of sam-
ples examined shall be roj~~anip cain- mna~ contain-
em ~ delivered ~to consume dal!Jc_I~ept
properly refn~èiit~J untilihey are exammned,yhich
shall be as soon as possmb1e~ft~ ~èollection or within
24 hours. The methods used for bac~emf~IogicaI exaii~ir
PAGENO="0069"
63
nations shall be those described in Append ices
and those described in the latest edition of Standar(l
Mctlunls for the l~xanunation oil )airy Prorlucts of [lie
American Public I Iraltli Association when not in (Oil-
Ilict Wi Lb these Methods and Standards.
lli(~ examinations shall inclu(le: a. lotal bacterial
colony counts (I) Certified Milk shall have a total
eou nt o Inot nmiore than 1 0,000 colonies iwr miii. (2)
(~rti fled Milk - ~j~urj ~I or Pasteurized Milk ma(lc
from Certified Milk shall have a total count of not
more than 10,000 colonies per nil, before J)astr~uriza-
Lion, in samples taken at the pasteurizing 1l~t,mt, and
not_mno~r(~,Jjiai1500, per ml. in route sam pies as de-
livi r d to eu'.tom r~ (~ I ith 2 "e ( 7 for I) 0 ti ii
colony counts for Certified Coat's Milk) h. `Coliform
colony counts: (1) Certi fled Milk shall have a eohiform
colony count of not nmmor~ iharul0 per ml.~ (~ Cciii.
fled MiIk~'- pasteurized or Pasteurized Milk made
from Certified l1llk"~lmaH have *a coli forum colony
count of not more than 10 per ml. before pasteuriza-
tion and not more than 1 per ml. in route samples as
d livi r (I to COflSU~( N
if counts excee(iing these standards are foum~d,' the
following steps shall be taken immediately: (1)
Samples obtained directly from the farm shall be cx-
arnined; (2) If the counts on these samples are high,
process samples from along the line of production
shall be examined until the source of high counts is
found; (3) If persistent difficulty is encountered in
keeping the total .countof Certified Milk - pasteurized
below 500 per ml. examine for thermoduric or1,ranlisms
by methods described in Appendix See. 3. If counts
within these standards are not restored within 10 days
and maintained, `certification may be suspended.
Once per month the Bacteriologist of each Milk
Comniission shall make or have made by the: State
Laboratory or other acceptable laboratory a titration
of Brucella ag~utiniins in the wiley of the milk or.
Ring Test from each Certified Milk Producer whether
the milk is raw or pasteurized.
Sec. 3. Physical and Chemical Methods and Standards
L At a temperature of 60° F. (15°C.) Certified
Milk shall have, a specific gravity of not less than
1.029 and contain not less than 12% of total solids
including fat.
b. Unless otherwise indicated on the label, it shall
contain an average of 3.5 per cent butterfat with a
tolerance for the average of 0.2 per cent above or
below 3.5 per cent and a minimum of 3.3 per cent for
individual samph~s. In case it is desired to nnain~ain an
PAGENO="0070"
64
aVerage of 1)11 ttedat. above Or bil ow 3.5 per cent the
average p~'~ cent of butterfat or the limits between
which it fluctuates shall be stated on the cap or the
eon tai tier, or by SOUI~ (lesignation wInch has legal
standing is generally understood iii the community
where the ittilk IS (list rihuted. In all cases the average
of mi tterfat shall be base(l ti[)Oi1 not fewer titan ten
santl)les over a period of not less tItan 60 (lays nor
more thait 90 days.
e. Certi lied ~ 111k - pasteti rizc(l shall show proper
pasteurizati on as indicated by phospha tase tests.
Sec. 4. Sediment and Flavor Tests
It is recotitittended that se(l1ment and flavor test l)e
reported on all samples with a required sediment test
of No. I or better.
Sec. 5. Detection of Microbial Inhibitants
(Antibiotics)
a. There shall be no antibiotics in Certified Milk,
regardless of the route used for administering.
b. `Flie ,nil k froni animals treated with antibiotics
shall he withheld 7~ hours or until the mitilk is free of
amitibiotics (see appendix).
TITLE 6
Buildings and Equipment
Sec. 1. Supervision and Reports
All bucldings and equipment on a Certified Milk
farm shall he under the supervision of the Sanitarian
of the Commission who shall make a thorough inspec-
(ion of the buildings, equipment and sanitary condi-
tions ol the en tire dairy farm at least omice a riionth
and more often if advisable, lie shall notify the Gout-
mission of any (1uestionable con (Ii lions existing and
shall l)rotnptly render monthly reports to the Cont-
mission and farm where they shall be kept on file.
Sec. 2. General
a. Location of Buildings. . - Buildings in which
GertUied Milk is produced and handled shall be
located so as to insure good drainage and at sufficient
distance front other buildings, dusty roads, cultivated
and (lusty fields, and all other possible sources of con-
tamination to safeguard the milk provided. In the case
of unavoidable proximity to tiusty roads or fields,
suitable arrangements shall be made to exclude dust.
They shall he so constructed as to afford proper shel-
ter.
b. Surrounding of Buildings. - The barn lots and
PAGENO="0071"
65
surroundings of all buildings shall be kept clean, free
from accumulations of rubbish and all conditions con-
ducive to fly breeding. They shall be kept graded
and drained. Adcquatc and functioning drains to con-
duct away the wastes from the barns and the dairy
building shall be provided. All manure shall be stored
or disposed of in such a manner to prevent breeding
of flies therein. Manure shall not be piled or stored
within 600 feet of the milking barii or dairy building
except~ by other means or Systems approved 1y the
Milk Commission.
c. Extermination o. Flies and Other Insects~- In.
addition to the elimination of fly-breeding conditions
as provided in paragraph b, the frequent extermina-
tion of flies and other insects in milking barns and
dairy building shall be accomplished by spraying or
equally effectiye methods. Insecticides and methods
used shall be approved by the local milk commission.
d. Exclusion of Rats and Vermin. - All necessary
measures shall be taken to prevent the entrance of
rats and vermin into banis and (Jairy l)uildings, and
proper methods as approved by the Sanitarian shall
be adopted for their destruction if they gain access.
e. WaterSupply. The entire water supply shall
be free from contamination and poiltition and shall
be sufficient for all dairy purposes. It shall be pro-
tected against flood or surface drainage. The purity of
each source of supply shall be checked by bacteriolog-
ical examinations according to standard methods of
the American Public Health Association at equal
intervals, at least three times a year and as often in
addition as conditions indicate it to be necessary, and
records of such examinations shall be filed at the farm
and with the Commission for a period of one year.
Samples for such examination shall be collected from
outlets in the milk plant. When the water is obtained
from a municipal supply, the records of the munici-
pality or state tnay be accepted in lieu of th~ above
requirements. No cross connections between potable
and non-potable water systems shall be permitted.
f. Drinking Fountains or Cups. - Sanitary drink-
ing fountains or disposable drinking cups for the use
of the employees shall be installed in convenient
locations both for the stables and dairy buildings.
g. Toilets. - There shall be one or more flush
toilets connected to a public sewer system or to an
individual sewage-disposal system. Such toilets and
sewerage systems shall be constructed and maintained
in accordance with local, county and state depart-
ments of health.
PAGENO="0072"
66
Such toilets shall be convenient to, but no~ open-
ing into, the barn and milk room. All toilet rooms
shall be kept clean and properly screened and have
conveniently available lavatory facilities with running
water, liquid or powdered detergent and individual
toWels. l~tnployees shall be required to wash and dry
their hands upon leaving toilet rooms.
h. Employees' Homes, Dormitories and Boarding
houses. - \Vhen employees live upon the premises
their (lorinitories or boarding houses shall be con-
structed and operated accor(liflg to plans approved by
the certifying Commission. Adequate modern bathing
and toilet facilities shall be provided for employees.
i. Visitors. - Visitors shall be so conducted as to
eliminate any possibility for contaminating or con-
tacting the milk or sterilized equipment and bottles.
They shall be excluded from the_milking barn and
dairy building during milking and milk handling oper-
atiotis. Arrangements for observing operations from
outside these rooms may be provided. This pars-
graph shall apply to members of employees' families,
field employees or others not receiving the same
medical supervision as the dairy employees, except
official inspectors.
j. Pollution. - A certified dairy should be a leader
in the control of pollution .. and should use every
means possible to protect our emwironmen t.
Sec. 3. Cow Barns
When cows are kept in other barns between milk-
ings, these barns shall be so constructed as to provide
a(lequate shelter. The floors shall be kept reasonably
dry and clean. Regulations with respect to ventilation
and windows (Title 6, Sec. 4, a, 3-4) shall apply also
to cow barns except that in niild climates windows
may be replaced by unglazed openings. Drinking and..
f(e(liIIg equipment shall be kept in a clean, sanitary..
cofl(litiolm. .* .
Sec. 4. Milking Barn or Room, and Equipment
a. Construction and Condition. - The milking
barmi or room shall bc'construeted so as to facilitate
keeping it in a clean, sanitary, well ventilated and
lighted condition. It shall be kept in good repair and
operating condition. (1) floors and gutters The
floors shall `be made of concrete or other impervious
and easily cleaned material and the gutters of.concrete
only. `I'hey shall be properly graded afl(l drained. .(2)
Interior walls and ceiling - These shall be 0. Jight
color and made of smooth concrete, I)l~1st(~r, tile, rust
resisting metal, or of well painted or varnished wood
PAGENO="0073"
67
with (lust tight joints and capable of shedding water.
Horizontal and slanting surfaces, winch might harbor
dust or other accumulations, shall be avoided as far
as possible. (3) Wi~idows and Lighting. In order to
provide adequate light and sunshine, window areas in
warm-barn environments should contain not less than
1/10th as much area as the floor space. In cnclose(I
cold-barn environments, "skylight panels" in the roof
should equal or exceed 1/20th of the floor area. In
warm climates where loafing areas arc open on one or
more sides, the "skylight panels" are unnecessary.
Windows as such are not necessary in cold-barn en-
*vironments. Minimum artificial lighting requirements
are as follows:
100-watt of light for each 2-3 stalls in the
milking facility, and
* 100-watt of light for çach 1,000 square feet of
floor space in the hedded area.
(4) Ventilation and air space - Stables shall be ade-
quately insulated `and provided with a functioning
and adequate system of ventilation to minimize of-
fensive odors and to prevent excessive condensation
of moisture, and each cow shall be provided with a
minimum of 60 square feet of space. Correspondingly
less space may be providCd for goats. (5) Stanchions
or ties - Stanchions or other forms of ties shall be of
modern sanitary construction. They shall be so ar-
ranged that droppings will fall for the most part into
the gutter. Provision shall be made to keep cows
standing between cleaning and milking. (6) Drinking
cups and feed mangers - When drinking cups are
used they shall be of modern sanitary construction.
Feed mangers shall be of smooth concrete or other
impervious easily cleaned material. (7) Feed mixing
rooms - All feed shall be mixed in a separate room
with dust tight wall and door if it adjoins the milking
barn or room.
b. Cleanliness. - The entire milking barn or room
and equipment shall he kept in a clean sanitary condi-
tion and free as possible from dust and all, other ac-
cumulations. Only bedding which is clean, dry, ab-
sorbent and reasonably free from mold and dust may
be used in the milking barn. Soiled bedding' and~
manure shall be removed from the milking barn at
least twice daily and the floor then swept and kept
free of refuse. Where cows are not kept in the milking
barn or room between milkings, the floors shall be
washed down after each milking unless freezing
temperatures exist..
PAGENO="0074"
68
Sec. 5. Milk Receiving Rooms
A iiiilk receiving room is defined as any room or
building located at or near the milking stanchions or
nulking parlor, and used exclusively as a central col-
lecting room for milk as brought from the barns.
Such rooms shall conform to the same specifications
as apply to the comistructipn, maintenance and cleanli-
ness of the milk handling rooms in the dairy buildings.
They shall be we11 screened, provided with automati-
cally closing doors and shall not have open corn-
municatiomi with the milking barns.
In each milk receiving room, adjacent vestibule, or
milking barn there shall be provided lavatory facilities
with continuously running water or water with fo0t
or arm control faucets, liquid or powdered detergent
and individual (preferably paper) towels for the use
of milkers.
Sec. 6. Dairy Building
A dairy building shall be provided for handling,
processing and storing of milk and milk products and
the cleaning, sterilizingand storing of milk equipment.
a. Construction and Condition. The dairy build-
ing shall be constructed so as to facilitate keeping it
clean, sanitary, well ventilated and well lighted. It
shall he kept in good repair and operating condition_
It shall not communicate directly with barns or dwell-
ings. (1) Floors - The dairy building shall have
smooth' floors of concrete or other water impervious
and easily cleaned material. They shall be well graded
and drained. (2) Interior walls and ceiling - These
shall be of light cokred, smooth surfaced, impervious
washabfe material. There shall be no objectionably
* placed overhanging pipes or conveyors. (3) Openings
- All openings shall be well screened and constructed
SO as to exclude flies and other insects and vermin.
All doors shall open outward if possible and be self
closing. (4) Lighting and ventilation - The building
shall be prcwidcd with adequate daylight and artificial
light. It shall be well ventilated. (5) Ucanliness -
all parts of the dairy building shall be kept clean and
sanitary and the milk and equipment handling rooms
shall be kept scrupulously clean, well painted and
free ~fromn dust and odors.
L Rooms Required. - If Certified Milk is pro-
duced, processed and bottled on the same premises,
the dairy building shall be provided with the following
separate rooms suitably equipped: (1) One or more
receiving rooms to be used exclusively for all Certified
Milk brought to the dairy building and from which it
PAGENO="0075"
69
.~liall be piped to the processing room unless the milk
can be piped directly from the milking room to the
processing room. (2) One or more rooms to he used
exclusively for cooling, processing and packaging Cer-
tified Milk or products therefrom. (3) One or more
rooms for cleaning and sterilizing milk equipment
and bottles. (If the hulk is produced for processing
and bottling elsewhere, the above rooms may be coin-
bined.) (4) There also shall be one or more refriger-
ated rooms used exclusively for.storage of bottled or
packaged milk or milk products.
Offices, laboratories, rooms for storage of equip-
ment and supplies used in the building, boiler rooms
and toilet rooms may be located in this building. The
latter two shall not communicate directly with the
milk or clean equipment storage rooms.
A properly constructed and isolated milking room
in which COWS are kept only (luring milking may he
located in the dairy building.
c. Use. - The various rooms. mentioned above
shall not be used for other purposes than those
specified cxcep.t that clean, sterilized milk bo~tles and
utensils may be stored for immediate daily use in the
milk handling rooms. No animals other than cows
within the milking room during milking shall be
allowed in the dairy building. No. part of the dairy
building may be used for dwelling or lodging.
Sec. 7. Dairy Building Equipment and Bottles
a. Necessary Equipment. - Adequate and efficient
milk handling equipment and containers approved
by the Commission shall be provided for producing,
holding, processing, cooling, bottling and sealing of
only Certified Milk and its products (See Title 2, Sec.
3) and for cleaning, sanitizing and refrigerating pur-
poses.
Adequate lavatory facilities with running water,
liquid or powdered detergent and individual towels
shall be conveniently to~ated in the milk handling an(l
toilet rooms.
b. Construction. - Milk handling equipment shall
be constructed so as to be easily cleaned and give
effective protection to the milk from contamination.
Vats shall be solid tanks. All equipment shall. be of
stainless steel or glass, except milking machine parts
customarily made of nibher or plastic. All milk shall
be carried through stainless steel or glass pipeline to a
bulk tank. The milk should not he exposed to air or
outside at any time.
c. Condition. - All equipment shall be kept in
PAGENO="0076"
70
goo(l repair dfl(l operating Cot1(litlOn. ,i\tilkitig machine
rubber parts shall be. in sound sanitary condition.
ll()t ties Shall be serVirea!)lV sound and undamaged.
IA~nipuIent used in tutilk handling smut1 be replaced as
soon as the inte?iOr surface is dented, or with open
seams." -
d. Cleaning and Sanitizing. - All milk handling
equipment, milking machines and multi-use bottles
shall he well clean'ed and sanitized after each use.
Equipment, materials and methods used shall be ap-
proved by the Commission. Methods shall include the
following procedures: (I) Immediately after use rinse
all equipment with cJeaiu cool water. (2) Next, thor-
oughly clean alt equipment and multi-use bottles with
a hot solution of a good soaptess cleaning detergent.
(3) Rinse thoroughly with clean water. (4) Last,
thoroughly sanitize with steam, boiling water, dry
hot air, approved chemicals or other equally effective
methods. (See Appendix, Sec 7) Approved paper
cartons and/or polyethylene plastic bottles may be
use(l.
Automated washing equipment for C.I.P. cleaning
shall he used following an appro~.ed sanitizing and
cleaning procedure. Milking e~ui~hent shall be dis-
mantled for cleaning and inspection once each week.
Milking machines shall be so dismantled that all
parts may be thoroughly cleaned and sanitized, care
being takcn. to remove all milk-stone. Rubber parts
shall be maintained in serviceably sound condition.
Vacuum lines shall be kept in clean and. sanitary
condition.
After being sanitized, equipment and bottles shall
be kept covered or. inverted in a room or cabinet free
from (lust or other possible contamination.
Milk l)Ottle CaSeS returned froni (lelivery routes or
subjected to other contamination and to be used for
hav~dling invurted sanitized bottles shall first be effec-
.tively cleaned and sanitized. . .
Thermometers shall be use(l on all steriliz~rs and
mechanical bottle wash e~. They shall be checked
for accuracy at frequent intervals, sped lied . by the
onl viii lou, by a standard tustr(l thermometer. Rue-.
ords of such checks and turn peratures main taincdshall
be kept on file at thu farm.
An atu Lornatie chemical sanitizing rinse shall he
used in all me(:hatuical bottle washers as the final rinse.
`l'hcsu' machines shall by operated according to the
mann facturer's recom nwndations.
\Vlieui chemical sanitizing solutions are used, eon-
centrations and times of expusu re as recofli mended
PAGENO="0077"
71
in the Appendix, shall be maintained. An approved
test shall be provided and the solutions checked at
frequent intervals, sped fled by the (o1n,nission, and
record of such tests kept on iiie at the farm. Equip-
ment sanitized with chemical sanitizing solu tions
should not be rinsed with water after sanitizing Intl
shall bewell drained before use.
The final test of cleanliness and sterility shall be
freedom front viable bacteria and visible foreign
matter.
PAGENO="0078"
72
TITLE 7
Veterinary Supervision
of the Herd
Sec. 1. Supervision and Reports
lii e care an(l han(lliflg of animals shall be u nder
the su pervision of the \`eterinarian srI erted by the
Commission. lie shall make frequent inspections of
the herd, and tiiake monthly reports to the Coin-
mission on forms furnished by the National ( ) flier. lie
shall file copies at the farm and immediatel notify
the Commission of any outbreak of disease among
the animals and of any (1ucstionable conditions in-
volving their health and care. A veterinary inspection
of the health of the herd shall be made at intervals of
not more than one month.
Each COW in milk shall be subjected to a careful
physical examinati (ill ~It least oiit~ e~icli 111 i'flt Ii, giving
special attention to the u(lder and external genitals.
Sec. 2. Herd Management
a. Identification of Cows. -- Ever~' cow in a Certi-
fied Milk herd shall be ear-tagged or tattooed with a
iHI ii~1 UT ~ Ii icli will prma tR ii len Li f~ her. )r other
itirthi ol appro~ ed h~ the Milk ( .I~tii IiIi~iOti . Pru~ isii'ti
shall he ticule for the replairtii.iit of lu~-t artags.
IL herd Records. Kver~ cow in the herd shall be
registered in a herd ree )rd which shall be acm rate1 v
kept an(l readily accessible to the milk ( ~ i~sIOt)
and official i I1slH( tors. Iliis record shall 111(1 u(le (lat es
of en trance an (I departti re roni the herd, ser~ ire and
freshening; (lates and results of Lu bereul in and Bru-
celki testing, veterinary an (I bacteriological xa ruina-
tions, abnormality of the milk as (leteeted by strip
cup or other methods, ill ness, injuries~ and all other
information of value to supervising agencies. The
record for every cow shall be kept on file at the farm
as lung as the cow is at the lariti and for at least six
flU)ntlls thereafter.
c. Milking and Calving Period. - Milk from all
cows shal be excluded from human consumption for
5 (lays full ( )Wi iig pa rturiti on. It is recoin in ended that
all cows receive a tiiiIiiflhiIIii (Iry p(i1o(l (if 45 days.
d. Pastures and Yards. -- Pastures or* yards to
~vliich the cows have access shall be free from stagnant
iiools and at so flleient (bstance from offensive con-
(iitiOhii4_ so that the cows shall so ffer no had effects
Irons thetis. Pastures or ~ar(is shall be free from in-
fect ions agents and Irons vegetation whi ichi may a fleet
the cows or their milk (leleteru)usl~ . Where milking
PAGENO="0079"
73
animals arc l)erlna(icntly mai IitaiIIc(l ill opeti corrals,
these corrals must be well drained and kept in a sani-
tary. con (Ii Li on. `lii cy shall be regularly seraf)e(l 8n (I
man tire han led away. It is i mporta ii t from t~ie stand-
point of (liscase control that both crews and trucks
doing this work shall not do similar cleaning on in-
controlled dames.
e. Feeding. - A well-balanced ration of high
quality nutrients shall be used that is adequate in
protein, energy, fiber, minerals and vitamins. The
ration will be designed to maintain healthy cows and
produce milk of ~normal composition and superior
flavor. Thc mcthpd: of feeding shall be such as to not
lower the quality or quantity of the milk produced.
f. Bedding. - No moldy hay or straw, bedding
from horse stalls or other unclean materials shall he
used for bedding the cows. Only bedding which is
clean, dry, absorbent and reasonably free from (lust
may be used.
Sec. 3. Disease Control
a. Isolation of the Herd. - No hogs, horses, stray
dogs, or fowls shall be allowed to come in or be in
proximity to Certified Milk herds (cows or goats) in
barns or yards except resident (logs and cats, which
must be vaccinated annually against rabies and any
other disease that applies to dogs and cats, at the
discretion of the owner or veterinarian. No animals
not known to be free from (I isease, and free I roni
Brimeella in fection as shown by the blood test, or IIOI
yet approved by the Veterinarian shall be allowed to
come in contact with the Certified Milk herd in barns,
yards or pastures. Other animals and fowl of the
animal kingdom free from disease shall be kept on the
premises and shall be under the supervision of the
AA\IMC veterinarian. No cow shall be used to pro-
(1)1(1 Certi fled ~lilk, that (101'S not have four heal I hv
quarters, Wi (Ii thit following IX ceptio ii. A cow with a
completely dry, non fu 1I(tioning If carter eati 1)1 used
to pr0(lLi~~ ( erti fird Milk from the other Lb ne normal
t~uarters (511. Title 8, Sect~on 3. Part 1)9)
b. Admission to the Herd. ihe responsibility for
admitting cows to the milking herd after inmr:hase or
of readmitti ng them a fter freshening or a fter isolation
because of disease, rests with the Veterinarian even
though he may at times delegate certain (luties to
other qualilled persons. I Ic shall avail himself of
laboratory facilities when they are indicated. Every
cow atimi tte(1 or readmitted to the milking herd shall
he examined by an approved veterinarian or her milk
shall be examined for total bacterial count, hemoly ti(:
PAGENO="0080"
74
strel) t( )C( )cci an(l otli ~r ni~isti tis organ isnis by an
proved bacteriologist. The milk of such animals shall
1101 1)e allowed to enter the Certi fled Milk supply
until favorable veterinary or bacteriological reports
have been received and placed in the herd record.
c. Tuberculosis. ( ) nI v nega Live Ii erls in a modi -
fied accredited area as designated liv the t . S. J)epart-
merit of Agriculture Uniform Methods and Rules for
Rovi tie luiberculosis kraulication. shall 1w used in the
pro(luetton of Certified Milk. ~\ hen an application is
made for certi hication, ever~ animal shall be tubercu-
liii tcste(l. No animal shall be added to a herd pro-
ducing Certi fled Milk unless such animal has origi-
siated from a negativ herd in a mod lied accre(li ted
area and has passed a tuberculin te~1 wi thin sixty (60)
(lays prior to admission to the herd. Certified herds
shall be retested for tuberculosis annually.
All tuberculin tests shall be made by a veterinarian
approved by the Commission and by the 1"ederal
Bureau of Animal Industry.
The dates of all herd tests shall be definitely ar-
ranged by agreement between the Milk Commission
and the supervising officials and a complete record of
all tests shall be made by the veterinarian making
the same and proniptly reported by him to the Secre-
tary of the Commission. Ihese records shall be kept
on file at the farm for one year and a summary of all
such tests shall be niiade available to the American
Association of Medical Milk Conirnissions for ~tatis-
(na1 pu rh)uses.
All reactors shall be reniove(l from the herd im-
mediately 111)011 discovery an(1 the milk shall be dis-
ear(led. The barns and exercise yards used by them
shall be clea ned and disi n feeted in a man tier approved
by the Commission.
d. Brucellosis_ - All herds approved for the pro-
duction of Certi lied Milk shall be o flicially accre(hite(l
(certified Rrueehhosis free) and maintained as Bruce1-
hx4is (lisease free and shall be teste(l at intervals riot to
excee(l every iii netv (90) da~ s b the Ring Test in an
accre(hi ted l3rn cellosis free state. `Fhie same herds shall
have their blood sera tested for agglutinins at intervals
riot 1)e exceed 12 months. i~ll herds producing Certi-
fled Milk iii states that are not accredited Brucellosis
free shall be tested by the Ri rig Test at intervals riot
to eXer('(l t hirtv-fi~ e (3~i) days a 11(1 have 1)100(1 sera of
all (`oWS ((stIll for aggl n ti nins at intervals riot to
excee(J (, 11)01) ths.
1) B n'a('t ors an (I suspects to be de Inn ed unride r
l'ederal Standards usi rig tested and approved pro-
PAGENO="0081"
75
(`edures only. Rea(tors JUhISt lie iruniedia (ely removed
from the herd for slaughter. Suspects are to he re-
moved from the certified milking string and either
501(1 for slaughter or re-tested wi Eli in mi iii in urn
thirty (30) day intervals 11 ntil tcs(e(l negative he lore
re-admission to the milking string.
(2) ~\he,i suspects are found in the herd, (he
shall he re-tested at mtervals of not over thirty (3())
(lays.
(3) All purchased herd a(lditions shall he tested
at the time of entering the herd arid retested in 60
days. however, if COWS are purchased from officially
accredited (Certified Brucellosis l'ree) herds, an of-
ficial negative test made within 30 days of purchase
shall qualify such COWS to enter the herd.
(4) `Ihe interpretation of 1)100(1 a~lutiiial ion
tests shall be that of the Animal and Plant I Iealtli
hispectioii Service, U. S. i)epartrnent of Agrirult tin.
(5) Tesls shall be ma(Ie under the su ~t~r~'isioii of
such agents as shall be acceptable to the local Medica
Milk Commission and the State health authorities
Reports of such tests shall be sent immediately to il'.
Milk Commission arid copies kept on file at the farri
for one year.
All provisions of this section (Title 7, Sec. 3, il
shall apply to goat herds.
(6) It is reeonlnier)(le(J that all rcl)laeenient (at ih~
shall be (ialfhood vaccinate(l for Brucellosis with
Strain 19 vaccine.
/~. Salmonella. - Milk from cows approved for th
(production of (erti fied milk must be free from Sal
( monella organisms.
\` (1) Cows that arc added to certified herds mus
<`pass a negative Salmonella test and be certified free 0
~thc organism prior to entering the milking line.
/ (2) All cows producing certified milk musE b
(~ted for Salmonella organisms a nu ni m urn (if on
time per year.
1. Withdrawals From the Milking String. - It i
the duty of the farm superintendent or the herdsmai
to se~ that any cow believed to be sick or disease
shall immediately be isolated from other cows in th
niilking string and that none of their milk shall entv
the Certified Milk Supply.
g. Mastitis and Abnormal Milk. - Any COW a'
fected with, either acute or chrome mastitis shall li
removed from the milking line and treated. Shii slrn
miot be returned to the milking herd tititil her imsilk
normal arid all residues front auhhiotie sources hay
been eliminated from her body.
PAGENO="0082"
76
Is. Notification of Veterinarian. - In the ever~t of
(lie occurrence of a disease which appears to be of a
~eriosss character, or if a number of cows become sick
at about the same tune, the dairyman shall withdraw
stitli (0W5 from the litr(l . (lestrov (11(1 r milk, and
itoh \ the Veterinarian immediately.
i. Disposition of Dead Animals. - The carcass of
any (lead animal whether diseased or not should he
(lis1)ose(l of in a sanitary manner. Methods of disposal
mimmist be approved by the local Medical Milk C)m-
mission. I ,ocal and state regulations may determine
to sonic extent how this is done.
TITLE 8
Milking, Milk Han~t~,
Transportation and t~ist'~ution
Sec. 1. Supervision and Reports
Milking, toil k handling, transportation and distri-
hu tion of Certi lied Milk shall be under the supervision
of the Sanitarian of the Commission who shall make
friqitent inspections of the dairy at times when the
alu )V~ operations are in progress. -lie shall render
monthly reports of such inspec(~OøS to the Corn-
mtme~sion and arm and shall immediately notify the
tin Imsission of any questionable conditions existing
on the tarni, or in the (listribution of the milk.
Sec. 2. General
a. Employees' Clothing. Milkers and other persons
handling the milk shall wear clean white suits and
caps or other suitable washable white and colored
combinations approved by the local nulk commission,
that shall he worn for no other purpose. They shall
use not less than three freshly laundered suits and caps
each week and these when not in USC shall be kept in
a clean place, protected from dust and dirt.
h. Things to Be Avoided by Employees. - Milkers
and other handlers shall refrain from putting the
hands to the nose and mouth. Evtuy~employee shall
~exercise great care to prevent milk contamination by
droplet infection from nose and throat secretions. Em-
ployees shall be required to wash and dry their hands
upon leaving the toilet rooms. Spitting shall be pro-
hibited in the parlors and in all parts of the dairy
building where the milk is handled. These precautions
are necessary to avoid possibility of any disease-
producing bacteria getting into the milk. Smoking is
prohibited during the time of milking and bottling.
PAGENO="0083"
77
Sec. 3. Milking
a. Protection of Milking Lqui~inient from Con-
taininatioii. (I) ( Janing of IIiill~i1ig lar, blur
milking. - ~`Oile(l l)(l(liIIg 11)(l Inanhir' shall lIe ri-
moved from Ill milking barn at eat twice daily, and
[lie floors shall hr sweilt and k1t free from re fuse.
Such cleaning shall he done not less [harm one hon r
before the milking [jill. (See Title ~, ~e 2, b)
(2) Spraying to (lestroy flies. - Spraying or
other efforts to eliminate flies ~liall le (loim(~ l)y
materials and methods approved l)~ the Sanitarian;
they should not be done (luring or immediately
before milking.
(3) Feeding hay after milking. - If hay is fe(' in
the milking barn, it shall be brought into the narn
only after milking.
(4) All cows shall be milked into stainless steel
or glass lines leading to a holding tank equipped with
a recording thermometer. The milk shall be ccx~le(l
promptly to 40 degrecs F. Provisions shall be made
for prompt and effective cleaning and sterilization of
the lines and equipment as soon as practical after the
last cow has been milked. The lines and equipment
riiust be given bactericidal treatment just prior to use
for the subsequent milking.
b. Preparation and Handling of Cows..
(1) Clipping. - Long haim shall be clipped from
the udder and flanks of the Cows, and from the tail
above the switch. The switch should be cut to clear
the ground or platform by at least four inches. If this
is not desirable with pure bred animals then the
switch shall be washed often enough to keep it clean.
* (2) Cleaning. - Every cow used in the produe-
tion of Certified Milk shall be clean before milking.
Whether cleaned by dry grooming or hosing, the cow's
udder must be given particular attention by wiping
* with. cloths used exclusively for this purpose. At the.
tni of milking no water shall he running down tim
udder and off the teats.
(3) Examination of fore-milk. - At the time of
even' milking and under t1I~ supei~ision of the herds-
man . or some delegated m:omnpetent-and reliable lore-
man, the first streams of milk from every teat shall
be rejected. It i5 required that such milk shall he
examined for evidence of mnastitis by examination of
the fore-milk by means of a suitable strip cup or
equally satisfactory method appruved b.y the Coin-
mission. Such milk shall not he milked upon the
floors or into the gutters of any stable or building
where COWS arc allowed to he down or remain after
PAGENO="0084"
78
milking. If any abnormal milk is disclosed by the strip
cup, the milk from that cow shall be discarded and
the cow shall be retnovc(I from the milking herd and
shall not he returned until approved by the Vet-
erinarian (See Title 7, Sec. 3, e and f).
(4) Milking. - Milking shall be done rapidly and
quietly and the cows shall be treated kindly. Managed
or rapid milking procedure is recommended.
(5) Milking three-quartered eOWS. - In tern. P
V~CUU~ on the UOUSC(l teat cup through the use of a
rubber cap or plug specifically manufactured for this
l)tlrpose. This procedure will allow the milking ma-
chine operator to nianipulate the unused teat cup as
to prevent any possibility of contamination.
(6) Milker'~s hands. - Adequate and conveniently
located lavatory facilities shall be provided for the
milkers. Immediately before milking, the hands oi the
milkers shall he thoroughly washed an(l scrubbed,
using detergents (liquid or powkre(l), running water
and brush, and carefully dried on clean individual
towels.
`Ihe milkers' hands shall be clean and dry at all
times, lie will not be required to wash his hands be-
tween the operation of each cow unless his hands
become soiled or wet.
Sec. 4. Milk Handling and Processing
a. Collecting and Filtering. Promptly after the
milk of each cow is drawn, it shall be removed from
the barn `to the milk receiving room and from there
to the (lairy building. Milk shall be transporte(l from
the milk receiving room to the dairy building con-
veyed in approved sanitary vessel to the point of
processing or bottling. The milk shall be passed
through modern filters. A sufficient number of filters
shall be proVi(le(l for every milking so that they may
he changed frequently if necessary. Filtering may be
(lone either in milk receiving rooms or in the dairy
building. No filter shall be used at more than one
milking.
h. Cooling. - immediately after reaching the dairy
buihuing the milk shall he cooled to a temperature
below 40 degrees F., and except during process of
pasteurization shall be maintained at a temperature
above freezing and below 40 degrees F. until de.
livere(l to the consumer.
c. Processing, Bottling and Sealing.
(1) Certified Milk shall be bottled and sealed by
means of approved meehanieal ei1uipmmn'nt on the farm
where it is 1)rOlltIer(l, e\('ept that wit I. the approval of
the local Medical Milk Commission; Certified Milk
PAGENO="0085"
79
from one farm may be processed and/or bottled at
another Certified Milk farm and labeled with the cap
of either farm. A producing farm may include a
number of units und~r the same farm and Commission
supervision.
A certified producer may transport his milk in an
insulated, stainless steel tank truck properly sanitized
and in an insulated, refrigerated truck, to a processing
plant other than a certified farm, its equipment, the
methods used and the standards maintained shall be
subject to the control of the local milk commission,
and it is their responsibility. All such certified milk
must be processed in sanitized equipment, bottled
and sealed prior to any other grade of milk. The label*
of this milk must carry the name of the Certified
farm, the supervising milk commission, processor and
distributor. Certified Milk in the finished package
product must comply with standards for Certified
Milk, in Title 5.
(2) Milk bottle caps and other closures shall be
stored in dust-tight packages in a clean room and
shall at all times be handled in such a manner as to
avoid contamination. After the milk has been cooled
and bottled, the bottles shall be capped and sealed
immediately with a closure approved by the Com-
mittee of the American Association of Medical Milk
Commissions, Inc. and in a manner satisfactory to the
Certifying Commission. The bottle caps shall be un-
contaminated and shall be applied only by a suitable
capping machine which diminates the possibility of
contamination. Outer milk bottle hoods shall be
handled in such a manner as to avoid contamination
of the, inner surface. Closures, shall be of sufficiently
strong and durable material to withstand leakage or
puncture dunng handling, transportation and delivery
of the milk. They shall be of such form. that they will
cover completely the pouring lips of the bottles and
it is desirable that they shall be of such construction
that when once removed they cannot be replaced
upon. the bottles without detection.
(3). Outer milk bottle closures whether made of
.one or more layers of material and used without an
additional plug cap are defined as single closures.
* Those used over a plug cap are defined as double
* closures. All types of milk bottle containers, caps or
* closures shall be subject to approval by the local com-
mission and the committee of the A.A.M.M.C. on
Milk Bottles, Containers and Closures. Both the seal
of the `A.A.M.M.C. and the script "Certified Milk"
must appear on all Certified Milk outer closures. Block
letter of the words Certified Milk is disapproved.
PAGENO="0086"
80
(4) Paper, glass, plastic, or other approVe(I coil-
tainers may be used for Certified Milk if they meet
the requirements for glass bottles as described in
paragi~aphs 2 and 3. - --
(5) Other or novel methods of milk handling,
processing, packaging, storage or (listribu tion may be
temporarily permitted by the Committee on Methods
& Standards, subject to whatever controls and con-
ditions it iiiay (leelli necessary.
d. Labeling. - The approved container used shall
be marked on their exposed surface with the approved
copyrighted and seal of the American Association of
Medical Milk Association of Medical Milk Commis-
sions, Inc., the name of the Certifying Commission,
the name of. the producing farm and other informa-
tion as required by the local medical milk commission
and the State or local boards of health. (See Title 8,
Sec. 4, c) It is recommended that bottle closures he
of the approved golden yellow color. The printing on
exposed surface of the closure should be in legible
type.
Sec. 5. Transportation and Distribution
a. Equipment. - During transportation, milk shall
l)e kept properly cooled and the containers (bottles)
shall be kept reasonably free from dust and dirt.
Trucks, trays and crates shall be kept clean. The
Medical Milk Commission shall exercise its authority
to determijie the type of truck necessary to safeguard
Certified Milk under the climatic conditions existing
in its area. Approved shipping cases shall be used so
that Certified Milk shipping cases shall be used so
that Certified Milk can be properly cooled and main-
tained i~t a low temperature. Ice shall come from
approved sources free of coliforni contamination.
b. Temperature. - Distributors handling Certified
Milk must keep it at a temperature above the freezing
point and below 450 F. from tIme time it is received
until delivered to the consumer. This means that
bottles shall be well packed in ice or refrigerated in
warni weather, and shall not be allowed to freeze in
cold weather.
c. IJelivery Time Limit. - The milking in any con-
secutive 24 hour period shall constitute a day's pro-
duct. Certified Milk is a premium product and should
be delivered to the consumer in the shortest possible
time after production as determined by each individ-
ual milk commission, with a maximum time limit of
144 hours (6 days) from the close of the day of pro-
duction. This will insure proper distribution of the
premium milk. However, it should be noted that Certi-
PAGENO="0087"
81
fled 1\lilk is good after this (late. Extension of this
time may be granted by the local nle(lical milk corn-
mission with approval of the MethIO(lS and Standards
Conrnii ttee.
d. Bottles From Quarantined Homes. - Bottles
shall not be collected from a house in which a com-
municable disease exists except under conditions pre-
scribed by the health authorities.
Sec. 6. Preservation of Vitamins and Good FIavo~
In the handling, holding and distribution of milk,
oxidation reactions may take place which tcntj, to
destroy ascorbic acid (vitamin C), to cause the (level-
opmcnt of oxidized flavor and possibly to cause other
less noticeable effects. To avoid these results the
folowing precautions shall be observed: The milk
shall only be allowed to come into con tact with
properly cleaned and sanitized rubber ni ilk ing parts,
stainless, steel or glass. If chlorine solution is used for
sterilizing equipment or utensils, it must be thor-
oughly drained out before milk is allowed to enter. In
the handling of milk IWO IC~ssary exposure to sunlight
shall be avoided and when delivered to the custmner
the milk shall be placed where it will be protected
from sunlight. (See also htle 3.)
As a control on the extent of oxidation changes in
milk, ascorbic acid tests, as described in Appendix,
See. 9, are recomlnen(le(l.
TITLE 9
Personnel, Medical
Supervision, etc.
Sec. 1. Supervision and Reports
The Physician appointed by the Commission shall
have medical and hygienic supervision of all em-
ployees and all other persons on a farm or plant pro-
ducing or processing Certified Milk. lIe shall make
reports to the Commission and farms, as hereinafter
indicated in this Title 9.
Sec. 2. Duties of the Physician
a. Medical Examinations. - Every person to be
employed in the dairy, (lorflhitories, or boarding house
in any capacity whatsoever shall be under the super-
:%i$IOI~ of the Physician and may be in receipt of a
medical examination report card before. I he employee
begi us work. The phvsicia ii in taking the hi story a
recording his exam iu)atioii shloLul(l bear in ~im uuud
rsl)eOiallv, such; a~ tuberculosis, typhoi(l fever and
PAGENO="0088"
82
other enteric diseases, an(l the streptococeal and
staphylococcal in fections. No person with active
tul)erculosis 5110111(1 he hire(1 ilil x-ray examination
an(l/or skiii test is mandator~'. Persons with a past
history of typhoid fever should not he hired until the
physician is satisfied that he is not a carrier of typhoid
organisms. A stool examination for typhoid bacillus
and other enteric pathogenic organisms shall be made.
A throat culture should be made to rule Out a
(Ii phtlieria carrier, and when indicate(l for hemolytic
organisms. It is recommended that for the informa-
tion of the physician every new employee shall have
his blood tested by the VDRL or equivalent test.
Satisfactory evidence of recent successful vaccination
or immunity against smallpox shall be presented.
After successful vaccination an employee shall not be
allowed to milk or handle cows until vaccination has
healed. All members of the families of employees on
the farms and other contacts shall be under the super-
vision of the Physician. Employees working in the
niilki ng and plant area or who are in close contact
wi LIi the milk shall he examined liv a physician every
ninety (90) (lays. At other times the Physician shall
cond net such medical e xa mi nations of employees or
other pei~ons on the farm as he or the Milk Com-
mission think necessary and have suitable laboratory
tests made whenever it is deemed advisable. He shall
see that fresh and reliable specimens are furnished to
the laboratory. All examinations shall be Cofl(lUcted
by laboratories and physicia mis a ppoin ted a mid ap-
proved by the Commission and satisfactory to the
health authorities. Complete records shall be filed
with the Commission.
b. Medical Inspection. - The physician may visit
the farm if he or the Commissi n deems it advisable.
lie shall be given an opportunity to examine and
interview all employees and residents of the farm, and
shall report to the Milk Commission upon its blank
forms supplied for that purpose. This report shall be
countersigned by the farm owner or superintendent
and ~ 1°l1Y shall be kept on file at the farm for one
\ear.
C! Special Examinations. - Upon report from the
kmim~ owner or superintendent of a farm or upon in-
lornialion from any other source, that any illness or
carrier state capable of transmission by milk is sus-
to exist on tIme farm, or among the employees,
of the farmmm. it shall lu Lime dii t~ of the Physician to
take inmniediate steps to safeguard tIme milk. The
Pimysieiaim shall examine tiim patient or suspect and
PAGENO="0089"
83
~t~urc In msel I. tIi~I(. (lie person is atten(le(l by i physi-
cia ii Iii good stan (Ii tig. .llie li)Vsieiaii shall iirotii ph v
report any ease o I contagious disease to the ( ominis-
sioti and the propi~r heal (Ii aut liorities and shall see
that (lie patient is removed from (lie prenlises or that
adequate quaranti II'~ is established and inaintai ned.
Sec. 3. Duties of the Farm Owner or Superintendent
It is the duty of the fariti owiur or superintendent
to exclude from work and contact with the cows or
in (lie handling of ittilk or of milk utensils any, em-
ployee who tiiay have sore throat, fever, (liarrhea, skiti
eruptwn or acute respiratory in fiction, to notify the
Pitysiciati and to follow such instructions as the
Miysieian Illay give.
Sec. 4. Duties of Employees
It is the (luty of every eiliployec to report iiiiinedi-
ately to the farm owner or superintendent any illness
which he ittay have, such as sore throat, fever, diarrhea
ski,, eruption, or acute respiratory infection and also
to report such ill ness to the Physician at the ti inc of
his inspection. lail nrc of an employee to make such
a report and to follow the directions received is to be
regarded as sufficient cause for his (lisnhissal.
Sec. 5. Management of Communicable Infections
No persons a If eted with any communica ide disease
which may b~ transniitted through iiiilk, or who has
recently been exposed to such in fection shall be eiii~
ployed in the produ(:tion or handling of Certified
Milk. No person known to be a carrier of any coni-
municable disease known to be milk-borne shall he
eiiiployed or reside on a Certi lied Milk fariii. Persons
known or suspected to have had typhoid fever shall
not be employed except with the approval of the Milk
Commission and with the knowledge and consent of
the proper health authorities. In the evetit that any
person employed or residing on a Certified Milk farm
becomes affected with any disease which titay be
transmitted through iiiilk such persons shall inimed-
iatelv be removed (rout the fartut or properly isolated
tinder the direction of the Physician and the Milk
Coni~uiissioii and the proper health authorities notified.
Sec. 6. Records of Employees
In order that records may be readily available for
inspection by proper officials there shall be kept on
the dairy premises as well as in the Commission
Office a record of every employee which shall give his
PAGENO="0090"
84
iianie ali(I address . . . date of dO ploy iIidfl t, 1115 mcdi-
cal history, results of physical examination by time
l'hysieian, and time results of army laboratory tests.
`lime Physician may check this record against the
tune hook or ti iiii record.
Any al)pl meant for dip1 oyment on a Certified Milk
farm or il ii ciii pl ny di' wlm 0 may be rejected or dis-
charged l)ecausc of being a carrier of pathogenic
organisms of diseases transmissible through milk shall
be reported by the Conmimmission to tIme Secretary of
the Anmerican Association of Medical Milk Coni-
iimissi otis, lii c. `lIme ~emritarv of (lie \ssociatioii mas'
report [lie lathes of' such i imdi'~ iii miab- It) all the \led ical
Milk Commissions of (1w As5uciation.
PAGENO="0091"
85
APPENDIX
Approved Laboratory Methods
and Recommendations
Sec. 1. Total Bacterial Counts
TotiLl bacterial counts of Certified Milk shall be
made by the agar plate method. The amounts of milk
inoculated into these plates shall be 0.1 and 0.01'ml.,
or in such amounts as to insure plates containing more
than 30 colonies and fewer than 300 colonies. See
latest edition of th~ American Public Health Associa-
tion, Inc., Standard Methods for the Examination of
Dairy Products,. or as outlined under Section 4,
page
Sec 2 The Determination of Coliform Organisms
The presence of these organisms in unpasteurized
milk usually indicates unclean milking, contaminated
Utensils or improper handling of milk. Rarely they
~rnay. come from infected udders. Their presence in
pasteurized milk indicates improper pastcuri'i.ation or
contamination of the milk after pasteurization. Prop-
erly pasteurized milk should contain no organisms of
the coli-aerogenes group.
The direct plating and over laying with medium of
1 ml. amounts of Certified Milk is desoxycholate agar
or violet red bile agar is recommended, since this gives
a direct enumeration of coli and aerogenès colonies of
characteristic redcolor and makes unnecessary further.
confirmatory tests unless it is desired to differentiate
coIl from aerogenes organisms. The growth of all
Gram positive organisms is inhibited, or greatly re-
tarded by this medium. For further details see latest
edition of A.P.H.A. Standard Methods for Exaniina-
lion of Dairy Products.
Sec. 3. Heat-Resistant Bacteria in Milk
a. Thermophilic.spore-forming bacteria. Seldom or
never are spore.forming bacteria found in the cow's
udder. Milk drawn from the udder under the cleanest
conditions should contain few or no bacterial sp9rcs.
Cow manure and dust contain many spores, as may
dirty milking utensils. The finding of bacterial spores
in milk, therefore, indicates contamination from one
of the above sources. Bacterial spores are not killed
by pasteurization. If miLk is heated at 80° C. (176°
F.) for 15 minutes, the vegetative bacteria are killed
and only the spores remain alive. Many of these spores
PAGENO="0092"
86
ire from ~uiaerohic I) eLena an(1 islien grown in milk
mm ruler nmmaerohn condit ions ~m lien produce gas or co-
agulation amid sometimes (IlgeStion of the milk.
ihe following ti~st is a mo(hulcation of that de-
sen bed l)y \Veinzirl. into clean, dr~ test Lu bes plugged
with cotton, place ~ibøimt 2 ml. of pet~o1atum and
sterilize them iii the hot air oven at 160° CL (320° F.)
or over br at least ont~ hour, or until the cotton be-
gins to turn brown. Ten ml. of each iiiilk to he tested
are pipetted into each,of 10 of the above tubes. The
tubes of milk arc then heated in a water bath at
80° C. (176° 1".) for 15 minutes. During this time
the petrolatuni melts arid Conies to the surface of the
milk. The tubes of milk are then to be cooled to
room temperature and incubated for 72 hours. Gas
forming in the milk raises the petrolatum up the side
of the tube. l)igestion is indicated by clearing of the
milk. Certified Milk should rarely show gas formation;
coagulation or digestion in any of the tubes. Other
grades of milk, whether pasteurized or raw, usually
show gas formation, coagulation or digestion in most
0.1 the tubes. A negative tube is o~j~jn which the milk
shows no evidence of growth, whatever.
b. Thermoduric.non.spore.forming bacteria. Cer-
tain non-spore-forming bacteria are resistant to pas-
teurization and may ~ausc high counts in pasteurized
milk. Such bacteria niay accumulate in milking ma-
chine part~, cooling, bottling or even pasteurizing
equipmenL Some may infect the udder of the cow.
They may pass unnoticed in grades of pasteurized
milk which are allowed to have counts of several
thousands per ml., but not in Certified Milk-pas-
ten rized which must have a count of not more than
500 per m~1.
lo deternune the presence of thermdduric bacteria
heat a sample of milk, in. a well stoppered tube in a
water bath at 62.8° C. (145° F.) for 30 minutes and
then plate out 0.1 ml. in Trypticase-Soy agar (BBL)
containing 0.2% of dextrose or Standard Method agar.
Then incubate plates for 48 hours at 350 C. (950 F.)
and `make counts. Any: form of Certified Milk should
seldom show any colonies. Thermoduric bacteria may
be eliminated by thorough cleaning and sterilization
of milking machines and milk handling equipment amid
withdrawal of infected cçws from the milking line.
Sec~ 4. Examination for Hemolytic Streptococci~
Deep colonies in1kh~ood agar pla~s are necessary for
the recognition and differentiation of streptococci.
The surface inoculation of blood agar plates is not
PAGENO="0093"
87
satisfactory. Blood agar plates poured as here recom-
mended may also serve for determining the total bac-
terial count of milk and in fact, for Certified Milk,
blood agar is sometimes a more suitable medium. If
blood agar is to ~be used for making total counts, use
only 5% of blood in the agar. The agàr used shall be a
meat infusion agar, as described in Standard Methods
for the Examination of Dairy Products; latest edition,
or Trypticase-Soy agar (BBL) without. dcx trose, or
Heat Infusion Agar (Difco).
Samples of milk should be diluted 1:10 and 1:100
in sterile salt solution (0.85% NaCI). One ml. amounts
of these dilutions shall be pipetted into sterile Pctri
dishes. To the melted agar cooled to between 45° C.
(112° F.) and 50° C. (122° F.), add 5% of sterile defi-
brinated horse or rabbit blood; human, cow or sheep
blood may be used if one has familiarized himself with
the appearances produced in them. The blood is im-
mediately well mixed with the agar and 10 to 12 ml.
are: poured into the Petri dishes containing the milk.
The Petri dishes shall be rocked immediately to insure
uniform mixing of the milk with the medium. When
the agar has solidified the plates shall be incubated in
an inverted position at 35° C. (95° F.) The Petri
dishes shall be 9Y2 to 10 cm. in diameter and shall
have glass or plastic tops; porous tops may not be
used. The plates should he examined after incubation
overnight and again after incubation for another day.
Beta hemolytic streptococci produce about the deep
colonies clear colorless zones of hemolysis. When
studied under the low power of the microscope beta
zones of hemolysis should show no blood corpuscles
remaining next to the deep colony. In the examina-
tion of blood agar plates it cannot be assumed that all
colonies with beta zones are streptococci since certain
strains of staphylococci, colori bacilli ~and other or-.
ganisms may also be hemolytic. Gram stained smears
from' the colonies or from subcultures from' ,the
colonies must be:examined. For the identification of
hemolytic streptococci two methods are' availible, the'
cultural' method and the serological method. CUL-
TURAL METHOD - For strongly presumptive diag-
nosis1 (1) from the blood agar plates fish deep beta'
bemolytic colonies: (2) inoculate from the same
colony, or from, a broth culture of the colony into
`Brown, J. H.: Significance of the Hemolytic Strep-
tococci Found ~n Milk. Cornell Vet. 1937, XX-
.VH,l0o.. , ,
PAGENO="0094"
88
(a) 1%. dextrose broth, (b) sorbitol broth and (d) hip-
purate broth.2 Strains which are sorbitol-negative,
hippurate-negative and which attain a pH not lower
than 4.8 in dextrose broth after incubation for 48
hours are to be suspected of being human pathogens
(usually serological Group A, occasionally Group C).
Such straitis shall be sent promptly to the nearest
Refer~nce' Laboratory of the A.A.M.M.C. for further
study and, if possible, should, also be studied by the
local Commission Laboratory. instructions as to de-
tails and for further study may be obtained from
the Committee on Methods and Standards of the
A.A.M.M~C. The hemolytic mastitis streptococci of
serological Group B are sorbitol-negative and hippur-
ate-positive. There are also many non-hemolytic
mnastitis streptococci. The so-called animal strains of
hemnolytic streptococci or serological Group C, less
frequently a cause of mastitis, are sorbitol-positivc
and hippuratc-negative, as are also those of Group E
by the usual methods of testing. Hemolytic strepto-
cocci of serological Group D attain a final acidity of
pH 4.0 to 4.5 in dextrose broth, are variable in their
sorbitol and hippurate reactions, do not lyse human
flbrin, and arc resistant to the temperature of pas.
teurization. SEROLOGICAL METHOD - When suit.
able Group-specific immune sera are available hemoly-
tic streptococci may be. rapidly identified by the
preciptin method of Lancefleld. ~ A simplified tech-
nique4 makes possible the identification of the' sero-
logical Group within 24 hours after the colonies are
fished from the blood agar plate, and with a minimum
of expense and labor; A description of the technique
may be obtained from" the Committee on Methods
and Standards of the A.A.M.M.C. Since cultural study
is necessary for the identification of species within
the groups, strains of streptococci found to belong to
Groups A or C should be sent to the nearest Regional
Laboratory of the A.A.M.M.C. for further study.
So far as is known only Group A hemolytic strep-
toco~ci have ca~ised milk-borne epidemics of septic
2Ayers, S. H., and `Ri~pp, P.: Differentiation of
Hemolytic Streptococci from Human and Bovine
Sources by the Hydrolysis of Sodium Hippurate.
Jour. Inf. Dis. 1932, XXX, 388.
3Lancefleld, R. C.: A Serological Differentiation of
Human `and other Groupsof Hemolytic Strepto-
cocci. J. Exper. Med., 1933, 199, LVII, 571.
4Brown, J. H.: Simplified Method for Group~ng
Streptococci by the Precipitin Reaction, J.A.M.A.,
1938, CXI, 310.
PAGENO="0095"
89
sore ~throat or scarlet fever.5, If any cow should be
found tO harbor GroupS A heinólytic streptococci si~c
shaII~.be imniediately and permanently renu)ved from
the herd. The milk from cows harboring (;roisi~ C
streptococci shall not. be used in CertifiedMilkpro-
duction,. and such animals shall be segregated from
the milking herd. Cows harboring strçptocod~i of
Group B shall be regarded as carriers Of mastitis strep-
tocou.i and putt ntmal ~ourtts of inft.ctiomi for olin r
animals in the herd.
Where facilities permit it is recommended that at
least once a month samples of milk should be taken
from groups of about 10 cows or from the milking
pails before they are emptied into the receiving tank;
that these samples should be diluted 1:20 with sterile
salt solution (0.85% NaCI), plated in blood agar and
~.tudicd for hunolvtmt ~trt ptocolL cm In cast thc pri s
ence of streptococci pathogenic for man is suspected
in any of the group sampks milk from the individual
cows of this group should be cultured and any.:eow
found to harbor time organisms should be permanently
removed from thç herd. This same procedure is to be
adopted if at any time there is any reason to suspect
that pathogenic streptococci may have gained en-
trance to the milk supply or that ammy ~ases of milk-
borne streptococcal disease have appeared among con-
sumers of the milk, or. that there may be present in
the herd cows shedding large numbers of bacteria in
their milk. This same procedure is of value in the
differential study of mastitis organisms.
In the routine streptococcus survey of milkers and
other personnel, swabs from the throat (and nose, if
advisable) shall be sent promptly to the laboratory
and there cultured by some such method as the
following: (1),Plac~ the swab into a test tube of about
5 ml. of broth ahd shake off the bacteria. One s~nahl
loop of the broth suspension mnoculatid into a 10 or
12 ml. tube of melted blood agar prepared as de-.
scribed above, usually makes a proper dilution for a
good plate which should contain not more than 100
to 200 colonies of all kinds. (2) Streak the swab
across one edge of the solidified surface of a nutrient
agar plate (preferably infusion agar without blood or.
dextrose, as described above). With the wire loop
streak the material from the original streak over the
remaining surface of the agar. Over the inoculated
5Tdlet, W S and Garner, R L The Fmbrmnolytmc
Activity of Hemoly tic Streptococci, J. Exp. Mcd.,
1935, LVIII, 483.
PAGENO="0096"
90
surface pour not more than 5 ml. of melted blood
~igar prepared as described above. After incubation
of the plates deep colovtio~ with beta zones of henio-
lysis are to be fished and the, streptococci identified
as described above.
Sec. 5. Suggested Routine Bacteriological Procedure
The following procedures will answer the purposes
for the. routine bacteriological examination of Certi-.
fled Milk. 1. Plate 0.1 ~nd 0.01 ml. of milk in blood
agar for total count and the detection of hemolytic
streptococci. 2. Plate 1 ml. of milk in desoxycholate
agar, or violet red bile agar, for detection of coliform
bacteria. 3. Prepare 10 tubes of 10 ml. of milk under
petrolatuan for the spore tests as described. 4. If the
counts arc high, examine for thermophihic and tlier-
anoduric bacteria (Appendix, Sec. 3, a; Sec. 3, b).
`Sec. 6. Diagnosis and Control of Mastitis
To supplement physical examination by the vet-
erinarian, bacteriological examination of the milk and
evi(lenee obtained by USe of the strip cup, the follow.
ing tests are valuable aids for the diagnosis of mastitis
but no one of theni alone need be regarded as con-
clusive unless it is strongly positive; the ph of the
milk a~ determined by the use of brom-thymol blue
or hrorn-cresol purple, determination of chlorides, the
catalase test, the California Mastitis Test, the rennct
test, leucoc~te count, milk sediment test, smears
from milk sediment or incubated milk samples, the
hlotis test. For further information see, "Bovine
Mastitis", Schalm, 0. W.; Carroll, E. j. and Jam, N. C.
(lea and Feibiger,-.1971), and for screening technics
see the latest (~(lition of `~Standard Methods for the
Examination of Dairy Products," Walter, W. C. (Ani.
Public I lealth Association, Inc., 1967).
It has been proven that the cow's udder is most
readily infected after milking by the growth of bac-
teria up through the teat canal in' the residue of milk
which may a~ernain at the teat opening in the canal.
Cleaning the teats after milking is a rational prophy-
lactic procedure for the prevention of udder infection..
The following procedure is suggested:
Use a chlorine solution, 250 ppm; or losan, .25
p~nn; or any approved teat-dip; and spray or dip each
teat after milking. lithe teats are dipped, `each teat
should be dipped its full length into a cup of any
above solution; all four teats may be dipped into the
same cup, but a fresh quantity should be used for
each c?w.
PAGENO="0097"
91
Sec. 7. Sanitizing Methods and Materials
a. High Temperatures.- This method of sanitizing
equipment is efficient if properly (lone but worthless
if the recomniended' times and temperatures are not
maintained. Steam confined in a suitably constructed
cabinet or closed piece of equipment sanitizes effec-
tively but whemi allowed to escape freely into the open
mimay be ineffective. The following conditions should
be maintained: (I) Steammi - Exposed for at least 15
minutes to a temperature of at least 2000 F'. (93.30
C.) in a cabinet or in closed equipment provided with
a thermometer Jocated in the coolest area. (2) hot
Water - Exposed for at least 5 minutes in water
maintained at 190° F. (87.8° C.) or abo~'e at the
outlet as indicated by properly placed thermometers.
(3) Dry heat - Exposed for at least 30 minutes to a
temperature not less than 225° F'. (1070 C.) in a
properly designed dry heat cabinet or room equipped
with a thLriilomLttr in tlit. tookst arca this txpo~urc
should include neither the heating-up nor cooling
time. It also implies that the equipment shall be moist
when placed in the cabinet or room.
b. Chemical Sanitizing Agents. - The reconunenda-
tions of the manufacturer should he followed in
using these preparations provided they meet Milk
Commission and health [)epartmuent requi remflentS.
(1) Chlorine and quarternary amnmoruum disin-
fectants - The following prinriples shiomil d be kept in
mind; (a) A concentrated forum of the sanitizing agent
should be obtained, known to have high stability arid
efhlciericy. (b) Fresh solutions of these products, par-
ticularly chlorine, should be prepared for each opera-
tion during the day. (c) Equipment must be clean and
free from organic matter since these agents are rapidly
inactiv~~ted by organic matter, and are ineffective un-
less brought into intimate contact with the bacteria.
(d) Soaps and many synthetic organic (letergents have
been found to reduce the effectiveness of quarternary
ammnomIiuni~ disinfectamits and should not he used in
:solutions with these agents: tri-sodiu in l)liosphate may
be used. (c) Caution in the use of chlonmme solutions
should be observed to prevent corrosion of metal
surfaces. (f) The following concentrations of these
chemical disin fecting agents are recommended for
dairy sanitizing purposes:
100 ppm, for the soak method of treatment.
200 ppm. for the flow method of treatment.
300 ppm. for the spray method of treatment.
.50-100 ppm. for final nnse of bottles washe(l by
mechanical bottle washers operated with caustic
treatment.
52-266 0-85-4
PAGENO="0098"
92
20()-30() ppm. in rinses for cows u(ltlcrs and as a
hand rinse.
(2) Caustic solution in mechanical bottle washers
- Cleaning and sanitizing of multi-use bottles is of
extreme importance because of possible contamina-
tion' from many sources during distribution. In opera-
tion of mechanical bottle washers there is an essential
relationship between temperature, time of contact
and concentration of the caustic solution. The time
of contact for each particular washer should be ob-
tained from the manufacturer, accurate thermometers
kept in use and a test set used regularly to maintain
proper solution strength. For a contact of 5 minutes
a caustic solution strength of 3% at 1300 F. (54.40
C.) is generally recommended.
(3) Caustic or lye solutions for rubber parts of
milking machine tc.at cup assemblies - A concentra-
tion of from 0.3 to 0.5% is recommended. This type
of solution is generally preferable to other commonly
used sanitizing solutions because it possesses the
property of dissolving casein and fat residues, particu-
larly in machines that are not completely disas-
sembled after each use.
Sec. 8. Determination of Curd Tension of Milk
(American Dairy Science Association)'
Reagent: The coagulant consists of 008N hydro-
(:hloric acid to which U.S.I'. (1:300) dry pepsin has
been added in the ámóunt of 450 mgms. per 100 ml.
This solution may be kept refrigerated and away from
light for not more than 10 days, but in case of doubt,
results obtained with it must be checked against
results obtained using a freshly prepared coagulant.
Apparatus: The instrument used in me~suring the
curd tension shall indicate in grams2 the force neces-
sary to cut the coagulum obtained as described below,
using the standard type of knife. The motion of the
knife or the vessel containing the coagulum shall be
automatic and at the rate of one inch in 7 to 8
seconds, obtained by lowering the knife or by raising
the vessel containing the coaguluin. The sensitivity of.
the instrument shall be such that readings can be made
to an accuracy of + or - 1.0 gram.
Note: The Hill method of determining the curd
tension of milk is described in editions of Methods
and Standards previous to 1941.
1J. Dairy Science, 1941, XXIV 825.
2Submarinc Signal Co. Curd Tension Meters made
priorto July 1941 do not read in grams. Reading
`may be converted to grams by multiplying by 1.10.
PAGENO="0099"
93
Standard Knife lli~ knif shall t,oiisist of ut,ht
radial blades, each having 9/16 inches of lineal cutting
edge and being 0.020.inches thick, spaced equally and
enclosed by a circular ring blade 1 3/4. inches outside
diameter, 3116 inches high and 0.031 inches thick.
The radial blades shall be attached t~ inside of the
circular ring blade and extend upward above it 2 1/16
inches, being reduced to a width of 5132 `inches above
the circular ring blade. Their upper cdges shall be
curved inward' andattached to a central spindle 5/16
inches in diameter. The lower or cutting edge of the
circular ring blade shall be tapered from the outside
at an angle of 30 degrees to the knife axis, to a dull
knife edge. The lower or euttin~edgcs of the radial
blades shall `be, tapered on each side at an angle of 15
degrees to th~ knik axis tb a dull knif edgc. 1h
cutting; edges of the ring blade and tl~e radial blades
shall lie approximately in the same plane, deviating
not more than, 1/32 inches~ The total linear cutting
edge. of the, knife shall be 9.8 inches 0.10 inches. All
joints shall be mortised and soldered smoothly and
the knife tonstructed' of a noñ-corrosiv,e metal.
Coagulation Vessel: The vessel used for coagulating
the milk shall be a heavy walled glass jar 3 to 4 inches
high (inside) having an inside diameter of 2 3/8 inches
+ or - 1/8 inch.1
Sampling Pipette: `l'he pipette used for measuring
and adding the milk sample to the jar containing the
coagulant shall be one made to deliver 100 ml., which
has had the tip removed and which empties by gravity
in approximately 4.5 secori (Is.
Water Bath: A suitable water bath shall be used to
temper the jars containing the coagulant before the
sample of milk ,is added and to hold the milk and
coagulant at the proper temperature `during the co-
* agulating period. Thç water levd shall come up on
the outside of the jar to a point no lower than the
* milk and coagulant level on the inside of the jar. The
volume of water shall be such that the temperature
* does not change more than 1.00 F. `during the 10
minute penod of cosgulation and preferablyshould
be agitated.
Procedure: Introduce 10 ml. of the coagulant into
the coagulation v~cl and set the vessel in the water
bath at 950 F~. (35° C.) The vessel containing the co-
agulant should be tempered for no less than 3 minutes
before introducing tli e milk samj.de. `
* The undiluted milk to be tested `is tempered to
950 F. (350 C.), as experience dictates, being'careful
not to exceed 1000 F. (37.80 C.) in the process. lime
PAGENO="0100"
94
tempering ShOLIld be ~icconiplishcd in a five minute
period immediately preceding the pipetting of the
sample. Introduce 100 ml. of the sample into the
coagulation vessel, using the tipless 100 ml. pipette.
The following and doubtless other jars meet these
specifications, W. M. Welch Scientific Co., Chicago,
No. 4612A (8 oz~); Central Scientific Co., Chicago
No. 10396 (7~4 ozs.); Owens Illinois Glass Co.,
Toledo, Mayonnaise jar (8 ozs).
This is to he accomplished by holding the pipette
vertically over the center of the vessel and blowing
the sample from the pipette as rapidly as possible.
No further mixing of the vessel contents is to be
employed and the vessel should not be disturbed in
the water bath. Place a watch glass or other suitable
covering over the vessel immediately.
hold the contents of the coagulation vessel at 950
F. + or - 1.00 F. for 10 minutes, the time in the
water bath being adjusted so that the cutting of curd
by the standard knife occurs at the expiration of 10
minutes + or - 30 seconds from the time the sample
was placed in the coàgu!ation Vessel.
Reading Results: The curd tension reading is the
maximum reading which is obtained at the moment
the knife penetrates the surface of the coagulum. The
test shall he made in duplicate or triplicate and results,
to he acceptable must not deviate more than 5 per
cent front the average. The average of the results, so
chccking~ constitutes the curd tension of the sample.
Sec. 9. Titration of Ascorbic Acid in Milk (New
Jersey Agricultural College)
Dye Solution: To 0.2 grams of 2-6 dichloropheno-
lindo1~hcnol' in a small beaker add 50 ml. of hot
distilled water. Break up the lumps with a stirring rod.
Decant the (lye solution through a filter and add more
water to the undissolved dye in the beaker. Repeat
until all is dissolved, then add water to make 1 liter
of solution. The solution should be stored in the cold,
must be standardized every day and should not be
used after it is two weeks old.
Metaphosphate Solution: Dissolve 5.0 grams of
metaphosphoric acid in 50 ml: of distilled water and
add sodium hydroxide solution to adjust the reaction
to phi 8.0 to 9.0, This solution is stable. Immediately
before using addS 1.5 ml. of glacial acetic acid to 10 ml.
of the metaphosphate solution.
lasted as 2-6 dichlorobenzenoneindophenol by the
l~astinan Kodak Co. The sodium salt of this corn-
~OL1 1111 can also be Lised.
Sharp, P. F.: Rapid Method for the Quantitative
PAGENO="0101"
95
Determination of Reduced Ascorbic Acid in Milk.
J. Dairy Sciences, 1938, XXI, 85.
Garret, 0. F.:: Determination of Ascorbic Acid
(Vitamin C) in Milk. `J. Milk Tech., 1938, I, 37.
Lorenz, A. L., and Arnold, L. J.: Standardization
of 2-6 dichlQrop~enolindoplIenol Dye with Ferrous
Compound. 1nd~ & Eng. Chem. Anal. Ed., 1938, X,
687.
Traum, J. and Henry, B. S.: Boric Acid for the
Preservation of Milk Naturally Infected with Brucehla
abortus, J. Inf. Dis., Nov. 1930, 47, p. 380.
Standardization of Dye Solution: Weigh exactly
0.50 grams of regent grade Mohr's salt (FcSO4
(NH4)2 S04.6H20), dissolve in distilled water, add
20 ml. of glacial acetic, and make UI) to I liter with
distilled water. This solution is stable for at least 6
`days~ To 10 ml. of this solution add 4 drops of the
metaphosphate solution and titrate with the dye
solution to a faint, pink color, visible for 30 seconds.
For a blank add 5 drops of acetic acid to a volume of
water equivalent to the ml. of the salt solution plus
the dye solution used in the titration. Titrate the
blank with the dye solution and subtract the reading
from the titration of the ~alt solution. One milligram
of Mohr's salt is equivalent to 0.2247 mg. of ascorbic
acid.
Procedure: To 10 ml. of milk add 1 ml. of acidified
metaphosphate solution and 10 ml. of distilled water.
Titrate with the (lye solution to a faint pink, visible
for 30 seconds. For a blank use milk to which 2 parts
per million of copper as copper sulfate has been added
24 hours previously.
Sec. 10. Tests for Brucella Agglutinins in Milk
Preservation and Shipment of Milk Samples. -
.\lilk samples for agglutination tests may be taken into
one. ounce screw-cap bottles, containing about one-
half thimbleful of boric acid crystals. The boric acid
arrests the growth of bacteria, preventing souring of
the milk, but does not interfere with the titration of
agglutinins. Such samples may be sent through the
mail without refrigeration. If samples are fresh and
refrigerated the addition of boric acid is not necessary.
a.. Titration `of Agglutinins in Whey.
Antigen. - A smooth strain of l3rucella ahortus is
grown in a suitable medium. From this growth aeon-
centrated .suspension is made in 0.85% NaCI contain-
ing 0.5% phenol. For use in the tests, this suspension
is diluted with the NaCl.phcnol solution to a turbidity
at which a wire loop, bent at a right angle, just (Jisap-
PAGENO="0102"
96
pears from view when lowered 2 cm. into a tube of
the antigen (reading 2 with the Gates turbidimeter.)
For further information regarding the preparation or
availability of suitable antigen communicate with
the Central Office, 405 Lexington Ave., New York 17.
N.Y.
Preparation of the Whey. - 0.5 ml. of 1% aqueous
solution of rennet is mixed with 5 ml. of milk drawn
from beneath' the cream after the milk has been cen-
tri:fuged or has stood until the cream has risen. The
milk and rennet must be mixed immediately and al-
lowed to clot with the test tube in a slanting position.
Place time slanted tube in a 56° C. (132° F.) water
bath for 30 minutes or incubate for 2 hours at 37° C.
(98.5° F.) Without shaking the tube and by means of
a capillary pipette carefully remove about 1 ml. of
dear whey.
The Test: - In clean, serological test tubes, free of
scratches, dilute the whey as follows:
Tube 1. 0.6 nil. of NaCI-phenol solution + 0.4 ml. of
whey
Tube 2. 0.5 ml. of NaCI-phenol solution + 0.5 ml.
from tube 1.
Tube 3. 0.5 ml. of NaCl-phenol solution + 0.5 ml.
from tube 2
Tube 4. 0.5 ml. of NaQ-phenol solution + 0.5 ml.
from tubc3
Tube 5. 0.5 ml. of NaCl-phenol solution (no whey;
ncgative.control)
Discard 0.5 ml. from tube 4, thus leaving 0.5 ml. in
each tube. Add 0.5 ml. of diluted antigen to each
tube; the tithes, thus containing whey dilutions of
1/5, 1/10, 1/20 and 1/40 respectively. (In testing the
milk of-individual cows, higher dilutions of whey are
used.) Incubate the tubes for 18 to 24 hours. Do not
shake the tube.s during the last 12 hours of incubation.
Reading of Results. - Read first by looking down
through the tops of the tubes. A compact sediment,
as seen in tube 5, is negative; a diffuse sediment, often
with curled edges, is positive. After this observation
the tubes may be shaken and viewed with a hand lens.
A smooth suspension is negative; visible clumps `indi-
cate a positive reaction.
Interpretation. - For herd milk, a positive result
in any tube is indication for testing composite samples
of milk from groups of about 10 cows, to be followed
by testing the milk or blood of individual anintals
within positive groups. For the milk of individual
cows, a positive result in whey dilutions of 1/20 or
teyond should be. followed by testing the milk from
individual quarters and the blood of the cow.
PAGENO="0103"
97
b. The Ring Test For. Whole Milk. - Place one
drop of the Ring1~est antigen in the bottom of a sniall
(Wassermann) test tube, taking care not to allow the
antigen to ma down the side of the tube. Add about
1 cc. of the whole milk to be tested. (To homogenized
or skim miIk~add 5 or 7 drops of negative cream).
Immediately mix thoroughly and allow to stand
undisturbed in a . moderately warm place (37° C.
(98.5° F.) incubator of water bath if available) for 30
minutes to 1 hours. The antigen is a heavy suspension
of dyed Brucella organisms. If the reaction is positive
the dyed, agglutinated bacilli will rise with the cream
and present a purple cream layer. If the reaction is
negative the bacilli remain dispersed in the underlying
milk and the cream layer is uncolored.
After proper dilution with 0.85% salt solution con-
taining 0.5% phenol the Ring Test antigen may also
be used for the titration of agglutinins in whey as
described above. .
If the herd milk gives a positive ring test, composite
samples of milk from groups of about 10 cows should
be tested, to be followed by testing the milk or blood
of individual animals within the positive groups. In
taking' milk samples for ring testing care must be
taken' to use clean containers free from contamination
by other milk.
Sec. 11. Detection of Microbial Inhibitants
(Antibiotics)
`rhis procedure is designed for the qualitative 1 de-
tection of small quantities of penicillin in milk. The
test organism, Sarcina lutea (A.T.C.C. 934 l),.is main-
tained on agar2 slants and transferred every 2 weeks.
For the detection of the most minute quantities of
other antibiotics more sensitive test organisms3 should
be used. Prepare an organism suspension as follows:
Streak an agar slant heavily with time organism and
incubate, for 24.. hours at 26° C. (790 F.) Wash the
growth off with several ml. of nutrient broth4, trans-
fer to the surface of 300, ml. of seed agar, in a Biux
bottle, and spread evenly over the surface with the aid
of sterile glass heads. Incubate for 24 hours at.26° C.
(79°F.) Wash the growth from the agar with 20 ml.
of nutrient broth. Ad~ust the vol u inc of this hulk sums-
pension so that it eon tains approximately 2.8 x .100
viable organisms per ml. as determined by plate count
or turbidimetrie measurement. Before the actual test,
determine by trial plates time amount of adjusted bulk
suspension to he added to yeast-beef agar5 to obtain
the optimum sensitivity. [sing this method, zones of
inh i hi tion shoti Id hi obtained from in ilk containing
PAGENO="0104"
98
as little as 0A)0~ U nits per uti. ( enerally, 0.3 to 0.5 niL.
of the inoculum per 100 nil, of agar is satisfactory.
Fo prepare the Petri dishes, add 10 ml. of agar2 to
sterile plates, distribute the media evenly, and allow
to harden on a perfectly levelsurfaçe. The Petri dishes
shall be 100 mm. in diameter and 20 mm. deep and
shall have porcelain covers glazed on the outside or
cover lids with filter pad inserts. The plates should be
covered at all times except when media and samples
are being introduced. Add the appropriate amount of
inoculum to yeast.beef agar5 which has been melted
and cooled to 48° C. (1200 F.), mix thoroughly, and
add 4.0 ml. to each plate. Immediately distribute the
agar evenly by tilting the plates from side to side with
a circular motion. Allow to harden and use the plates
the same day. Tile milk shall he tested usingeither
stainless steel cylinders of filter paper discs. The
cylinders 6sliall have an outside diameter of 8 mm., an
inside (hanleter of 6 mm. and a height of 10 mm., all
dimensions plus or minus 0.1 mm. Using sterile for.
c~j~s~,a cylinder dropping de~iôe place a number of
cylind~tis on the inoculated agar surface. Fill 2 or
more cylinders with the milk sample. The paper
discs7 shall be Y2 inch in diameter. Using sterile for-
ceps to hold a disc, immerse it in the milk for a
second, withdraw it, shake off any remaining droplets
with a snap of the wrist, and place the disc on the
surface ol the inoculated agar~ Use 2 or more discs for
each santple. Include on each plate as a control, a
milk sample containing 0.01 unit of penicillin per ml.
Incubate the plates at ~6° C. (79° F.) for 16 to 18
hours, after which they are inspected.
Certified Milk produces no zones of inhibition around
the cylinders or discs.
This method was worked out in collaboration with
the Division of Antibiotics, Food and Drug Admini-
stration, U. S. Department of Health, Education, and
Welfare.
PAGENO="0105"
99
1Quantitive procedures for penicillin and other anti-
biotics~are given in "Assay Methods of Antibiotics"
by Grove and Randall, M. D. Publications, Inc.,
1955, New York~
2Peptone 0.6%, pancreatic digest of casein `.0.4%,
yeast extract 0.3%, beef extract 0.15%, dextrose
0.1%, agar 1.5%, final pH 6.5-6.6. This and the two
subsequent media are available in dehydrated form
from Baltimore Biological Laboratory, Inc., Balti-
more 18, Md., or Difco Laboratories,' Inc., Detroit
1,Michigan.
3The recommended organisms are B. cereus `var
mycoides (A.T.C.C. 11778) for the tetracyclines,
B. subtilis (A.T.C.. 6633) for the streptomycins,
M. flavus(A.T.C.C.' 10240) or S. subflava (A.T.CC.
7468) for. hacitracin, M.1pyogenes var a~bus (A.T~
C.C. 12228) for. neomycin, and Bord. bronchi-
septica (A.T.C.C. 4617) for polymyxin.
4Peptone 0.5%, yeast extract 0.15%, beef extract
0.15%, 8OdiUm chloride 0.35%, dextrose 0.1%, di-
potassium phosphate 0.368%, monopotassium
phosphate 0.132%, final pH 7.
5Peptone 0.6%, yeast extract 0.3%, beef extract
`0.15%, dextrose 0.1%, agar, 1.5%, final pH 6.6.
6Availablè from the S & L Metal Products Corp.,
25 Lafayette St., Brooklyn 1, N. Y.
7Available from Carl Schicicher and Schucll Co.,
New York, N. Y., S and S No. 740-E.
PAGENO="0106"
100
METHODS AND STANDARDS
FOR THE PRODUCTION OF
THE AMERICAN ASSOCIATION OF
MEDICAl MIlK COMMISSIONS, INC.
PAGENO="0107"
101
METHODS AND STANDARDS
FOR THE PRODUCTION OF
L. Allen McDonough, M.D.
President
THE AMERICAN ASSOCIATION OF
MEDICAL MILK COMMISSIONS, INC.
960 Johnson Ferry Road, N.E.
Atlanta, Georgia 30342
Phone 404-255-1701
Paul N. Fleiss, M.D.
Secretary and Treasurer
1842 Hillhurst
Los Angeles, California 90017
Charles M. Ozanian, D.V.M.
Chairman of the Board
Revised
1984
PAGENO="0108"
102
INTRODUCTION
Certified Milk Producers have a 91 year history of producing nutri-
tious safe, clean milk. Throughout the years the Certified producers have
endeavored to produce the highest quality milk in the dairy industry.
They have always been leaders in utilizing modern dairy technology. They
have alw~y~ complied with Federal, State and local regulations.
The American Association of Medical Milk Commissions will always
demand that the Certified producers continue to produce the best possible
milk and milk products, and where possible improve upon them. Our goal
is that Certified Milk and Certified Milk products continue to be health
promoting and safe. The American Association of Medical Milk Commissions,
Inc. will continue to sponsor research that will help produce the best
quality milk and milk products. Since milk products make up approximately
25% of the American diet (the per capita consumption being about 6 oz.
milk a day) we intend that by monitoring their products, the Certified
producers will give us products that will improve the health, strength
and intelligence of the American people.
(Adopted by the American Association of Medical
Milk Commissions, Inc. - June, 1984)
PAGENO="0109"
103
CONTENTS
TITLE 1
HISTORICAL INTRODUCTION I
TITLE 2
DEFINITION OF CERTIFIED MILK 2
1. Definition 2
2. Raw Certified Milk, the Basic Product 2
3. Pasteurized Certified Milk 2
4. Certified Crleam, Half and Half and Non-Fat Milk 2
5. Special Certified Milks 3
6. Labeling.Special Certified Milks 3
7. Certified Goat's Milk 3
TITLE 3
NUTRITIONAL VALUE AND FLAVOR OF MILK 4
TITLE 4
MEDICAL MILK COMMISSIONS 4
1. Organization 4
2. Duties of Medical Milk Commissions 5
TITLE 5
LABORATORY STANDARDS 6
1. Supervision and Reports 6
2. Bacteriological Methods and Standards 6
3. Physical and Chemical Methods and Standards 7
4. Sediment and Flavor Tests 7
5. Detection of Microbial Inhibitants (Antibiotics) 7
TITLE 6
BUILDINGS AND EQUIPMENT 8
1. Supervision and Reports 8
2. General 8
3. Barns
4. Milking Barn or Room and Equipment 9
5. Milk Receiving Rooms 10
6. Dairy Building 10
7. Dairy Building Equipment and Bottles 11
TITLE 7
VETERINARY SUPERVISION 12
1. Supervision and Reports 12'
2. Herd Management 13
3. Disease Control 13
TITLE 8
MILKING, PROCESSING, DISTRIBUTION 15
1. Supervision and Reports 15
2. General 15
3. Milking 15
PAGENO="0110"
104
4. Milk Handling and Processing . 16
5. Transportation and Distribution 18
6. Preservation of Vitamins and Good Flavor 18
TITLE 9
PERSONNEL, MEDICAL SUPERVISION 18
1. Supervision and Reports 18
2. Duties of the Physician 18
3. Management of Communicable Infections 19
4. Records of Employees 19
APPENDIX
APPROVED LABORATORY METHODS AND RECOMMENDATIONS 20
PAGENO="0111"
105
METHODS AND STANDARDS
FOR THE PRODUCTION OF CERTIFIED MILK
Page 1
Title 1
Historical Introduction
Certified Milk had its origin in the medical profession. In 1893
Dr. Henry L. Coit of Newark, N.J. formulated a plan whereby he and his
colleagues might obtain for infant feeding a supply of clean, safe, pure
nutritious milk, the best which the knowledge of the time could produce.
In accordance with this plan the Medical Society of Essex County, N.J.
appointed a Medical Milk Commission which entered into contract with a
dairyman (Stephen Francisco of Caldwell, N.J.) willing and able to produce
this milk which was to be "certified" by the Commission and labeled with
the copyrighted and trademarked name "Certified Milk". Other medical soci-
eties soon followed the example of the Essex County Medical Society and
by 1909 there were 58 local Medical Milk Commissions, functioning in dif-
ferent parts of the country; each formulating its own methods and standards
but showing a remarkable-similarity in fundamental requirements.
In 1907 most of these local commissions were organized into the Ameri-
can Association of Medical Milk Commissions, Inc. which had for its objects
the adoption of uniform methods and standards for the production of Certi-
fied Milk and the extension of the movement throughout the country. Four
standing committees were appointed: Medical Examination of Employees;
Chemical Standards; Bacteriological Standards; and Veterinary Inspections
and Protection Against Tuberculosis. The personnel of these committees,
giving their services without pay for many years for the development of
methods and standards is cause for pride: Doctors W. H. Park, M.J. Rosenau,
D.L. Edsall, L.L. Van Slyke, Henry Dwight Chapin, Rowland G. Freeman,
M.P. Ravenel, Francis H. Slack, A.R. Ward, Leonard Pearson and others.
These committees submitted reports which were adopted by the associations
and in 1909 were published in the form of "a Manual of the Working Methods
and Standards for the use of the Medical Milk Commission." Since that
time the Methods and Standards have been revised from year to year at
the annual conventions of the American Association of Medical Milk Commis-
sions, Inc. in accordance with the advancing scientific knowledge.
Certified Milk has retained a position of leadership in the dairy
industry which has exerted an influence far greater than volume of its
sales may indicate. It's the object of this Association to retain this
leadership and it's the belief of its members that regardless of what
subsequent treatment may be given to milk, improvements of the product
as to safety and nutritional factors can best be accomplished at the source
of production. It is the belief of the Association that Certified Milk
is the highest grade of milk obtainable. Recognition of the standing of
the Association is to be found in the laws of many states and municipali-
ties which require that Certified Milk shall be produced in accordance
with the Methods and Standards as currently published by the American
Association of Medical Milk Commissions (or words to that effect) and
by a similar definition which occurs in the United States Public Health
Service Milk Ordinance.
PAGENO="0112"
106
METHODS AND STANDARDS
FOR THE PRODUCTION OF CERTIFIED MILK
Page 2
Title 2
Definition of Certified Milk
Sec. 1.
CERTIFIED MILK IS PRODUCED BY DAIRIES OPERATED IN ACCORDANCE WITH
THE METHODS AND STANDARDS ADOPTED BY THE AMERICAN ASSOCIATION OF MEDICAL
MILK COMMISSIONS, INC. It is produced under the direct supervision of
local Medical Milk Commissions or other agencies recognized and approved
by the A.A.M.M.C. Herein the term "Medical Milk Commission" may be under-
stood to apply to any such recognized and approved agency.
Only milk produced in accordance with the Methods and Standards and
by approved dairies shall be labeled CERTIFIED MILK and shall bear the
copyrighted seal of the American Association of Medical Milk Commission,
Inc.
The requirements in these Methods and Standards for the Production
of Certified Milk shall be regarded as minimal and may be augmented by
the requirements of local Milk Commissions. Any deviation from these Meth-
ods and Standards, without lowering fundamental standards, may be sanc-
tioned but must be acceptable to the Committee on Methods and Standards
in conformity with the constitution and by-laws of the American Association
of Medical Milk Commissions, Inc.
Sec. 2. Raw Certified Milk - The Basic Product
CERTIFIED MILK IS A BASIC PRODUCT AND MUST BE PURE, CLEAN, FRESH,
NUTRITIOUS MILK IN ITS NATURAL STATE, NOT HAVING BEEN HEATED, AND NOTHING
HAVING BEEN ADDED OR TAKEN AWAY. Unless otherwise labeled it is to be
cow's milk. It must be produced and handled strictly in conformity with
these Methods and Standards. It shall be free from objectionable odor
and flavor. Any modification or processing of Certified Milk shall be
plainly indicated on the label as hereinafter specified.
Sec. 3. Pasteurized Certified Milk
Certified Milk produced in accordance with these Methods and Standards
may be subsequently pasteurized and labeled Pasteurized Certified Milk.
It shall be pasteurized and bottled through equipment not for the handling
of any other grade of milk or milk product except that, upon recommendation
of the Milk Commission and after due consideration of each application,
the Committee on Methods and Standards may grant permission for the milk
to be pasteurized and bottled through freshly cleaned and sanitized equip-
ment of milk. (See Title 2, Sec. 7.) Whether processed or not every precau-
tion shall be taken to insure that Certified Milk is not contaminated
by any other milk. In any case the location, the processing and milk-
handling equipment, the methods used, and the standards maintained shall
be subject to the control of the Milk Commission.
Sec. 4. Certified Cream, Certified Half and Half, and Certified Non-Fat
(Skim) Milk
PAGENO="0113"
107
METHODS AND STANDARDS
FOR THE PRODUCTION OF CERTIFIED MILK
Page 3
All requirements covering the production, handling and standards of Certi-
fied Milk, except those referring to butterfat, shall also apply to Certi-
fied Cream and Certified Non-Fat (Skim) Milk. The percentage of butterfat
in Certified. Cream shall either be stated on the labels or conform to
established local custom and legal requirements.
Certified Half and Half shall be made from Certified Milk and Certi-
fied Cream. The percentage of Butterfat in Certified Half and Half shall
be either stated on the label or conform to established local customs
or legal requirements.
Certified Non-Fat (Skim) Milk is defined as non-fat milk produced
by centrifugal separation of Certified Milk to comply with Federal or
state laws.
Sec. 5. Special Certified Milks
The production of milk with special and nutritional properties, may
be sold as Certified Milk providing the fluid whole milk, non-fat milk
or cream used is Certified and meets all the requirements of Methods and
Standards. The Methods and Standards for these products shall be approved
by the local health authorities, Committee on Methods and Standards and
Medical Milk Commissions.
a. Certified Vitamin D Milk - is defined as whole Certified Milk
with the addition of 400 USP units of Vitamin D per quart.
b. Certified Pasteurized-Hombgenjzed Milk - may be produced and
labeled in accordance with these Methods and Standards.
c. Certified Non-Fat (Skim) Milk with Vitamins A and D added - may
be produced and labeled in accordance with these Methods and Standards.
d. Certified Low Sodium Milk - may be produced and labeled in accor-
dance with these Methods and Standards and is treated so that its sodium
content is reduced to less than 50 milligrams of sodium per quart, or
contains less than 5 mg. sodium per 100 gms. or less than 12 mg. sodium
per 8 oz. glass.
e. Certified Acidophilus Milk - may be produced and labeled in accor-
dance with these Methods and Standards and is inoculated with a pure cul-
ture of Lactobacillus Acidophilus.
f. Other products made by culturing or churning Certified Milk or
Cream - may be labeled "Made from Certified Milk" or "Made from Certified
Cream."
Sec. 6. Labeling Special Certified Milks
Labels for special Certified milks may bear the Seal of the American
Association of Medical Milk Commissions. The wording for such labels shall
be submitted to and approved by the committee on Methods and Standards
of the American Association of Medical Milk Commissions. Such products
must be made under the supervision of the local Medical Milk Commission.
Sec. 7. Certified Goat's Milk
Certified Goat's Milk is hereby defined to be the lacteal secretion
obtained by the complete milking of one or more healthy goats properly
fed and kept, excluding that obtained within fifteen days before and five
days after kidding, or such longer period as may be necessary to render the
PAGENO="0114"
108
METHODS AND STANDARDS
FOR THE PRODUCTION OF CERTIFIED MILK
Page 4
milk practically colostrum-free which contains not less than 10.7% of
milk solids, and not more than 89.3% of watery fluids, or less than 2.8%
of milk fat. The bacterial count for raw goat's milk shall not be more
than 10,000 colonies S.P.C. per ml. and not more than 500 colonies per
ml. after pasteurization. The coliform requirement shall be less than
10 per ml. on the raw milk and not more than 1 per ml. after pasteuriza-
tion.
Title 3
Nutritional Value and Flavor of Milk
Two important influences in maintaining the highest nutritional value
and also the best flavor in milk are, (1) the feeding of the cows, and
(2) the care with which the milk is handled and processed. Both of these
involve considerable detailed knowledge and application, but there are
two key vitamins towards which special attention can be directed. Vitamin
A in milk is very definitely influenced by the ration of the cow, and
if feeds are produced so that they have a high vitamin A content, they
will also tend to be high in other factors which may influence the quality
of the milk.
The forage crop feeds, hay, silage and pasture supply most of the
vitamins and other nutrients which influence the quality of the milk,
as well as helping to maintain normal health in the animals. The production
of good forage crop feeds requires: proper soil fertility, adapted vari-
eties of crops, harvesting at the best stage of growth, and for stored
feeds, good preservation and storage. The natural vitamin A content of
milk will vary from season to season due to ration changes unless care
is taken to see that animals get an adequate daily intake of vitamin A
or its precursor, carotene. Only pasture or green chopped forages can
be depended upon to furnish vitamin A activity as carotene, for much of
the vitamin A activity of harvested forages is lost during the first six
months of storage.
The chief factors in the handling and processing of milk which affect
its nutritional value are (1) Freedom from contamination, (2) oxygen
content of the milk, (3) length of time betwen production and use, (4)
heat treatment and (5) exposure to light. Here again Certified Milk produc-
ers should apply the results of the extensive studies which have been
reported in this field.
The flavor of milk is closely associated with its nutritional value.
The methods outlined for producing milk of high nutritional value are
also important for producing the best milk flavor.
All rations fed to lactating animals shall be supplemented with trace
minerals in accordance with the latest recommendations of the National
Research Council.
Title 4
Organization and Duties of Medical Milk Commissions
Sec. 1. Organization
PAGENO="0115"
109
METHODS AND STANDARDS
FOR THE PRODUCTION OF CERTIFIED MILK
Page 5
Medical Milk Commissions may be appointed (1) by a recognized Medical
Society, (2) by public health officials, (3) by the Board of Trustees
of the A.A.M.M.C. which may itself serve as a Medical Milk Commission
or (4) as provided for by law in the community where the milk is to be
marketed.
Before such a Commission shall be recognized under the terms of
these Methods and Standards, it must be approved by vote of the Board
of the American Association of Medical Milk Commissions, Inc., and formal
notification of such approval be issued by the president and secretary
of the above association. The Board of the Association may rescind such
approval at any time for cause and after hearing.
Sec. 2. Duties of Medical Milk Commissions
a. Officers and Supervisors of Medical Milk Commissions. In addition
to electing a president, secretary and treasurer, the Commission shall
appoint the following supervisors to enforce the Methods and Standards:
a physician, a veterinarian, a laboratory director and a sanitarian who
may or may not be members of the Commission. The physician and the veteri-
narian must be duly licensed practitioners. The Commission may delegate
the duties of inspection and enforcement to other Commissions certifying
the same farms or dairies, or with the approval of the Committee on Method
and Standards of the American Association of Medical Milk Commissions,
Inc. to state or municipal authorities. The laboratory director must
possess adequate chemical and bacteriological knowledge and skill, and
must have access to the necessary laboratory facilities. At the discre-
tion of the Commission the work of the laboratory director may be divided
among two or more properly qualified persons. The terms of employment
of the above mentioned supervisors and the means of defraying the expenses
of their work shall be determined by the Commission. These supervisors
shall be required to render to the Commission and farms monthly reports
of their inspections and examinations and copies of these reports may
be sent to every member of the Commission. All records of the Commission
shall be open to inspection at any time by the secretary of the American
Association of Medical Milk Commissions, Inc., or his duly authorized
representati ye.
The above mentioned Supervisors of the Commission shall perform
the duties herinafter specified.
b. Methods of Certification. After the Commission has applied for
and received a certificate of recognition and approval signed by the
president and secretary of the American Association of Medical Milk Com-
missions, Inc., it may receive application for certification from dairy-
men who desire to undertake the production of Certified Milk. Dairymen
producing Certified Milk are herinafter referred to as Producers. Upon
receipt of application for certification, the Commission shall institute
an investigation by its members and/or supervisors to determine whether
or not the applicant has proper interest, intentions, personnel, live-
stock and equipment for the successful production of Certified Milk.
If the result of such an investigation is favorable the Commission may
certify the milk and shall enter into an agreement with the producer
to preduce Certified Milk under the Methods and Standards. The secretary
PAGENO="0116"
110
METHODS AND STANDARDS
FOR THE PRODUCTION OF CERTIFIED MILK
Page 6
of the American Association of Medical Milk Commissions, Inc. shall insti-
tute an investigation by its members and/or Supervisors to determine
whether or not the applicant has proper interest, intentions, personnel,
livestock and equipment for the successful production of Certified Milk.
If the result of such an investigation is favorable, the Commission may
certify the milk and shall enter into an agreement with the producer
to produce Certified Milk under the Methods and Standards. The secretary
of the A.A.M.M.C. shall immediately be notified o such action, so that
permits may be issued for licensed manufacturers to supply the producer
with approved containers and closures and formal acknowledgement of certi-
fication may be issued.
In this procedure it is understood that (1) certification is the
responsibility of the Medical Milk Commission, (2) the Commission's certi-
fication shall continue as long as its standards and requirements are
maintained but (3) certifications of a Producer may be suspended at any
time after due hearing by either the Commission or by the Council of
the American Association of Medical Milk Commissions, Inc. for failure
to operate in accordance with the Methods and Standards or to meet financ-
ial obligations to the Commission or to the American Association of Medi-
cal Milk Commissions, Inc., (4) full financial responsibility and liabil-
ity with the Producers and (5) all money collected by the Medical Milk
Commission from producers shall be used solely for expenses of the Commis-
sion.
c. Report of Medical Milk Commissions. Every Medical Milk Commission
shall render a quarterly report to the office of the Association, and
also shall render special reports whenever requested to do so by the
secretary.
Medical Milk Commissions shall promptly report to the secretary
of the Association any outbreak or epidemic of communicable disease
suspected or known to be milk-borne in the communities where Certified
Milk is produced or distributed so that the Association may be of all
possible service.
Title 5
Laboratory Standards for Certified Milk
Sec. 1. Supervision and Reports
The maintenance of laboratory standards for Certified Milk shall
be under the supervision of the laboratory director of the Commission
who shall be held responsible for the inspections and tests specified
in Title 5. He shall promptly render reports to the Commission and farms
and shall immediately notify them if high bacterial counts or other ques-
tionable conditions are found.
Sec. 2. Bacteriological Methods and Standards
Routine bacteriological examinations shall be made. These samples
shall be properly refrigerated until they are examined, which shall be
as soon as possible after collection or within twenty-four (24) hours.
The methods used for bacteriological examinations shall be those described
in the Appendix.
PAGENO="0117"
111
METHODS AND STANDARDS
FOR THE PRODUCTION OF CERTIFIED MILK
Page 7
The examinations shall include: (a) Total bacterial colony counts:
(1) Certified Milk shall have a total count of not more than 10,000 colo-
nies per nil. (2) Pasteurized Certified Milk shall have a total count of
not more than 10,000 colonies per ml. before pasteurization, in samples
taken at the pasteurizing plant, and not more than 500 per ml. in finished
product samples. (see Title 2, Sec. 7 for bacterial colony counts for
Certified Goat's milk.) (b) Coliform colony counts: (1) Certified Milk
shall have a coliform colony count of not more than 10 per ml. (2) Certi-
fied Pasteurized Milk shall have a coliform colony count of not more than
10 per ml. before pasteurization and not more than 1 per ml. in finished
product samples.
If counts exceeding these standards are found, the following steps
shall be taken immediately: (1) Samples obtained directly from the farm
shall be examined; (2) If the counts on these samples are high, process
samples from along the line of production shall be examined until the
source of high counts is found; (3) If persistent difficulty is encountered
in keeping the total count of Certified Pasteurized Milk below 500 per
ml., examine for thermoduric organisms. If counts within these standards
are not restored within ten (10) days and maintained, certification may
be suspended.
Once per month the Bacteriologist of each Milk Commission shall make
or have made by the State Laboratory or other acceptable laboratory a
titration of Brucella agglutinins in the whey or the milk or Ring Test
from each Certified Milk Producer whether the milk is raw or pasteurized.
Sec. 3. Physical and Chemical Methods and Standards
a. At a temperature of 60 degrees F. Certified Milk shall have a
specific gravity of not less than 1.029 and contain not less than 12%
of total solids including fat.
b. Unless otherwise indicated on the label, it shall contain an
average of 3.5 percent above or below 3.5 percent and a minimum of 3.3
percent for individual samples. In case it is desired to maintain an aver-
age of butterfat above or below 3.5 percent the average percent of butter-
fat or the limits between which it fluctuates shall be stated on the cap
or the container, or by some designations which have legal standing and
is generally understood in the community where the milk is distributed.
In all cases the average of butterfat shall be based upon not fewer than
ten samples over a period of not less than 60 days nor more than 90 days.
c. Certified Pasteurized Milk shall show proper pasteurization as
indicated by phosphatase tests.
Sec. 4. Sediment and Flavor Tests
It is recommended that sediment and flavor tests be reported on all
samples with a required sediment test of No. 1 or better.
Sec. 5. Detection of Microbial Inhibitants (Antibiotics)
a. There shall be no antibiotics in Certified Milk, regardless of
the route used for administering.
b. The milk from animals treated with antibiotics shall be withheld
72 hours or until the milk is free of antibiotics.
PAGENO="0118"
112
METHODS AND STANDARDS
FOR THE PRODUCTION OF CERTIFIED MILK
Page 8
Title 6
Buildings and Equipment
Sec. 1. Supervision and reports
All buildings and equipment on a Certified Milk Farm shall be under
the supervision of the Sanitarian of the Commission who shall make thorough
inspections of the buildings, equipment and sanitary conditions of the
entire dairy farm. He shall notify the Commission of any questionable
conditions existing and shall promptly render reports to the Commission
and farm where they shall be kept on file.
Sec. 2. General
a. Location of Buildings. Buildings in which Certified Milk is pro-
duced and handled shall be located so as to insure good drainage and at
sufficient distance from other buildings, dusty roads, cultivated and
dusty fields, and all other possible sources of contamination to safeguard
the milk provided. In the case of unavoidable proximity to dusty roads
or fields, suitable arrangements shall be made to exclude dust. They shall
be so constructed as to afford proper shelter.
b. Surrounding of Buildings. The barn lots and surroundings of all
buildings shall be kept clean, free from accumulations of rubbish and
all conditions conducive to fly breeding. They shall be kept graded and
drained. Adequate and functioning drains to conduct the wastes away from
the barns and the dairy building shall be provided. All manure shall be
stored or disposed of in such a manner to prevent breeding within 600
feet of the milking barn or dairy building except by other means or systems
approved by the Milk Commission.
c. Extermination of Flies and Other Insects. In addition to the
elimination of fly-breeding conditions as provided in paragraph b, the
frequent extermination of flies and other insects in milking barns and
dairy buildings shall be accomplished by spraying or equally effective
methods. Insecticides and methods used shall be approved by the local
Milk Commission.
d. Exclusion of Rats and Vermin. All necessary measures shall be
taken to prevent the entrance of rats and vermin into barns and dairy
buildings, and proper methods as approved by the Sanitarian shall be adop-
ted for their destruction if they gain access.
e. Water Supply. The entire water supply shall be free from contamin-
ation and pollution and shall be sufficient for all dairy purposes. It
shall be protected against flood or surface drainage. The purity of each
source of supply shall *be checked by the bacteriological examinations
according to standard methods of the American Public Health Association
at equal intervals, at least three times a year and as often in addition
as conditions indicate it to be necessary, and records of such examinations
shall be filed at the farm and with the Commission for a period of one
year. Sampeles for such examination shall be collected from outlets in
the milk plant. When the water is obtained from a municipal supply, the
records of the municipality or state may be accepted in lieu of the above
requirements. No cross connections between potable and non-potable water
systems shall be permitted.
f. Drinking Fountains or Cups. Sanitary drinking fountains or dispos-
able drinking cups for the use of the employees shall be installed in
convenient locations both for the stables and dairy buildings.
PAGENO="0119"
113
METHODS AND STANDARDS
FOR THE PRODUCTION OF CERTIFIED MILK
Page 9
g. Toilets. There shall be one or more flush toilets connected to
a public sewer system or to an individual sewage-disposal system. Such
toilets and sewerage systems shall be constructed and maintained in accor-
dance with local, county and state departments of health.
Such toilets shall be convenient to, but not opening into, the barn
and milk room. All toilet rooms shall be kept clean and properly screened
and have conveniently available lavatory facilities with running water,
liquid or powdered detergent and individual towels. Employees shall be
required to wash and dry their hands upon leaving toilet rooms.
h. Employees Homes, Dormitories and Boarding Houses. When employees
live upon the premises their dormitories or boarding houses shall be con-
structed and operated according to plans approved by the certifying com-
mission. Adequate modern bathing and toilet facilities shall be provided
for employees.
i. Visitors. Visitors shall be so conducted as to eliminate any
possibility for contaminating or contacting the milk or sterilized equip-
ment and bottles. This shall apply to members of employees' families,
field employees or others not receiving the same medical supervision as
the dairy employees, except official inspectors.
j. Pollution. A certified dairy should be a leader in the control
of pollution and should use every means possible to protect our environ-
ment.
Sec. 3. Barns
When animals are kept in other barns between milkings, these barns
shall be so constructed as to provide adequate shelter. The floors shall
be kept reasonably dry and clean. Regulations with respect to ventilation
and windows (Title 6, Sec. 4, a, 3-4) shall apply also to animal barns
except that in mild climates windows may be replaced by unglazed openings.
Drinking and feeding equipment shall be kept in a clean, sanitary condi-
tion.
Sec. 4. Milking Barn or Room and Equipment
a. Construction and Condition. The milking barn or room shall be
constructed so as to facilitate keeping it in a clean, sanitary, well
ventilated and lighted condition. It shall be kept in good repair and
operating condition. (1) Floors and gutters - The floors shall be made
of concrete or other impervious and easily cleaned material and the gutters
of concrete only. They shall be properly graded and drained. (2) Interior
walls and ceiling - These shall be of light color and made of smooth con-
crete, plaster, tile, rust resisting metal, or of well painted or varnished
wood with dust tight joints and capable of shedding water. Horizontal
and slanting surfaces, which might harbor dust or other accumulations,
shall be avoided as far as possible. (3) Windows and Lighting - In order
to provide adequate light and sunshine window areas in warm-barn environ-
ments should contain not less than 1/10th as much area as the floor space.
In enclosed cold-barn environments, "skylight panels" in the roof should
equal or exceed 1/20th of the floor area. In warm climates where loafing
areas are open on one or more sides, the "skylight panels" are unnecessary.
Windows as such are not necessary in cold-barn environments. Minimum arti-
ficial lighting requirements are as follows: 100-watt of light for each
PAGENO="0120"
114
METHODS AND STANDARDS
FOR THE PRODUCTION OF CERTIFIED MILK
Page 10
2 - 3 stalls in the milking facility, and 100-watt of light for each 1,000
square feet of floor space in the bedded area. (4) Ventilation and air
space - Stables shall be adequately insulated and provided with a function-
ing and adequate system of ventilation to minimize offensive odors and
to prevent excessive condensation of moisture, and each cow shall be provi-
ded with a minimum of 60 square feet of space. Correspondingly less space
may be provided for goats. (5) Stanchions or ties - Stanchions or other
forms of ties shall be of modern sanitary construction. They shall be
so arranged that droppings will fall for the most part into the gutter.
Provision shall be made to keep cows standing between cleaning and milking.
(6) Drinking cups and feed mangers - When drinking cups are used they
shall be of smooth sanitary construction. Feed mangers shall be of smooth
concrete or other impervious, easily cleaned material. (7) Feed mixing
rooms - All feed shall be mixed in a separate room with dust tight wall
and door if it adjoins the milking barn or room.
Cleanliness. The entire milking barn or room and equipment shall
be kept in a clean, sanitary condition and free as possible from dust
and all other accumulations. Only bedding which is clean, dry, absorbent
and reasonably free from mold and dust may be used in the milking barn.
Soiled bedding and manure shall be removed from the milking barn at least
twice daily and the floor then swept and kept free of refuse. Where cows
are not kept in the milking barn or room between milkings, the floors
shall be washed down after each milking unless freezing temperatures exist.
Sec. 5. Milk Receiving Rooms
A milk receiving room is defined as any room or building located
at or near the milking stanchions or milking parlor, and used exclusively
as a central collecting room for milk as brought from the barns. Such
rooms shall conform to the same specifications as apply to the construc-
tion, maintenance and cleanliness of the milk handling rooms in the dairy
buildings. They shall be well screened, provided with automatically closing
doors and shall not have open communication with the milking barns.
In each milk receiving room, adjacent vestibule, or milking barn
there shall be provided lavatory facilities with continuously running
water or water with foot or arm control faucets, liquid or powdered deter-
gent and paper towels for the use of milkers.
Sec. 6. Dairy Building
A dairy building shall be provided for handling, processing and stor-
ing of milk and milk products and the cleaning, sterilizing and storing
of milk equipment.
a. Construction and Condition. The dairy building shall be construc-
ted so as to facilitate keeping it clean, sanitary, well ventilated and
well lighted. It shall be kept in good repair and operating condition.
It shall not communicate directly with barns or dwellings. (1) Floors
- The dairy building shall have smooth floors of concrete or other water
impervious and easily cleaned material. They shall be well graded and
drained. (2) Interior walls and ceiling - These shall be of light colored,
smooth surfaced, impervious washable material. There shall be no objection-
ably placed overhanging pipes or conveyors. (3) Openings - All openings
shall be well screened and constructed so as to exclude flies and other
insects and vermin. All doors shall open outward if possible and be self
PAGENO="0121"
115
METHODS AND STANDARDS
FOR THE PRODUCTION OF CERTIFIED MILK
Page 11
closing. (4) Lighting and ventilation - The building shall be provided
with adequate daylight and artificial light. It shall be well ventilated.
(5) Cleanliness - all parts of the dairy building shall be kept clean
and sanitary and the milk and equipment handling rooms shall be kept scrup-
ulously clean, well painted and free from dust and odors.
b. Room Required. If Certified Milk is produced, processed and bot-
tled on the same premises, the dairy building shall be provided with the
following separate rooms suitably equipped: (1) One or more receiving
rooms to be used exclusively for all Certified Milk brought to the dairy
building and from which it shall be piped to the processing room unless
the milk can be piped directly from the milking room to the processing
room. (2) One or more rooms to be used exclusively for cooling, processing
and packaging Certified Milk or products therefrom. (3) One or more rooms
for cleaning and sterilizing milk equipment and bottles. (If the milk
is produced for processing and bottling elsewhere, the above rooms may
be combined.) (4) There also shall be one or more refrigerated rooms used
exclusively for storage of bottled or packaged milk or milk products.
Offices. Laboratories, rooms for storage of equipment and supplies
used in the building, boiler rooms and toilet rooms may be located in
this building. The latter two shall not communicate directly with the
milk or clean equipment storage rooms.
A properly constructed and isolated milking room in which cows are
kept only during milking may be located in the dairy building.
c. Use - The various rooms mentioned above shall not be used for
other purposes than those specified except that clean, sterilized milk
bottles and utensils may be stored for immediate daily use in the milk
handling rooms. No animals other than those being milked shall be allowed
in the dairy building. No part of the dairy building may be used for dwel-
ling or lodging.
Sec. 7. Dairy Building Equipment and Bottles
a. Necessary Equipment. Adequate and efficient milk handling equip-
ment and containers approved by the Commission shall be provided for pro-
ducing, holding, processing, cooling, bottling and sealing of only Certi-
fied Milk and its products (See Title 2, Sec. 3) and for cleaning, saniti-
zing and refrigerating purposes.
Adequate lavatory facilities with running water, liquid or powdered
detergent and individual towels shall be conveniently located in the milk
handling and toilet rooms.
b. Construction. Milk handling equipment shall be constructed so
as to be easily cleaned and given effective protection to the milk from
contamination. Vats shall be solid tanks. All equipment shall be of stain-
less steel or glass, except milking machine parts customarily made of
rubber or plastic. All milk shall be carried through stainless steel or
glass pipeline to a bulk tank. The milk should not be exposed to the open
air at any time.
c. Condition. All equipment shall be kept in good repair and operat-
ing condition. Milking machine rubber parts shall be in sound sanitary
condition. Bottles shall be serviceable sound and undamaged. Equpment
used in milk handling shall be replaced as soon as the interior surface
is dented, or with open seams.
PAGENO="0122"
116
METHODS AND STANDARDS
FOR THE PRODUCTION OF CERTIFIED MILK
Page 12
d, Cleaning and Sanitizing. All milk handling equipment, milking
machines and multi-use bottles shall be well cleaned and sanitized after
each use. Equipment, materials and methods used shall be approved by the
Commission. Methods shall include the following procedures: (1) Immediately
after use rinse all equipment with clean cool water. (2) Next, thoroughly
clean all equipment and multi-use bottles with a hot solution of a good
soapless cleaning detergent. (3) Rinse thoroughly with clean water. (4)
Last, thoroughly sanitize with steam, boiling water, dry hot air, approved
chemicals or other equally effective methods. Approved paper cartons and/or
polyethylene plastic bottles may be used.
Automated washing equipment for C.I.P. cleaning shall be used follow-
ing an approved sanitizing and cleaning procedure. Milking equipment shall
be dismantled for cleaning and inspection once each week.
Milking machines shall be so dismantled that all parts may be thor-
oughly cleaned and sanitized, care being taken to remove all milk-stone.
Rubber parts shall be maintained in serviceably sound condition. Vacuum
lines shall be kept in clean and sanitary condition.
After being sanitized, equipment and bottles shall be kept covered
or inverted in a room or cabinet free from dust-or other possible contamin-
ati on.
Milk bottle cases returned from delivery routes or subjected to other
contamination and to be used for handling inverted sanitized bottles shall
first be effectively cleaned and sanitized.
Thermometers shall be used on all sterilizers and mechanical bottle
washers. They shall be checked for accuracy at frequent intervals, speci-
fied by the Comission, by a standard tested thermometer. Records of such
checks and temperatures maintained shall be kept on file at the farm.
An automatic chemical sanitizing rinse shall be used in all mechanical
bottle washers as the final rinse. These machines shall be operated accord-
ing to the manufacturer's recommendations.
When chemical sanitizing solutions are used, concentrations and times
of exposure as recommended, shall be maintained. An approved test shall
be provided and the solutions checked at frequent intervals, specified
by the Commission, and record of such tests kept on file at the farm.
Equipment sanitized with chemical sanitizing solutions should not be rinsed
with water after sanitizing but shall be well drained before use.
The final test of cleanliness and sterility shall be freedom from
viable bacteria and visable foreign matter.
Title 7
Veterinary Supervision of the Herd
Sec. 1. Supervision and Reports
The care and handling of animals shall be under the supervision of
the Veterinarian selected by the Commission. He shall make frequent inspec-
tions of the herd, and make monthly reports to the Commission. He shall
file copies at the farm and notify the Commission of any outbreak of dis-
ease among the animals and of any questionable conditions involving their
health and care. A veterinary inspection of the health of the herd shall
be made at intervals of not more than one month.
Each animal in milk shall be subjected to a careful physical examin-
ation at least once each month, giving special attention to the udder
and external genitals.
PAGENO="0123"
117
METHODS AND STANDARDS
FOR THE PRODUCTION OF CERTIFIED MILK
Page 13
Sec. 2. Herd Management
a. Identification. Every animal in a Certified milk herd shall be
ear-tagged or tattooed with a number which will permanently identify her,
or other method approved by the Milk Commission. Provision shall be made
for the replacement of lost eartags.
b. Herd Records. Every animal in the herd shall be registered in
a herd record which shall be accurately kept and readily accessible to
the Milk Commission and official inspectors. This record shall include
dates of entrance and departure from the herd, service and freshening;
dates and results of tuberculin and brucella testing. The record for every
animal shall be kept on file at the farm as long as she is at the farm
and for at least six months thereafter.
c. Milking and Parturition. Milk from all animals shall be excluded
from human consumption for 5 days following parturition. It is recommended
that all animals receive a minimum dry period of 45 days.
d. Pastures and Yards. Pastures or yards to which the animals have
access shall be free from stagnant pools and at sufficient distance from
offensive conditions so that the animals shall suffer no bad effects from
them. Pastures or yards shall be free from infectious agents and from
vegetation which may affect the animals or their milk deleteriously. Where
animals are permanently maintained in open corrals, these corrals must
be well drained and kept in a sanitary condition. They shall be regularly
scraped and manure hauled away. It is important from the standpoint of
disease control that both crews and trucks doing this work shall not do
similar cleaning on uncontrolled dairies.
e. Feeding. A well-balanced ration of high quality nutrients shall
be used that is adequate in protein, energy, fiber, minerals and vitamins.
The ration will be designed to maintain healthy cows and produce milk
of normal composition and superior flavor.
f. Bedding. Only bedding which is clean, dry, absorbent and reason-
ably free from dust may be used.
Sec. 3. Disease Control
a. Isolation of the Herd. No animals not approved by the Veterinarian
shall be allowed to come in contact with the Certified Herd in the barns,
yards or pastures. No cow shall be used to produce Certified Milk that
does not have four healthy quarters, however, a cow with a completely
dry, nonfunctioning quarter can be used to produce Certified Milk from
the other three normal quarters (see Title 8, Sec. 3, Part b, 5).
b. Admission to the Herd. The responsibility for admitting animals
to the milking herd after purchase or of readmitting them after freshening
or after isolation because of disease, rests with the Veterinarian even
though he may delegate certain duties to other qualified persons. Every
cow or goat admitted or readmitted to the milk herd shall be examined
by an A.A.M.M.C. approved veterinarian. The milk of such animals shall
not be allowed to enter the Certified milk supply until favorable veter-
inary reports have been received.
c. Tuberculosis. Only negative herds in a modified accredited area
as designated by the U.S. Department of Agriculture Uniform Methods and
Rules for Bovine Tuberculosis Eradication, shall be used in the production
of Certified Cows Milk. When an application is made for certification,
every cow shall be tuberculin tested. No cow shall be added to a herd
PAGENO="0124"
118
METHODS AND STANDARDS
FOR THE PRODUCTION OF CERTIFIED MILK
Page 14
producing Certified Milk unless such animal has originated from a negative
herd in a modified accredited area and has passed a tuberculin test within
sixty (60) days prior to admission to the herd. Certified herds shall
be retested for tuberculosis annually.
All tuberculin tests shall be made by a veterinarian approved by
the Commission and by the Federal Bureau of Animal Industry.
The dates of all herd tests shall be definitely arranged by agreement
between the Milk Commission and the supervising officials and a complete
record of all tests shall be made by the veterinarian making them and
promptly reported by him to the secretary of the Commission. These records
shall be kept on file at the farm for one year and a summary of all such
tests shall be made available to the American Association of Medical Milk
Commissions for statistical purposes.
All reactors shall be removed from the herd immediately upon discovery
and the milk shall be discarded. The barns and exercise yards used by
them shall be cleaned and disinfected in a manner approved by the Com-
mission.
d. Brucellosis. All herds approved for the production of Certified
Milk shall be officially accredited (certified brucellosis free) and main-
tained as brucellosis disease free. Herds shall be tested at intervals
not to exceed every ninety (90) days by the Ring Test in a accredited
brucellosis free state. The same herds shall have their. blood sera tested
for agglutinins at intervals not to exceed twelve (12) months. All herds
producing Certified Milk in states that are not accredited brucellosis
free shall be tested by the Ring Test at intervals not to exceed thirty-
five (35) days and have blood sera of all animals tested foragglutinins
at intervals not to exceed six (6) months.
(1) Reactors and suspects to be defined under Federal Standards using
tested and approved procedures only. Reactors must be immediately removed
from the herd. Suspects are to be removed from the Certified milking string
and re-tested within minimum thirty (30) day intervals until tested nega-
tive before re-admission to the milking string.
(2) All purchased herd additions shall be tested at the time of enter-
ing the herd and retested in sixty (60) days. However, if animals are
purchased from an officially accredited (certified brucellosis free) herd,
an official negative test made within thirty (30) days of purchase shall
qualify such animals to enter the herd.
(3) The interpretation of blood agglutination tests shall be that
of the Animal and Plant Health Inspection Service, U.S. Department of
Agriculture.
(4) Tests shall be made under the supervision of agents acceptable
to the local Commission and the state health authorities. Reports of such
tests shall be sent to the Milk Commission and copies kept on file at
the farm for one (1) year.
(5) It is recommended that all replacement cattle shall be calfhood
vaccinated for Brucellosis with Strain 19 vaccine.
e. Withdrawals from the Milking String. It is the duty of the farm
superintendent or the herdsman to see that any animal thought to be sick
or diseased shall be immediately isolated from other animals in the milking
string and none of their milk shall enter the Certified milk supply.
f. Mastitis and Abnormal Milk. The milk from any animals with either
acute or chronic mastitis shall be withheld and not used for human consump-
tion until her milk is normal and all antibiotic residue has been elim-
PAGENO="0125"
119
METHODS AND STANDARDS
FOR THE PRODUCTION OF CERTIFIED MILK
Page 15
mated.
g. Notification of Veterinarian. In the event of the occurrence
of a disease which appears to be of a serious nature, or if a number of
animals become sick at about the same time, the dairyman shall withdraw
such animals from the herd, destroy their milk and notify the Veterinarian
immediately.
h. Disposition of Dead Animals. The carcass of any dead animal whe-
ther diseased or not should be disposed of in a sanitary manner. Methods
of disposal must be approved by the local Medical Milk Commission. Local
and state regulations may determine to some extent how this is done.
Title 8
Milking, Processing and Distribution
Sec. 1. Supervision and Reports
Milking, milk handling, transportation and distribution of Certified
Milk shall be under the supervision of the Sanitarian of the Commission
who shall make frequent inspections of the dairy at times when these opera-
tions are in progress. He shall render monthly reports of such inspections
to the Commission and farm and shall notify the Commission of any question-
able conditions existing on the farm or in the distribution of the milk.
Sec. 2. General
a. Employees Clothing. Milkers and other persons handling the milk
shall wear clean suits and caps approved by the local milk commission,
which shall be worn for no other purpose. They shall use not less than
three freshly laundered suits each week and these when not in use shall
be kept in a clean place, protected from dust and dirt.
b. Things to be Avoided by Employees. Milkers and other handlers
shall refrain from putting hands to the nose and mouth. Every employee
shall exercise great care to prevent milk contamination by droplet infec-
tion from nose and throat, secretions. Spitting shall be prohibited in
the parlors and in all parts of the dairy building where the milk is han-
dled. Smoking is prohibited during the time of milking and bottling.
Sec. 3. Milking
a. Protection of Milking Equipment from Contamination.
(1) Cleaning of Milking Barn Before milking. Soiled bedding and manure
shall be removed from the milking barn at least twice daily and the floors
shall be swept and kept free from refuse. Such cleaning shall be done
not less than one hour before milking (see Title 6, Sec. 2, b).
(2) Flies. Efforts to eliminate flies shall be done by materials
and methods approved by the Sanitarian. They should not be done during
or immediately before milking.
(3) Feeding Hay After Milking. If hay is fed in the milking barn,
it shall be brought into the barn only after milking.
(4) All animals shall be milked into stainless steel or glass lines
leading to a holding tank equipped with a recording thermometer. The milk
shall be cooled promptly to 40 degrees F. Provisions shall be made for
prompt and effective cleaning and sterilization of the lines and equipment
as soon as practical after the last animal has been milked. The lines
must be given bactericidal treatment just prior to use for the subsequent
milking.
PAGENO="0126"
120
METHODS AND STANDARDS
FOR THE PRODUCTION OF CERTIFIED MILK
Page 16
b. Preparation and Handling of Animals.
(1) Clipping. Long hairs shall be clipped from the udder and flanks
and from the tail above the switch. The switch should be cut to clear
the ground or platform by at least four inches. If this is not desirable
with pure bred animals then the switch shall be washed often enough to
keep it clean.
(2) Cleaning. Every animal used in the production of Certified Milk
shall be clean before milking. Whether cleaned by dry grooming or hosing,
the animal's udder must be given particular attention by wiping with cloths
used exclusively for this purpose. No water shall be running down the
udder and off the teats when milking.
(3) Examination of fore-milk. At every milking the first streams
of milk from every teat shall be regected. It is required that such milk
shall be examined for evidence of mastitis by a method approved by the
Commission. Such milk shall not be milked upon the floors or into the
gutters of any stable or building where animals are allowed to lie down
or remain after milking. If any abnormal milk is disclosed, the milk from
that animal shall be discarded and she shall be removed from the milking
herd and not be returned until approved by the Veterinarian. (see Title
7, Sec. 3 e and f.)
(4) Milking. Milking shall be done rapidly and quietly and the animals
shall be treated kindly. Managed or rapid milking procedure is recommended.
(5) Milking Three-quartered Cows. Interupt vacuum on the unused teat
cup through the use of a rubber cap or plug specifically manufactured
for this purpose. This procedure will allow the milking machine operator
to manipulate the unused teat cup as to prevent any possibility of contami-
nation. (This section shall also apply to goats with an unused teat.)
(6) Milkers' Hands. Adequate and conveniently located lavoratory
facilities shall be provided for the milkers. Immediately before milking,
the hands of the milkers shall be thoroughly washed and scrubbed, using
detergents (liquid or powdered), running water and brush, and carefully
dried on clean individual towels.
The milkers' hands shall be clean and dry at all times. He will not
be required to wash his hands between the operation of each cow unless
his hands become soiled or wet.
Sec. 4. Milk Handling and Processing
a. Collecting and Filtering. Promptly after the milk of each cow
is drawn, it shall be removed from the barn to the milk receiving room
and from there to the dairy building. Milk shall be transported from the
milk receiving room to the dairy building conveyed in an approved sanitary
vessel to the point of processing or bottling. The milk shall be passed
through modern filters. A sufficient number of filters shall be provided
for every milking so that they may be changed frequently if necessary.
Filtering may be done either in milk receiving rooms or in the dairy build-
ing. No filter shall be used at more than one milking.
b. Cooling. Immediately after reaching the dairy building the milk
shall be cooled to a temperature below 40 degrees F., and except during
the process of pasteurization shall be maintained at a temperature above
freezing and below 40 degrees F. until delivered to the consumer.
PAGENO="0127"
121
METHODS AND STANDARDS
FOR THE PRODUCTION OF CERTIFIED MILK
Page 17
C. Processing, Bottling and Sealing.
(1) Certified Milk shall be bottled and sealed by means of approved
mechanical equipment on the farm where it is produced, except that with
the approval of the local Medical Milk Commission, milk from one farm
may be processed and/or bottled at another Certified farm and labeled
with the cap of either farm. A producing farm may include a number of
units under the same farm and Commission supervision.
A certified producer may transport his milk in an insulated, properly
sanitized stainless steel tank truck to a processing plant other than
a certified farm. Its equipment, the methods used and the standards main-
tained shall be subject to the control of the local milk commission. All
such certified milk must be processed in sanitized equipment, bottled
and sealed prior to any other grath of milk. The label of this milk must
carry the name of the Certified farm, the supervising milk commission,
processor and distributor. Certified Milk in the finished package product
must comply with standards for Certified Milk, in Title 5.
(2) Milk bottle caps and other closures shall be stored in dust-
tight packages in a clean room and shall at all times be handled in such
a manner as to avoid contamination. After the milk has been cooled and
bottled, the bottles shall be capped and sealed immediately with a closure
approved by the Committee of the American Association of Medical Milk
Commissions, Inc. and in a manner satisfactory to the Certifying Commis-
sion. The bottle caps shall be uncontaminated and shall be applied only
by a suitable capping machine which eliminates the possibility of contam-
ination. Outer milk bottle hoods shall be handled in such a manner as
to avoid contamination of the inner surface. Closures shall be of suffi-
ciently strong and durable material to withstand leakage or puncture during
handling, transportation and delivery of the milk. They shall be of such
form that they will cover completely the pouring lips of the bottles and
it is desirable that they shall be of such construction that when once
removed they cannot be replaced upon the bottles without detection.
(3) Outer milk bottle closures whether made of one or more layers
of material and used without an additional plug cap are defined as single
closures. Those used over a plug cap are defined as double closures. All
types of milk bottle containers, caps or closures shall be subject to
approval by the local commission and the committee of the A.A.M.M.C. on
milk bottles, containers and closures. Both the seal of the A.A.M.M.C.
and the script `Certified Milk" must appear on all Certified Milk outer
closures. Block letters of the words Certified Milk is not approved.
(4) Paper, glass, plastic or other approved containers may be used
for Certified Milk if they meet the requirements for glass bottles as
described in paragraphs 2 and 3.
(5) Other or novel methods of milk handling, processing, packaging
storage or distribution may be temporarily permitted by the Committee
on Methods and Standards, subject to whatever controls and conditions
it may deem necessary.
d. Labeling. The approved container used shall be marked on their
exposed surface with the approved copyrighted seal of the American Associ-
ation of the Medical Milk Commissions, Inc., the name of the Certifying
Commission, the name of the producing farm and other information as re-
quired by the local medical milk commission and the state or local regula-
tory agencies.
PAGENO="0128"
122
METHODS AND STANDARDS
FOR THE PRODUCTION OF CERTIFIED MILK
Page 18
Sec. 5. Transportation and Distribution
a. Equipment. During transportation, milk shall be kept properly
cooled and the containers (bottles) shall be kept reasonably free from
dust and dirt. Trucks, trays and crates shall be kept clean. The Medical
Milk Commission shall exercise its authority to determine the type of
truck necessary to safeguard Certified Milk under climatic conditions
existing in its area.
b. Temperature. Distributors handling Certified Milk must keep it
at a temperature above the freezing point and below 45 degrees F. from
the time it is received until delivered to the consumer.
c. Delivery Time Limit. The milking in any consecutive 24 hour period
shall constitute a day's product. Certified Milk is a premium product
and should be delivered to the consumer in the shortest possible time
after production as determined by each individual milk commission. It
should be noted that Certified Milk is good past this date.
Sec. 6. Preservation of Vitamins and Good Flavor
In the handling, holding and distribution of milk, oxidation reactions
may take place which tend to destroy ascorbic acid (vitamin C), to cause
the development of oxidized flavor and possibly to cause other less notice-
able effects. To avoid these results the following precautions shall be
observed: The milk shall only be allowed to come into contact with properly
cleaned and sanitized rubber milking parts, stainless steel or glass.
If chlorine solution is used for sterilizing equipment or utensils, it
must be thoroughly drained out before milk is allowed to enter. In the
handling of milk unnecessary exposure to sunlight shall be avoided and
when delivered to the customer the milk shall be placed where it will
be protected from sunlight.
Title 9
Personnel, Medical Supervision, etc.
Sec. 1. Supervision and Reports
The Physician appointed by the Commission shall have medical and
hygienic supervision of all employees involved with the production of
Certified Milk. He shall report to the Commission and farms.
Sec. 2. Duties of the Physician
a. Medical Examinations. The Physician, in taking the history and
recording his examination, should note any diseases which may be spread
from person to person. No person with active tuberculosis should be hired;
and x-ray examination or skin test is mandatory. Persons with a past his-
tory of typhoid fever should not be hired until the physician is satisfied
that he is not a carrier of typhoid organisms. A stool examination for
typhoid bacillus and other enteric pathogenic organisms shall be made.
Throat cultures should be made to rule out a diptheria carrier, and when
indicated for hemolytic organisms. It is recommended that for the informa-
tion of the Physician every new employee shall have his blood tested by
the VDRL or equivalent test. Employees working in the milking and plant
PAGENO="0129"
* 123
METHODS AND STANDARDS
FOR THE PRODUCTION OF CERTIFIED MILK
Page 19
area or who are in close contact with the milk shall be examined by a.
physician at least every ninety (90) days. At other times the Physician
shall conduct such medical examinations of employees or other persons
on the farm as he or the Milk Commission think necessary and have suitable
laboratory tests made whenever it is deemed advisable. All examinations
shall be conducted by laboratories and physicians appointed and approved
by the Commission and satisfactory to the health authorities. Complete
records shall be filed with the Commission.
b. Medical Inspection. The Physician may visit the farm if he or
the Commission deems it advisable. He shall be given an opportunity to
examine and interview all employees and residents of the farm and shall
report to the Milk Commission. This report shall be countersigned by the
farm owner or superintendent and a copy shall be kept on file at the farm
for one year.
c. Special Examinations. Upon report from the farm owner or super-
intendent of a farm or upon information from any other source, that any
illness or carrier state capable of transmission by milk is suspected
to exist on the farm, or among the employees of the farm, it shall be
the duty of the Physician to take immediate steps to safeguard the milk.
The Physician shall examine the patient or suspect and assure himself
that the person is attended by a physician in good standing. The Physician
shall promptly report any case of contagious disease to the Commission
and the proper health authorities and shall see that adequate quarantine
is established and maintained.
Sec. 3. Management of Communicable Infections
No persons affected with any communicable disease which may be trans-
mitted through milk, or who has recently been exposed to such infection
shall be employed in the production or handling of Certified Milk. No
person known to be a carrier of any communicable disease known to be milk-
borne shall be employeed or reside on a Certified Milk farm. Persons known
or suspected to have typhoid fever shall not be employed except with the
approval of the milk Commission and with the knowledge and consent of
the proper health authorities. In the event that any person employed or
residing on a Certified Milk farm becomes affected with any disease which
may be transmitted through milk such persons shall be immediately removed
from work.
Sec. 4. Records of Employees
In order that records may be readily available for inspection by
proper officials there shall be kept on the dairy premises a record of
every employee which shall give his name and address, date of employment,
his medical history, results of physical examination by the Physician
and the results of any laboratory tests.
Any applicant or any employee involved with the production of Certi-
fied Milk who may be rejected or discharged because of being a carrier
of pathogenic organisms of diseases transmissible through milk shall be
reported by the Comission to the secretary of the A.A.M.M.C., Inc. The
secretary of the Association may report the names of such individuals
to all the Medical Milk Commissions of the Association.
52-266 0-85--S
PAGENO="0130"
124
METHODS AND STANDARDS
FOR THE PRODUCTION OF CERTIFIED MILK
Page 20
Appendix
Approved Laboratory Methods and Recommendations
To maintain those qualities of dairy products not discernible by
the consumer, it is necessary to perform tests which must be done by labor-
atory procedures. The ultimate aim of these procedures shall be to provide
a product in which the original nutritive qualities, flavor and appearance
have been preserved and to ensure that no harmful organisms or substances
are present to adversely affect the consumer.
An acceptable methodology must be found and adhered to. The American
Association of Medical Milk Commissions, Inc. elects to utilize in full,
the procedures and standards found in the latest edition of "Standard
Methods for the Examination of Dairy Products" published by the American
Public Health Association, 1015 Eighteenth Street, N.W., Washington, D.C.
20036.
PAGENO="0131"
125
Dr. FLEISS. OK.
Mr. WAXMAN. Mr. Dannemeyer.
Mr. DANNEMEYER. Dr. Bolton, are you familiar with the salmo-
nella outbreak from properly pasteurized milk that occurred in Ar-
izona, and also the outbreak of salmonella infection that occurred
from improperly pasteurized milk in Kentucky?
Dr. BOLTON. I think I probably have those in my files. I know I
have the improperly pasteurized one, but these were again out-
breaks or epidemics. Epidemics are unusual, meaning clusters as
Dr. Fierer mentioned, with the milk. You are talking about a spo-
radic thing here.
Mr. DANNEMEYER. The point of your testimony was that pasteuri-
zation is the cure-all for this prospective menace from the contin-
ued availability of certified raw milk. And you are conceding that
pasteurized milk does cause salmonella outbreaks.
Dr. BOLTON. First of all, sir, I did not say pasteurization was the
cure-all. Pasteurization is a step forward in the annals of public
health insofar as protecting people from pathogenic organisms. But
if equipment doesn't work properly or if milk is grossly contami-
nated or standards are not up to par, you can get sick from pas-
teurized milk. You stand a greater chance of getting sick, however,
according to all the data we have, from drinking raw milk than
pasteurized milk.
Mr. DANNEMEYER. Dr. Bolton, are you aware of the 800-some, of
yersinia enterocolitica, a pathogenic organism not unlike salmonel-
la found in three or four different cities in pasteurized milk?
Dr. BOLTON. I am aware of that, yes. There have been epidemics
again with pasteurized milk.
Mr. DANNEMEYER. On the logic that you are following, if I under-
stand it, to get rid of the menace to the public from the continued
availability of certified raw milk you suggest we pasteurize milk.
Now, you are conceding that notwithstanding pasteurization of
milk in these United States we are continuing the manifest cases
of illness?
Dr. B0LT0N. No, extremely rare, sir, with pasteurized milk.
Mr. DANNEMEYER. Couldn't it also be said that the claims of ill-
ness from salmonella and certified raw milk are extremely rare?
Dr. BOLTON. When the risk studies have been done, they show
that raw milk drinkers have something like a 53, or is it 153 times
greater risk of getting salmonella dublin infections than people
who do not drink it.
Mr. DANNEMEYER. You know, if the goal is a perfect world,
wouldn't it be logical to also ban pasteurized milk?
Dr. BOLTON. No, it would be logical to pasteurize milk and have
good standards of dairy cleanliness so you would try to cover your
bases both ways, because you cannot make safe raw milk. I will dis-
agree with you and with Dr. Fleiss because we know that cattle
carry this organism. No matter how clean you make the dairy, and
it is good they do, and I wish all dairies were good about their
standards of cleanliness, but it is going to break down somewhere.
It is as if so what if a few people die from raw milk, we really
should not take this so lightly, however. We need to take all avail-
able precautions we can about a food meant to be consumed in a
raw state.
PAGENO="0132"
126
Mr. DANNEMEYER. Are you saying that somebody has died, that
the proximate cause of the death was the consumption of certified
raw milk?
Dr. BOLTON. In my opinion, yes, many people.
Mr. DANNEMEYER. OK.
Do you know a gentleman by the name of Dr. Werner, an offi-
cial?
Dr. BOLTON. Yes, and I have talked to Dr. Werner about his depo-
sition which you probably have in hand there.
Mr. DANNEMEYER. Dr. Werner said he was unaware of any
person who actually died from consumption of raw certified milk.
Are you aware of that?
Dr. BOLTON. Dr. Werner's deposition has been cut up in pieces
there. If you read the entire part of his statement given in the dep-
osition, you would see that he explained he is an epidemiologist
and that the evidence is there, that he has not personally gone out
and investigated each of these to establish the causal relationship.
Mr. DANNEMEYER. I think the--
Dr. BOLTON. He is an epidemiologist, sir.
Mr. DANNEMEYER. I think the statement I made is a fair state-
ment of what he said.
Dr. BOLTON. I think you are cutting up his statement and not
giving his full statement.
Mr. DANNEMEYER. He said he was unaware of any person who
actually died from consumption of raw certified milk. Are you de-
nying Dr. Werner said that?
Dr. BOLTON. I talked to Dr. Werner about this very point about 2
days ago. He was really upset about this because he saw it on the
flyer sent out to the people to get them in here for this meeting
today. He said.
They cut up my deposition. I went into a lengthy discussion about the epidemio-
logic proof linking this, and they go in and zero in on one little statement.
Mr. DANNEMEYER. He made his statement under oath, didn't he?
Dr. BOLTON. That is an incomplete statement, sir. I would sug-
gest you look at his whole statement, whole deposition.
Mr. WAXMAN. If the gentleman will yield to me, I have a letter
dated February 12, 1985, from S. Benson Werner, M.D., Medical
Epidemiologist, Department of Health Services, State of California.
He would like to have that letter inserted into the record. I have
not had a chance to review it, but as I understand, Dr. Werner is
making clarifications. His letter is titled, "Re: false and misleading
propaganda directed by Alta-Dena Dairy."
I think this letter would be further elucidation of Dr. Werner's
position. So, since he is not here, we have whatever document my
colleague has and this letter that we will also put in the record.
[The information follows:]
PAGENO="0133"
127
DEPARTMEHT OF HEALTH SERVICES
February 12, 1985
Congressman Henry A. Vaxman
2418 Rayburn Office Building
Washington, D.C. 20515
RE: False and Misleading Propaganda Distributed by Alta Dena Dairy
Dear Congressman:
As I was personally cited in the attached propaganda/petition entit1ed~
"Keep Government Out of Our Refrigerators," I would like to point out rather
serious misstatements of fact in the information distributed by Alta Dena
in advance of your Subcommittee's scheduled meeting in Los Angeles on
Wednesday, February 13, 1985. (A copy of the propaganda/petition is attached.)
Despite what was written, the association between certified raw milk
use and Salmonella dublin infection in California is statistically indisputable,
large, and causal. These important findings were supported by an independent
study of California's data by the UCLA School of Public Health (that was con-
ducted with funds that were provided, incidentally, by the Los Angeles County
Medical Milk Commission which certifies Alta Dens's milk). In a study of
S. dublin cases which occurred outside of California, the Centers for Disease
Control independently confirmed that raw milk was the only implicated risk
factor.
There is no doubt thatthat "not one" but many individuals have become
infected by drinking raw milk. The epidemiologic, statistical, and laboratory
evidence are irrefutable despite dairy allegations to the contrary as stated
on the attachment.
As we have emphasized, S. dublin cases associated with use of raw milk
have not appeared in outbreak form in California but have occurred sporadical~v,
and the pathogen appears to attack those exposed individuals in our population
who have infirmities or who are either very young or very old, although healthy
people are certainly at risk as well. We estimate over S million people in
California meet our criteria for compromised health status--a substantial
proportion of the State's population. Finally, despite what was stated, the
overwhelming majority of milkborne outbreaks of salmonellosis (and of campylo-
bacteriosis too, for that matter) have been due to raw milk, not pasteurized
milk. A conservative estimate is that more than 9O~f all milk produced in
this country is pasteurized but that more than 90% of all milkborne outbreaks
have been due to raw milk.
lhesc and other issues are covered far more fu]l~ in a written statement
submitted for your hearing by this State's Infectious Disease Section.
Sincerely yours,
SBW:FRM S. Benson Werner, M.D.
Enclosure--- MedicmlEpidemiologtst
Infectious Disease Section
PAGENO="0134"
February 1985
Dear Friend:
Once again Alta-Dena Certified Dairy and raw certified milk
are under attack. This time, Congressman Henry Waxman is hold-
ing hearings at U.C.L.A. in Los Angeles to ban raw certified
milk. (See enclosed flyer for date, location and time.)
While testimony can only be received from those invited by
Congressman Waxman, the hearings are open to the public and
your visible support can make a difference.
The issue of freedom of choice and the future availability
of raw certified milk needs your support. Please attend and
write to Congressman Waxman so your voice can be heard (see
enclosed petition).
Thank you for your support.
Si ncerely,
~ .~~-~-2~--
THE STUEVE FAMILY
ALTA-DENA CERTIFIED DAIRY
cr
128
`The da~ryttsat
cares about your health
PAGENO="0135"
129
KEEP OOVERNMENT OUT OF OUR REFRIOER4TORS
ATTEND IN PERSON THE SUB-COMMITTEE ON HEALTH & ENVIRONMENTS HEARINGS TO BAN RAW
CERTIFIED MILK:
WEDNESDAY, FEBRUARY 13, 1985 at 9:00 am to 3:00 pm
U.C.L.A. CAMPUS, MARION DAVIES CHELDREN'S CLINIC, MOSS AUDITORIUM
404 HILLGARD STREET, ROOM A2-342
LOS ANGELES, CALIFORNIA
YOUR SUPPORT IS NECESSARY TO PROTECT THE FUNDAMENTAL RIGHT OF
FREEDOM OF CHOICE
HEARINGS ARE UNDERWAY AT THE STATE AND FEDERAL LEVEL THAT MAY BAN THE SALE AND DIS-
TRIBUTION OF RAW CERTIFIED MILK. WE DEMAND TO KNOW WHY. THESE ARE THE FACTS:
* 120,000 PEOPLE CONSUME OVER 250,000 GLASSES OF RAW CERTIFIED MILK DAILY IN
CALIFORNIA. THERE HAS NEVER BEEN ONE CASE OF ILLNESS FROM THE CONSUMPTION
OF RAW CERTIFIED MILK IN OVER 30 YEARS.
* S. BENSON WERNER, M.D., STATE DEPARTMENT OF HEALTH, SAYS THAT HE DOES NOT
KNOW OF ONE PERSON WHO HAS BECOME ILL FROM CONSUMING RAW CERTIFIED MILK, NOR
DOES HE KNOW OF ONE OUTBREAK FROM RAW CERTIFIED MILK IN 30 YEARS.
* THE ONLY OUTBREAK OF SALMONELLA FROM MILK OCCURRED FROM PROPERLY PASTEURIZED
MILK IN ARIZONA AND IMPROPERLY PASTEURIZED MILK IN KENTUCKY.
* PASTEURIZATION DESTROY ESSENTIAL ENZYMES, VALUABLE IMMUNE FACTORS AND NUTRI-
ENTS.
* RAW CERTIFIED MILK IS, AND HAS BEEN, THE SAFEST, MOST WHOLESOME FOOD PRODUCT
AVAILABLE TO MAN, BAR NONE!
If you can't attend the hearings, please sign and send the petition below.
* * * * * * * * * * * * * * * * * * * PETITION * * * * * * * * * * * * * * * * * * *
UNDERSTANDING THAT SOME DIETS AND PHYSICAL CONSTITUTIONS PREFER AND REQUIRE RAW
MILK, I SUPPORT THE CONTINUED SALE AND DISTRIBUTION OF RAW CERTIFIED MILK AND RAW
CERTIFIED MILK PRODUCTS.
DAlE: ____________________
SIGNED: ____________________________________________________
NAME
ADDRESS
CITY, STATE, ZIP CODE _______________________________________________________________
Mail: Congressman Henry Waxman, 2418 Rayburn House Office Building, Washington,
D.C. 20515. Or, call him at (213) 651-1040, Los Angeles Office or (202)
225-4952, Washington, D.C. Office
2/85
PAGENO="0136"
130
Mr. DANNEMEYER. Dr. Bolton, are you familiar with the campylo-
bacter infection associated with certified milk in Atlanta, GA,
which occurred between May and June, 1981, and further that the
culture survey failed to document the presence of the organism
campylobacter in the suspected milk?
Dr. BOLTON. Finding it in milk is a difficult process. Later you
will have a chance to talk to John Orsborn, with the Department
of Food and Agriculture for California. The techniques for recover-
ing compylobacter are difficult. As a matter of fact, isolating it
from human beings has been very, very difficult until about the
last 4 to 5 years.
The techniques for recovering it from milk have now been per-
fected, and they have a sanitarian or laboratory technician with
the California Department of Food and Agriculture who has finally
perfected a technique to get this out. This is where they have liter-
ally planted the germ in a sample of milk and said OK, let's see
you grow it out of there. We just mixed it in. So, it has been diffi-
cult, but it is coming on line now.
It is like with this outbreak where the kids here went to the
dairy, drank raw milk; the kids who in British Columbia went to a
raw milk dairy, drank it, got campylobacter. As a matter of fact,
these dairy epidemics of campylobacter with school field trips
cropped up in British Columbia, Georgia, California, so much so
that this week the U.S. FDA has mailed a special alert to the
health departments all over the U.S.A. saying:
Tell your school departments if kids go on field trips to dairies of any sort, caution
the teachers that under no circumstances are the children to consume any raw milk
products at these dairies.
This just hit the mail or is just hitting the desk of the various
health departments throughout the country this week.
Mr. DANNEMEYER. Of course, there are other sources for campy-
lobacter besides milk?
Dr. BOLTON. Of course, person-to-person spread and other ways.
But these are bunched-up cases. Most of the time we had sporadic
cases of campylobacter, but we get 10 or 12 kids 2 days atter a visit
to a raw milk dairy who are sick with high fever and bloody diar-
rhea. And it is no fun, sir.
Mr. DANNEMEYER. Dr. Fierer, what is your response to this? I
think you told us in your testimony that you had three patients
die.
Dr. FIERER. That is right.
Mr. DANNEMEYER. That manifested salmonella dublin, is that
right?
Dr. FIERER. Yes.
Mr. DANNEMEYER. How many serotypes of salmonella are there
known to medical science?
Dr. FIERER. Probably 1,000.
Mr. DANNEMEYER. And dublin is just one of them, isn't it, really?
Dr. FIERER. Dublin is one of them, yes, as is typhoid.
Mr. DANNEMEYER. Are you familiar with where salmonella
dublin is in the list of 10 or 20 most commonly reported salmonel-
las to the CDC Atlanta, GA?
Dr. FIERER. Yes.
PAGENO="0137"
131
Mr. DANNEMEYER. Where is it?
Dr. FIERER. Way down.
Mr. DANNEMEYER. How far down?
Dr. FIERER. Oh, it is down among the infrequently isolated orga-
nisms.
Mr. DANNEMEYER. For instance, in 1978, the records of CDC dis-
close, I think, that the top source of salmonella was typhimurium,
with a little over 10,000 cases; No. 20 was branderop, of 204 cases.
Salmonella dublin didn't make the top 20, did it?
Dr. FIERER. No; but if you made a list of people dying from sal-
monella infections, you would find dublin in the top 10.
Mr. DANNEMEYER. Have you made that list?
Dr. FIERER. Yes.
Mr. DANNEMEYER. Have you?
Dr. FIERER. Yes.
Mr. DANNEMEYER. And?
Dr. FIERER. That is in the State of California. I have not made it
for the United States.
Mr. DANNEMEYER. And what period of time did this list include?
Dr. FIERER. Last couple of years.
Mr. DANNEMEYER. All right. Have you published that?
Dr. FIERER. No.
Mr. DANNEMEYER. Then in 1979, the 10 top salmonella typhimur-
ium with 10,000, No. 1, and 592 for s. anatum. Salmonella dublin
was down that year, too?
Dr. FIERER. Yes.
Mr. DANNEMEYER. In fact it is fairly low, it is so small it is not
even listed in terms of-it is not in the top 10 or 20, is it, sir?
Dr. FIERER. That is true in terms of total isolates, that is certain-
ly true.
Mr. DANNEMEYER. One of these three people that you say, pa-
tients of yours that died, did one have AIDS?
Dr. FIERER. One had AIDS, one had chronic lymphocytic leuke-
mia, and one had malignant melanoma carcinoma.
Mr. DANNEMEYER. Is it your testimony that in those three cases
you have just described that the proximate cause of the death of
those patients was the consumption on their part of certified raw
milk?
Dr. FIERER. Two of them. The AIDS patient survived the salmo-
nella infection. He was hospitalized in intensive care for approxi-
mately a month with respiratory failure as a result of it. He did
get better. He got AIDS from a blood transfusion. We didn't know
he had AIDS. He was a previously healthy man. He left the hospi-
tal and then came back in with pneumocystis pneumonia and died.
I don't see anything funny about that. I don't see why people are
laughing. People have died.
Mr. DANNEMEYER. I didn't laugh, sir.
Dr. FIERER. I know you didn't.
Mr. DANNEMEYER. You know, I think the interest of members of
the audience to your testimony was the fact that to a layman when
you described the illnesses these three patients had, to suggest that
the proximate cause of the death was to consumption of certified
raw milk, raised a question of credibility.
PAGENO="0138"
132
Dr. FIERER. It does? I don't understand who here is a physician
who can decide proximate cause of death.
Mr. DANNEMEYER. That is for triers of fact to resolve. But I
think--
Dr. FIERER. Oh.
Mr. DANNEMEYER. In two of the cases you say the proximate
cause was consumption of certified raw milk. Is that right?
Dr. FIERER. Salmonella dublin infection, yes, that was in people
who drank raw milk.
Mr. DANNEMEYER. Was that the cause listed on the death certifi-
cate?
Dr. FIERER. Yes.
Mr. DANNEMEYER. Did you sign the death certificate?
Dr. FIERER. No.
Mr. DANNEMEYER. Was the physician who did sign the death cer-
tificate someone you knew? You were the treating physician,
weren't you?
Dr. FIERER. I was the infectious disease consultant. We have a
teaching hospital and I am a professor of medicine. The resident
signed the death certificate.
Mr. DANNEMEYER. How long had these two patients who died
been suffering from the diseases that you described that they had
prior to death, roughly?
Dr. FIERER. The lady with a chronic lymphocytic leukemia had it
for about 1 year; the man who had the malignant melanoma, I
don't know how long he had it. I am sorry.
Mr. DANNEMEYER. How long had these patients been consuming
certified raw milk?
Dr. FIERER. The woman who had the leukemia had been drinking
raw milk for at least 2 years. The man who had the melanoma, I
can't tell you. He came in in a coma from meningitis, and I never
had a chance to talk to him.
Mr. DANNEMEYER. Would you agree with the statement that for
a single case of salmonella infection it would be very difficult to
determine the source because there are a lot of risk factors in-
volved?
Dr. FIERER. That general statement, yes.
Mr. DANNEMEYER. You also agree with the statement that
though people cook meat and poultry, for the most part statistics
show people are still contracting salmonella from meat and poultry
or from cross-contamination or improper handling and storage of
it?
Dr. FIERER. I wouldn't know whether it is most but certainly
some.
Mr. DANNEMEYER. I have no other questions, Mr. Chairman.
Mr. WAXMAN. Dr. Bolton, you showed us a sign from the city and
county of San Francisco. I assume that was an ordinance adopted
by San Francisco?
Dr. BOLTON. Yes; it was.
Mr. WAXMAN. As a warning to people, certainly to certain high-
risk individuals not to purchase raw milk.
Dr. BOLTON. Yes.
Mr. WAXMAN. Yet you advocate a ban. Why don't you advocate a
warning?
PAGENO="0139"
133
Dr. BOLTON. A warning label on cigarettes has done no good. A
warning label on raw milk, unless it is very striking, that says this
product can kill you, or this product has potentially lethal side-ef-
fects, with a biohazard sticker or something that is very eye-catch-
ing, people will not pay much attention to it. I really think it
would be better if you are not going to ban it, to at least have
people have to sign a paper like if I am going to send somebody in
for an operation and a surgeon is going to put tubes in the child's
ear or take out his appendix. The parents sign a paper saying that
the doctor explained this procedure and the risks and benefits, and
I understand them and I authorize the doctor to go ahead.
If you were going to sell it and not take it off the shelves, I think
a statement is necessary that would outline the health risk of it to
be signed by the purchaser saying I have read all this and I don't
care, I will take my chances.
Mr. WAXMAN. I guess the question is whether you think patients
have adequate information about the risks and benefits of raw
milk?
Dr. BOLTON. Absolutely not.
Mr. WAXMAN. The question then is if we added the warning label
would they have that information available to them and should we
say to them notwithstanding the fact that they have that informa-
tion that they can disagree if they want to take their chances.
Dr. Fierer, do you have any thoughts on that?
Dr. FIERER. I really don't know whether a warning label would
do any good. If that was proposed I would support it.
Mr. WAXMAN. As opposed to nothing?
Dr. FIERER. As opposed to nothing, definitely.
Mr. WAXMAN. We have had suggestions like when children
might go on a field trip. Their informed judgment is not the judg-
ment we usually accept as an informed judgment. I guess there are
other complications. But I was interested in your reaction.
Dr. BOLTON. A warning label will really do it. We are dealing
with a toxic waste problem. You have a product contaminated with
a biologic toxic waste. It is an intermittent contamination even in
the face of good sanitation. Would you really want an infant formu-
la to stay on the market if you knew it was intermittently contami-
nated by a harmful chemical? Obviously the answer is no.
You say what about harmful bacteria? Should we look at that
differently from the way you look at a deadly chemical?
Mr. WAXMAN. Your testimony indicates-let me review it. The
Academy of Pediatrics has become more concerned about the ques-
tion of raw milk lately because of an increasing incidence of illness
in recent years. Is that correct?
Dr. BOLTON. That is true.
Mr. WAXMAN. Is it an increasing incidence?
Dr. BOLTON. Yes; but still not in great numbers. In California
maybe 20 or so pediatric cases this year. A percentage of them
have lymphoma, things like this, leukemia. But the tack of saying,
well, so many other people die from getting other salmonella, or
else from some other thing, why be concerned about this, is like
saying why be concerned about somebody running over somebody
with a car when thousands of people get run over by buses or
something like this.
PAGENO="0140"
134
You have to take every child's life as a sacred thing and say this
child deserves the protection of our society, of our public healthful
department to try to see to it that the child has clean milk.
Mr. WAXMAN. Do you know of any evidence that raw milk is
more healthy for you?
Dr. BOLTON. I know of absolutely no evidence to that effect.
I have studied the-this has been reviewed by Dr. Helen Swener-
ton of U.C. Davis, by the CDC, and in literature search other
people, and with the exception of the proponents of raw milk-basi-
cally the industry and their allies-the majority of the medical lit-
erature I have read indicates that there is less than 10 percent
bind up in certain ingredients or certain things that are not really
biologically important anyway because these things come from
other sources in the human diet. There is no basic nutritional dif-
ference between them.
Mr. WAXMAN. We have heard a lot about salmonella. Is that the
only organism to worry about when we are talking about raw milk,
Dr. Fierer?
Dr. FIERER. No. There are others. I concentrated on salmonella
dublin in particular because it is such a serious illness for the
people, at least in California, who acquire it. But you have heard
there is a long list of organisms that can be acquired from raw
milk including Listeria, Yersinia, et cetera. These organisms differ
somewhat in that they are widely distributed through the food
chain and there are plenty of other sources for them.
Mr. WAXMAN. Dr. Bolton, one last question. Is the Academy con-
cerned about the promotion of raw milk for infants?
Dr. BOLTON. We have been very concerned.
Mr. WAXMAN. All three of you gentlemen seem to think raw
milk is inappropriate for infants. It is not a good food for them.
They are the most susceptible to the disease. Do you have any com-
plaint that there is a certain amount of encouragement for raw
milk for infants?
Dr. BOLTON. Yes; in the advertisements which you have stated
and I have copies of those things describing it as the perfect food
for infants. I feel that is a very dangerous thing to do. The Acade-
my has an official statement on this that says for raw milk, except
for the mother's own breast milk, raw milk should not be fed to the
infant at any time.
Mr. WAXMAN. I have no further questions. Do you have any
others?
Mr. DANNEMEYER. Yes.
Dr. Fierer, the records of the CDC disclose in 1981 there were
2,456 cases of food poisoning from salmonella of all types.
Dr. FIERER. You mean epidemics?
Mr. DANNEMEYER. They classified them as attributable to food,
part of an outbreak. That was the classification.
Dr. FIERER. All right.
Mr. DANNEMEYER. The largest number in 1981 came from chick-
en.
Now, since we are concerned about the adverse impact on
humans from salmonella, in your instance you are talking about
certified raw milk which produced in that same year-according to
the records of the CDC-26 cases.
PAGENO="0141"
135
Dr. FIERER. What year is this?
Mr. DANNEMEYER. In 1981 the CDC reports 26 related to milk,
122 related to chicken. Now if the logic of your view says to get rid
of the 26 cases that came from milk, pasteurize it or get rid of it,
shouldn't we also ban chicken?
Dr. FIERER. That is a list of food-related epidemics. When the epi-
demic occurs you know something has gone wrong because that is
out of the ordinary.
What that tells me is that it is a very easy thing to prepare
chicken incorrectly and, in effect, a lot of people do.
Mr. DANNEMEYER. From the standpoint of--
Dr. FIERER. That is not a day-to-day threat.
Mr. DANNEMEYER. Since we are looking out for the health of our
consumers, we have a responsibility, those of us in Government,
and if our goal is eradication of salmonella--
Dr. FIERER. That is not my goal.
Mr. DANNEMEYER. Then to be consistent shouldn't we eliminate
any food product that has produced salmonella food poisoning?
Dr. FIERER. I couldn't go about telling you how to do that. That is
not my goal. That is an unrealistic goal.
Mr. DANNEMEYER. What do you mean?
Dr. FIERER. To eliminate all salmonella infections is an unrealis-
tic goal. I would never attempt it.
Mr. DANNEMEYER. That is puzzling.
Dr. FIERER. Why?
Mr. DANNEMEYER. Why would salmonella from chicken be less
inimical to the health of humans than salmonella from milk?
Dr. FIERER. For one thing, as I thought I emphasized, one of the
infections that is acquired from milk is salmonella dublin, which is
potentially lethal; whereas you never get that from chickens. Most
of the chicken infections, chicken-associated infections are relative-
ly self-limited cases of gastroenteritis. It would be nice if we didn't
have them, but they are one of the plagues of mankind that we live
with.
That will be my major point.
Mr. DANNEMEYER. In other words, salmonella, you agree, is a
ubiquitous substance. Is that right?
Dr. FIERER. Not ubiquitous.
Mr. DANNEMEYER. All right. How about pork, 120 cases in 1981.
Shouldn't we ban pork?
Dr. FIERER. I don't think there was a single case of salmonella
dublin from pork.
Mr. DANNEMEYER. Egg nog, 74. Shouldn't we get rid of egg nog?
Dr. FIERER. I don't know about egg nog.
Mr. DANNEMEYER. How about shellfish?
Dr. BOLTON. I would like to comment on this if I could.
Mr. DANNEMEYER. If you wait, I will come to you next.
Dr. BOLTON. OK.
Mr. DANNEMEYER. Forty cases from shellfish. Shouldn't we get
rid of that?
Dr. FIERER. We should try to control it, and I think the public
health authorities have. Its a major source of hepatitis in the
United States. Most public health authorities attempt to control
raw shell fish.
PAGENO="0142"
136
Mr. DANNEMEYER. Turkey, for instance, produced 455 cases.
Shouldn't we get rid of turkey?
Dr. FIERER. No; I wouldn't say that.
Mr. DANNEMEYER. Dr. Bolton, let's take another year, 1980; 2,381
cases of salmonella food poisoning reported to the CDC in that
year. Take 1978, it might be a better year for comparison. In that
year there were all together 33 cases of salmonella food poisoning,
and 23 of them related to pasteurized milk. That is to be contrasted
with pork, producing 850 cases in 1978.
Shouldn't we get rid of pork?
Dr. BOLTON. If you take everything that you have mentioned
there and say, are we really balancing things, and so are we talk-
ing about getting rid of milk? No; we are talking about making it
safe by heat treatment or pasteurizing.
The thing that makes chicken and pork safe for consumption is
cooking.
Mr. DANNEMEYER. Wait a minute, notwithstanding the cooking,
whatever preparation was involved by the preparer, the records of
the CDC disclose that in 1978 there were 379 cases from turkey,
850 from pork, 147 from beef. In other words, we consumers have
almost reached the point where we cannot be trusted with our own
food preparation, and in order to improve the lot of the lives of all
of us, we should, if the goal is elimination of salmonella, get rid of
all these food products that produce salmonella, shouldn't we?
Dr. BOLTON. No, sir; you should heat-treat them, pasteurization,
heat treatment. You cook pork. You cook chicken. If you don't cook
pork, not only are you going to get salmonella, but you will stand a
good chance of getting trichinosis and a lot of other problems. But
the breakout there is the cooking factor.
When you go into that, OK, we will suffer pasteurized milk out-
breaks, this will happen. Or if it is not properly done or cleanliness
breaks down, certainly no system is perfect. But one of the things
that girls are taught and that boys are taught and that other
people are taught is you don't eat pink chicken. If you get chicken
improperly prepared--
Mr. DANNEMEYER. What you just said, nothing's perfect in this
world, isn't that really the crux of this controversy? It strikes me
that people of a persuasion of yourself and Dr. Fierer-good-mean-
ing, well-intentioned people, I concede that-are attempting to
assert a standard of performance or achievement for in this case
certified raw milk, in terms of its ability to be consumed by a con-
sumer, and that you are ignoring a vast majority of other food
products that are available to consumers on the tables of people of
California.
Dr. BOLTON. I will not give you that point. We are not sitting
back saying it is OK to have salmonella in these other places. You
try to cook and control this by heating because heating will control
or kill the salmonella.
Mr. DANNEMEYER. In 1 year, if I could find it, we had CDC re-
porting that the source of salmonella was water in 78 cases of sal-
monella poisoning. From water.
Dr. BOLTON. That happened to be related to a cistern where
there were birds roosting on the roof. The drain water was collect-
ed in the cistern and consumed by the people.
PAGENO="0143"
137
You should go back and look at the epidemics you quoted be-
cause you are using rough statistics.
Mr. DANNEMEYER. In 1979 there were 200 cases from hospitals,
and to be consistent should we shut down hospitals?
Dr. BOLTON. Salmonella will spread in hospitals if people don't
wash their hands carefully or if the food is not prepared carefully.
Salmonella can be transmitted person to person. It's a big factor.
You must wash your hands.
Mr. DANNEMEYER. Would it follow we should shut down the hos-
pitals in America and we can stop salmonella?
Dr. BOLTON. No. You have to get people to wash their hands, sir.
Mr. DANNEMEYER. Well, the point is there is nothing perfect in
this world.
Dr. BOLTON. So you are going to spot us so many leukemics and
lymphoma patients and say, OK, let them die because it is not a
perfect world?
No. You try to protect those people.
Mr. DANNEMEYER. Let me ask you one other question, if I may.
Are you familiar with those who claim that there is a nutritional
loss from the pasteurization of milk? I am not asking if you agree
with those. Are you familiar with those claims?
Dr. BOLTON. I have read their claims and the counterclaims I
have read. I happen to believe the counterclaims. My opinion is dif-
ferent from Dr. Fleiss, but I have reviewed this and I believe there
is no great nutritional loss from pasteurization. The health risk is
greater.
Mr. WAXMAN. Let me admonish the audience that we won't have
any reactions. You are guests here, and this is a public meeting;
but we are not asking for public reactions to statements made by
the witnesses. That would be inappropriate.
Mr. DANNEMEYER. Dr. Fierer, are you familiar with the claims of
people who have done research, scientific research, who assert
there is a significant nutritional loss from the process known as
pasteurization of milk?
Dr. FIERER. I am. You sent me some of them yourself.
Mr. DANNEMEYER. Did you read them?
Dr. FIERER. Oh, yes.
Dr. Fri~iss. And you have concluded that they are lacking in
what?
Dr. FIERER. In scientific merit.
Mr. DANNEMEYER. In your opinion.
Dr. FIERER. Yes.
Mr. DANNEMEYER. Thank you very much.
Mr. WAXMAN. Thank you, Mr. Dannemeyer. Gentlemen, thank
you very much for your testimony.
We now call our third panel. I regret that the Los Angeles De-
partment of Health Services was unwilling to permit Dr. Shirley
Fannin, chief of the county communicable disease control, to par-
ticipate in this hearing. We do have Dr. James Chin, who is chief
of the Infectious Disease Section of the California Department of
Health Services; Dr. Morris Potter is a veterinary epidemiologist
from the Centers for Disease Control, and Dr. Patton Smith, who is
assistant director, Division of Animal Industry, California Depart-
ment of Food and Agriculture. Dr. Smith is accompanied by Dr.
PAGENO="0144"
138
John Orsborn, who is chief of venterinary and laboratory services.
Also, Dean Thomas is president of Delst Chemical Co. & Research
Inc. I would like to welcome all of you to this hearing.
We have on the list John Adams of the National Milk Producers
Federation, to testify after this, but he will have to leave, so I
would like to have Mr. Adams, National Milk Producers Federa-
tion, come forward at this time, if he would.
We are aware of the fact you have a tight schedule. We hoped to
have had you up earlier, but I will ask you to give us your testimo-
ny first and see if there are questions, and we can allow you to
leave.
STATEMENT OF JOHN ADAMS, DIRECTOR, MILK REGULATORY
AND ANIMAL HEALTH AFFAIRS, NATIONAL MILK PRODUCERS
FEDERATION
Mr. ADAMS. Thank you very much, Mr. Chairman, I appreciate
your courtesy.
I am John Adams. I am director of milk regulatory and animal
health affairs of the National Milk Producers Federation, located
at 1840 Wilson Boulevard, Arlington, VA.
The National Milk Producers Federation is a national farm com-
modity organization representing nearly all of the several hundred
dairy marketing cooperatives serving this Nation. These coopera-
tives and their producer members market a significant volume of
all of the milk sold commercially in the United States.
The membership of the federation has long supported the need
for pasteurization of all milk and milk products sold to consumers.
Not only has the federation recognized the basic necessity of pas-
teurization for the protection of the public health, the federation
has also been actively involved in developing and supporting the
National Conference on Interstate Milk Shipments since its incep-
tion in 1950. The NCIMS is an organization of State governments
and the Food and Drug Administration, who jointly participate in
the National Conference on Interstate Milk Shipments known as
NCIMS.
This national conference is held every 2 years to develop the
Grade A pastuerized milk ordinance and conference procedures.
These documents serve as a basis for reciprocity agreements be-
tween the states governing milk shipments and receipts. They also
form the basis of a sound cooperative State-Federal program de-
signed to protect the public health from the cow to the consumer.
This program has been cited by the second National Conference on
Food Protection as a model for the entire food industry. Without
the requirement of pasteurization, no comparable public health
program can exist for the consumption of raw milk.
Seldom, if ever, has there been such an overwhelming array of
scientific evidence indicting raw milk consumed in a raw state.
Seldom, if ever, has there been such an array of universal public
support for banning the sale of raw milk in interstate commerce
for beverage consumption.
The entire milk industry, both producer organizations and proc-
essors, support such a ban. Federal agencies, State governments
and consumer organizations have registered continued concern
PAGENO="0145"
139
that no action has been taken at the federal level to ban the sale of
unpasteurized products sold to consumers. The FDA Hearing
Clerk's file is replete with resolutions, letters of concern and scien-
tific evidence supporting a prohibition of the sale of unpasteurized
milk and milk products sold directly to consumers. Yet, for unsub-
stantiated reasons, there has been no concrete action taken by
Health and Human Services to prohibit the sale of a food which
continues to pose a public health threat.
If there were not such a simple way of reducing or eliminating
such a public health threat as pasteurization would provide, per-
haps we could understand the delay. However, in the face of all the
scientific evidence indicting unpasteurized milk, it is unconscion-
able that no action has been taken by HHS to lift the stay imposed
by FDA in 1974. This stay has continued to permit the interstate
shipment and sale of unpasteurized milk and milk products for
direct sale to consumers.
We are therefore, encouraged by the ruling of U.S. District Court
Judge Gerhard Gesell on January 14, 1985. As a result of the
court's direction, we hope HHS will proceed to clear the way for
FDA to propose regulations which will require all milk and milk
products moving in interstate commerce for direction human con-
sumption to be pasteurized. We are hopeful that this subcommittee
can support such a much needed requirement which is so essential
for protecting the public health.
There are no sound or justifiable public health or scientific rea-
sons for not requiring pasteurization of all milk and milk products
sold in final packaged form to consumers. To do otherwise will con-
tinue to undermine the great progress which has been made in this
Nation to produce and market very safe and wholesome pasteur-
ized milk and pasteurized manufactured milk products.
Mr. Chairman, I referred to the scientific evidence. You have re-
ceived that. Obviously there are different opinions regarding the
evidence, but I have prepared and would like to submit for the
record, a number of references which perhaps will add to the al-
ready complete FDA hearing record:
One is a reprint from the Journal of the American Medical Asso-
ciation entitled, "Unpasteurized Milk-the Hazards of a Health
Fetish" by Morris Potter, and you will hear him speak today. In
this review, the hazards and purported benefits of raw milk con-
sumption are reviewed to "help the practicing physician and other
health professionals more fully appreciate the risk posed to human
health by raw milk."
Quoting further from the comment section of his review, which I
hope everyone has read:
The relative merits of raw and pasteurized milk have been debated for at least 90
years. In this period, the theoretical health benefits of raw milk have never with-
stood careful scientific scrutiny. I would like to acknowledge for your benefit that in
this particular review article, the situation dealing with nutritional benefits is dealt
with. I think if you will read that, there are differences, but the differencesare less
than 10 percent and are not considered statistically significant at the 5 percent level.
So I think we need to be careful when we talk about nutritional benefits because
the scientific scrutiny of the nutritional benefits has not stood up in terms of the
statistical relationships.
Conversely, since October 19, 1984, when the review article was published in JAMA,
we know of at least one documented and reported outbreak of salmonella found in raw
milk sold in southwestern Oregon. Based on a news release dated November 15, 1984,
PAGENO="0146"
140
issued by the Oregon State Health Division, salmonella dublin was isolated from
Reservation Ranch brand raw milk bottled on November 5 in Smith River, CA. A
routine sample of this milk was reported to have been received in the Food and Dairy
Division Laboratory, Oregon Department of Agriculture on November 6 and the
presence of salmonella dublin was confirmed on November 15th. According to this
release, "Oregon has experienced several raw milk associated disease outbreaks since
1978 involving salmonella dublin, salmonella typhimurium and camphylobacter
jejuni." Therefore, the "Oregon State Health Division recommends that only pasteur-
ized milk and other dairy products be used."
Mr. Chairman, a Federal regulation banning interstate shipment
of raw milk for direct beverage consumption would assist a number
of States which deem it necessary or desirable to restrict or ban
the sale of unpasteurized milk and milk products within their own
governing boundaries.
There have been few times when so many from all sectors of the
public, whether producer, consumer or professionally oriented,
have realized the necessity to take action to protect the public
health. The great majority of those in the dairy industry realize
that protection of the public health is and must continue to be our
most important consideration. At a time when so much public at-
tention is focused on the need to protect the public health and pro-
vide a safe and wholesome food supply, it is unconscionable that we
continue to delay action to provide protection for the public against
sale of unpasteurized milk or milk products in interstate commerce
for direct beverage consumption.
Thank you very much.
[Mr. Adams' prepared statement and reprint referred to follow:]
PAGENO="0147"
141
National Milk Producers Federation
Mr. Chairman, my name is John B. Adams. I am Director of Milk Regulatory
And Animal Health Affairs of the National Milk Producers Federation, located at
1840 Wilson Boulevard, Arlington, Virginia. The National Milk Producers~
Federation is a national farm commodity organization representing nearly all of
several hundred dairy marketing cooperatives serving this Nation. These
cooperatives and their producer members market a significant volume of all the
milk sold commercially in the United States.
The membership of the Federation has long supported the need for pasteuri-
zation of all milk and milk products sold to consumers. Not only has the Fede-
ration recognized the basic necessity of pasteurization for the protection of
the public health, the Federation has also been scti~ely involved in developing
and supporting the National Conference on Interstate Milk Shipments (NCIMS)
since its inception in 1950. The NCIMS is an organization of state governments
and the Food and Drug Administration who jointly participate in the "National
Conference on Interstste Milk Shipments" known as "NCIMS." This national con-
ference is held every two years to develop the Grade "A" Pasteurized Milk
Ordinance and "Conference Procedures." These documents serve as a basis for
reciprocity agreements between the States governing milk shipments and
receipts. They also form the basis of a sound "Cooperative State-Federal
program designed to protect the public health from the cow to the consumer.
This program has been cited by the secoiid National Conference on Food Protec-
tion as,a model for the entire food industry. Without the requirement of
pasteurization, no comparable public health program can exist for the con-
sumption of raw milk,
PAGENO="0148"
142
Seldom, if ever, has there been such an overwhelming array of scientific
evidence indicting raw milk consumed in a "raw" state. Seldom, if ever, has
there been such an array of universal public support for banning the sale of
raw milk in interstate commerce for beverage consumption.
The entire milk industry, both producer organizations and processors,
support such a ban. Federal agencies, State governments and consumer organi-'
zations have registered continued concern that no action has been taken at the
Federal level to ban the sale of unpasteurized products sold to consumers. The
FDA Hearing Clerks file is replete with resolutions, letters of concern and
scientific evidence supporting a prohibition of the sale of unpasteurized milk
and mIlk products sold directly tà consumers. Yet, for unsubstantiated
reasons, there has been no concrete action taken by Health and Human Services
to prohibit the sale of a food which continues to pose a public health threat.
If there were not such a simple way of reducing or eliminating such a
public health thi~eat as pasteurization would provide, perhaps we could under-
stand the delay. However, in the face of all the scientific evidence indicting
unpasteurized milk, it is unconscionable that no action has been taken by HHS
to lift the stay imposed by FDA in 1974. This stay has continued to permit the
interstate shipment and sale of unpasteurized milk and milk products for direct
sale to consumers. We are, therefore, encouraged by the ruling of 13.5.
District Court Judge Gerhard Gesell on January 14, 1985. As a result of the
Court's ~1irection, we hope 11115 will proceed to clear the way for FDA to propose
regulations which will require all milk and milk products moving in interstate
commerce for direct huñian consllmption t9 be pasteurized. We are hopeful that
this Subcommittee can support such a much needed requirement which is so
essential for protecting the public health.
PAGENO="0149"
143
There are no sound or justifj~able public health or scientific reasons for
not requiring pasteurization of all milk and milk products sold in final pack-
aged form to consumers. To do otherwise will continue to undermine the great
progress which has been made in this Nation to produce and market very safe and
wholesome pasteurized milk and pasteurized manufactured milk products.
Mr. Chairman, Ihave referred in my statement to the scientific evidence
which supports an MRS ban on the interstate sale of unpasteurized milk and milk
products for direct consumer consumption. Most of this evidence is now a part
of the FDA hearing record. We have prep~red, however, several references which
may provide additional supporting evidence for a ban on interstate shipment of
raw milk for direct human consumption, so I would ask that these references be
included along with my statement for the hearing record.
One of these references is a reprint form the Journal of the American
Medical Association entitled "Unpasteurized Milk-The Hazards of a Health
Fetish" by Morris Potter and associates (CDC, Atlanta, Georgia published in
JAMA, October 19, 1984-Vol. 252, No. 15). In this review, the hazards and
purported benefits of raw milk consumption are reviewed to "help the practicing
physician and other health professionals more fully appreciate the risk posed
to human health by raw milk." Quoting further from the comment section of this
review: "The relative merits of raw and pasteurized milk have been debated for
at least 90 years. In this period, the theoretical health benefits of raw milk
have never withstood careful scientific scrutiny." "Epidemic richets and
scurvy and the other dire consequences of milk pasteurization prophésized by
early raw milk advocates have not occurred." "Conversely, the fact that raw
milk presents a substantially greater inherent risk of infectious disease has
been demonstrated repeatedly." "Surprisingly, the controversy continues."
PAGENO="0150"
144
Since October 19, 1984 when the review article was published in JAMA, we
know of at least one documented and reported outbreak of Salmonella found in
raw milk sold in Southwestern Oregon. Based on a News Release dated November
15, 1984 issued by the Oregon State Health Division, Salmonella dublin was
isolated from Reservation Ranch brand raw milk bottled on November 5 in Smith
River, California. A routine sample of this milk was reported to have been
received in the Food and Dairy Division Laboratory, Oregon Department of
Agriculture on November 6 and the presence of Salmonella dublin was confirmed
on November 15. According to this release, "Oregon has experienced several raw
milk-associated disease outbreaks since 1978 involving Salmonella dublin,
Salmonella typhimurium and Camphylobacter jujuni. Therefore, "The Oregon State
Health Division recommends that only pasteurized milk and other dairy products
be used."
Mr. Chairman, a Federal regulation banning interstate shipment of raw milk
for direct beverage consumption would assist a number of states which deem it
necessary or desirable to restrict or ban the sale of unpasteurized milk and
milk products within their state boundaries.
There have been few times when so many from all sectors of the public,
whether producer, consumer or professionally oriented, have realized the
necessity to take action to protect the public health. The great majority of
those in the dairy industry realize that protection of the public, health is and
must continue to be our most important consideration. At a time when so much
public attention is focused on the need to protect the public health and
provide a safe and wholesome food supply, it is unconscouncable that we
continue to delay action to provide protection for the public against sale of
unpasteurized milk or milk products in interstate commerce for direct beverage
consumption.
John B. Adams, Director'
Milk Regulatory And Animal Health Affairs
PAGENO="0151"
Unpasteurized Milk
R~pdsttndfros,JAMAtt R.Jecoulof9.A,,,s,ks, MedioulMzocluM,
OOebut 19. 1984, Moss 252
Cop~vçh1 1984. M,edco, MOOaIM,oclcts,,
The Hazards of a Health Fetish
Morris E. Potter, DVM; Arnold F. Kaufmann, DVM; Paul A. Blake, MD; Roger A. Feldman, MD
AS THE dairy industry began to
industrialize in the ISOOs, the mass
production and distribution of milk
and dairy products led to widespread
outbreaks of milkborne disease. The
greatest perceived milkborne hazards
of the time were poor sanitation and
handling procedures, as well as dis-
eased dairy cows. Repeated outbreaks
of typhoid, scarlet fever, diphtheria,
diarrheal disease, and septic sore
throat were caused by milk that was
produced, transported, and sold under
unhygienic conditions.
Nationwide problems with contam-
inated milk led to two public health
movements that attacked the pur-
veyors of bad milk and each other
with equal alacrity. The certified milk
movement promoted sanitation in all
phases of milk production and mar-
keting under the oversight of medical
milk commissions but denounced pas-
Fto,t, Ito Oioiuion of Buotetiul Disnssss, Contst
fotIstuctioc~ Ossases, C.etsss lot PnnussCocttot.
Musts.
Rsptkttesqeoststoflloiaios ot8actetiotDisensos
Costs, tot kstestioss Oseusos, 1800 Clifton Rd NE.
Atlasta, GA 30333 (St Potts,).
2048 JAMA, Oct 19, 1984-Vol 252, No. 15
teuri;Ation, claiming that it caused
nutritional deficiencies, allowed the
marketing of sterilized filth, and
destroyed the natural flavor of milk.
Conversely, the pasteurized milk
movement denounced certified milk
as unsafe despite the sanitary precau-
tions.' Ultimately, the best of both
movements became public policy.
Pasteurization was accepted as the
primary safeguard for the nation's
milk supply after several epidemics
were traced to certified raw milk,
while the sanitary concepts of the
certified milk movement were incor-
porated into milk hygiene codes as
important adjunctive safeguards.
The apparent public health impact
of safe milk was substantial; for
example, the number of infant deaths
due to diarrhea in Washington, DC,
dropped from 477 in 1894, the year
before sanitary requirements for milk
were strengthened, to 72 in 1909.'
Although there is no objective evi-
dence that milk pasteurization has an
adverse effect on human nutrition or
health, the sale of raw milk (certified
and uncertified) has persisted and
even increased in recent years under
intensive promotion by "health food"
enthusiasts using arguments similar
to those advanced in the 1890s.
In this review, we discuss the has-
ardn and purported benefits of raw
milk consumption to help the practic-
ing physician and other health pro.
fessionals more fully appreciate the
risk posed to human health by raw
milk and to enable them to under-
stand and rebut arguments advanced
in support of consumption of raw
milk.
DefinitIons
Milk, as discussed in this review, is
cow milk unless otherwise specified.
Coat milk is increasingly promoted as
a health food, but constitutes less
than 1% of total milk consumption in
the United States.
Raw (unpasteurized) milk may be
certified or uncertified. Certified raw
milk is produced in accordance with
methods and standards established
by the American Association of Medi-
cal Milk Commissions, Inc (an indus-
try-supported organization). This
milk is produced by a few large
dairies and is often sold, where state
laws allow, in retail food stores.
Uncertified raw milk is typically pro-
duced in small volumes by individual
dairy farmers and sold on the prem-
ises of the producing farm or by home
delivery.
Pasteurized milk is milk heated for
specified time and temperature com-
binations designed to kill all micro-
145
State of the Art
M. Therese Southgate, MD, Section Coordinator
* Meaningful differences in nutritional value between pasteurized and
unpasteurized milk have not been demonstrated, and other purported
benefits of raw milk consumption have not been substantiated. Conversely,
the role of unpasteurized dairy products In the transmission of infectious
diseases has been established repeatedly. To effectively counsel patients
attracted by the health claims made for raw milk, practicing physicians must
understand both the rationale used by proponents of raw milk and the
magnitude of the risk involved in drinking raw milk.
(JAMA 1984;252:2050-2054)
Unpasieseized Milk-Potter ci ci
PAGENO="0152"
Comparison of Nutritional Values published a report about his observa-
In Raw and Pasteurized Milk lions on cats fed varying combina-
tions of raw and heat-treated milk
Pasteurization causes minor and raw and cooked meat. In his first
changes in milk, and advocates of raw and largest series of experiments,
milk have at one time or another Pottenger observed many diseases in
claimed that virtually every detect- cats fed raw milk and cooked meat,
able change has profound health but essentially no disease in those fed
implications. Pasteurization affects raw milk and raw meat. Raw milk
six milk constituents with known advocates have erroneously cited this
nutritional benefits: three vitamins article as having reported that din-
for which milk is a minor source ease occurred in cats fed pasteurized
(thiamine, B,, and C), calcium, pro- milk (eg, Llyod F. Smith, MD's article
tom, and fat. Thiamine is reduced Why Certified Raw Milk, Let's Live
from approximately 0.45 to 0.42 mg/ Magazine). Smaller experiments re-
I; vitamin B, is reduced at a maxi- ported in the same article showed
mum from 3 to 2.7 pg/Is; and vitamin that a diet of one-third raw meat and
C is reducc(f from 2.0 to 1.8 mg/L. two.thirdn milk (pasteurized or not)
None of these losses exceeds 10%, and (lid not provide adequate nutrition for
none can be considered important, cats.
About 6% of calcium is rendered The major health benefits claimed
insoluble, and about i/o of milk pro- for raw milk are summarized in Table
tein is coagulated. The major etTect 1. These claims, except for a few
on fat is a slight disaggregation of fat recent variants, were rebutted more
glubules, resulting in a reduced cream than 40 years ago by Wilson in his
line in whole milk. The observed monograph Tue Pasteurization of
changes have no effect on the bio- Milk. This book is required reading
availability of these three nutrients.' for anyone interested in the topic.
Raw milk has also been said to con-
tain untlefined and un,letectal,le Infectious Disease Hazards
health promoters, such as an anti- of Raw Milk
stilTness factor invaluable for treat- Abundant evidence has shown that
ment of arthritis, hut ouch claims raw milk serves as the oource of
have not been substantiated in the bacteria that cause outbreaks of din-
mc,lical literature, ease in humans: in recent years, most
Numerous studies of the relative frequently salmonellonin and campy-
nutritional merits of raw and pus- lobacteriosis. In the investigations of
teurized milk have been conducted in such outbreaks, the epidemiologic evi-
animals and humans, and us differ- dence, combined with knowledge
t'nces were detectable. One animal abost the occurrence of specific path-
study deserves particular attention ogens in cattle and the isolation of
because a misrepresentation of the some of these pathogens from raw
results has become prominent in the milk, leaves no doubt that rasv milk is
raw milk folklitre. In 1916, Pottenger' a vehicle for disease in humans.
146
Table 1-Purported Health Benefits Derioed From Drinking Raw Milk'
~
nobnnqiientiy pnxdoeod tsr thin sxxtzrtisr,
Eyhucorsrrnittarsu to disnuro Us esidoxso eristo is xsppsit of this shim is, us milk; ox the soirtinry, rnilkbomn dinrunu ann 0 probtom
is nsisiit stodiux soorpn,ieu mu zed poxteaszod milk
Erhursur fortuity Thin ooeoopt en bunod ox reisreprosnrtutisn of nxirmnt funding ntoduno that ousisud dutioioirt duoto
Contuirs ksrotisiut nxzyrrzs. Some enzymes urn ieactiuutod by puntosmiuutisx. bst thrnr errzymrn urn pu'obnbty ,szotisntrd by pxpnirr
hornixeon. ned zotikodius nodior guntrio uviduiy; hsoesyn oootnxt of cow milk ixoesurtoufi. uxd hsrresmn urn rot ,ynotuuuted by
punteorizutise tnmpnmntoron; rho nmuii qouxtity of uxtibody ix esrmui milk, nhitn rot ,ruohsztrd by pun.
in rot sbno,bzd in thu humor intuxtirni frost
Csntnien sidelined nsbntoesnn iosh Thnnu oiai,rn weouerrt to (trIo morn thnr ureodotrs
CocOs's iustobuciiii Luotskusiih urn ssets,vi,rnetn rutherthuri eutorut loin of milk; puntrorinud daoy prolostS coetu500n zdded
iaOobnoitii urn as~lbto
organisms that transmit disease to
humans through milk. Currently ac-
cepted time-temperature combina-
tions ioclnde 63 °C for 30 minutes,
71.6 °C for 15 s, and 89 e~ or higher
for 1 s. Pasteurization does not steri-
lize milk, but doe~ make the milk safe
to drink. Pasteurization should be
distinguished from homogenization
(emulsification of milk fat) and for-
tification (addition of vitamins A
and/or D). In the health food litera-
ture, commentaries about the pur-
ported nutritional hazards of pasteur-
ized milk tend to blend the three
processes into one. Like pasteurized
milk, raw milk may be sold homoge-
nized and with vitamins A and 1)
added.
The regulatory standards for pas-
teurized milk vary by state, hut these
standards all meet or exceed those in
the Grade A Pasteurized Milk Ordi-
nance recommended by the Food and
Drug Administration. Individual
state regulations on the sale of raw
milk also vary, with some prohibiting
such sales, ethers allowing sales only
on the premises of the proilocer, and
others setting up stanilards jtaral-
leling their pasteurized milk ordi-
nance. All milk ordinances set mini-
mum standards for dairy animal
health, personnel health, environ-
mental hygiene, and milk quality.
Quality control programs supple-
menting the official regulatory pro-
grams are commonplace in the dairy
industry. The standards for hygiene
of certified feaw milk that are estab-
lished by the American Association of
Medical Milk Commissions, bc, rep-
resent only one of many such pro-
grams.
JAMA, Oct 19, loud-Vol 252, No. t5
Unpasteurized Milk-Potter of at 2049
PAGENO="0153"
147
Modern sanitary and health stan-
dards observed by the dairy industry
have made contamination from envi-
ronmental sources, including humans,
an infrequent problem. In contrast,
programs relying solely on sanitary
and health standards have not suc-
ceeded in eliminating contamination
caused by symptomatic or asympto-
matic infection in the milk-producing
animal. Contamination from animals
with organisms such as Salmonella
and Campylobacter has thus become
the primary hazard for raw milk
consumers.
Salmoneliosts
Many outbreaks of oalmonellosis
due to consumption of raw or improp-
erly pasteurized milk, nonfat dry
milk, and cheese have been de-
scribed." Salmonellae have been iso-
lated from raw milk repeatedly
during investigations of such out-
breaks." Milk is an ideal growth
medium for Salmonella, and some
strains of Salmonella can even sur-
vive in cultured milk products, such
as yogurt, for as long as two weeks.
Surveillance of human salmonello-
sis in the United States is based
primarily on reports of isolates iden-
tified at state public health laborato-
ries, and these isolates are believed to
represent only a small percentage of
the cases that occur. Most isolates
belong to a few common serotypes, so
epidemiologic investigations are usu-
ally not initiated unless there is an
unusual incidence of a relatively rare
serotype or a serotype that is a mark-
er for a particular problem. There-
fore, the relationship of sporadic
cases to a common source is usually
not detected when they are caused by
a common serotype. Isolates of Sal-
monella dublin, a relatively rare sero~
type known to be host adapted to
cattle, are more likely to be investi-
gated and identified as being derived
from raw milk than are the corn-
manly isolated serotypes. Numerous
studies in multiple locations have
confirmed the role of raw milk in the
transmission of S dublin to hu-
mans."' Based on their 1982 data,
California health authorities calcu-
lated that the risk of S dublin infec-
tion was 84 times higher in persons
who consumed raw milk than in per.
sons who did not (S. B. Werner, MD,
oral communication, October 1983).
Salmonella dublin infections are of
particular concern because the associ-
ated illness tends to be severe. The
relative virulence of S dublin is illus-
trated by its ability to invade the
bloodstream' and the rates of hospi-
talization and mortality for infected
individuals."' Salmonella dublin is 13
times more likely to be isolated from
blood than are other Salmonella nero-
types, and more than half of the
patients with S dublin infection are
hospitalized. In two reports, 10% to
20% of the cases of S dublin infection
were fatal." Risk of S dublin infec-
tion is significantly higher in persons
over the age of 40 years and in
persons with underlying chronic ill-
nesses or taking antacids."
The problem of raw milk-associated
salmonellosis is not restricted to S
dublin. From a baseline of three Sat.
monella typhimurium isolates in four
years, the number of isolates of S
typhimurium from persons in a
three-county area of Oregon in-
creased to 27 in three months in early
1983.' Epidemiologic investigation in-
criminated raw milk and cream from
a single dairy, and S typhimurium
with the same plasmid profile was
isolated from milk, milk filters at the
dairy, the dairy cows, and the ill
Re,cently, in Vermont, eight persons
(aged 10 months to 60 years) in four
families had diarrhea, abdominal
cramps, and fever." All had drunk
raw milk from a single dairy. Salmo-
nella det'by was isolated from the
patients and the milk. In 1980, a
multiresiotant S typhimurium was
isolated from patients and milk (lur-
ing an outbreak of enteritis involving
105 persons who had drunk raw milk
from a single source in Montana."
Campylobacteriosis
Since culture of diarrheal stools for
Campylobacter jejuni became com-
mon, many milkborne outbreaks of
campylobacteriosis have been de-
tected. Fourteen (61%) of 23 Campy.
lobacter outbreaks reported to the
Centers for Disease Control (CDC)
from 1980 through 1982 were traced
to consumption of raw milk (Mark
Finch, MD, unpublished data, Decem-
ber 1983). In a detailed one-year study
of sporadic campylobacteriosis con-
ducted in Iowa in 1982 and 1983, 35'S
of the ill persons had drsink raw milk
during the week before onset of ill-
ness; drinking raw milk was the only
significant difference between cases
and controls (P<.05; relative risk,
9.3)."
In the United States, outbreaks of
campylobacteriosis associated with
drinking unpasteurized milk have
recently been reported in Arizona,
California, Colorado, Georgia, Kan-
sas, Maine, Oregon, and Pennsylva-
nia." In the outbreak of campylo-
bacteriosis in Arizona," two cohort
studies showed that households with
members who drank raw milk re-
ported diarrheal disease significantly
more frequently than those in which
no one drank raw milk, with relative
risks of 4.7 and 3.4. In the Georgia
outbreak, illness due to campylobac-
teriosis in 30 households was strongly
associated with consumption of raw
milk (odds ratio, 29.5), while contacts
with pets, livestock, or well water
were not associated with illness." As
in Arizona and Georgia, only con-
sumption of raw milk was signifi-
cantly associated with enteritis in the
other outbreaks.
Other Diseases
Other bacterial diseases associated
with drinking unpasteurized milk
from cows include brucellosis, coli-
bacillosis, listeriosis, tuberculosis,
corynehacteriosis, staphylococcosis,
streptococcosis, streptobacillosis, and
yersiniosis (Table 2). These diseases
are now infrequently reported as
milkborne diseases in the United
Slates, hut they illustrate the wide
range of potential hazards.
Milk other than cow's milk has also
been associated with diseaoe in hu-
mans. Toxoplasmosis has been associ-
ated with raw goat milk," and bru-
cellosis and campylobacteriosis have
followed consumption of raw goat's
milk cheese." The virus of tickborne
encephalitis is shed in milk, and fresh
cheese made from unpasteurized
sheep milk has been associated with
this disease." Toxin-producing staph-
ylococci have been isolated from
cheese made from raw sheep's milk.0
Comment
The relative merits of raw and
pasteurized milk have been debated
for at least 90 years. In this period,
the theoretic health benefits of raw
milk have never withstood careful
Uspatteurized Milk-Poller et at
2050 JAMA. Oct 19. 1984-Vol 282, No. 15
PAGENO="0154"
scientific scrutiny. Epidemic rickets
and scurvy and the other dire con-
sequences of milk pasteurization
prophesized by early raw milk advo-
cates have not occurred. Conversely
the fact that raw milk presents a
substantially greater inherent risk of
infectious disease has been demon-
strated repeatedly. Surprisingly, the
controversy continues.
Regulation of the sale of raw milk
often inyolves discussion of freedom
of choice. A major feature of the
individual's right to free choice, how-
ever, is informed consent, and incor-
rect information on the purported
benefits of drinking raw milk is so
widespread that truly informed con-
sent is difficult to achieve. Also, in
matters of foodstuffs, parents make
choices for their children. Therefore,
the children of advocates of raw milk
are exposed to the risks of infectious
diseases without a full understanding
of the danger.'~" Children also tend to
drink what is given to them in school
without questioning its safety. There
have been numerous outbreaks of
enteric diseases in schoolchildren giv-
en raw milk while on field trips to
dairies in the United States," and a
large outbreak of campylobacteriosis
traced to the consumption of free raw
milk at school was reported in
England.'
Observations in England and
Wales, where an estimated 3.5% of
the milk is consumed without pas-
teurization. support the contention
that raw silk is an unsafe food
product. In the period 1951 through
1980, these two countries reported 233
outbreaks of communicable disease
attributed to milk or dairy products,
with approximately 9,400 cases and
four deaths." Seventy-five percent of
the outbreaks and about 40% of the
cases were associated with raw milk;
most of the remaining cases involved
faulty pasteurization or obvious post-
pasteurization contamination. Con-
tamination by Salmonella caused 74%
of the outbreaks in this period. A
detailed cost-benefit analysis per-
formed to determine the value of a
ban on the commercial sale of raw
milk in Scotland clearly demon-
strated a favorable ratio on the basis
of the costs of milkhorne nalmonello-
sis alone." The role of raw milk as a
vehicle of C jejuni infection, however,
was not tlemonstrated until 1978,
when many laboratories began to look
for the organisms in diarrheal stools.
Since then, many raw milk-associ-
ated Cttmpylobacter outbreaks involv-
ing thousands of cases have been
reported by English investigators."'
When one considers the known
health risks, it is apparent that raw
milk is not being singled out for
unwarranted attention by public
health authorities. Other ready-to-
consume foods of domestic animal
origin are subjected to processing
procedures rendering them safe for
consumption and are microbiological-
ly monitored for adequacy of process-
ing. Raw foods of animal origin, such
as chicken, may be contaminated with
Salmosella and Campylobacter, but
routine bacteriologic monitoring of
these foods is nut done because these
raw foods are normally cooked before
consumption. Furthermore, extensive
efforts are made to inform the public
of the hazards and the proper cooking
procedures for these products, and
practical measures to eliminate the
contamination are not available.
In food hygiene, as in the operating
room, clean is not synonymous with
safe. The raw milk industry points
to standards such as total bacterial
counts as proof of safety, hut the high
incidence of disease associated with
raw milk is strong evidence that these
standards are unreliable indexes of
safety. Milk is an excellent vehicle of
infection because its fat content pro-
tects pathogeno from gastric acid,
and, being fluid, it has a relatively
short gastric transit time. Thus, low-
level contamination, which would be
readily controlled by pasteurization,
Unpasleurized Milk-Putter et at 2051
148
Table 2 -Milkbonne Bacteniat Diseases at Less Frequent Occurrence ,n the Uutted Staten
becceltunis to humans: in ha united States. appraaiotately 0th at ha reported cases urn attcbutmttocOnsonrptOn
at cepastruriend daile ptodoctn; products or anu third at thesa canen era do,nnst~caty produend"
Eechenchia cull Outbreaks at diarrhea haoa bean reported in persons otto mnssenad anpanteueend cnaam" and Bce ctrnesa". plan'
,nid-nrediatad entitnicroblal-rasistant £colihaon also bean molded rant ndb°
Listen-is rnooaeytogenau Lintuod ot000tlytOOerrea hen been isolated ton, unpenteotiend cue ued aheep rvtk"": sheddtng of L,etenu ,n ens,
persists to, lung periods at lIen alter the nOb passes thu oisuat eaaminution tullouing t,star,os;n": autdonce ut mOb-
buena liateriosia a tttooans has tuna nntabkstrad"
Mycubactehats tubzrculoaie, sutticienttuttarctn bacilli ore aactetad by a single cue tnith tuberculoas manttttn tn teaks thu rnttb at 100 clean cues
MycabaCterluot bocia lntectisaa tat duets"; in 000. tubaruatosis ces diagnosed in 3 dairy herds tn Attune: 1302 at 3,760 cartln
tastad tar tuhetoulosin aura positiua"
Cot-ytrebacrztiute pseudo- A cusa at acudatioa tonnititis and cenoicat lynrphadenitis that tesultad ,n prolonged honptralteum;un aas dencobed tn
tubeecutoaie 30-mar-old eon ahosa closest rennet dsrtestio anircal euponore ann dcebtng rea coca and neat's etik"
Staptrylocaoccs cutout Staphylococci in etilk. either true ntastitio milk ne borneo centurciuatiau. cause gustranntanhs tn nonsttrners etren they
ingest the treat-stable entnrotoeie peuduced be the staphyt0000sl5t
Stt'epteoaocus sp gtteptocucni cause auatiety at diseasas in hunters end load animals and era rnportant saprophytns m rr,tk and nib
products: like the staphylococci, they nay be present in milk in alga combats ctten they cause tnastttts n the nslk-
ptodusinuaeirnal: StneptoeoocoO eoocpidootiousis a common cease at tnaslittn in nattla. and m,lkhornn uotbneaks
in humans tolteeed by acute poststteptocoocal glonrerolonephrttts hace bean reported": a reonet cut-
bnoak has be en associuted cith consueption ut cheese made toot tao ntlk'°
Steeptobaeillus ,noetilitot'nris In the 10205, there cern some uaty large nutbreaks at strnptobauilosis teased a cursunrptton at rec mtlk". ctsen S
trreoilitourris Is saluted rem milk, the presumption of sontamiration by tuts In made: tie cnltkaly that thu dsnesa
ooutd ptessnt a nrilkhoeee problent na dairy pracccieg sceantly accepted ntaedatds at deny heutene
Vm'eieia eotet'oeelileca Yet-oieia etmlz,-oeo!itica is trequently bond in animal nruironnrnnla, cay be present n unpustnunted milk at h~h con-
centrations, end gtoas at teltiserator tamperatu'es"t in u study 0 Ontutta. Setonmune" toond Yeneerte te 105.01
the tea milk senrples. 9'S, 01 the cheese curd nuerples, none ot the cheddar cheese semplen, and I at 265 pasteut-
mend milk samples; Yzr-000ic ente,'ooetimica aen isolated Item rac milk met scspnctnd toctttorne autbreak et unnstnto-
sisinMonttaal'5
JAMA, Oct 19, 1984-Vat 252, No. 15
PAGENO="0155"
presents an important hazard to the
raw-milk consumer. This hazard is
magnified when the consumer has
less resistance to infection because of
age or underlying disease.
The promotion of raw milk as pro.
1. Magruder GL: Further oboervatiuon on the
milk supply of Washington, DC. JAMA 1910;
55501-509.
2. Kelley ER, Oshorn SH: Further euidero'eax
to the relative importuner of milk infection in
the t,-annmisoion of eertain communicable dis-
of man, Am JPohlie Health 1930l1866-73.
3. Kon SE: Nutritional effeetn on milk of
chemical additices and proeenoin~ is F~19h
International Conojroaa on Natritiow Washing-
too, D.C. Washington, DC, Food and Agriculture
Organinalion, 1960, ppl-8.
4. Kon SK: Milbond Milk P,-odaetein llamas
Nutrition, FAD Nutritional Studies 27. Rome,
Food and Agriculture Organization, United
Nations, 1972
5. Graham tIM: Alteration of nutritice value
rcnalting from processing and fortification of
milk and milk products. J Dairy Sci 1974;
57:738-745.
6. Pottenger FM Jr ElTect.af heat-processed
fonda and melubuliaed vitamin D milk on dento-
facial slractures of experimental animals. Am J
1)rthcul l946318467.485.
7. Wiloun CS: The Panteat-i:ulion of Milk
London, Butler & Tanner Ltd. 1942.
8. Taylor DN, Bird JM, Mover JS, et a!:
Sol,noxrlla dahlin infections in the United
Slates, 1979-1980. Jlnfecl Die 1982A4h322-327.
9. Small RG, Sharp 2CM: A milk-home out-
break due to Salmonella dublin, J Hyg Cam-
bridge 1979:8595-100.
10. Schroeder SA: What the sanitarian should
know ahout aalmonellae and staphylococci in
milk and milk products. J Milk Food Tech
l967;315376-380.
II. Krogh BP: The survival of paihogeon in
chceae and milk powder. J Dairy Rca 1971;
3091-Ill.
12. Collins RN, Teegec MD, Goldsby JR. et al:
lnlerntateoolbreakafSalmonellansewbnoneuiek
infection traced to powdered milk. J.4MA 1969;
21131138-044.
13. Fonlaire RE, Cohen ML. Martin WT, et al:
Epidrmie aolmonelloniu from cheddar ohncac:
Sureeillunrc and prevention. Am J Npidcmiol
188l;lll:247-253.
14. Marlh EH: Sulmonellae and salmonellonis
usaoeiated with milk and milk productn.JDai,-y
Sei l969;52283-315.
15. Gibnun EA: An outbreak of &nlnsono'lla
dublin infection in goats. Vet lIce l957;691026-
1020.
16. Bulgin MS. Anderson BC: Salmonellools in
gusts. JAm Vel Med Assoe l98l;l7&729.723.
17. Werner SB, Humphrey CL, Kamei 1: Anuo-
eioliun between raw milk and human Salmonella
duhlio infcotian. RrMedJ 19752238.241.
10- lOoser MJ, Feldman RA: Solnsono-lla basIc-
ren,iu: Reporlu to the Centers far Dincaae Con-
trol, 1968-1979. J Infect Die 1981:1421743-741.
19. Salmonella dablin associated with raw
milk: Washington State. MMWR. lOOl;318373-
374.
20. Ficrer 2: lnvusiocSalmanu-lla dublin infer-
tiannauooeiated with drinking raw milk. WualJ
Med l983;l38:665-669.
21. Oct-gun l)ivinion of Health: Row milk
aoau-iat,-,l oalmonella outbreak in northeouters
Oregon. Communicable Die Summary 1183;
:121-2.
211. Vogt RL, Hakey A, Allen 2: Salmonella
,-ntt-n-ttidio nerotype derby and connomption of
viding major health benefits beyond
those of pasteurized milk han not
been supported by tho evidence. In
contrast, the hazards of raw milk
have beon proved. Sale of raw milk,
however, in still permitted. Phyui-
References
raw milk. J 1st/i-cl Iba 1981:1441158.
23. Salmonelloois associated with run milk:
Montana. MMWR 1981:318211-212.
24. Sebmid OP. Schaefer R, Sehucfcr J, et at:
human campylobacterioois in a medium-aincd
lana city, ahotracted, in lIed Islenaeicxo-e (`on-
feresce oxAntimicrohialAgu-ntn ondC#cmotta-n--
apy. Wanhingtan, DC, American Society for
Microbiology, 1983, p160.
25. Taylor ON, Porter BW, WilliamnCA, rtal:
Campglohaeter enteritin: A large aothrcah
traced to commercial raw milk. Weal J Med
1035,137:365-369.
26. Taylor RP, Weinstein WM~ Bryner ill:
Campylahas-ler fetus infection in human sub-
jects. Anoocialion with raw milk. Am J Med
1979:66:779-783.
27. Blaser MJ, C ravens J, Powers BW, et at:
Campylahacbm enteritin usnociated with anpas-
lcarined milk. Am JMed l975;67:7l5-718.
28. Patter ME, RInser Mi, Sikcn BK, rt ol:
lloman Campyluhorlo-s- infection unsorioted with
errlified raw milk. Am J Epidemiol 1903;h17:475-
483.
29. Outbreak of Campylohaelum entecitis oust-
rialed with raw milk: Cannon. MMWR 1181;
318210-228.
30. Maine Dept of Damon Serviecu: Raw milk
and human gastrointestinal dinense: Problems
implicated with the legalioed sale of rectified
ran milk. EpiGram, December 1981, pp 1-2.
31. Raa-milk associated illness: Oregon.
MMWR 198L,31h90-57.
32. C~mpylohacteriasis annacialed with raw
milk e~nnamption: Pennsylvania. MMWII 1983;
35337-344.
33. Ricmann lIP, Meyer ME, Theis ill, st a!:
Tonoplasmosiu in en infant fed unpuoteurined
gout milk. J Pcdialr 1975:87:573-576.
34. Sucks JJ, Roberto RR, Brookn NF: Tuna-
plunmosin infection aaaocialed with raw goat's
milk. JAMA 19852401728-1732.
35. Fan MD. Itasfmann AF Bracclloais in the
United Slates, 1965-1974. J Infect Din 1077;
136:312-310.
36. Young 163. Suuannapsrrat U: Bcuecllonis
oatkrcok attributed to ingestion of aspastcor.
iced goat chrese. Arch Isis-n-n Med 1975:135:240-
243.
37. Eekmon M8. Brucellosia linked to Mnnieao
checse. JAMA 1975;232.636-637.
38. Gilbert CL, Dsvoren RA, Cole ME, ct oh
Midtrimrntmr abortins associated with neptico-
mia mooned by Campnjloboeterjs-juos. l0-d JAuot
1981:1:505-506.
39. Crcnibana M, Scks'yaoa M, Slapalaoa 5, et
al: Sheep milk-boron cpidcmic of lit-b-borne
encephalitis in Slovahin. Intervin-okvjy 1971:5:57-
61.
49. H sjek V: ldontificotion of cnterolanigcnio
staphylococci from sheep and sheep cheese. Apgd
I/ntis-on Microbial 1978:35:264-260-
41. Ootaria Ministry of llealth: Suspected raw
m:lk-as.naeiated eampylahacterionis. Brilish Cu-
lamhia. Cost Din Wet-hip Rep 1983:9-19:73-75.
42 White FMM, McCarthy ME: Row milk and
health in humans. Can Med Arson, J 1982;
126:1268-1262.
43. Jones I'll, Willis AT, Robinson DA, ct at:
Compylokacter cntecitin anaooiatcd with theecs-
oomptios of free school milk. J Ilyg (`amt,-i:loe
1981;07:l55-162.
44. Gathraith NO, Forbes P. Cliffortl C: Cnm-
municulsle diseanc associated with milk and
dairy products in England and Walns 1951-80. Bc-
Med J1985240176l-l765.
45. Cohen DR. Porter IA, Reid TMS, et a!: A
cost benefit ntody of milk-ho roe nolmonclbasin. J
Ilyg Cambridge 1583;9l:l7-23.
46. Jones DM, Rohisnon DA, Eldridgc J: Sero-
logical stadirs in two natbmcahn of Campylahac-
icr jejani infection. J Hyg Cacshridgc 1981;
117:163-170.
47. Robinson nA Jones DM: Milk-borne Cam-
psdttao-t,-c infection. tIc Med J 198l;2821374-
1376.
40. llobbs hOC, Rowe B, Kendall M, et al:
Escken-ichia coti 027 in adult diarrhea. J Hyg
Cambridge 1976:77:393-400.
49. Marier R,WelloJG,Swusssn RC,ntal:As
wathmcak of enleropathogesic Eoebcmichia cxli
foadkornc disease traced to importrd French
rhenur. Lancet 197551376-1370.
56. Johnston OW, Bruce 2,111112: hvcidcvcc uf
antibiotic-resistant Enehen-iehia coliin milk pro-
duecd in the went of Ss,stland. J Apyl Ilaeleriol
198ljit:77-83.
51. Dijkslra SC: Inocotigutiwnu on the surviv-
al timco of Lislen'ia bacteria in nanpnnsion of
brain tissue, silage and feces and is milk.
Zentlrothl Rabteriol 1971;2l6:52-95.
52. tlull RF: fnfevtisan abortions in owes.
Compcsd Constin Ed l982;4:2l6-22l.
53. Gray ML, Killinger AH: Lialcria mosoenj-
togeses and liateric infections. Buclen-iol Rev
1966;31b309-382
54. Kalis P, LeFruch JL, Smith W, et a!:
Listerosis. Am JMed Sci l976;27l:159-l69.
55. Kleehamg 1111: Tuhereol:,siu and other
myeuhaettrisuiu, in llohhcrt WT, McCullsek WI,
Schnsrresberger PR lcdu): Di.ncaaco Tcosmnilh-d
From Animula to Man, ed 6. Springfield. Ill,
Charles C Thomas Publisher, 1975, p315.
56. Mathis BM. LanglcyJ: Bovine tuberculosis
inns Arinona dairy herd.JAm Vel MedAaaoc
1901:178.141-142.
57. Goldhcmger AC, Lipsky BA, Plorde 22:
Soppsrutivn geeoolomataan lympkadooitia
caused by Corsjnehucleriam ovia(pneadotohcrco-
lasts). Am JClin Palhol 1981;76:406-490.
58. Parry WH: Milk-borne diseases. Loscet
l966;211l6-219.
59. Bamnham N, Thumntos TJ, Lange K:
Nephritiu caused by Streptococcus oooepidessi-
s-sun (Lsncefield group C). Lancel 1983:1:945-940.
60. Group (7 strrptocuvcal infections anssci~
ated with eating humcmado chneno: Ncw Mcsics.
MMWII l903;35510~516.
61. Place ElI, Sutton 1K: Erythema arthrit-
icum epidemicom )hluorrkill fever). Arch Isles's
Msd l934;M:659-(84.
62 vantrappn (7, A60 110, Gekocs K, 01 at:
Yeroinia csteritis. Mcd Clix North Am 1985
66:639-653.
63. Black RE Yerninimis, in l.ast 3M led):
Maony-Roncnau Public lleallh and Preventive
Mrdicino-, ed 11. New York, Appleton-Century.
Crofta, 1980, chaps, pp456-457.
64. Sohiemasos DA: Association of Yerainia
snte,-ocalilica with the manufacture of cheese
anslorearrmnreinpastrurioedmilk.ApplEnvi-
ran Microbial 1978;36:274-277.
65. Ilcalth and Welfare Canada: Yernisia
,-nlrroeolilicu gantroentorilis uatbccuk: Mon-
treal. Can Din Weekly Rep 1976;573-74.
linpaalesrized Milk-Potter el al
149
cians and other health professionals
muut be aware of the facts concerning
risks and benefits from raw milk to
better advise patients who have ques-
tions about the safety and benefits of
raw milk consumption.
2052 JAMA, OcI 19, 1984-Vol 252. No. 15
Pcioteol and Published in the United Staten of ,flmecica
PAGENO="0156"
150
Mr. WAXMAN. Thank you, Mr. Adams.
In the opinion of the Milk Producers Federation, is it scientifical-
ly and commercially feasible to produce and market raw milk that
is safe for human consumption?
Mr. ADAMS. No, it is not. We take great pride today, as has been
pointed out earlier this morning, in maintaining a high level of
sanitation, environmental hygiene and veterinary practice. But the
overwhelming consensus within the National Conference on Inter-
state Milk Shipments, which represents all State governments and
the Federal Government on this issue, has been since 1950 that
pasteurization was absolutely essential; that it was essential as a
part of a total package of sanitation and public health in terms of
providing the best protection that we could provide for all the
people. So pasteurization is a very inherent and important part of
providing overall assurance to the American people.
We support the position of NCIMS which recognizes the impor-
tance of requiring raw milk to be produced under sanitary condi-
tions and pasteurized. This is a position supported by many public
health agencies and associations that you have cited earlier.
Mr. WAXMAN. Thank you.
Mr. Dannemeyer, do you have any questions for Mr. Adams?
Mr. DANNEMEYER. Yes, I do. Thank you, Mr. Chairman.
Mr. Adams, are you familiar with the publications by physicians
and others that attribute the loss of nutritional value as a result of
heat process, known as pasteurization, to milk?
Mr. ADAMS. I am not intimately familiar with all of them. I have
read some of them and I have known of them in the past involving
this issue for several years. Yes, I am familiar with the fact that
those publications exist.
Mr. DANNEMEYER. And people who produce them and some of
whom testified today, claim that there is a nutritional loss from
the heat process known as pasteurization. Are you familiar with
those claims?
Mr. ADAMS. I am familiar with their claims, but in our opinion,
they are unsubstantiated claims and we have supplied for your
record a paper from the National Dairy Council that reviews such
claims. It is part of the references we have provided today for the
record. In the two references provided, the science of statistical sig-
nificance is reviewed. What is significant-and that is the key
question here-what is the significant nutritional difference statis-
tically?
I don't believe the evidence, the overall evidence, supports the
claim that there is a subtantial difference.
Mr. DANNEMEYER. Are you familiar with the work of a physician
by the name of Annand in England?
Mr. ADAMS. No, I am not.
Mr. DANNEMEYER. Dr. Annand is a physician who traced the in-
crease in incidence of arterialschlerosis of patients that began con-
suming pasteurized milk. In other words, 2 or 3 years after the group
who normally used and consumed raw milk, they then began using
pasteurized milk, there was a significant, marked increase in the
incidence of arterialschlerosis in those population groups that
made that change.
Are you familiar with that work?
PAGENO="0157"
151
Mr. ADAMS. I am familiar with the basic theory that is known-
we refer to it as the Oster theory. That theory has been greatly
studied. There is no basic scientific evidence to justify that theory.
Mr. DANNEMEYER. Pardon me, I am not talking about Dr. Oster.
Dr. Oster's claim is that the process known as homogenization is
approximately related to increase of arterioschlerosis. Dr. Annand
claims that the consumption of pasteurized milk is responsible for
the increased incidence of arteriosclerosis. Are you familiar with
the claim of Dr. Annand?
Mr. ADAMS. I am not particularly familiar with that claim, but
we will be glad to supply for the record, I believe, other informa-
tion which would not support it, and that will come from the Na-
tional Dairy Council.
Mr. WAXMAN. I think the next panel would be better equipped to
discuss this.
Mr. DANNEMEYER. Are you familiar with the case in Arizona of
the 66 people who evidenced symptoms of salmonella from con-
sumption of pasteurized milk?
Mr. ADAMS. I am not particularly familiar with that, but we do
have a situation where you can have postpasteurization contamina-
tion. That is probably the situation in most cases where we have
had problems with pasteurized milk. It has come from contamina-
tion, people contamination, following pasteurization and that is due
to a breakdown in the system, and that is something that we
always face, something we try to eliminate. But again, we are deal-
ing with human beings in the work chain, and distribution prob-
lems, so those kinds of problems are always going to have a poten-
tial for occurring.
Mr. DANNEMEYER. There were 1,004 cases in 1982 in Memphis,
TN from Yersinia enterocolitica from pasteurized milk, was there
not?
Mr. ADAMS. Yes, and if you will go back and look at the epidemi-
ology behind those cases, for the most part, I think, it was attrib-
uted to postpasteurization contamination. So you cannot attribute
them necessarily to a breakdown in the pasteurization itself.
Mr. DANNEMEYER. In the perfect world, if that is what we are
seeing, cause us to conclude that in order to avoid any of these ill-
nesses, we should just say to the people of America, we can't drink
milk at all?
Mr. ADAMS. What we should say is that the milk industry is most
seriously interested in minimizing the overall risk and pasteuriza-
tion is absolutely critical to minimizing that overall risk. It is like
an added insurance policy and if we can provide that added insur-
ance, then we want to do it, and we want to do it in the spirit of
protecting the overall public health.
Mr. DANNEMEYER. But there are hundreds of thousands of people
in the State of California and in America who claim that they
want to drink certified raw milk because it is nutritionally superi-
or, and they also claim that there is an increased incidence of arte-
riosclerosis from consumption of pasteurized milk. Shouldn't these
people who want to consume certified raw milk be able to do that?
Mr. AD~s. That should be an issue that the State of California
has to deal with, but in terms of interstate commerce, what we are
dealing with in terms of this particular hearing, as far as its appli-
PAGENO="0158"
152
cation right now at the Federal level, is do we ban interstate ship-
ment?
Mr. DANNEMEYER. It is the same issue, isn't it?
Mr. ADAMS. Well, it is the same issue in terms of the potential
public health threat, but it is a different issue in terms of the me-
chanics of how you get to the solution to the problem.
Mr. DANNEMEYER. To me it is a question of balancing of risks
and I think that the evidence has disclosed that very well.
Thank you, Mr. Chairman.
Mr. WAXMAN. Thank you, Mr. Dannemeyer.
Mr. Adams, thank you for being with us. We appreciate your tes-
timony.
Dr. Chin, why don't we start with you?
Let me indicate to all the gentlemen here, as we indicated to you
in advance, your prepared statements will be made part of the
record in full. We would like to limit you to no more than b min-
utes in your summary of that statement. We need to do that in
order to get the full opportunity for all the witnesses to be heard
and to have questions and answers as well.
STATEMENTS OF JAMES CHIN, M.D., CHIEF INFECTIOUS DISEASE
SECTION, CALIFORNIA DEPARTMENT OF HEALTH SERVICES;
MORRIS E. POTTER, DVM, VETERINARY EPIDEMIOLOGIST,
CENTER FOR INFECTIOUS DISEASES, CENTERS FOR DISEASE
CONTROL; R. DEAN THOMAS, PRESIDENT, DELST CHEMICAL &
RESEARCH, INC.; AND PATTON SMITH, DVM, ASSISTANT DIREC-
TOR, CALIFORNIA DEPARTMENT OF FOOD AND AGRICULTURE,
ACCOMPANIED BY JOHN ORSBORN, DVM, CHIEF, VETERINARI-
AN LABORATORY SERVICES
Dr. CHIN. Thank you. I won't take the full 5 minutes.
I am Dr. James Chin. I am chief of infectious disease section for
the California Department of Health Services. This is a position I
have held since 1970, and I am also a lecturer in epidemiology in
the UC School of Public Health in Berkeley, associate editor of one
of the other leading infectious disease text books used in this coun-
try.
I would say at the very beginning to Mr. Dannemeyer, I am not
here to declare war on salmonella. However, I think a lot of my
remarks will not be interpreted as friendly to raw milk.
I would summarize my testimony that basically is an update of
the testimony that our infectious disease section submitted to the
FDA hearing. Data collected and analyzed by our infectious disease
section have very clearly documented over the past decade the con-
tinuing association of certified raw milk with human infectious dis-
ease problems.
Our findings linking human disease to raw milk are not unique
and have been reported from other States and other nations, and
in recurring fashion, as variations on a theme. The locales change,
the names of the dairies change and numbers of cases change, but
the end result is raw milk has regularly caused human disease.
While raw milk represents less than 10 percent of all milk pro-
duction in both this country and in the United Kingdom, more
than 90 percent-we are not talking about a perfect world, we are
PAGENO="0159"
153
talking about more than 90 percent of all milk-borne disease is re-
lated to raw milk use. Given the existence of salmonella and cam-
pylobacter in cattle, cow's milk if consumed raw is clearly poten-
tially hazardous.
As indicated in prior testimony, there is no way that present
technology can prevent the pathogens from entering the milk by
occasional fecal contamination during the milking process or by
direct innoculation from mammary shedding through an infected
udder. People from our California State Food and Agriculture De-
partment can comment more on such findings.
Review of the risks associated with the use of raw milk in Cali-
fornia for 1980 to 1983 was made by a group at UCLA supported by
a grant from the American Association of Milk Commissions. These
investigators concluded, after extensive examination of available
data on human disease associated with use of raw milk, and certi-
fied raw milk, that, first, there appeared to be a residual causal as-
sociation of certified raw milk with salmonella dublin infection,
such that in California in 1980-83, raw milk use elevated the aver-
age risk of reported salmonella dublin infection by a factor of any-
where from 14 to 180 times with possibly a stronger effect in 1983.
Second, up to a third or a half of the reported salmonella dublin
caseload in California could be attributed to certified raw milk.
Third, for the 4-year period 1980-83, there appeared to have been
between 23 and 25 deaths attributable to salmonella dublin infec-
tions acquired from raw milk, with perhaps half of these deaths oc-
curring in 1983.
Fourth, certified raw milk users with compromized health status
had far higher rates of salmonella dublin and far higher mortality
rates than certified milk users in good health or noncertified milk
users in compromized health.
This study, like virtually all other studies published in the medi-
cal and scientific literature, finds the association of raw milk with
some human infectious disease problems to be indisputable, to be
large, and to be causal.
I will be happy to answer any questions later.
[Dr. Chin's prepared statement follows:]
PAGENO="0160"
154
Disease in California Associated
with Certified Raw Milk
from
Infectious Disease Section
California Department of Health Services
2151 Berkeley Way
* Berkeley, California 94704
I. Introduction
There are presently in California 15 raw milk dairies - 6 goat dairies
and 9 cow dairies. Togetherthey produce less than 1% of all the
market milk distributed in the State. P4iiong them are two certified
* raw milk dairies; one is a certified raw goat milk dairy that produces
400 gallons/day and the other is a certified raw cow milk dairy,
(Alta Dena Dairy) that produces 10,000-12,000 gallons/day. The Alta
Dena volume represents 80 to 85% of all raw milk produced in
California. Some of that certified raw milk (CRM) is distributed,
through middlemen, in interstate commerce.
Over the last 15 years our *surveillance of milkborne disease in
California has shown that virtually all of it has been associated
with Alta Dana's CRM. During this period, two bacterial diseases have
occurred in users of this milk: salmonellosis (particularly
Salmonella dublin) and campylobacteriOsis. Each is discussed
below.
II. SalmonellOsjl
A. History - Unlike the experience reported by other states and
nations, raw_milk-associated salmonellosis in California has not
occurred in outbreak form but rather _~p~~dicai]1 in time and
place. This pattern of disease occurrence suggests that the
contamination (discussed below.) of certified raw milk is intermit-
tent and low grade. However, the problem is increasing, despite
the fact that the surveillance of salmonellosis in California has
not changed in decades. (State law requires-that all specimens
from which salmonella are isolated be submitted to the State
laboratory for typing. Virtually all salmonella cases are thus
identified by laboratories; public health follow-up is often
carried out locally before serotyping results are available.) - In
1981 there were 46 S. dublin cases; in 1982 there were 70 cases;
in 1983 there were 123; and in 1984, .141-cases were identified.
Undoubtedly, many more cases of S. dublin occur than are iden-
tified .since only a part of those ill will visit a doctor for an
illness, and an even smaller part will have a specimen taken for
laboratory analysis. Estimates of the number of actual cases for
every identified case range from 10 to 100: the commonest sal-
monella serotypes are thought to have the greatest number of
unreported cases. Furthermore, many other salmonella serotypes --
of the 2100 serotypeS known -- have been recovered from CRM in
California, so probably many more salmonella cases (in addition to
those due to S. dublin) are related to CRM use. However, S.
dublin provides a convenient epidemiologic marker for investiga-
tion since it is specifically host-adapted to cattle, much as S.
typhi is adapted to humans, S. putiorum and S. gallinarum to
chickens, and S. choierae-sui8 to swine.
PAGENO="0161"
155
B. Character of S. dublin disease - The demographic characteristics
of S. dublin cases consistently differed from cases infected with
other serotypes. S. dublin patients tend to be older and their
health is often further compromised by one or more chronic
conditions. It may he that persons with compromised health status
are at much greater risk of infection and disease from low levels
*of salmonella contamination in food than is the population at
large. In California, about 20% of.the population would he clas-
sified as having compromised health status with regard to S.
dublin infection, if we include in the group: (1) those under 1 or
75 and over; (2) those who are pregnant; (3) those with cancer,
diabetes, hematologic disorders, liver disease or alcoholism,
arthritis, collagen, vascular or renal disease; (4) those receiv-
ing chemo-, radiation or corticosteroid therapy; and (5) those
with gastrointestinal, neurological and post-traumatic conditions.
A large proportion of the S. dublin cases had cancer, particularly
lymphoma and leukemia, or were taking systemic corticosteroids
and/or c `icr imrnunosuppressants for a large variety of disorders.
At least 7 had AIDS. Through the years, more than 80% of cases
consist~itly had S. dublin recovered from blood and other extra-
intestinal sites such as cerebrospinal fluid, lung, abdominal
cavity, etc. This finding is not simply a reflection of the older
age of the i~ypical S. dublin host: when age-~sex matched controls
infected with other salmonella serotypes were compared for source
of positive specimen, less than 15% were identified by cultures of
blood and other extra-intestinal sites (i.e., 85% of cases with
other salmonella infections were identified by stool culture).
Another indication of the severity of S. dublin infection is the
fact that 75% of S. dublin patients required hospitalization
compared with only 35% of matched cpntrols. Finally, deaths among
S. dublin patients have run between 20 to 25% for the last 15
years. Death in one out of every 4 or 5 patients must be regarded
as due to a very severe disease. For 1981-1983, we identified 63
deaths among 239 patients with S. dublin infection.
C. Association with CRM - In both 1981 and 1982, 24% of S. dublin
cases reported use of CRM. Not only was 1983 a record year for
cases (123) hut there was also an increased association of cases
with CR11 use (44%) (Reference B. Data for 1984 are not yet
complete, hut among those cases for whom data are available, 36%
reported use of CR11. No other risk factor has been as prevalent
among cases, and even though S. dublin is host-adapted to cattle,
only a small percent (15% or less) of cases through the years
reported use of either lightly cooked ("rare") or uncooked beef or
beef liver.
The risk of contracting 9. dublin in California from use of CR11
has been estimated to he 458 per million population (based on the
assumption that each user drinks one pint daily). This is 158
52-266 0-85-6
PAGENO="0162"
156
Disease in California Associated
with Certified Raw Milk
times the risk of the population-at-large who do not drink raw
milk (Reference 1). When cases were compared with age, sex and
residence matcl~ed controls who were infected about the same time
with other salmonella serotypes, a chi square test gave a value of
41, a value which would be expected to occur by chance alone, less
than once in 100,000,000 times (Reference 2). The relative risk
is among the highest values reported in epidemiologic studies.
Just as the majority of smokers do not develop lung cancer, so,
too, the majority of CRM users apparently do not develop S. dublin
disease. That there are not more reported S. dublin cases is
likely due to the fact that the population that drinks CRM is
small and the contamination is low grade and probably
intermittent.
D. Isolations from Milk - Since 1977, a total of 191 sal monel 1 a
isolations have been made from CRM by 14 different laboratories
(local, state, and federal), including the FDA's laboratories in
both San Francisco and Los Angeles. Other laboratories typically
sample only 1 or 2 containers of milk, but on each of the 3 or 4
times that FDA sampled CRM it tested 20-40 containers of one day's
production: on each of those occasions FDA found at least several
containers positive for S. dublin. Such results for a single
production lot suggest either unequal distribution of contamina-
tion in the milk so that some containers are contaminated and
others are not, or that contamination is routinely present
(perhaps at very low levels) but is missed in some containers
because present technology is not sufficiently sensitive to detect
it. The dairy's own quality control laboratory cannot be relied
upon to identify salmonella in CRM (see discussion in attached
Reference 3, a sworn declaration entered into evidence by Richard
M. Ruby of the FDA's Los Angeles Laboratory). The only State
agency that tests CRM (and other raw milk) on a routine basis is
the California Department of Food & Agriculture which tests 2
containers of milk from each dairy herd only once/month in dry
months and twice/month during wet months.
E. Antibiograms - Antibiogram tests of human S. dublin isolates
demonstrated a statistically significant association between
antibiogram patterns of isolates recovered from CRM users and the
antibiograms patterns recovered from CRM itself (References 4 -
6). Those who did not drink CRM had a variety of otTi~F
antibiogram patterns. The epidemiologic and antibiogram links
between 5. dublin and raw milk make biologic sense in view of S.
dublin's recognized adaptation to cattle.
F. Summary - California has clearly documented the association of S.
dubiin disease with raw milk use (specifically CRM). Our findings
also show that S. dublin has greater virulence than most other
salmonella serotypes (more hospitalizations and more frequent
PAGENO="0163"
157
isolations from blood and other deep body sites). A study con-
ducted by the Centers for Disease Control in 1979 and 1980 of
sporadic S. dublin cases that occurred elsewhere in the nation,
~femonstrated these same points (Reference 7).
III. Carupylobacteriosis
A. Serologic Study - In the investigation (Reference 8) of a cluster
61' 4 cases of Campylobacter infection in Los AngeTes, 3 reported
use of the same brand of CRM (as reported above involving S.
dublin infection) whereas only 3 of 49 control subjects reported
raw milk use (p = 0.0003). The investigation was followed up by a
serologic survey conducted among a pediatric outpatient group.
Four of 23 (17%) of raw milk drinkers had demonstrable antibody
titer to carnpyiobacter jejuni whereas none of 13 non-drinkers of
raw milk had a titer.
8. Outbreak, 1984 - An outbreak of Cainpylobacter jejuni occurred in
!l':.:i 1984 among 12 of a class of 28 kindergarteners and their
chaperones who were provided CRM at. the dairy's bottling plant
(Reference 9). It was the same CRM implicated in the ongoing
Salmonella dubl.in problem. C. jejuni was confirmed in stools of 9
of the 12 ill people: the pathogen was not recovered from school-
mates who had not made the field trip.
IV. Corroboration by Other Studies
The findings linking human disease to raw milk are not unique to
California but have been reported from other States an~ other nations
in recurring fashion, -as variations on a theee. -The locales change,
the names of the dairies change, and the numbers of cases change but
the end result is that raw milk has regularly caused human disease.
While raw milk represents less than 10% of all milk production in both
this country and the United Kingdom, more than 90% of all milkborne
disease is related to raw milk use. Given the existing prevalence of
salmonellosis and campylobacteriosis in cattle (which ray or may not
appear ill due to those infections), bovine milk, consumed raw, is
clearly hazardous: there is no way that present technology can
prevent the pathogens from entering the milk' by occasional fecal
contamination during the milking process (salmonella and
campylobacter) or by direct inoculation via mammary shedding through
an infected udder (salmonella). Only- pasteurization can he relied
upon to destroy these pathogens in raw milk. The Federal Register of
August 3, 1984, beginning on page 31,067, provided a useful bibliog-
raphy, but it is far from complete. For example, in May of 1983 the
Director of the Centers for Disease Control (Dr. Foege) responded to
an important list of questions (References 10-14) posed by the
California Chapter of the American Academy of Pediatrics (Dr. Bolton);
Foege concluded in a covering letter that `Because the accumulated
PAGENO="0164"
158
evidence indicates that unpasteurized (raw) milk is inherently unsafe,
the Centers for Disease Control supports pasteurization of milk and
milk products (Reference 12). Foege extensively documented the
association between raw milk and human disease in this country and
abroad, both from raw milk and certified raw milk. Foege's detailed
and well-referenced responses to many other questions in *his brief
paper merit careful review by all who want or need to be versed in the
current state of knowledge. Though S. dublin is relatively rare among
the 2100 salmonella serotypes, it is one of the common causes of
milkborne outbreaks. Further, an important national study conducted
by COG in 1979 and 1980 showed raw milk to be the mqst important risk
factor for sporadic cases as well (Reference 7). As Foege put it, raw
milk is `an important source of S. dubTin infections outside of
California, as well as within California" (Reference 13). Moreover,
the COG stidy (Reference 7) corroborated California's findings that S.
dublin was particularly invasive, that it resulted in serious mor-
bidity and high mortality, and that the infected hosts often were
compromised by underlying health problems.
The same clinical findings on the invasiveness of S. dublin were
independently reported in a later publication (Reference 15) from San
Diego which, like COG, also reported a case-control study that impli-
cated raw milk (the same brand of CRM as discussed earlier). As
mentioned earlier, California published a review of its 1983 S. dublin
cases (Reference 1); this was followed by COG's publication of the
matter in Morbidity & Mortality Weekly Report (Reference 16). In
their editorf~i note, COG reported how widespread was milkborne
salmonellosis; and that in recognition of `the economic burden of
railkborne salmoneliosis, Scotland banned the sale and distribution of
raw milk in 1983. The tremendous success that Scotland has had in
eliminating community outbreaks of milkborne disease since compulsory
pasteurization was introduced August 1, 1983, is. reported in attached
Reference 17.
A review of the risks associated with use of raw milk in California
for 1980-1983 was made by a group at UCLA supported by a grant from
the American Association of Medical Milk Commissions (References 18).
These investigators concluded after their extensive examination of
available data on human disease associated with the use of raw milk
and certified raw milk, that: (1) there appeared to he a residual
causal association of certified raw milk with S. dubtin infection,
such that in California during 1980-1983 raw milk use elevated the
average risk of reported S. dublin infection by a factor of 14-180
times, with possibly a stronger effect in 1983; (2) between a third
and a half of the reported S. dublin case load in California could be
attributed to certified raw milk; (3) over the four-year period 1980-
1983, there appeared to have been between 23 and 25 deaths
attributable to S. dublin infection acquired from raw milk, with
perhaps half of those deaths occurring in 1983; and (4) CRM users with
PAGENO="0165"
159
compromised health status had far higher rates of reported S. dublin
infection and far higher mortality rates than CRM users in good health
or than non CRM users in compromised health. Essentially then, this
study like the others cited found that the association of certified
raw milk with S. dublin infection is indisputable, large and causal.
REFERENCES~
1. Infectious Disease Section: California Morbidity /fl2, March 30, 1984.
Salmonella dublin in California: Increasing incidence and increasing
association with certified raw milk exposure.
2. Infectious Disease Section: (Unpublished) Case/control study of 1983
Salmonella data establishes certified raw milk as the most important
risk factor for S. dublin infection.
3. Declaration of R. M. Ruby of Food & Drug Administration, January 23,
1983.
4. Antibiogram study of S. dublin isolates from humans and certified raw
milk, California, January 1, 1977-April 20, 1978.
5. Further statistical tests on the antibiogram patterns of S. dublin
recovered from humans and certified raw milk between January 1, 1977-
April 20, 1978.
6. Statistical study of antibiogram patterns of S. dublin isolates
recovered from humans and certified raw milk in California in calendar
year 1982.
7. D. N. Taylor, et al.: Salmonella dublin infections in the United
States, 1979-1980. J Inf Dis 146:322-327, 1982.
8. Taylor PR, Weinstein NM, Bryner JH. Ccvnpylobacter fetus infection in
human subjects: association with raw milk. Amer J Med 66:779-782, May
1979.
9. Infectious Disease Section: California Morbidity /~23, June 15, 1984.
Campylobacter outbreak associated with certified raw milk products,
Los Angeles County.
10. Memo by S. B. Werner on the Centers for Disease Control `s position
regarding raw milk, June 2, 1983.
11. Letter to James Chin from John Bolton, May 28, 1983.
PAGENO="0166"
160
12. Covering letter by William H. Foege (Director, Centers for Disease
Control) to Dr. Bolton, May 27, 1983.
13. Seven. page statement by William H. Foege (Director, Centers for
Disease Control) entitled Questions and Answers on Safety of Raw
Milk". . -.
14. Letter to William H. Foege by John Bolton, May 4, 1983.
15. J. Fierer: Invasive S~zimoneiia dubiin infections associated with
drinking raw milk. West J Med 138:665-669, May 1983.
16. Centers for Disease Control: Saimonel~a dubiin and raw milk
consumption. Morbidity & Mortality Weekly R~port 33(14):196-198,
A~'ril 13, 1984.
17. Latter to Morris E. Potter from J. C. M. Sharp, May 29, 1984.
18. Richwald GR, Greenland S. An assessment of risks associated with raw
mi~k consumption in California. (Unpublished) 1984.
All references are available upon request from:
Infectious Disease Section
2151 Berkeley Way
Berkeley, CA 94704-9980
PAGENO="0167"
161
Mr. WAXMAN. Thank you.
Dr. Potter.
STATEMENT OF MORRIS POTTER, DVM
Dr. P0TrER.Thank you, Mr. Chairman.
The division of bacterial diseases of CDC is responsible for con-
ducting surveillance programs, reference activities, epidemiological
investigations, and field and laboratory studies of bacterial dis-
eases. By these activities the division has accumulated and ana-
lyzed information on infectious diseases that have been transmitted
to humans by consuming raw milk and raw milk products.
Medical history is replete with evidence of the risks of drinking
unpasteurized milk. Despite this knowledge, unpasteurized milk
continues to be an important source of human disease. The most
frequently documented associations between unpasteurized milk
and illness are the numerous outbreaks and sporadic cases of bacte-
rial infections, primarily campylobacter and salmonella species
that have occurred in the United States in the last 20 years. To
best understand this association with illness, it is useful to examine
the data in greater detail.
From 1980 to 1983, 53 percent of the food-borne outbreaks of
campylobacteriosis reported to CDC from many States were associ-
ated with drinking unpasteurized milk. In a detailed 1-year study
of sporadic cases of campylobacteriosis conducted in Iowa, in 1982
and 1983, 35 percent of all of the ill persons had drunk unpasteur-
ized milk during the week before onset of illness and drinking un-
pasteurized milk was the only significant difference between cases
and controls. In a study we conducted in Georgia, campylobacter
jejuni was found in the feces of 40 percent of 193 healthy cows.
All these data lead us to conclude that consumption of unpas-
teurized milk carries an unavoidable risk of campylobacter infec-
tions.
Salmonellosis also frequently causes a diarrheal illness. Howev-
er, the very young, older individuals, and persons with compro-
mised host defenses are more likely to develop systemic, or blood
and organ system infections with potentially fatal outcomes. This
latter group of patients with underlying disease are persons to
whom foods with purported special health value may have particu-
lar appeal.
Individual salmonella strains belong to one of 2,100 different
groups called serotypes. Certain salmonella serotypes are most fre-
quently isolated from specific animals. For example, salmonella
cholerae-suis from hogs and Salmonella dublin from cattle. These
two serotypes can also infect humans. When they do, they can
cause a range of illness from mild to fatal.
Over 40,000 salmonella isolates are reported in the United States
each year and many more are unreported. In outbreaks in which
the vehicle of transmission is identified, meat and poultry are the
most common sources of salmonella infections. Dairy products, in-
cluding raw milk, are associated with a small proportion of out-
breaks.
The evidence from outbreak investigations that unpasteurized
milk is the vehicle for many salmonella infections in humans clear-
PAGENO="0168"
162
ly is supported by a review of the CDC national salmonella surveil-
lance activity data. In the period 1965-83, 11 outbreaks of salmo-
nellosis associated with drinking unpasteurized milk involving
more than 300 persons were reported. In addition, sporadic cases of
Salmonella dublin infection in California and in other States have
been associated with drinking unpasteurized milk.
Information derived from two recent surveys indicate that the
commercial sale of unpasteurized milk to the final consumer is pro-
hibited in 20 States, and permitted in 24 States. Six States restrict
the sale of unpasteurized milk to direct farm sales to the final con-
sumer. During the 4-year period 1980-83, 515 isolations of salmo-
nella dublin were reported to the National salmonella Surveillance
Activity. Ninety-four percent of the isolates were reported from the
24 States permitting the commercial sale of unpasteurized milk,
whereas only 5 percent occurred in the 20 States not allowing Un-
pasteurized milk sales.
Although this observed relationship alone does not prove causa-
tion, when the numbers of isolates are adjusted by the 1981 popula-
tion statistics, the reported rate of isolation of salmonella dublin is
10 times greater in those States permitting commercial sale of un-
pasteurized milk than in States that do not.
A nationwide case control study-excluding California and
Oregon-in 1979 and 1980, revealed that the risk of salmonella
dublin infection was 18 times higher in persons who drank unpas-
teurized milk than in those who did not. Isolates of salmonella
dublin, a relatively rare serotype known to be host-adapted to
cattle, are more likely to be investigated and found to be derived
from unpasteurized milk than those types more commonly isolated
from humans and animals. Thus, salmonella dublin infections
transmitted by unpasteurized milk represent only the tip of the ice-
berg of salmonella infections transmitted by unpasteurized milk.
Unpasteurized dairy products also have been repeatedly shown
to be the vehicles for a variety of other human pathogens. In addi-
tion to the risk from known pathogens, consumption of unpasteur-
ized milk has also been responsible for a prolonged disease of un-
known etiology for which no effective treatment has been found de-
spite intensive efforts. Consumption of unpasteurized milk was
linked to an outbreak of chronic diarrhea involving 122 persons in
Minnesota in 1984. The illness was characterized by acute onset of
diarrhea with marked urgency, and between 6 and 25 episodes of
diarrhea per day, and lasted more than nine months for most
cases. Approximately 8 percent of the long-term consumers of un-
pasteurized milk from the implicated dairy have had onset of diar-
rhea since the outbreak began. When last contacted in November,
88 percent of the patients were still ill.
From the early 1900's until the end of World War II, prior to
widespread pasteurization, outbreaks of human illness, including
diarrhea, TB and brucellosis, were frequently caused by drinking
unpasteurized milk. Since 1952, 49 of the 53 milk-borne disease out-
breaks reported in the CDC's morbidity and mortality weekly
report were associated with unpasteurized milk. The evidence
available to us today is sufficient to show that unpasteurized milk
is a vehicle for salmonella dublin, other salmonella serotypes, and
campylobacter jejuni infections in humans in the United States.
PAGENO="0169"
163
Pasteurization is a safe and effective method for drastically re-
ducing the risk to health from milk and milk products.
[Dr. Potter's prepared statement follows:]
PAGENO="0170"
164
MORRIS E. POTTER, D.V.M.
VETERINARY EPIDEMIOLOGIST, CENTER FOR INFECTIOUS DISEASES,
CENTERS FOR DISEASE CONTROL
I am Morris Potter, Veterinary Epidemiologist, Division of Bacterial
Diseases, Center for Infectious Diseases, Centers for Disease Control. I am
pleased to respond to the committee's invitation to discuss the adverse health
effects of consuming raw or unpasteurized milk. The Division of Bacterial
Diseases is responsible for conduct of surveillance programs, reference
activities, epidemic investigations, and field and laboratory studies of
bacterial diseases. By these activities the Division has accumulated and
analyzed information on infectious diseases that have been transmitted to
humans by consuming raw milk and raw milk products.
Medical history is replete with evidence of the risks of drinking
unpasteurized milk. Despite this knowledge, unpasteurized milk continues to
be an important source of human disease. The most frequently documented
associations between unpasteurized milk and illness are the numerous outbreaks
and sporadic cases of bacterial infections, primarily Campylobacter and
Salmonella species, that have occurred in the United States in the last 20
years. To best understand this association with illness it is useful to
examine the data in greater detail.
In 1980 - 1983, 18 (53%) of the 34 foodborne outbreaks of
campylobacteriosis reported to CDC were associated with drinking unpasteurized
milk'. In the United States since 1980, outbreaks of campylobacteriosis
associated with drinking unpasteurized milk have been reported in several
States from all parts of the country210. An outbreak of campylobacteriosis
in Arizona2 invoived approximately 190 cases of illness in persons from 88
families who drank one brand of unpasteurized milk. In another outbreak, SO
cases of campylobacteriosis in 30 households were compared with well persons,
PAGENO="0171"
165
and disease was strongly associated with having drunk unpasteurized milk4.
In addition, within households with at least one ill person, those who were
ill had drunk larger amounts of unpasteurized milk than had well persons. In
a detailed I-year study of sporadic cases of campylobacteriosis conducted in
Iowa in 1982-1983, 35% of all ill persons had drunk unpasteurized milk during
the week before onset of illness, and drinking unpasteurized milk was the only
significant difference between cases and controls (p ~
3 3 ~ ~
<~actly the complexity of milk
composition. This complexity reflects the intricacy of the
physiological effects of milk on newborn of the same species of
mammals - Mi 1 k is responsible for the mai r~tenance of the 1 ink betwoen
mother and offspring suddenly broken by the act of birth (S.K. kon,
1972. °) - The young thrives on the mother's milk until it begins
taking other foods. The value of milk of certain species is
restricted when used by grown up mammals of the same species and by
PAGENO="0251"
245
newborns of another species. Nevertheless, milk, according to Kon
(i.e. p. 11) `is almost unique as a balanced source of most of man's
dietary needs" of importance here especially is the effect of cow milk
on the immune response of newborn.
To show the intricacy of the problem let's look at the lipid
composition of milk (2,3) Table I, and specifically fatty acid
composition of milkf at (4), Table II.
Table I is based on milk average composition containing 4.Ol~
total milk lipid. Table II (taken from article of Brunner , 5) is a
set of results obtained from the cream portion of composite Ayrshire
milk. These tables show how unusually complex is milk composition.
Brunner notices that "in opposition to the crystallization habit of
the mixed triglycerides of total milkf at, this high-melting glyceride
fraction exhibits distinct polymorphic phase transitions, viz
gamma--> alpha--> beta'--> beta--> when a rapidly chilled specimen is
slowly warmed'.
Protein fractions of milk show also a very high degree of
hetergeneity. Table III presents distribution and properties of
principal milk proteins. This table is taken from Brunner's article
(5) and presents data obtained by Jennes (6), Rose (7) and Swaisgood
(B).
Caseins for instance, known to laypeople as ~casein, a milk
protein, are a highly heterogeneous group of phosphoproteins
consisting of three principal components (alpha s,-casein.beta-casein
and kappa-casein and several minor components (among them gamma-
casein)
Very important parts of milk proteins (qualitatively and not
quantitatively) are milk enzymes. Twenty five different milk enzymes
have been described (5, p. 632 and 633). Their location in milk
PAGENO="0252"
246
differ. Some of them are in micellar casein, some in serum, some in
fat globule membranes, some in Golgi membranes, some in plasma
membrane and some in endoplasmic reticulum. Description of these
enzymes requires special biochemical glossary not easily available to
non-professionals. It should be said here, however, that enzymes,
which chemically are proteins, form a network of biological catalysts,
modifiers of biological reactions. in living systems. All the
reactions catalyzed ( modified) by enzymes form what we call
metabolism. Enzymes recognize chemicals in living systems and
transform the recognized chemicals ( substrates) into products. The
enzymes of milk are very important for an infant using this milk.
They are also important for proper utilization of milk components by
other groups of users of milk. The proper activity of milk enzymes
depends on the intactness of their microenvironment: on the lack of
destruction of their localization structures within milk itself.
Even salts of milk present a high degree of complexity. First,
it is necessary to state that milk ash and milk salts are no
synonymous terms (Brunner, 5, l.c., p 634). Ash is the residue
remaining after the incineration of milk at 600 degrees Celcius. It
has no biological structure. It consists of the oxides of sodium,
potassium, calcium, magnesium, iron, phosphorus and sulfur and
chlorides.
The salts of milk show variety, often colloidal structures in a
highly labile equilibrium with milk proteins (compare Brunner, 5,
l.c., p635). High temperatures, as Brunner remarks, l.c., "shift the
equilibrium in favor of the complexed form of calcium reducing the
concentration of the ionized calcium".
The complexity of the milk structure which we tried to present in
PAGENO="0253"
247
a simplified form here is very strongly affected by processing of
milk.
Heat Treatment of Milk
The development of pasteurization (e.g. 61.8 degress Celcius for
30 minutes or 71.8 degrees Celcius for 15 seconds or ultrahigh
temperature pasteurization: 93.4 degrees C for 3 seconds to 149.5
degrees C for 1 second; Brunner 1.c.) has had a very important effect
on the epidemiology of human populations which have been using milk
during the last hundred or so years. The process has been invented to
destroy pathogenic organisms in milk (it has been standardized on
destruction of Mycobacterium tuberculosis). At the times when the
infectious diseases were a invincible threat to human societies
pasteurization was a big step forwards. Today! at the age of
antibiotics! the environmental presence of factors which decrease our
immune response and induce chronic metabolic diseases is a much bigger
threat. The progress of food technology and the industrialization of
our dairy industry introduce new forms of foods which did not pass the
scrutiny of human evolution. This should always convince us to allow
these groups of our society which are poorly adapted to new forms of
foods to use the old forms of foods when other dangers of these old
forms of foods are under control.
Specifically I think about the effects of heat treatment on milk.
Heat-induced protein-protein interacting are according to Brunner,
l.c. p. 646 `extensive and complex. We know for instance that milk
processed at high temperature does not form a proper curd when treated
with rennin (or rennet enzyme, a pepsin-like proteinase used as a
milk-coagulating enzyme of young mammals and requiring calcium ions
for it effect), therefore such milk! by this procedure, cannot be used
to produce cheese. This is an excellent example of the changes of
PAGENO="0254"
248
biological properties of milk as a result of the heat treatment.
The detailed discussion of such effects would be too
professional: good for physiologists and clinicians and not for
the general public. The generalization is clear: many properties of
milk are lost or modified by processing, especially by the heat
processing.
To name a few more examples, we quote after Brunner further: (5,
p. 647) `aside from the partial destruction of vitamin C and portions
of the B vitamins, high temprature processes induce the so called
"browning" reaction (of milk) which progresses during storage until
the products are no longer acceptable'. As the principal participant
of this reaction is the epsilon amino group of lysine-- the "browning'
decreases the availability of this essential amino acid from milk.
Relatively more recent treatment of milk, introduced after
pasteLlrization. is homogenization of milk. The main reason
homoc~enization was introduced was not a health reason: it was an
industrial reason. Homogenization attempts to secure stabilization of
the lipids of milk against the density separation.
What is still not fully appreciated is the fact the
homogenization alters the protein systems of milk. Aqain the details
should be left to scientific discussions. For a very good summary we
refer the readers to the sub-chapter on homogenization in the
excellent book edited by Fennema (l.c. 5, p 64B). Formation for
instance 1gM-kappa casein complex induced by homogenization stabilizes
the fat emulsion but modifies the immune properties of milk. There
are scientific studies on the negative effects of this phenomenon in
the children, the main users of milk.
PAGENO="0255"
249
We know today that several recently discovered milk components
(immunoglobulin A, immunoglubulin M, immunoglobulin F, lactoferrin, C3
and C4 of the complement system, to name the few) show susceptibility
to damage caused by pasteurization (10).
All the data presented in this discussion and taken from the
scientific literature refer to raw milk unless specifically stated
otherwise.
The scientists studying physiology of milk, always base their
finding on raw milk as a reference situation. Why do they do it?
They study an unmodified biological phenomenon and not an artifact
distorted by human technology unless the effect of this technology is
to be investigated (11).
Table IV present localizations of milk enzymes in the intact
(raw) milk structures. The processing e.g. homogenization by
destroying the structures modifies and abolishes the activities of
milk enzymes.
The new knowledge about mi 1 k should al low us to reexamine our
approach to raw milk as a marketable food product and object of food
processing.
PAGENO="0256"
250
Conclusions
Attention of nutritionists and food technologists has been
focused on the nutritive value of gross components of milk, a set of
data available to them since the turn of the century. This attitude
led to simplified views on the role of milk in nutrition, especially
in the nutrition of infants and children. Milk was considered as a
sr~ of protein, lactose, fat, certain vitamins and some minerals.
This attitude also put no restriction on many technological procedures
in milk processing. The progress of nutritional biochemistry and
biochemical analytical methodology as applied to milk revealed not
only new milk components and details of milk structure but also led to
the discovery of new nutritional effects of milk (e.g in the
maintenance of the immune response of an infant) available in raw milk
and less detectable in processed forms of milk.
We all agree today that the raw milk supply should be derived
from healthy cows with healthy udders and be produced under sanitary
conditions. When such conditions are fullfilled, the market
availability of raw milk should be maintained next to other forms of
milk. More and more scientific data indicate today that the users of
raw milk, especially the inf ant users of it. in our industralized and
polluted environment do benefit from the effects of newly discovered
milk ingredients.
PAGENO="0257"
251
k~gr~'pt)y
1. W.6. Gordon and E.O. Whittier. `Fundamentals of Dairy Chemistry"
(B.H. Webb and A.H. Johnson, eds) AVI Pubi. Westport, Conn. 1965, pp
1-36.
2. F.E. Kurtz. "Fundamentals of Dairy Chemistry" l.c. pp 91-169.
3. R. Jenness and S. Patton. "Principles of Dairy Chemistry" Wiley,
N.Y. 1958.
4. S.F. Herb, P. Magidman, F.E. Luddy and R.W. Riemenschneider. 3
Amer Oil Chem Soc 39, 142, 1962.
5. J.R. Brunner, Chapter 14 of "Principles of Food Science part I".
Ed. O.R. Fennema, Marcel Dekker Inc. N. Y. 1976, p. 619.
6. R. Jenness in "Milk Proteins, Chemistry and Molecular Biology"
(H.A. McKenzie, ed) vol 1. Academic Press, N.Y. 1970, pp 17-40.
7. D. Rose, J.R. Brunner, E.B. Kalan, B.L. Larson, P. Melnychyn, H.E.
Swarsgood and D.F. Waugh. 1970. J. Dairy Sci. 53 , 1, 1970.
8. H.E. Swaisgood. Crit. Rev. Food Technol. 4, 375 (1973).
9. S.K. Kon "Milk and Milk Products in Human NLtrition" 2nd ed. Food
and Agriculture Org. of the U.N. Rome 1972.
10. G.J. Reynolds, 0.1. Lewis Jones, D.M. Isherwood et al "A
Simplified System of Human Milk Banking" 1982, Early Hum. Dcv.
(Netherlands) vol 7 no. 3 pp 281-292.
11. J.W. Meduski, M.D., Ph.D., USC School of Medicine, Personal
Communi cation.
52-266 0-85-9
PAGENO="0258"
9~-9S 39.0
0.25-0.48 0.14
0.016-0.038 0.01
0.85-1.28 0.4
0.011-0.015 0.00~
0.011-0.023 0.007
0;10~0.44 0.1
0.2-1.0 0.3
0.013-0.068 0.02
0.22~0.41 0.1
0.007 0.003
0.0007-0.009 0.0C2
252
TABLE I.
Lipid Compositiob of MIII
A1~roxltnate concentritioo
Perc~itage of
lipid
of
gfliter
Lipid class (range
values)
Triglycerides
DiglycerideS
MonoglyCeIide$
Ketcmcid glt~cerldes
AldehydogeftiC glycerides
Glyceryl ethers
Free fatty acids
PbospbolipMIS
Cerebrosides
Sterols
Squalene
Carotenoidi
Fat-soluble vitamins
PAGENO="0259"
253
£AbL.&. LI.
Fatty ACId Composition of Milkfat
Acldb - Acidb
Iaturatnd acids
40 279 50 001
6:0 2.34 7:0 0.02
8:0 1.06 9:0 0.03
10:0 3.04 110 0.03
12:0 2.87 13:~ 0.06
14:0 8.94 15:0 0.79
16:0 23.8 17:0 0.70
18:0 13.2 19:0 0.27
20:0 0.28 21:0 0.04
22:0 0.11 23:0 0.03
240 0.07 25:0 0.01
26:0 0.07 - -
Branched-chain acldt
14:Obr 0.10 13:Obr 0.04
16:Obr . 0.17 15:ObTAC 0.24
18:Obr Trace 15:ObTBC 0.38
20:Obr Trace 17:0 brA0 0.35
- - 17:0 brBC 0.25
Monounsaturatid acids
0.27 15:1 0.07
0.14 .17:1 0.27
l4:IC 0.76 19:1 0.06
* 1.79 21:1 0.02
29.6 23:1 0.03
20:1 0.22
22:1 0.03
24:1 0.01
Polyimaturated acids
D1~ TrIenes
18:2 2.11 18:3 0.50
0.63 18:3C01ü1 0.01
0.09 20:3 0.11
20:2 0.05 22:3 0.02
22:2 0.01
T.tsa~S
30:4 0.14 *0:5 0.04
22:4 0.05 22:5 0.06
~?IpTSS prec.dI~ tb Colon designate the ewnber ot carbon atoms ~prIaI~
~ acid *harnas boss foUowir~ tha colon ds.ig'te tha mnaber 01
~ bond. In ~ narbon chain. -*
CA and B dssignat. Isomers.
?er~1 d~lo bmsl.
bclnd.s cia, trana, and iar~I1 Iu~l,-bond Isomers.
1~claiaa cia and trina Isomers.
- ci. ,trme; t,t - t a ,nas;~ ec*J *
PAGENO="0260"
TABLE Ill
Distribution and Properties of the Principal Milk Proteinsa
A~rozimate concentraUon
.
Approximate
koe%ectrtc
Percentage of
total protein
*
.
molecular
point
Component
(range of values)
g/liter
Polymorphe
P
-811
-8-8-
weight
p14
Caseina
75-85
(250)b
.
46
~51-Casein
45-55
13.7
A, B, C, D
8
0
0
23,500
5.0
~-Caaein
26-35
6.2
A1,A2,A3,B,C,D
5
0
0
24,000
4.5
k-Caasin
6-15
3.7
A, B
1
2
0
19,0000
3.7-4.2
y-Ca.ein
3-7
1.2
`A1,A2,A3,B
1
0
0
20,000
5.8
Whey proteins
15-25
(5,2)b
.
`
.
.
fl-Laotoglobulin
"7-12
3.0
A, B, C, B
A, B
0
1
2
lM,000 ~
5.3
~-1aotaalbumln
2-5
0.7
0
0
4
14,200
5.1
ImmunoglobullS
1.5-2.5
0.6
-
0
0
VsrlabLs~
l60,000~
5.6-6.0
erum albumin
0.74.3
0.3
0
1
17
69,000
4.7
Minor proteins
2,0-4.0.
0.6
.
.
aCompilad partially from data presentad by Jannese Rose at ii. , and Swaisgood
*bAssumed average composition: 2.50% casein, 0.52% whey protein.
CMOIecular wstght of osrbohydrat.-(rss species; species containing up to I 1~ carbohydrate moicileR (.1)00 daltons psr
`~ moiety) exist.
mixture o(glycoprotein..
5Primary structure Is irKilviduelly variable.
*tFour chain molecules, coneistir~g of two light and two heavy chains lotermolecularily bound through -8-8- groups. Light
sal heavy chains contain intramolecular -8-8- loops.
~Approxft~te molecular weight of monomers IgGl and lgG2; 1gM is a pentamer (..1,000,000) and IgA is a dimer (.400.000).
PAGENO="0261"
255
Table IV
c~ -Mannos idase
Lipase
Protease
Esterase -
Lactoperoxidase
Lysozyme
a-Atnylase
8-Anmlase
Riboriuclease
Sulfhydryi oxidase
Catalase
Alkaline phosphatase
Acid phosphatase
Aldolase
Xanthine oxidase
Phosphcxiiesterase
NADH-cytochrome c reductase
Acetylcholinesterase
Mg2~-activated ATPase
Glucose-6 -phosphat.ase
5 `-Nucleotldase
UDP-Galactose hydrolase
UDP-Glucose hydrolase
UDP-Cmiactosyl transferase
Triglyceride synthetase
E. C.3.2.1.24
E. C. 3. 1. 1.3
E.C.3.4.4. -
E.C.3. 1. 1.1
E. C. 1.11.1.7
E. C. 3.2.1.17
E.C.3.2. 1.1
E.C.3.2. 1.2
E. C.2. 7. 7. 16
E.C. 1.8.3.-
E. C. 1. 11. 1.6
E.C.3. 1.3.1
E.C.3.1.3.2
E. C.4. 1.2.7
E.C. 1.2.3.2
E.C.3.1.4.1
E.C. 1.6.2.1
E.C.3.1.1.7
E. C. 3. 6. 1.4
E. C. 3. 1. 3. 9
E.C.3.1.3.5
Enzymes Identified in Milk
Enzyme
(trivial name)
*
Class ificationa
number
-
Distributionb
MC
MC
MC
S
S
S
S
S
S
S
FGM, MC, S
FGM, S
FGM, S
FGM, S
FGM
FGM
FGM, ER
FGM
FGM
FGM
FGM, PMC
FGM, PMC
FGM, PMC
E.C.2.4. 1.22 GM, S
ER
*Ac(,~Jing to Committee on Enzymes of the International Union of Biochemists
L2J.
bDesjg~ates location in milk; viz., MC, rnicellar casein; 5, serum (whey);
FGM, fat globule membrane; GM, Golgi membrane; PM, plasma membrane;
aed ER, endoplastnic reticulum.
CServe as marker enzymes for PM a~ FGM.
PAGENO="0262"
256
Mr. WAXMAN. Thank you very much, Mrs. Gooch. In your testi-
mony you acknowledge the fact that there are high risk individuals
and you think perhaps a warning to them so they could make an
informed decision would be a reasOnable course to take, certainly
far preferable, if I understand what you are saying, to banning it
competely.
Is that a fair statement?
Mrs. GoocH. I personally am not sure there would be a need for
a warning, but certainly if given the alternative I would prefer a
warning over the banning of the milk.
Mr. WAXMAN. We have had some people tell us that with infants
it would be less than advisable to give them raw milk, with people
who have been ill and whose immune system might be less than
fully active that they ought to refrain from raw milk.
Don't you think those people ought to be informed of that?
Mrs. GoocH. I heard that testimony, yes.
However, in the paper I present to you, you will find other testi-
mony that states that immune factors in certified raw milk are far
greater and may have potential benefits that regular pasturized
milk does not have.
Mr. WAXMAN. So, you dispute the statement that infants ought
to avoid using raw milk?
Mrs. GoocH. Certainly most of the customers that come in and
purchase raw milk do give the raw milk to infants after they have
been removed from breast feeding, and they choose the raw milk
for their children over pasteurized milk because of the research
they have indeed done about the benefits.
But getting back to the labeling situation, I would far prefer a
label, a warning label, in relation to the choice of not having that
product at all.
Mr. WAXMAN. Thank you.
Mrs. GoocH. Let people make up their own minds through the
process of education as to what they want to do.
Mr. WAXMAN. Mr. Stueve, what do you think of the idea of high
risk groups? Do you think there are high risk groups that ought to
refrain from use of raw milk for that high risk group?
Mr. STUEVE. Babies.
Mr. WAXMAN. Yes, and invalids?
Mr. STUEVE. If a mother can't nurse a small baby, and a pediatri-
cian gives them a formula-you can't give the whole cows milk to a
baby-but you have a formula, then you boil the water but not the
milk. With a small baby like that-I will call it the formula milk-
if baby is fussing and crying and you put it on raw milk formula,
in 24 hours the baby sleeps like it should be sleeping. It gets all the
food value which it cannot get from the others. It is impossible.
Mr. WAXMAN. So, you would subscribe to the statement that raw
milk's easy digestibility makes it the ideal formula milk for babies?
Mr. STUEVE. Right; the same with people that are not well, there
is far more of a factor there in the food value that they receive
than what you are talking about, because I maintain nobody gets
salmonella from my milk. We haven't had any contaminated
produce nor do we intend to have any.
PAGENO="0263"
257
Mr. WAXMAN. Over the years we have heard that mothers have
been advised that milk for formula should be heated to enhance di-
gestibility.
Do you think the generations of mothers were wrongly informed
by their pediatricians?
Mr. STUEVE. Yes, absolutely.
Mr. WAXMAN. You do?
Mr. STUEVE. Absolutely.
Mr. WAXMAN. Now, you do not consider unmodified cows milk
unsuitable for newborns, you consider it desirable for newborns, is
that your testimony?
Mr. STUEVE. I think the best thing for a baby is for the mother to
nurse it. If she can't, the next best thing is certified raw milk with
a formula. You boil the water, but not the milk.
Mr. WAXMAN. Then you dispute there are any high-risk catego-
ries of individuals?
Mr. STUEVE. No; high risk, none.
Mr. WAXMAN. It is the ideal thing for everybody?
Mr. STUEVE. I think the best thing a baby can get, like I men-
tioned, again, is the mother's nursing, but if she can't the next best
thing is to be fed raw milk, not soya milk or pasteurized formula
milk, because you have a processed food and the baby is starving
from it. I maintain where a mother doesn't nurse a child and it's
been on the pasteurized formula milk, it will have some kind of
problem before it is 21 years old.
Mr. WAXMAN. There is a group called the American Association
of Medical Milk Commissions-this is a group that does the certifi-
cation for milk products.
Mr. STUEVE. Right.
Mr. WAXMAN. They recently revised their quality control proce-
dures and as I understand it, in their new revision they deleted the
requirement that certified raw milk be free from salmonella orga-
n~sms.
Are you familiar with that deletion?
Mr. STUEVE. First of all, can I go back a little bit?
The health department put this into effect in 1969 in a bill. They
start picking up my milk every Monday morning for the milk
commission lab, as well as our own lab. So, it ~as written in, but it
had meant nothing, absolutely meant nothing. All this checking for
salmonella has been a waste of time and money for the State as well
as ourselves.
Mr. WAXMAN. The State doesn't? This commission sets standards
for it?
Mr. STUEVE. Right.
Mr. WAXMAN. This is a trademark used, and they certify milk.
Mr. STUEVE. Because it was the way it was written, sort of writ-
ten that all cows had to be free from salmonella and, you know,
that is almost an impossibility because a cow can have salmonella
in her stool feces but passes through, it is gone and it does not shed
in the milk. It is very rare, it is as rare as hen's teeth almost for a
cow to shed salmonella through her milk because this cow would
be sick if she had it in her blood and chances are she will die and
she wouldn't be producing milk.
PAGENO="0264"
258
Mr. WAXMAN. With all the controversy about salmonella being
in milk, why suddenly does this commission decide that one of its
standards would no longer be to check for salmonella?
Mr. STUEVE. We still do it. We check our milk every day, every
day, for salmonella.
Mr. WAXMAN. You say "we," are you--
Mr. STUEVE. Alta-Dena Dairy.
Mr. WAXMAN. How about the milk commission?
Mr. STUEVE. The commission gets it at least once a week or twice
a week.
Mr. WAXMAN. But they changed their rules. They said they are
no longer going to check to see whether there is-no longer require
that certified raw milk be free from salmonella.
Mr. STUEVE. That is correct.
It is a waste of money. It is not necessary because salmonella has
been no problem. If you have an outbreak of salmonella in a res-
taurant, sure you go in and find where it is. We never had an out-
break. Look at our record. None.
Mr. WAXMAN. I have heard about recalls. Who ordered them?
Mr. STUEVE. We didn't. We never recalled our milk. We say
there is nothing wrong with the milk-use it.
Mr. NOVELL. May I address that, Mr. Chairman?
Mr. WAXMAN. Yes.
Mr. NOVELL. Thank you.
The recalls are the basis for isolation for the salmonella. One
thing you have to understand is in our society where salmonella
can be found in McDonald's hamburgers-it has been, frequently-
and can be found in other areas there is no other product checked
for salmonella on a routine basis.
Mr. WAXMAN. That can be found in--
Mr. NOVELL. It is ubiquitous.
Mr. WAXMAN. Has it been found in raw milk?
Mr. NOVELL. Sure it has been found in raw milk.
Mr. STUEVE. And in our--
Mr. WAXMAN. Who ordered the recalls?
Mr. NOVELL. The State of California ordered the recalls. Those
recalls are not based on any illness. They are based on an attempt
at isolation.
Mr. WAXMAN. They are based on trying to prevent illness, aren't
they?
Mr. NOVELL. I don't believe so. If they were, they would be more
concerned about the outbreak of yersinia entercoutia bacteria from
pasteurized milk in a state that doesn't allow raw milk. If they
were more concerned about it they would have investigated the 115
salmonella dublin cases that came from cooked roast beef.
Mr. WAXMAN. When they recalled the milk that had salmonella
in it, the purpose of that was not to prevent illness, but to do what?
Mr. NOVELL. To eliminate the product over a period of years to
the consuming public that wanted it. You see they can--
Mr. WAXMAN. And you say that recalls are part of a conspiracy
to remove raw milk from the consuming public?
Mr. NOVELL. I will not use the word conspiracy. I believe there
are some people that feel raw milk shouldn't be available and that
is the issue.
PAGENO="0265"
259
Mr. WAXMAN. What about recalling just a few items?
Mr. NOVELL. Pardon me?
Mr. WAXMAN. We had testimony from a woman this morning
who said that she found later that the milk had been recalled, that
it had salmonella in it, and that had caused medical problems,
caused her, in fact, to lose her children; but now when she found
out that milk was recalled-what did that mean?
Mr. NOVELL. I don't know what it means, but you are misstating
the facts of the matter, and that is in litigation, and I am sure like
the rest of the litigation that occurs in the matter of Alta-Dena
Dairy it will be completely vindicated. But if I can answer your ini-
tial question, the isolations are for routine testing. If it was done in
supermarkets and restaurants and hospitals we would isolate sal-
monella. The interesting thing is that from 192 isolations of salmo-
nella in California there should be thousands and thousands of ill-
nesses but there are not any. The people claim there are allegedly
600 cases of illness from raw milk throughout the United States,
yet twice that many cases occurred on just two occasions in two
States where raw milk is banned. It was from pasteurized milk.
So what is everybody saying, that we should have a zero-risk? We
won't have any pasteurized milk either.
Mr. WAXMAN. I appreciate what you had to say. Just to clarify
where we have differences of testimony. One place, by the way, Mr.
Stueve, where there is no difference in the testimony, everybody
claims that your dairy is quite sanitary and you take a great deal
of precautions.
Mr. STUEVE. I invite you to come and see it. I would like for you
come and see it.
Mr. WAXMAN. I will see if we can do it one of these days. You are
certainly to be congratulated because you are trying to do the best
you can in sanitation.
But where we have differences of opinion in testimony today is,
that there are some who say that there are individuals who are
high risk for infection from various pathogens including salmonel-
la, and some people have said the high risks are infants, invalids,
elderly. This has been disputed.
The witnesses before me right now have-you, Mr. Stueve, and
Mrs. Gooch have disputed that.
Second, is-whether salmonella and other pathogens can or are
more likely to be in raw milk. You say no. Others say yes. So, these
are the differences we have.
The third area of difference in the testimony is whether with all
the sanitation measures you take, whether that, in fact, will elimi-
nate the pathogens in the milk, and there is a question of whether
that is accurate or not.
Some people claim that pasteurization on top of everything else,
would, as a heating process, destroy those pathogens.
I gather what you are saying to us in your testimony is that raw
milk need not be pasteurized at all because there are no pathogens
anywhere.
Have I accurately stated that?
Mr. STUEVE. I didn't say there would be no pathogens. I say our
certified raw milk is the safest milk in the world, bar none. But
when you want to do that kind of testing like--
PAGENO="0266"
260
Mr. WAXMAN. But it's not safe if you have pathogens in it.
Mr. STUEVE. Well--
Mr. NOVELL. That is not true. If it is in the environment, Mr.
Chairman, in the food environment, and it is throughout our food
environment-you are talking about salmonella-of course, there
are problems from time to time.
Mr. WAXMAN. Any product-let me--
Mr. STUEVE. If you have a food item with salmonella in it-sal-
monella is really not a pathogen, because if I have salmonella, I
can't give it to you unless I am unclean and I give you some food to
eat. Otherwise I can't give it to you.
Mr. WAXMAN. If I have a food item with salmonella or other
pathogens in it, that is not the healthiest item in the world to eat.
Mr. STUEVE. I guarantee you, you eat salmonella weekly, if not
daily, because in such a minute quantity that doesn't bother you.
Because when we took a sampling by the Moore swab system, we
took sandwichs from five different restaurants and we brought
them in and we find one out of four with salmonella.
Mr. WAXMAN. That is another dispute we have had this morning
and into this afternoon, whether salmonella makes any difference
or not. We had testimony from Mr. Thomas, and he didn't think it
made a lot of difference, and others thought it did.
You would subscribe to Mr. Thomas' point of view, that it doesn't
make a lot of difference if you are exposed to it?
Mr. STUEVE. If we had a salmonella in milk-first of all, if we
take a plate test, the plate would be brown, and then you would
have a contaminated product, and we would have it off the market
ourselves, real fast. But the way we produce our milk-and when
you are trying to isolate this with a Moore swab system, we take
that again and check it and it is not there, so that is why I ques-
tion it. The milk was not refrigerated.
So, I say it had been there for days and had a salmonella in it. I
don't believe that. I want to see who tested it because it is not easy
to check and see if you have a salmonella to start with, and say it
is a salmonella dublin. It has to be sent out to Ames, IA, or the
Centers for Disease Control in Atlanta, to really type it.
Mr. WAXMAN. Thank you very much.
Mr. Dannemeyer.
Mr. DANNEMEYER. Thank you, Mr. Chairman.
Mr. Stueve, there was testimony earlier by one of the witnesses
about campylobacter involving the products of Alta-Dena Dairy. Do
you have comments about that?
Mr. STUEVE. That is an odd deal, too, because we were in Sacra-
mento, and I didn't find out until we were in Sacramento, when it
was brought up. This group had their own symposium and brought
in campylobacter from my milk.
When we find out about it-this particular group said kids came
to the dairy, the health officer came out and the tour guide showed
how they got certified or kefir milk or ice cream. Then it was
shown that the kids from there, when they saw the plant-they
come out and they love the calves, because at the county fair all
the kids come out and pet the calves.
So, we have a couple of calves out there-so they petted the
calves, and there is a water trough half underneath the fence, and
PAGENO="0267"
261
they splashed around the water. If they got it from raw milk-for
gosh sakes, there was thousands and thousands of gallons out
there, they would all have gotten it.
So, it didn't come from the milk, it came from the outside, from
petting calves or water splashing.
I think Dr. Orsborn can verify this also. This is where you get
campylobacter, but not from ingestion of raw certified milk the
way we handle our milk, because we produce our milk with one
coliform, sometimes zero coliform, and the plates are low.
How can you get campylobacter out of it? It is impossible.
First of all Dr. Winn says it is impossible and evidence from the
Centers for Disease Control--
Mr. DANNEMEYER. OK.
Mr. STUEVE. But again you see what happened, what I am talk-
ing about, conspiracy, organized crime.
This was picked up and brought up to Sacramento to bring out,
and put out in the news media that campylobacter was in our milk
before we even found out ourselves about it. I am telling you we
are up against a conspiracy, organized crime here.
Mr. DANNEMEYER. Thank you very much.
I think that record would be deficient on this issue unless we
state a little bit briefly of one of the problems, as I see it, in this
entire controversy.
This producer of certified raw milk has brought a product to the
people of California. There is a need for it. But this producer has
been, and still is, under the jurisdiction of the following public enti-
ties, the State Department Public Health, the State Department of
Agriculture, the County of Los Angeles Public Health, and the Los
Angeles County Medical Milk Commission.
Each of those public entities has their own particular bias to
pursue. And that abundance of governmental regulations of this
producer of certified raw milk is partly responsible for this entire
controversy.
The Department of Agriculture of the State of California has kind
of been in the middle of this controversy, but there are two or
three individuals in the State Department of Public Health who,
when they went through medical school years ago, were taught by
their professors that all milk should be pasteurized, and they still
believe that, and they are sincere in that belief.
But they have adopted as a cause for the achievement of their
career in public health in California, that they want to be known
in the anals of public health as the people who are responsible for
eradicating from the consumers of our state the menace known as
certified raw milk.
And they have almost limitless resources. They have lawyers,
they have statisticians, they have biologists, they have cohorts
working from the Centers for Disease Control in Atlanta, GA, and
around the country, and they have just circled the wagons in a
circle, and their view is getting a little smaller.
As the data from Mr. Thomas points out, you have to shake your
head. There is a existing standard for E. coli, a pathogen in milk.
For that pathogen, not more than 10 colonies per milliliter pro-
duced more deaths than salmonella in 1979.
PAGENO="0268"
262
Yet, we are not doing anything, we are not hearing anything
from the public health world about proceeding against food prod-
ucts that contain E. coliform bacteria, which produces more deaths
than salmonella.
Yet, we hear all this effort about eliminating certified raw milk
from the consumers choice, a product which is healthful and
needed, and nutritious, at a time when they are doing nothing
about these 11,255 cases of salmonella food poisoning.
I am disappointed, Mr. Chairman, in Dr. Chin-who is a nice
gentleman-that he didn't come in with his flag declaring war on
salmonella in California, because logically he should be doing that.
We know why-he will be laughed from his office as a public offi-
cial if he proposed we eliminate hospitals and water and beef and
turkey. Why? Because the producers of those products are so basic
to our culture that we couldn't really function without them.
So, they have zeroed in on this producer of certified raw milk
and brought the whole resources of the State to bear on them, all
flying under the flag of public health. I think it is a tragedy. It is a
perversion of what public activities and laws are all about.
I think the correct course we should take with our colleagues is
just let people make a choice as to what products they choose to.
pursue.
Thank you very much.
Mr. WAXMAN. Thank you, Mr. Dannemeyer.
You just heard my colleague, Mr. Dannemeyer's, description of
the people in the public health world who think there is a problem
with salmonella. He said he thinks they are well-meaning but mis-
taken. They have some notion that pasteurization was an advance
that killed these pathogens in salmonella, but in fact, they are
wrong. That is his description.
Your description is they are part of organized crime.
What do you mean by that?
Mr. STUEVE. Because as I give you my-what I read for you-we
started taking them on. Humphrey is the one that carried the ball
all the time. He is the one that came-if you recall now Dr.
Werner, Dr. Bolton, and Dr. Fierer are also involved in this. I was
told these three were in school together, so, you see the circum-
stances on that.
But everything points right down. This is an organized crime to
knock Alta-Dena out of certified raw milk, and probably, if they
could, they would probably have no more raw milk in these United
States of America.
That would be one of the biggest objects they would try to create.
But the biggest thing is it is a conspiracy on us because we took
on, one, the health department and beat them in court. That is the
biggest point.
I was told at that time-in fact, in 1969 I was the mayor of Mon-
rovia, and before served on the city council-you can't fight city
hall, I felt when you are right you have to stand up for it. You
can't lay down.
Mr. WAXMAN. Let's hold back the audience response so we can
finish up the meeting.
I want to explore this one issue with you because it seems to me
you are saying because some people disagree with you and would
PAGENO="0269"
263
reach the conclusion that raw milk, because they believe it is un-
healthy for the American public, should be banned-even though
you strongly disagree, to say they are part of organized crime is a
pretty extreme statement.
Do you stand by that statement?
Mr. STEVVE. Yes, I am.
Mr. NOVELL. May I respond to that, Harold?
Mr. WAXMAN. I want to hear Mr. Stueve's statement, because he
made the comment on it. If you make extreme statements like
that, I must tell you, that sounds so extreme to me that it chal-
lenges your credibility in other statements you make, if this is not
one you can stand on.
Mr. STUEVE. When Louis Pasteur brought in pasteurization it
was used for wines, and the beer producers picked it up-not in
Germany where they drink it so fast, but for bottled beer. But draft
beer is still raw here. But the wine people turned back-they are
making it. Gallo and Wenty, they are making it all raw again be-
cause they found out they have more flavor and better tasting
wines with it.
The milk people picked it up to "kill all evil." I still predict to
you by the year a little over 2000, over half the people in Califor-
nia will be back to raw milk again because they will find out how
much more they are missing over this time, like growing heart dis-
ease.
Mr. WAXMAN. I understand, but why did you say, "organized
crime." It is a point you assert and I respect that fact.
Mr. STUEVE. How can any--
Mr. WAXMAN. Why do you say the people you disagree with, who
may be well intentioned, are part of organized crime?
Mr. STUEVE. Why did they put into the bill that time and stick
salmonella in it, into the bill in 1969? At that time they couldn't
find it with that technique. So later on they put in a Moore swab
system, and going that way I think you can find anything you want
to.
So, it was on purpose put in there. So, right away in 1970 why
did they come in full force and pick on our milk all the time? Even
Dr. Chin came and said, yes, there still could have been a Q-fever
in milk, and they had a test made up for our younger herd and
made a testing and they became a laugh. Because Q-fever is air-
borne and you cannot get it from ingesting.
The same with this other here, with salmonella. Why didn't we
have an outbreak? Look around. We had no breakout. You find this
one case, and the biggest case, of salmonella dublin, which was
Vandenburg Air Force Base from cooked roast beef, and everybody
eats meat, so why show the other, why does it come to us only one
case at a time? It is ridiculous.
Mr. WAXMAN. I understand.
Thank you very much.
Mr. DANNEMEYER. Do you have anything? Mr. Novell wanted to
respond.
Mr. NOVELL. Specifically, when you look at statistics that is
where it becomes suspicious and that is where this "conspiracy"
arises that Mr. Stueve talks about. For example, there was a study
published in 1979 by Dr. Werner and Dr. Humphrey about 113
PAGENO="0270"
264
cases over a 5-year period in California, and they said 35 of the
people were associated with raw milk. That particular study left
out the 115 from cooked roast beef.
Mr. WAXMAN. Do you believe the people who wanted to ban raw
milk are part of organized crime.
Mr. NOVELL. I wouldn't use the words organized crime. I don't
think that he is using that by intending to refer to what you-it is a
colloquialism. I don't think Mr. Stueve means to infer-that there is
Mafia involved.
Mr. WAXMAN. I wanted that explained. You think it is a colloqui-
alism?
Mr. NOVELL. Yes. But when you refer to the studies that Mr.
Potter referred to by Dr. Taylor-Dr. Taylor in 1979 and 1980 it
was-finds that in 18 States there are 57 cases of salmonella
dublin, other than California and Oregon, and 12 people contracted
it from raw milk-but what he put in his study, but buried, that 8
people drank milk not intended for commercial use and one person
was from India.
When you compare that with the control, which is 5 out of 62,
you have 3 of 57. So, there was lower risk for raw milk users.
When you take Dr. Potter's study, I respect his view, but he said
in his study the people that drank most of the milk got sick. That
is not true. Mr. Thorn was one of the persons in his study. He
drank most of the milk and he didn't get sick. His child who didn't
drink the milk got sick.
So, there was no explanation for that particular one. That study
even admitted they did not isolate the organism in the milk. They
also didn't know of seasonal variations. Nor could they say it was
related to the milk.
I could go on and on and on. I have submitted this in writing, but
every study we look at has this in it. Everytime somebody says the
statistics are unassailable it is simply false. The statistics are
there. There is twice as much illness from pasteurized milk and
only two occasions from two nonraw-milk States than from all the
raw milk alleged illness in all the United States.
So, if you want to get back to "where is the risk?", I submit to
you that the risk is in the areas where people are not paying atten-
tion to sanitation, and that to reduce the risk we have to do that as
has been suggested earlier.
Thank you.
Mr. WAXMAN. Thank you very much.
I want to thank the three of you very much for your testimony.
There are people in the audience who feel strongly and want to add
to this record.
We will be pleased to receive any written comments that any of
you want to make and put it in the record with the transcript that
we will share with our colleagues in Washington.
Mr. WAXMAN. I thank everybody who participated in this hear-
ing we appreciate your activity and assistance. We stand ad-
journed.
[Whereupon, at 1:40 p.m., the hearing adjourned.]
[The following letters were received for the record:]
PAGENO="0271"
265
February 20, 1985
Honorable Henry A. Waxman
Chairman, Subcommittee on
Health and the Environment
2415 Rayburn House Office Building
Washington, D. C. 20515
Dear Hr. Waxman:
I attended the hearing on The Health Risks and Benefits of
Unpasteurized Milk held February 13, 1985, at the University
of California, Los Angeles.
This same type question arose last fall in the California
legislature. At that time officers of all the Cooperatives
who operate processing facilities in the state visited the
Governor's office and, in unison, opposed a relaxation of
the present law. This group represents aboUt 70% of the
milk producers and about 80% of the milk produced in Cali-
fornia.
This group opposed the legislation because every reported
case of milk borne Salmonella dublin gives the entire Dairy
Industry a bad reputation. This group is unanimous in its
opposition to the sale and distribution of raw milk.
I hope your Subcommittee will recommend the Food and Drug
Administration enforce the present law banning raw milk sales.
Very truly yours,
DY'~NISH CREAMERY ASSOCIATION
Galen W. Brunner
President and General Manager
GWB: 1 f
cc: John Adams, NMPF
P.O. BOX 11865. FRESNO, CAIJFORNIA 93775 / PHONE (209) 233-5154 / GALEN W. BRUNNER, GENERAL MANAGER
PAGENO="0272"
266
AMERICAN MEDICAL ASSOCIATION
/ 535 NORTH DEARBORN STREET CHICAGO, ILLINOIS 60610 PHONE(312)645-5000 . TWX 910-221-0300
.IAMESH. SAMMONS, M.D.
Executive Vice President
(645-4300)
February 28, 1985
The Honorable Henry A. Waxman
U.S. House of Representatives
Washington, D.C. 20515
Re: Milk Pasteurization
Dear Chairman Waxman:
On February 13, 1985, the House Energy and Commerce Committee held a
field hearing concerning the risks and benefits of pasteurized milk. The
American Medical Association believes that all milk sold for human
consumption should be required to be pasteurized because convincing
scientific evidence exists that raw milk poses a significant public
health threat. We recently expressed our view on this issue to the Food
and Drug Administration. A copy of our statement along with an article
published in the Journal of the American Medical Association concerning
the health hazards of drinking unpasteurized milk is enclosed.
We hope this information proves useful to you.
Sincerely,
James H. ammons, M.D.
JHS/hf
l758p
PAGENO="0273"
267
`3 AMERICAN MEDICAL ASSOCIATION
3, f 53SNORTH DEARBORN STREET * CHICAGO, ILLINOIS 60610 . PHONE(312) 645-5000 TWX 910-221-0300
JAMESH.SAMMONS, M.D.
Ezeculwe Vice President
(645-43501
October 29, 1984
Frank Young, M.D., Ph.D.
Commissioner
do Dockets Management Branch (HFA-305)
Food. and Drug Administration
Room 4-62
5600 Fishers Lane -
Rockville, Maryland 20857
Re: Docket No. 81 N-0204C Milk
Pasteurization as published in tha
Federal Register of August 3,
1984, (49 F.R. 31065)
Dear Dr. Young:
In the Federal Register of August 3, 1984, the Food end Drug
Administration (FDA) published a notice requesting inforration as to
whether there is a public health concern regardiog the marketing and
human consumption of raw milk, including certified raw milk, and raw milk
products. The FDA also requested comments concerning whether it is the
most reasonable regulatory option to require that all raw silk and rca
milk products sold for huaan consumption should be pasteurized.
There ia convincing scientific evidence that raw milk poses a
significant public health risk. Raw silk has been identified as the
source of bacteria that have caused outbreaks of ualmonellos~s and
carspylobacterlosis. Other serious bacterial diseases linked to the
drinking of unpasteurized tailk include tuberculosis, staphylococcocic,
brucellosis, listeriosis, colibaciliosis and corynehacteriosis. Because
milk has a fat content that protects pathe3ens from gastric acid acid Ii~ a
a relatively short gcistric transit time, unpasteurized milk can be a ~o~d
vehicle for the transmisciou of infectious diseases.
The Al-IA believes that all silk sold for hucoac consusrption should 3-a
required to be pasteurized. Pasteurization kills the bacteria that
transmit disease to humans. In addition, pasteurization has not baen
found to have any adverse health effects. Finally, studies have found
teat rcw nile provides no significant health benefits over those ~iOV1~i.d
by pasteurized milk.
We have included a copy of an article publ~mhed in the October 19,
1984 Journal of the_A~erican Medical Associntion that discusses the
health hazards of drinking unpasteurizeci milk.
We appreciate the opportunity to express our view.
Sincerely, /~
/1 ,,/f~
L_~.~af~3 fc~'~ 4 ~ *
James H. ~sIsiflaicsu M.D.
INS/hf
Enclosure
l6llp
PAGENO="0274"
268
Cupyught 1084, Aco,iuo, Mrdie&Az,ouietiec
State of the Art
M. Therese Southgate, MD, Section Coordinator
Unpasteurized Milk
The Hazards of a Health Fetish
Morris B. Potter, DVM; Arnold F. Kaufmann, DVM; Paul A. Blake, MD; Roger A. Feldman, MD
AS THE dairy industry began to
industrialize in the 1800s, the mass
production and distribution of milk
and dairy products led to svidespread
outbreaks of milkborne disease. The
greatest perceived milkborne hazardo
of the time were psor sanitation and
handling procedures, as svell as dis-
eased dairy cows. Repeated outbreaks
of typhoid, `scarlet fever, diphtheria,
diarrheal disease, and septic sore
throat were caused by milk that svas
produced, transported, and sold under
unhygienic conditions.
Nationsvide problems with contam-
inated milk led to two public health
movements that attacked the pur-
veyors of bad milk and each other
ovith equal alacrity. The certified milk
movement promoted sanitation in all
phases of milk production and mar-
keting under the oversight of medical
milk commissions but denounced pas-
teurization, claiming that it caused
nutritional deficiencies, allowed the
marketing of sterilized filth, and
destroyed the natural flavor of milk.
Conversely, the pasteurized milk
movement denounced certified milk
as unsafe despite the sanitary precau-
tions.' Ultimately, the best of both
movements became public policy.
Pasteurization was accepted as the
primary safeguard for the nation's
milk supply after several epidemics
overe traced to certified raw milk,
while the sanitary concepts of the
certified milk movement svere incor-
porated into milk hygiene codes as
important adjunctive safeguards.
The apparent public health impact
of safe milk ovas substantial; for
example, the number of infant deaths
due to diarrhea in Washington, DC,
dropped from 477 in 1894, the year
before sanitary requirements for milk
were strengthened, to 72 in 1909.
Although there io no objective evi-
dence that milk pasteurization has an
adverse effect on human nutrition or
health, the sale of rasv milk (certified
and uncertified) has persisted and
even increased in recent years under
intensive promotion by "health food"
enthusiasts using arguments similar
to those advanced in the 1890s.
In this review, we discuos the haz-
ards and purported benefits of raw
milk consumption to help the practic-
ing physician and other health pro-
fessionals more fully appreciate the
risk posed to human health by raw
milk and to enable them to under-
stand and rebut arguments advanced
in support of consumption of raw
milk.
Definitions
Milk, as discussed in this reviesv, is
cow milk unless otherwise specified.
Goat milk is increasingly promoted as
a health food, but constitutes less
than 1% of total milk consumption in
the United States.
Raw (unpasteurized) milk may be
certified or uncertified. Certified rasv
milk is produced in accordance with
methods and standards established
by the American Association of Medi-
cal Milk Commissions, Inc (an indus-
try-supported organization). This
milk is produced by a fesv large
dairies and is often sold, where state
laws allosv, in retail food stores.
Uncertified raw milk is typically pro-
duced in small volumes by individual
dairy farmers and sold on the prem-
ises of the producing farm or by home
delivery.
Pasteurized milk is milk heated for
specified time and temperature com-
binations designed to kill all micro-
* Meaningful differences in nutritional value between pasteurized and
unpasteurized milk have not been demonstrated, and other purported
benefits of raw milk consumption have not been substantiated. Conversely,
the role of unpasteurized dairy products in the transmission of Infectious
diseases has been established repeatedly. To effectively counsel patients
attracted by the health claims made for raw milk, practicing physicians must
understand both the rationale used by proponents of raw milk and the
magnitude of the risk involved in drinking raw milk.
(JAMA 1984;252,2050-2054)
F,sx 1hz Di,uisc of Bsctz,ie! Diszzszs, Cello
lcfeufious Diszmo~, Cmtn,sfo, Diszosn Coct,cf,
Rop0lt1oquzstltu Diui9c,, cfSsetn,iulDuzzlzl.
Czutz, to, Icf~otio~s Disnusm, 1600 Cuff 0, Rd NE.
Allude. 58 3033319' Poftz,l.
2048 JAMA, Oul 19, 1984-Vol 252, No. it
Unpasleurized Milk-Potter el al
PAGENO="0275"
organisms that transmit disease ts
humans through milk. Currently ac-
cepted time-temperature csmbina-
tisns include 63 °C fur 30 minutes,
71.6 `C for 15 s, and 89 °C or higher
for 1 s. Pasteurization does not steri-
lize milk, but doe~ make the milk safe
to drink. Pasteurization should be
distinguished from homogenization
(emulsification of milk fat) and for-
tification (addition of vitamins A
and/sr D). In the health food litera-
ture, commentaries about the pur-
ported nutritional hazards of pasteur-
ized milk tend to blend the three
processes into one. Like pasteurized
milk, raw milk may be sold homoge-
nized and svith vitamins A and D
added.
The regulatory standards for pas-
teurized milk vary by state, but these
standards all meet or exceed those in
the Grade A Pasteurized Milk Ordi-
nance recommended by the Food and
Drug Administration. Individual
state regulations on the sale of raw
milk also vary, with some prohibiting
such sales, others allowing sales only
on the premises of the producer, and
others setting up standards paral-
leling their pasteurized milk ordi-
nance. All milk ordinances set mini-
mum standards for dairy animal
health, personnel health, environ-
mental hygiene, and milk quality.
Quality contrsl programs supple-
menting the official regulatory pro-
grams are commonplace in the dairy
industry. The standards for hygiene
of certified rasv milk that are estab-
lished by the American Associatisn of
Medical Milk Commissions, Inc, rep-
resent only one of many such pro-
JAMA, Out 10, 1984-Vsf 252, No. 15
Comparison of Nutritional Values
in Raw and Pasteurized Milk
Pasteurization causes minor
changes in milk, and advocates of raw
milk have at one time or another
claimed that virtually every detect-
able change has profound health
implications. Pasteurization affects
six milk constituents with known
nutritional benefits: three vitamins
for which milk is a minor source
(thiamine, B,, and C), calcium, pro-
tein, and fat.' Thiamine is reduced
from approximately 0.45 to 0.42 mg/
L; vitamin B,, is reduced at a maxi-
mum from 3 to 2.7 pzg/L; and vitamin
C is reduced from 2.0 to 1.8 mg/L.
None of these losses exceeds 10%, and
none can be considered important.
About 6% of calcium is rendered
insoluble, and about 1% of milk pro-
tein is coagulated. The major effect
on fat is a slight disaggregation of fat
globulou, resulting in a reduced cream
line in whole milk. The observed
changes have no effect on the his-
availability of these three nutrients.'
Raw milk has also been said to con-
tain undefined and undetectable
health promoters, such as an anti-
stiffness factor invaluable for treat-
ment of arthritis, but such claims
have not been substantiated in the
medical literature.
Numerous studies of the relative
nutritional merits of rasv and pas-
teurized milk have been conducted in
animals and humans, and no differ-
ences were detectable. One animal
study deserves particular attention
because a misrepresentation of the
results has become prominent in the
raw milk folklore. In 1946, Pottenger'
published a report about his observa-
tions so cats fed varying combina-
tions of raw and heat-treated milk
and raw and cooked meat. In his first
and largest series of experiments,
Pottenger observed many diseases in
cats fed raw milk and cooked meat,
but essentially no disease in those fed
raw milk and raw meat. Raw milk
advocates have erroneously cited this
article as having reported that dis-
ease occurred in cats fed pasteul-ized
milk (eg, Llyod F. Smith, MD's article
Why Certified Rasv Milk, Let~s Live
Magazine). Smaller experiments re-
ported in the same article showed
that a diet of one-third raw meat and
two-thirds milk (pasteurized or not)
did not provide adequate nutrition for
cats.
The major health benefits claimed
for raw milk are summarized in Table
1. These claims, except for a few
recent variants, were rebutted more
than 40 years ago by Wilson in his
monograph The Pasteurization of
Milk. This book is required reading
for anyone interested in the topic.
Infectious Disease Hazards
of Raw Milk
Abundant evidence has shown that
raw milk serves as the source of
bacteria that cause outbreaks of dis-
ease in humans: in recent years, most
frequently salmonellosis and campy-
lobacteriosis. In the investigations of
such outbreaks, the epidemiologic evi-
dence, combined ovith knowledge
about the occurrence of specific path-
ogens in cattle and the isolation of
some of these pathogens from raw
milk, leaves no doubt that rasv milk is
a vehicle for disease in humans.
269
Table f.-Parported Health Benefits Derived From Drinking Raw Milk'
Promotes proper development of tooth This claim in primarily dnri,ed from a stady of boys ohs drank raz milk end bud a lao incidence of caries;
and nedaees,ns,do,oo of carrot no comparisons ooro made oilh persons ohs drunk pasroarlood milk; no neiontitis evidence has boon
Enhances ms/stance tsd;soaso No eoderco eo;srs nsappso of this claim ton tao milk; on the cart,ary, mi/kborno disease oas a problem
Enhances tert,l;ty Th,s concept is based on misrepresentation of animal foadirg sfader fhaf involsed denciort diets
Connors bonor;c;al oroymos, Some oroymes are `nacrisafod by pasloariaation, bar hose enaymos are probably inavli,alod by popsin
hnrmoros. and arl~brd~os and/or gasrr;v acidify; hormone csnlonf of coo milk isancenfain. and hormones aronof inacri,ared by
pasreavzar,sr fomperafaros; rho smull qaanriry of antibody in normal mi/k. ohio nsf inaclisalod by pus-
is not absorbod in ho haman inresrinal tract
Csnfalrscndetyned sabtransossa5, Those claims amoant to littlo more than anecdoles
Contort lactsbac,/l, Lacrobac,//, are contaminants rather than natural flora of n/k; panteariozd dairy prodayts sontaining added
lantsbayill arc asailablo
Unpastesrized Milk-Potter ml of 2049
PAGENO="0276"
Modern sanitary.and health stan-
dards observed by the dairy industry
have made contamination from envi-
ronmental sources, including humans,
an infrequent problem. In contrast,
programs relying solely on sanitary
and health standards have not suc-
ceeded in eliminating contamination
caused by symptomatic or asympto-
matic infection in the milk-producing
animal. Contamination from animals
with organisms such as Salmonella
and Campylobacler has thus become
the primary hazard for raw milk
consumers.
Salmonellosis
Many outbreaks of salmonellosis
due to consumption of raw or improp-
erly pasteurized milk, nonfat dry
milk, and cheese have been de-
scribed.'' Salmonellae have been iso-
lated from raw milk repeatedly
during investigations of such out-
breaks.' Milk is an ideal growth
medium for Salmonella, and some
strains of Salmonella can even sur-
vive in cultured milk products, such
as yogurt, for as long as two weeks.
Surveillance of human salmonello-
sb in the United States is based
primarily on reports of isolates iden-
tifIed at state public health laborato-
ries, and these isolates are believed to
represent only a small percentage of
the cases that occur. Most isolates
belong to a few common serotypes, so
epidemiologic investigations are usu-
ally not initiated unless there is an
unusual incidence of a relatively rare
serotype or a serotype that is a mark-
er for a particular problem. There-
fore, the relationship of sporadic
cases to a common source is usually
not detected when they are caused by
a common serotype. Isolates of Sal-
monella dublin, a relatively rare sero-
type known to he host adapted to
cattle, are more likely to be investi-
gated and identified as being derived
from raw milk than are the com-
monly isolated serotypes. Numerous
studies in multiple locations have
confirmed the role of rasv milk in the
transmission of S dublin to hu-
mans." Based on their 1982 data,
California health authorities calcu-
lated that the risk of S dublin infec-
tion was 84 times higher in persons
who consumed raw milk than in per-
sons who did not (S. B. Werner, MD,
oral communication, October 1983).
Salmonella dublin infections are of
particular concern because the associ-
ated illness tends to be severe. The
relative virulence of S dublin is illus-
trated by its ability to invade the
bloodstream' and the rates of hospi-
talization and mortality for infected
individuals."' Salmonella dublin is 13
times more likely to be isolated from
blood than are other Salmonella nero-
types, and more than half of the
patients with S dublin infection are
hospitalized. In two reports, 10% to
20% of tlse cases of S dublin infection
were fatal.' Risk of S dublin infec-
tion is significantly higher in persons
over the age of 40 years and in
persons with underlying chronic ill-
nesses or taking antacids.''
The problem of raw milk-associated
salmonellosis is not restricted to S
dublin. From a baseline of three Sal-
monella lyphimurium isolates in four
years, the number of isolates of S
lyphimurium from persons in a
three-county area of Oregon in-
creased to 27 in three months in early
1983.' Epidemiologic investigation in-
criminated raw milk and cream from
a single dairy, and S typhsmu'tum
with the same plasmid profile was
isolated from milk, milk filters at the
dairy, the dairy cows, and the ill
persons.
Recently, in Vermont, eight persons
(aged 10 months to 60 years) in four
families had diarrhea, abdominal
cramps, and fever." All had drunk
raw milk from a single dairy. Salmo-
nella derby was isolated from the
patients and the milk. In 1980, a
multiresistant S typhimursum was
isolated from patients and milk dur-
ing an outbreak of enteritis involving
105 persons who had drunk raw milk
from a single source in Montana."
Campylobacteriosis
Since culture of diarrheal stools for
Campylobacter jejuni became com-
mon, many milkbsrne outbreaks of
campylobacteriosis have been de-
tected. Fourteen (61%) of 23 Campy-
lobacter outbreaks reported to the
Centers for Disease Control (CDC)
from 1980 through 1982 were traced
to consumption of raw milk (Mark
Finch, MD, unpublished data, Decem-
ber 1983). In a detailed one-year study
of sporadic campylobacteriosis con-
ducted in Iowa in 1982 and 1983, 35%
of the ill persons had drunk raw milk
during the week before onset of ill-
ness; drinking raw milk was the only
significant difference between cases
and controls (P'z.OS; relative risk,
9.3)."
In the United States, outbreaks of
campylobacteriosis associated with
drinking unpasteurized milk have
recently been reported in Arizona,
California, Colorado, Georgia, Kan-
sas, Maine, Oregon, and Pennsylva-
nia." In the outbreak of campylo-
bacteriosis in Arizona," two cohort
studies showed that households with
members who drank raw milk re-
ported diarrheal disease significantly
more frequently than those in which
no one drank raw milk, with relative
risks of 4.7 and 3.4. In the Georgia
outbreak, illness due to campylobac-
teriosis in 30 households was strongly
associated with consumption of rasv
milk (odds ratio, 29.5), svhile contacts
with pets, livestock, or well ovater
were not associated with illness." As
in Arizona and Georgia, only con-
sumption of raw milk was signifi-
cantly associated with enteritis in the
other outbreaks.
Other Diseases
Other bacterial diseases associated
with drinking unpasteurized milk
from cows include brucellosis, coli-
bacillosis, listeriosis, tuberculosis,
corynebacteriosis, staphylococcosis,
streptococcosis, streptobacillosio, and
yersiniosis (Table 2). These diseases
are now infrequently reported as
milkborne diseases in the United
States, but they illustrate the wide
range of potential hazards.
Milk other than cow's milk has also
been associated with disease in hu-
mans. Toxoplasmosis has been associ-
ated with raw goat milk,"' and bru-
cellosis and campylobacteriosis have
followed consumption of raw goat's
milk cheese.'" The virus of tickborne
encephalitis is shed in milk, and fresh
cheese made from unpasteurized
sheep milk has been associated with
thin disease." Toxin-producing staph-
ylococci have been isolated from
cheese made from raw sheep's milk."
Comment
The relative merits of raw and
pasteurized milk have been debated
for at least 90 years. In this period,
the theoretic health benefits of raw
milk have never withstood careful
Unpasteurized Milk-Potter ci at
270
2050 JAMA. Oct 19, 1984--Vol 282, No. 15
PAGENO="0277"
scientific scrutiny. Epidemic rickets
and scurvy and the other dire con-
sequences of milk pasteurization
prophesized by early raw milk advo-
cates have not occurred. Conversely,
the fact that raw milk presents a
substantially greater inherent risk of
infectious disease has been demon-
strated repeatedly. Surprisingly, the
controversy continues.
Regulation of the sale of raw milk
often involves discussion of freedom
of choice. A major feature of the
individual's right to free choice, how-
ever, is informed consent, and incor-
rect information en the purpsrted
benefits of drinking raw milk is so
widespread that truly informed con-
sent is difficult to achieve. Also, in
matters of foodstuffs, parents make
choices for their children. Therefore,
the children of advocates of raw milk
are exposed to the risks of infectious
diseases without a full understanding
of the danger.'" Children also tend to
drink what is given to them in school
without questioning its safety. There
have been numerous outbreaks of
enteric diseases in schoolchildren giv-
en raw milk while on field trips to
dairies in the United States," and a
large outbreak of campylobacteriosis
traced to the consumption of free raw
milk at school svas reported in
England."
JAMA, Oct 19, 1984-Vet 252, No. 15
Observations in England and
Wales, where an estimated 3.5% of
the milk is consumed without pas-
teurization, support the contention
that raw milk is an unsafe food
product. In the period 1951 through
1980, these two countries reported 233
outbreaks of communicable disease
attributed to milk or dairy products,
with approximately 9,400 cases and
four deaths." Seventy-five percent of
the outbreaks and about 40% of the
cases were associated with raw milk;
most of the remaining cases involved
faulty pasteurioation or obvious post-
pasteurization contamination. Con-
tamination by Salmonella caused 74%
of the outbreaks in this period. A
detailed cost-benefit analysis per-
formed to determine the value of a
ban on the commercial sole of raw
milk in Scotland clearly demon-
strated a favorable ratio on the basis
of the costs of milkborne salmonello-
sin alone." The role of raw milk as a
vehicle of C jejuni infection, however,
was not demonstrated until 1978,
when many laboratories began to look
for the organisms in diarrheal stools.
Since then, many raw milk-associ-
ated Campylobacten- outbreaks involv-
ing thousands of cases have been
reported by English investigators."
When one considers the known
health risks, it is apparent that raw
milk is not being singled out for
unwarranted attention by public
health authorities. Other ready-to-
consume foods of domestic animal
origin are subjected to processing
procedures rendering them safe for
consumption and are microbiological.
ly monitored for adequacy of process-
ing. Raw foods of animal origin, ouch
as chicken, may be contaminated with
Salmonella and Campylobacteo', but
routine bacteriologic monitoring of
these foods is not done because these
raw foods are normally cooked before
consumption. Furthermore, extensive
efforts are mode to inform the public
of the hazards and the proper cooking
procedures for these products, and
practical measures to eliminate the
contamination are not available.
In food hygiene, as in the operating
room, clean is not synonymous with
safe. The raw milk industry points
to standards suds as total bacterial
counts as proof of safety, but the high
incidence of disease associated with
raw milk is strong evidence that these
standards are unreliable indexes of
safety. Milk is an excellent vehicle of
infection because its fat content pro-
tects pathogens from gastric acid,
and, being fluid, it has a relatively
short gastric transit time. Thus, loss--
level contamination, which would be
readily controlled by pasteurization,
271
Table 2.-Mo/kborne Bacterial Diseases of Less Frequest Occurrence in the United States
Agent Ces,mests
Bsiee/ia sp Wo,/donde, es/k and other deity p,sduxts sortooniruted cith Brace//asp ore the p/n/ny uehis/,s of
breoel/osis to hotness; in the Onited States, epprooi~nutc/y 10% of the reported eases are anniboted tosonserrption
otanpasteunzeddairyproduots; prodaststoronettnirdotthesesase,are dxnnstisa/lyprodusnd"
Eeeheoehoz coO Outbreaks of diarrhea hues been reported in persons cho 000sun,ed unpasteu,ized croon" asd eticehooso"; plan.
rsd'r,edigted untin/icrobia/-r,sigtant Eeo/ihaee also bees isolated true ni/h'0
Los/zoo tn0000ytogzreo Looter/a ,n000rytogznec has been isolated turn unpasteurized soc and shoop ni/k"; shedding of Linteria in ni/k
persots for lonu periods or torrn attor the r,ilk posses the aisuu/ noarninction to/toeing lisneriosis"; saidoosc ct ni/k-
borne 5ster/onis is hunnans has been cstobtshed°'
Myrobaytznoo,n tobnee/os,o, Ouft,s,ent tobenale bcsi/5 are excreted by a s/nub soc cith tubersu/sos nnastitio to rake then//hot too clean
Myeoboenenann beau ontzot;oas ton intarts"; in 1900. tuberculosis eas diagnosod in 3 dairy herds in Anizonu; 302 013,760 cattle
tested or tuberculosis zone position"
Cooyoebuetenen pnexde- A sase ot noudatoac tonso//itis and cerxiool lynphgdenitis hot tesa/ted in prolonged hospitaszutisn ous desedbed in a
tabz,-ya/oocou 35'yearo/d non ct/os, clesest resent donestis urinal eoposore cas drinking toe soc's end goon's nt/k"
Staphyloyoeoonaooreuu Stuphylosocci in ni/k, zither non nasnitis ni/her honor ocrtaninution, 000sc oustroentedtis in consuners chen they
ingest the houtstable enterotooin prodused by the staphylocooci"
Sn'epnootoeeausp Stnepronsesisooseaaoniety of diseases in hananu and bc,, Oninu/s and one innponann suprophylos in nilk and ni/k
produsts; lobe hr staphy/ocosci, boy nay be pncsent in ni/k in large nunbnrs eher thry cause nun/i/is in the ni/k'
prod using anina/; Sto'cptcyoeeaocoocpideniyeo is usonnen cause ot nosti/is incur/c. end n/kbonne oanbreaks
on bongos to//seed by anato poststneptososy~/ g/onnra/onephritis huan boon reported"; a
bnnok has boon essosiuted cith sonsionpnion otchonsu nude tnon rue ni/k"
Strzptobaeo//au ncno5/onnoo In the t920s, them core sons sery Igru, outbreaks ot strep/obaci//osis traced to oonsunpnon et roe ni/k"; chen S
nooo/ilornoo os isolated non ni/k, the pnesonption of conteninution by tar, is nude; it/s on/ike/y that this disease
could present a nilkbsrnu problem in a doiry prustising canently u500pred standards etduiny hyginne
Yzrn,nooznnayoyoayya Vzrnonoa zotzroao/ohya is t~zqoent/y t500d in urinal eneironnorts, noy be present in onpusteunioed ni/k at high con
cennratoons, and uroes at reftogenuror tenpenatotes"; in a study in Ontario, Oshienunn" sand Yzruioio in 0% of
the nau no/k sunpbes, 0%ot the shoosu curd sanp/os, nOmO 0/the sheddor cheese sunpbes, and 1 at 265 paslea,.
oed n/k sunpins; Yeo'c,oio zonyo-oeo/i/iaa egs iss/uted coo toe ni/k inasospesled tosdbsroo oonbruuk or ycrsinio.
Unposteuriznd Milk-Po9er ef 0/ 2051
PAGENO="0278"
presents an important hazard to the
raw-milk consumer. This hazard is
magnified when the consumer has
less resistance to infection because of
age or underlying disease.
The promotion of raw milk as pro-
viding major health benefits beyond
those of pasteurized milk has not
been supported by the evidence. In
contrast, the hazards of raw milk
have been proved. Sale of raw milk,
however, is still permitted. Physi-
clans and other health professionals
must be aware of the facts concerning
risks and benefits from raw milk to
better advise patients who have ques-
tions about the safety and benefits of
raw milk consumption.
1. Mograde,- GL: Faethze obseeo'atiooccn the
milk mpply of Washington, DC. JA.'cIA 1910;
55:501-509.
2. Kelley ER, Osboen OH: Faether zoidenceos
to the eclotice impoelasce of milk infection in
the tranomissios of cortais commocicooble dis-
easescf not. Am JPsblic Hmolth 1920;1O:O6-73.
3. Kon OK: Noteitianal effects on milk of
chemical additions atd peocesning, in Fcflh
Iolcc-notionool Coegn-coo on A'atvilimc. Wonhiocg.
Ion, D.C Washington, DC, Food and Agcicaltore
Orgotizalio,c, 1960, PP1.0
4. Koo SE: Milk ond Milk Pc'odscl, in Hsmonc
N,alc'itimo, FAD Noteitionol Stodie, 27. Rome,
Food otd Agc-icaltac'e Oegasicatiso, United
Nations, 1972.
5. Graham 051: Alteeotios of cotnitine colon
rzsolting from peoceosing and fortitcalios off
milk ttd milk pc-odacts. J Doic'y Sci 1974;
57:739-745.
6. Poltesgee PSI Je: Effect of heat-peoceosed
foods and metakoliced nitamin D milk on de,ctn-
facial steoctaees of enpceimeotol animal,. Am J
Oc'lhod l946;30467-405.
7. Wilson GO: The Paclcsc-iaolionc of Milk.
London, Batlee & Tassee LId, 1942.
0. Tayloe DN, Bizd JM, Macno JO, zt al:
Salmonella dcaklis itfectiost in the United
Slates, 1979-1980. J Infccl Dio 1902;140:322-327.
9. Small RD. Sharp JCM: A milk-hoenc not-
heeak doe to Salmonella doblino. J Hog Cam-
hnidgc 1979;82:95.lOO.
IS. Schrcedce SA: \Vhat the canitaniaco ,koold
ksna: aboat salmonella, end staphylococci it
milk and milk peodacls. J Milk Fond Tech
1907;3l:370-300.
11. Keogh BP: The seminal nf pathogens in
cheese and milk ponnd,c'. J Dairy Rca 1971;
30:91-111.
12. Collins RN, Teegee MD, Galdsby JB, ct al:
Interstate nolbezok nf Salmonella ncnaln'nnma'ick
infection traced to ponndcred milk. JAMA 1968;
203:839-844.
13. Fn,ctaine RE, Cohen ML, Mactic \VT, ct oh
Epidemic salnonneIlasis from cheddar cheese:
Sac'neillance and peenention. Am J Epidcmiol
1980;lll:247-253.
14. Marth EH: Salmonellac and salmoncllonis
asnociatedocithmilkandmilkpeodacts.JDoic'y
Sci 1969;52:283-315.
15. Gibson EA: An natkeeak nf So.lmnnclla
dnklin infeetinn in goat,. Vet Roe 1957;69:102l-
1028.
16. Balgis MO, Andee,oc, BC: Salmnnellonio in
goatn. JAm Vol McdAccoc 1981;178:720-723.
17. werner on, Homphrey GL, Kamci 1: A,en-
ciatios betoneen eon milk and haman Salmonella
dshlinc infection. Be' MedJ 1979;2:238-241.
10. Blaner MA, Feldman BA: Salmonella bade-
remia: Repents to the C,ntees fne Disease Con-
trnl, 1968-1979. J Infect Din 1901;l43:743-746.
19. Salmonella dnblin associated oith moon
milk: Wa,hingtcn Stat,. MMWR 1901;30:373-
374.
20. Fierce J: Innasine Salmonella dcahlio infec-
tiaccostoeioted nilh deinking ran milk. Weal J
Med 1983;138:665-609.
21. Oregon Diaioion of Health: Rose milk
associated ,almonella catbeeak in noetheonteen
Oeegnn. Cmnmnnicable Dis Sammac-y 1903;
301-2.
22. Vcgt RL, Hokey A, Allen J: Solmasello
cnlccitidio sceotype decOy and consamptins nO
References
roan milk. J Infect Dia 1981;l44:608.
23. Salmanellnois associated nnith ran milk:
Montana. MAfWR l981;30:2ll-2l2.
24. Sebmid GP, Schaefsr R, Ochaefee J, at al:
Haman canopylabacteriasis in a mediam-ai,ed
lona city, abstracted, in S3cd Intccscicnec Con-
fcccnec moAntimicc'obialAgcntc and Chcmoihcc-
a~. Woshicgtnn, DC, American Society fne
Miceohiology, 1903, p 160.
25. Taylor DN, Porter BW, Williams CA, sI al:
Campylobaclcc esteritis: A large oothecak
traced In commercial cane milk. Wool J Med
1182;137:36l-369.
26. Taylor RP, Weinstein WM, Bryser JH:
Campyloboetce felon isfzction is hamas oak'
jectn Association milk eon' milk. Am J Med
1979;66:779-783.
27. Blasee MJ, Crao-ecn J, Poe-set BW, cI al:
Campyiaboclcc enteritis aasnciated milk ocpas-
tcaeined milk. Am JMcd 1979;67:715-7l8.
20. Pntler ME, Blasce MA, likes RK, cl ci:
Homan Compylaboctce- infection asoocioted milk
ccelified man milk. Am JEpida'miall9O3;117:475-
403.
29. Onthecak nf Compylahoclce enteeltis
ciated milk ran' milk: Kastan. MMWR 1981;
35:218-225.
30. Maine Dept nf Haman Sernicet: Boos' milk
and hamas gaotrointeotinal disease: Petblemo
implicated onith lbs lcgalincd cole nf eeetified
ram milk. Epi-Gcam, December 1981, pp 1-2.
31. Baa-milk atsociated illneno: Oeegos.
MMWR 1901;30:90-97.
32. Campylobacteriotio associated onith ran'
milk conoamptias: Pennsylnasia. MMWR 1903;
35337-344.
33. Riemann HP, Mcycc ME, Theio JH, et al:
Tonnplssmnois in an infant fed aspotteac-ised
gtat milk. JPcdiolc 1975;87:573-576.
34. Sacks JJ, Rnbeeln RB, Bennks NP: Toon-
planmtoio infectio,c annaciated a-ilk ran' goat's
milk. JAMA 1902;248:1728-1732.
35. Pane OlD, Kaofma,cn AP: Bmocellaoio in 1hz
United Staten, 1965-1974. J Infect Din 1977;
136:312-316.
36. Ynong EJ, Oanacnnpacest U: Beacellaoio
aatbreak attriboted Is ingestiaso of onpootear-
med goat cheese. Aech 184cc-n Med 1975;135:240-
243.
37. Echman MR: Broecllosio linked In Mesican
cheene. JAMA 1975;232:636-637.
30. Gilbert DL, Dannrcn RA, Cale ME, et ol:
Midleimeoter aboelios assnciated milk septice.
mia canoed by Compylabactccjcjsni. McdJAsnt
1981;t:585-586.
39. Geesikona M, Sckeyona M, Stopalona 5, et
al: Sheep milk-koenc epidemic of tick-bores
znecphalilio in Slanakia. Intcs'nicalogy 1975;5:57-
61.
40.HajekV:IdentiScationtfsnteeatotigettic
otaphylacncci fcnm oheep and theep ehecoz. Appl
Entcicccn Mieecbial 1978;35:264-26S.
41. Ontarit Mini,tey of Heallb: Snspccted eon
milk-aotaciated eampylnbacterioois: Beitish Co-
lombia. Coo Din Wcckly Rep 5903;9-1h73-75.
42. While FMM, SleCarthy ME: Race milk asd
health in hama,on. Con Mcd Aaam 1 1982;
120:1260-1262.
43. Jnnes PH, Willis AT, Robinntn DA, c-I al:
Campylnbactee enteeitis ansacialed cnilh thecon-
samplino nf fete schtol milk. 1 Hyg Combn-idgc
1981;87:I55-162.
44. Galbraith NO, Focbco P. Cliffnrd C: Cam-
monicable dioeasc aottciatcd n'ith milk and
dairy prndacln ist England and Wales 1951.80. Bc
Med 1 1982;248:1761.1765.
45, Cnhcn DR. Fcc-tee IA, Reid TMO, c-I al: A
cost benefit tlady nf milk-b orne salmonelltsil. 1
Hyg Camhcidge 1983;9l:t7-23.
46. Janet DM, Rnbinlnn DA, Eldridgn J: Ocea-
Ingical stadien in too aatbreako of Campylakae-
lee jejsni infection. 1 Hog Csmbcidge 1981;
07:163-170.
47. Rabinoos DA, Jones DM: Milk-banne Com-
pyloboetce infectios. Bc Med 1 1981;28S:1374-
1376.
48. Hobbs BC, Roan B, Kendall M, c-I al:
Eachecichia coli 027 in adolt diaeehea. 1 Mpg
Combcidgc 1976;77:393-400.
49. Marier R, Wells AG, On-anson BC, c-I at: An
natbreah nf enteenpalbogenic Eaehcciehia cali
foodbaenn disease teaced to inpoeted Fmesch
cheete. Lanect 1973;21376-S378.
50. Johnnttn DW, Ssoee A, Hill A: Incidence nf
antibintic-ceointanl Eochceichia cali in milk pcI-
daced in the osest of Scatland.JApplBoclcn-ial
19S3;54:77-83.
51. Dijkotra RG: Isnestigatians as the name-in-
times nO Listecio baclceia in soopcntion nf
beam tissac, silage and feces and in milk.
Zestcolbl Bahtcciol 197S;21O:02-95.
52. Hall RP: Infectioos aboetiono in
Campend Ccntio Ed 1902;4:216-221.
53. Gray ML, Killinger AH: Listecio ctanmy-
ago-coca and litlec-ic isfentinns. Rcelcnal Ret,
1966;3h309-382.
54. Kalio F, LcPmoeh JL, Smith W, et al:
Liotcmoois. Am J Med Sci 1976;271:159-169.
51. Klncbaeg HH: Tobarcolonis and nther
snycnbacoeeinoio, in Habbeet WT, MeCollack VIP,
Ochnorresberger PR lcds): Diacasco Tconnmitted
Fcam Animoln to Man, ed 6. SpeingOnld, Ill,
Chaeleo C Thamaa Pablinher, 1975, p 315.
56. Malhin BM, Langley J: Banine toheecolonin
in an Ariznna daiey bend. JAm Vet Med Ascae
t981;175:141-142.
57. Goldbeeger AC, Liptky BA, Plnrdc JJ:
Sappaeatine grostolomatoat lymphodenitis
caaned by Cacysebactecitam ania(pseadalabec-eo.
loom). Am 1 Clin Pathal 198t;76:486-490.
58. Pac-ry WH: Milk-boene diseasen. Laneet
1960;0216-219.
59. Baenham M, Thtmnton TJ, Lnnge K:
Nephritit eaoncd by Slceptmneeon eonepidecni-
(Loncefield genap C). Lnncct 1903;1:945-948.
60. Gmoop C olreplncoccal infectians assnci-
sled ocith eating homemade cheese: Neon' Menien.
MMWR 1983;3051O-51f.
61. Place EH, Sottts LE: Erythema aelbeit-
icaco epidemicam (Heneehill fener). Acch Intone
Mcd 5934;54:659.604.
62. Vanteappen G, Agg HO, Geboes K, et al:
Yeccinia estnritis. Med Clis Nocth Am 1902;
66:639-653.
63. Blank RE: Yeeoiniosis, in LasI JM (ed):
Mancy-Roocnos Public Health and Pcecenolinc
Medicine, ad 11. Neon Ynek, Appletto-Ccnlas-y-
Ceofto, 1980, chap 9, pp456-457.
64. Schinmann DA: Association nf Yecoistia
entcn-ocolitieo ns'ith Ike manofactsee tf cheese
and nceaec-aneeinpanleocincdmilk.ApplEnci-
con Miccoleicl 197S;3k274-277.
65. Health and Welfaec Canada: Yeccinia
enlecocolitica gassecentemitis natbmeah: Mtn-
Ic-cal. Con Din Weekly Rep 1970,073-74.
2052 JAMA, Ont 19, 1984-Vol 252, No. 15
Unpastnamiznd Milk-Patter cot at
272
Peiteled and Published in he United States a! dmee:ca
PAGENO="0279"
273
STATEMENT OF EVELYN B. BINZ
The following is an answer to the article in the summer 1984 Public Citi-
zen criticizing the U.S. Dept of Health and Human Services for stalling on
a proposal to ban the Bale of raw milk.
j There has been a decline in the consumption of milk in recent decades,
but raw milk use increased for a time. Government health officials favor the
large dairies which sell only pasteurized and homogenized milk, bought from
many different farms. They are overly strict in inspecting raw milk, a con-
venient object of official zeal,-getting rid of all that disease caused by
raw milk, they tell us. But there are few if any really verified serious or
fatal cases of illness from raw milk sanitarily- produced. -
2 Raw milk is more digestible than pasteurized bebause the nutrients are
unchanged by heat. Vitamin C is retained and milk sugar is not carmelized,etc.
Homogenization changes the milk physically and chemically. The fat globulem
are fractionalized to distribute the cream evenly through the milk and an en-
zyme is produced, xanthine oxidase. Some scientists think that these changes
may irritate the lining of the blood vessels and cause the deposit of a pro-
tective layer of cholesterol plaque.
3 Many users of raw milk choose it for health reasons.
4 Some doctors are ignorant of the value of raw milk nutrionally, and some
may find it convenient to blame its use for-their treatment failures,
~ Pasteurization does lessen the danger of disease from unclean practices
when milk is collected from many sources, but Alta Dena uses the milk only
from their own healthy, tested cows. Milk from the family cow, the world over,
is not boiled or even parboiled. It is known to be unharmful even though raw.
Animals given a choice between raw and pasteurized milk select the raw. Boiled
milk because it is considered constipating Is sometimes used as a cure for
diarrhea.
~ The organism Salmonella dublin occui~s commonly in air and can easily be
passed to unprotected milk by a cough or'~ven rubbing the hands over the speci-
men being analyzed and allowing time for i~ncubation.
A health food such as raw, natural milk, produced under the standards of
Alta Dena Dairies should not be banned except on incontrovertible evidence
of serious illness caused by it and this has not occurred. Raw milk sours
naturally and is a healthful food; it does not putrefy as heated milk does.
Only in raw milk does milk's lactic acid have bacteriostatic powers; it kills
bacteria if 2~~ive~ ~ . -
PAGENO="0280"
PAGENO="0281"
EMERGENCY REYE'S SYNDROME
PREVENTION ACT OF 1985
FRIDAY, MARCH 15, 1985
HOUSE OF REPRESENTATIVES,
COMMITTEE ON ENERGY AND COMMERCE,
SUBCOMMITTEE ON HEALTH AND THE ENVIRONMENT,
Washington, DC.
The subcommittee met, pursuant to notice, at 10 a.m., in room
2322, Rayburn House Office Building, Hon. Henry A. Waxman
(chairman) presiding.
Mr. WAXMAN. Today we are considering the "Emergency Reye's
Syndrome Prevention Act of 1985." We are also examining the ade-
quacy of steps taken by the Department of Health and Human
Services and the aspirin industry in the past few months to alert
the public to the possible dangers associated with the use of aspirin
during certain childhood diseases.
This hearing deals with a very serious disease-a deadly illness
that strikes down hundreds of perfectly healthy children each year.
This tragedy is made all the worse by the fact that this disease
might be preventable. The public needs to know whether every pos-
sible precaution is being taken to spare families the agony of need-
lessly losing a child.
Reye's Syndrome mainly strikes children up to 19 years of age. It
is often fatal and may produce brain damage when the victim lives.
It typically follows chickenpox or influenza, both of which increase
during the winter months. Just when children seem to be recover-
ing from those illnesses, they may suddenly get desperately ill and
lapse into a coma with Reye s Syndrome.
For several years, a growing body of scientific evidence has sug-
gested that the use of aspirin is associated with Reye's Syndrome.
Nearly 3 years ago the evidence was strong enough to lead a tech-
nical committee of the American Academy of Pediatrics to con-
clude that there is a high probability that the administration of as-
pirin contributes to the causation of Reye's Syndrome.
That committee recommended that aspirin not be prescribed for
children with influenza or chickenpox and called on the govern-
ment and aspirin manufacturers to inform the public of the rela-
tionship with Reye's Syndrome.
Earlier this year, the Institute of Medicine reviewed new data
from a Public Health Service pilot study and once again found a
strong association between Reye's Syndrome and the use of aspirin.
They recommended that steps be taken to protect the public health
even before the full study is completed.
(275)
PAGENO="0282"
276
Shortly thereafter, Secretary Heckler announced that the De-
partment would pursue a voluntary approach. She asked the aspi-
rin industry to put warning labels on aspirin products. She raised
high hopes that industry compliance would be rapid and effective.
When the Secretary announced the voluntary program, we ex-
pressed the concern that unnecessary delays or noncompliance
could be fatal to many children and young adults. On January 11,
we requested that the Secretary report back to the subcommittee
by today on specific aspects of the voluntary program.
From information that has been made available to the subcom-
mittee thus far it appears that this voluntary effort is failing on
four counts:
1. The labels that have been negotiated are inadequate and
vague. They do not mention Reye's Syndrome and only suggest
that parents consult a physician before using aspirin for children
with chickenpox or flu;
2. Little consideration was given to assuring that the label was
displayed in a prominent format clearly visible to consumers;
3. With the possible exception of one manufacturer, the labels
will not appear on aspirin bottles until after the current flu season;
and
4. Not all of the industry is even represented in the negotiations
on voluntary labeling.
The scientific evidence for the link between aspirin and Reye's
Syndrome is strong and consistent. But we are all aware that all
studies have their limitations. The recently released pilot study is
just that, a pilot study for a larger study that should proceed. The
scientific evidence, however, is not at issue here. The Secretary of
Health and Human Services has determined that the scientific evi-
dence calls for protective action now. She has announced that pre-
ventive action should not be delayed until the larger study is com-
pleted.
More and more studies may lead to better decisions. But some
scientific questions may never be resolved to everyone's satisfac-
tion. We know there are still people who are willing to dispute the
link between cigarettes and lung cancer. When a threat to the pub-
lic's health might exist, public officials must decide when to act.
The Secretary has made that decision.
What is of concern to this subcommittee is whether the Depart-
ment and the aspirin industry have done enough to protect the
public from this fearsome disease. If the problem is Reye's Syn-
drome, why not say so on the label? If the problem is aspirin, why
not require the warning on all aspirin products? If the problem is
influenza, why ignore the current flu season?
The Emergency Reye's Syndrome Prevention Act would take
steps that might well have been ordered by the Department of
Health and Human Services in January, or perhaps even years
ago. A clear warning would be required on all aspirin products,
along with an eye-catching logo that will attract people to actually
read the label. All advertisements would have to contain the same
warning.
Fortunately, this terrible s~yndrome is rare. But that is no conso-
lation to parents who didn t know that giving aspirin to their
young child could be deadly. Nor is it any consolation to families
PAGENO="0283"
277
with a teenager who dIed or suffered brain damage because there
was no obvious warning on the aspirin bottle.
The National Reye's Syndrome Foundation tells us that six chil-
dren died of Reye's Syndrome in the first 2 months of this year.
Even one unnecessary death is too many. Children cannot protect
themselves. Parents cannot protect their children from dangers
they know nothing about. If the Department of Health and Human
Services can identify risks but then is unwilling or unable to take
strong enough measures, the Congress must act.
We look forward to discussing these questions with our witnesses
today.
[The text of H.R. 1381 follows:]
PAGENO="0284"
278
99TH CONGRESS
1ST SESSION * *
To amend the Federal Food, Drug, and Cosmetic Act to provide for warnings
concerning the use by children of drugs containing aspirin, and for other purposes.
IN TIlE HOUSE OF REPRESENTATIVES
FEBRUARY 28, 1985
Mr. WAXMAN introduced the following bill; which was referred to the Committee
on Energy and Commerce
ABILL
To amend the Federal Food, Drug, and Cosmetic Act to pro-
vide for warnings concerning the use by children of drugs
containing aspirin, and for other purposes.
1 Be it enacted b?J the Senate and House of Representa-
2 tives of the United States of America in Congress assembled,
3 SECTION 1. SHORT TITLES
4 This Act may be cited as the "Emergency Reye's Syn-
5 drome Prevention Act of 1985".
6 SEC. 2. ASPIRIN WARNING.
7 Section 502 of the Federal Food, Drug, and Cosmetic
8 Act is amended by adding at the end thereof the following:
9 "(u) During the period beginning upon the expiration of
10 30 days after the date of the enactment of this paragraph and
PAGENO="0285"
279
2
1 ending on the date the requirements of paragraph (v) take
2 effect, if it is a drug which contains a salicylate unless the
3 container in which it is sold at retail bears the statement
4 prescribed by paragraph (v)(1)(A) and unless each retail es-
5 tablishment at which it is offered for sale displays prominent-
6 ly, where the drug is held for sale, a notice containing such
7 statement.
8. "(v)(1) If it is a drug which contains a salicylate unless
9 in accordance with paragraph (2)-
10 "(A) its labeling contains the following statement:
11 `WARNING: This product should not be given to indi-
12 viduals under the age of 21 years who have chicken
13 pox, influenza, or flu symptoms. This product contains
14 aspirin or another salicylate which has been strongly
15 associated with the development of Reye's Syndrome,
16 a serious and often fatal childhood disease.'; and
17 "(B) the manufacturer, packer, or distributor (in-
18 cluding all retail establishments) thereof includes in all
19 advertisements and other printed and descriptive
20 matter issued or caused to be issued by the manufac-
21 turer, packer, or distributor with respect to any drug
22 which contains a salicylate the statement required by
23 clause (A).
PAGENO="0286"
280
3
1 "(2)(A) The statement required by subparagraph (1)(A)
2 shall be in the following form:
WARNING: This product should not be given to
individuals under the age of 21 years who have
chicken pox, influenza, or flu symptoms. This
product contains aspirin or another salicylate
which has been strongly associated with the
development of Reye's Syndrome, a serious and
often fatal childhood disease.
3 "(B) In the label required by clause (A), the arrow shall
4 be printed in yellow and the circle shall be printed in red.
5 "(3) The Secretary shall promulgate such regulations as
6 may be necessary to implement the requirements of subpara-
7 graphs (1) and (2).".
8 SEC. 3. REGULATION DATE.
9 The Secretary of Health and Human Services shall pro-
10 mulgate the regulations required by section 502(v)(3) of the
11 Federal Food, Drug, and Cosmetic Act not later than 180
12 days after the date of the enactment of this Act.
PAGENO="0287"
281
Mr. WAXMAN. Before I call on our very distinguished first wit-
ness, a Member of the U.S. Senate, I want to recognize Congress-
man Wyden for any opening comments he wishes to make.
Mr. WYDEN. Thank you very much, Mr. Chairman.
I want to commend you for your outstanding work in this area,
particularly in protecting the young people of this country. It
seems to me what we face here is a very clear case of foot-dragging
on the part of Public Health Service and the Food and Drug Ad-
ministration. It seems to me that they have essentially written off
the current flu season that is just ending.
The reason these hearings are so important is that we need to
make sure that steps are taken so we don't miss the boat on yet
another flu season. There is no question about the scientific evi-
dence in this area. The evidence is crystal clear that there is a link
between Reye's Syndrome and aspirin and that the public needs to
be protected. During the course of this hearing we need to identify
the bottlenecks within the Department, within the Public Health
Service, and the Food and Drug Administration that are prevent-
ing critical information about the health risks from aspirin from
actually reaching the public. So I am very appreciative of Chair-
man Waxman's leadership in this area, and look forward to our im-
portant hearings.
Thank you, Mr. Chairman.
Mr. WAXMAN. Thank you, Mr. Wyden.
We are pleased to recognize a new member of our subcommittee.
We are delighted that he is a member of the subcommittee and
with us today, Congressman Bates. If you have an opening state-
ment, you may present it now. If not, we are just pleased to have
you with us.
Mr. BATES. No, Mr. Chairman. I am just here to gain some in-
sight into this problem. Thank you.
Mr. WAXMAN. Not a new member but a distinguished and long-
term member of the subcommittee, the gentleman from New York,
Mr. Scheuer. I recognize him at this time.
Mr. SCHEURER. No statement, Mr. Chairman.
Mr. WAXMAN. Thank you very much.
Senator Metzenbaum is the author of the Emergency Reye's Syn-
drome Act of 1985 in the Senate. Senator, we are delighted you
have come to our subcommittee to present testimony in support of
this legislation. This is another example of your leadership in the
area of consumer protection and recognition of the need for govern-
ment to intervene to protect the public health. We are pleased to
welcome you at this time.
STATEMENT OF HON. HOWARD H. METZENBAUM, A U.S. SENATOR
FROM THE STATE OF OHIO
Senator METZENBAUM. I am very delighted to appear before your
committee and I am frank to admit to you that each morning
before I drink my orange juice I say: Isn't the country fortunate
that Henry Waxman is the chairman of the Subcommittee on
Health and Environment.
I do that each morning.
Mr. WAXMAN. What is in that orange juice?
PAGENO="0288"
282
Mr. WYDEN. And your other meals as well, right?
Senator METZENBAUM. That is right.
And of course it's a fact, and of course I say it first facetiously
but it is a fact that I think the country is fortunate.
Mr. WAXMAN. It isn't true?
Senator METZENBAUM. The country is fortunate that you have
stepped forward on so many health issues and been willing to pro-
vide the leadership that is needed in order to legislatively act when
so many others would be willing to drag their feet, and to think
about it, appoint commissions or committees to make further stud-
ies.
Here we have a situation where we know the problem. Reye's
Syndrome is linked with aspirin as far as children are concerned, if
they take it when they have chickenpox or influenza. It is indispu-
table. The facts are there.
Now, in connection with some health matters, we don't know the
answer, and if we knew the answer, it would be such a bonanza as
far as the health aspects of this country are concerned, of cancer,
heart ailments that occur. We don't always have the answer. It is a
high percentage.
What we would give to find an answer for that at the present
time. But in connection with Reye's Syndrome, we know that the
ingestion of aspirin by children when they have chickenpox or in-
fluenza does have the potential to harm the children. That is
irrefutable, and we can prevent it, so why not.
We are not saying ban the sale of aspirin. We are saying make
the parent aware of the risk. Tell the parent with a label that
highlights it in color, and says what the problem is.
Now, the Secretary and the industry have worked out a volun-
tary kind of agreement, but that is not good enough. The child is
ill. The child is crying. The bottle of aspirin is there, and the
parent sees on the bottle "Consult your physician first." The
parent says: "I can't reach the doctor. It is two o'clock in the morn-
ing. He doesn't want me to call. And besides, this afternoon I un-
derstand he plays golf, and that is his privilege."
But the fact is the baby is hurting. So the parent says: "Well, it
won't hurt that much. I'll just give him or her two aspirins."
That is not an adequate answer. That is begging the question, be-
cause if the doctor says what the doctor should say, the doctor is
going to say "don't give the child the aspirin." So why not put it on
the label? We have got to make the warning strong. We have got to
make it specific, and if I am not mistaken, Mr. Chairman, this may
be the first instance in which legislators, you, I and the others who
have joined with us, have ever proposed in legislation that you
even have to have the color on the label indicating so that it is not
just lost in the black and white, but it has the yellow and the red
to highlight it, so that the parent won't miss it.
We have seen that voluntary cooperation doesn't work. They
tried it with infant formula, legislation that I was involved in and
you supported, and it didn't work there. We have seen it with re-
spect to food labeling, and it hasn't worked. You buy almost any
product today and you can't find out what you are getting in that
product.
PAGENO="0289"
283
Knowing what we know, how can we be satisfied until we are
sure that we are doing everything possible to protect the children?
Now, the FDA will say, as I understand it, the evidence is not
complete. They want to see what the results are with respect to
voluntary participation. I would say as the grandparent of two
little children that I love very dearly, or as the parent of any other
child, why expose that child to any risk at all, if there is no need to
do so?
Children of America are exposed to enough risks at the present
time without exposing them to something that we know is danger-
ous. Some risks we can't do anything about. This is something we
can do something about, and I believe, Mr. Chairman, that the
speed with which you have moved forward in connection with this
hearing indicates that you are not going to do wnat so many others
would like us in the Congress to do, and that is to dance around
the issue, to play the music, to orchestrate the issue, but not to act
decisively. And I say to you that I will use every ounce of strength
and pressure and persuasiveness that I have as far as moving this
matter forward in the U.S. Senate, and I feel confident that you
are going to be successful in your endeavor in the House.
I congratulate you upon it, and pledge you my total cooperation.
Thank you, Mr. Chairman.
Mr. WAXMAN. Thank you very much, Senator Metzenbaum. I ap-
preciate the testimony you have given, because I was astounded at
this voluntary agreement that the Secretary negotiated. First of
all, not all the aspirin companies were even part of the negotia-
tions, so some may not even go along with what she worked out.
She decided there is a public health threat and the public should
be informed about this connection between aspirin and Reye's Syn-
drome. But then she wants to have on the labels-and probably not
even until next year-just call your doctor when you are about to
use the aspirin for flu. That is what most people think aspirin is
for, relief of symptoms of flu.
And then think of children who will self-medicate-they don't re-
alize we are talking about up to 19 years of age-that seems to me
about the most inadequate kind of warning label possible. Volun-
tary efforts aren't bad, but it looks like the voluntary effort here
was one where they agreed to put this label on, and not give her
trouble, because the industry seems to know how ineffective that
label would be.
Then, of course, what disturbs me is this is March. The flu
season, December, January, February, March, maybe into April, we
have so little time to warn people for this year, and already a
handful of children who otherwise should have been able to have
this illness prevented have already died. Maybe this hearing will
reach some families, because I don't think the warning label the
Secretary negotiated will, but we have got to move legislation.
Voluntary efforts are fine if they work, but voluntary efforts that
don't have the chance of really reaching the public are meaning-
less. Therefore I think as you do, I know, that Congress must pass
a law stating the logo, the warning, the kind of campaign that has
a chance to inform the public about the danger of a disease that
might be prevented if parents would know not to use aspirin for
their children for those symptoms.
52-266 0-85--b
PAGENO="0290"
284
Senator METZENBAUM. Mr. Chairman, the evidence is so over-
whelming that it shouldn't be done, and yet I know that you will
have appearing before you this morning representatives of the in-
dustry and other spokespersons who will come forward to indicate
that we should not act, and that we ought to let the voluntary pro-
cedures prevail.
I would hope that you would ask-if not on your own behalf on
my behalf-if you had a child or you have a child, `r a grandchild,
would you be willing to give that child or grandchild aspirin at the
time of influenza or chickenpox. And if you wouldn't be willing to
do that, how can you as an industry representative or public offi-
cial not do everything possible to see that no other child or grand-
child takes aspirin into their stomachs at the time they have chick-
enpox or influenza.
What bothers me is why the industry isn't here saying you don't
need legislation; we will do it. You are right. Why they are using
that kind of political maneuvering to do it on a voluntary basis, are
we going to affect their sales-yeah-much? So what? So what?
Maybe if we had some malpractice suits or lawsuits that frightened
them as happened in so many other arenas, maybe that would be a
deterrent.
But what bothers me is that here is a known problem, not just a
fictitious one, not one that is a figment of the imagination, and if it
is a known problem why don't they do something about it and why
do we have to use our efforts to pass legislation to force them to do
something that they should be doing on their own. Thank you.
Mr. WAXMAN. Thank you very much. Mr. Wyden.
Mr. WYDEN. Thank you, Mr. Chairman.
Just one very quick question, Senator, and I appreciate your ex-
cellent statement. It seems to me that what you have said is that
this problem is one of political judgments. The scientific evidence is
very clear. This isn't a question of not being able to go forward be-
cause of budget cuts. What has happened is the Department has
made a political judgment not to go forward with an aggressive
program. That is why kids are getting hurt. It is politics pure and
simple.
Senator METZENBAUM. I think that is correct, because I know of
no reason. If there was some legitimate reason not to go forward,
not to slam the door shut, then I could be sympatico. I could under-
stand it. But in this instance it seems to me that for some reason
somebody has been able to sell a bill of goods that is the wrong bill
of goods, and I think the critical question is: Would you be willing
to let your children or grandchildren ingest aspirin at the time of
chickenpox or flu? And, if not, then why would you as a public offi-
cial or an industry spokesperson sit here and argue against this
mandatory matter?
Mr. WAXMAN. Thank you. Mr. Bates.
Mr. BATES. No comment.
Mr. WAXMAN. Mr. Scheuer.
Mr. SCHEURER. I just want to thank the distinguished Senator
from Ohio for coming here. He can always be counted upon not
only for wisdom and insight and high order of intellectual acumen,
but sheer unadulterated guts, and that is frequently a scarce com-
modity in these precincts. We appreciate your coming.
PAGENO="0291"
285
Senator METZENBAUM. Coming from you, Mr. Scheuer, I appreci-
ate it very much. Thank you very much.
Mr. WAXMAN. Thank you very much, Senator.
I would now like to call forward four sets of witnesses to come
and testify as a panel. First, John and Terry Freudenberger, presi-
dent of the National Reye's Syndrome Foundation; Dr. Joel M.
Taubin, vice president of the National Reye's Syndrome Founda-
tion; George and Diane Dumigan from New Haven, CT; Jimmy and
Gail Happle from Florence, SC. Will you all come forward and
please take seats up here.
We want to welcome you to this hearing today. We appreciate
your being with us. We want to hear from each of you very briefly
on the problem. It would be appropriate to start with Dr. Taubin.
STATEMENTS OF JOEL M. TAUBIN, M.D., VICE PRESIDENT, NA-
TIONAL REYE'S SYNDROME FOUNDATION; JOHN E. AND TERRY
FREUDENBERGER, PRESIDENT, (NRSF); JIMMY AND GAIL
HAPPLE, FLORENCE, SC; AND GEORGE AND DIANE DUMIGAN,
NEW HAVEN, CT
Dr. TAUBIN. Thank you, Congressman Waxman. We are all here
for really one purpose because we care and we all in one way have
been touched by a loss or an ailment affecting our children or child
with it. There is no question that we have been searching and
trying to understand why our child died. Greg was age 11, in 1978
had chickenpox. We didn't think much about it. He developed the
symptoms of chickenpox, and the rash started to improve. He had
the muscle aches, the headache, the rash. Our physician said watch
him, give him some fluids. He had some headaches, low-grade
fever, and, as you say, we reached for the aspirin bottle.
We gave him aspirin at that time, and within 24 to 48 hours he
developed all the classic symptoms, which I didn't recognize at that
time, of Reye's Syndrome. The illness lasted for 2 weeks in the in-
tensive care unit. It was so intensive that my wife Sonya and I
stayed there for 2 weeks.
I remember back in medical school, going to a grand round of
medical lectures on Reye's Syndrome, being told at that time by
the department of pediatrics it is such a rare disease I will prob-
ably never see it. I didn't see it until it happened to my son, and I
am certainly well aware of it now. Since then, as a very active
member of the Reye's Foundation trying to get the awareness
through what the disease is, the symptoms, and always search and
say what happened, what did we give Gregory? Was it something
in our house, our environment? Was it something in my body,
would my other daughter at that time develop the same thing,
never knowing until the past several years that the association and
now the real association with a drug that is so common-it is a
good drug, we use it in other forms of medicine, but it is so
common that everyone takes it for headaches, for playing sports,
for nervous tension.
Before a meeting like this you may take four aspirin sort of with-
out thinking, and certainly no one really calls their physician and
says, "Do I need a prescription?" You don't need one. Everyone has
it on their shelf, everyone has it in their drawer in the office, and
PAGENO="0292"
286
take aspirin. So we keep searching, keeping looking. And now we
found something, something when you say: Gee, we gave it to our
son, can we stop another parent from losing children. Is there any-
thing that can prevent or inhibit this dreaded disease. And it is an
intensive disease.
The child is well, absolutely well, playing sports, doing well in
school, and develops a routine flu or a virus or chickenpox. You
worry a little bit about it, but then it goes on to its devastating dis-
ease. Within .24 hours the child is in a coma. Arid it is devastating
to lose a child. There is nothing worse, ever, than having a healthi
child die of some disease. And even worse, if you kno* it may be
preventable. The question, and the reason we are here, is to help
support this legislation and to make awareness, not the physician,
they should know about it now.
It is in the journals now. It is given throughout the conferences.
The residents at our hospitals now are aware of it, emergency room
doctors are aware of it. Even the parents are becoming aware of it
now. They are saying: I want to give him something else. I know I
heard, but I know something about aspirin.
What about the parents that don't know something about it or
the parents on a weekend or an evening, maybe a 19-year-old who
may be in college, may not have had a parent around; he may de-
velop some symptoms and take some aspirin off the shelf. No pre-
scription needed with that. How can we stop it? We have got to
look for something with this.
I think the question that was raised here today, and I asked the
members of the other foundations, the Aspirin Foundation or the
aspirin companies, would they give their child or grandchild or a
child of any kind aspirin. And I can't imagine one of them saying: I
have no problems. I give him aspirin.
I just can't imagine somebody coming before this committee or
coming to me personally face to face and saying: I have no problem
with that. The statistics aren't really in, and I have no fear about
giving them aspirin.
If they do that, then they can sit at this table.
I appreciate the efforts. I strongly urge the members of this com-
mittee and everyone here to think twice and say we have got to
make some effort and stop it here. Thank you.
Mr. WAXMAN. Thank you very much. Mrs. Taubin, did you want
to add anything?
Mrs. TAUBIN. No, thank you.
Mr. WAXMAN. Mr. Freudenberger.
STATEMENT OF JOHN E. AND TERRY FREUDENBERGER
Mr. FREUDENBERGER. Mr. Chairman and committee members, I
want to preface my statement by saying thank you. From the
bottom of my heart, I appreciate the time you are spending to help
solve the problems associated with Reye's Syndrome. I am here
today as a parent of a child who was killed by Reye's Syndrome. I
am also here as the founder and president of the National Reye's
Syndrome Foundation. But most of all, I am here to represent the
children of this country.
PAGENO="0293"
287
The cause of my concerns may be that little bottle of children's
aspirin that was always in our medicine cabinet at home. That
little bottle of aspirin may be the reason that our daughter Tiffinni
died in 1973. I have been fighting Reye's Syndrome for the past 12
years by building the National Reye's Syndrome Foundation~ Brief-
ly, the foundation is made up of 130 chapters located in 40 States.
We raise and provide moneys for two purposes: One, to save lives
through increased awareness, and number two, to eliminate Reye's
Syndrome as a medical problem through research.
The foundation started as an all-volunteer organization of par-
ents, and has grown to the extent that we now need a paid staff to
maintain the day-to-day operations. The fight against Reye's Syn-
drome has been plagued by mistakes and misinformation. In the
very beginning someone gave Reye's Syndrome the label "rare."
Now everyone including members of the media call Reye's Syn-
drome "rare."
Even the Surgeon General, in his public service announcement,
is calling Reye's Syndrome rare. We are not dealing with a rare
disease. We are dealing with a disease that struck 175 children in 1
year in Ohio alone. We are not recommending that people be
warned of a disease that strikes rarely, but rather that they be
warned of a disease that strikes all too frequently and often fatally.
In 1974 the National Institute of Health also made a mistake
that delayed recognition of Reye's Syndrome as a medical problem.
They refused to allocate research moneys to Reye's Syndrome be-
cause they didn't think that Reye's Syndrome was a significant
medical problem. NIH no longer holds that view, but Reye's Syn-
drome research was delayed for many years because of it.
The study that implicated Reye's Syndrome was a mistake in
planning. The only reason the study was conducted was because
the Centers for Disease Control fiscal year was ending, and the
CDC hadn't spent all of its allocated money. A quick phone call
was made, an agreement reached, and within a month a Reye's
Syndrome study was undertaken.
The next mistake was made by the Food and Drug Administra-
tion, when the Food and Drug Administration yielded to the aspi-
rin manufacturers pressure and reversed its decision to label aspi-
rin containing medicines. The aspirin manufacturers disputed the
validity of the original study, and aggressively opposed labeling, to
the extent that they even filed a lawsuit against FDA.
In addition, they formed an organization that they called the
Committee on the Care of Children, to give themselves an anony-
mous and more credible platform to oppose aspirin's implications
in Reye's Syndrome.
The proposed legislation is trying to avoid yet another fatal mis-
take. The conclusion that this committee must finally reach seems
simple. First, all of the principals including the aspirin manufac-
turers are in agreement that all aspirin medicines should be la-
beled. All that needs to be decided is whether you want a clear,
strong statement or whether you want to trust the judgment and
the motives of the aspirin companies.
If a mistake is to be made this time, I urge that that mistake be
made on the side of caution and on the side of children. I urge that
PAGENO="0294"
288
you recommend and support the proposed labeling legislation.
Thank you.
* [Testimony resumes on p. 306.].
Attachments to Mr. & Mrs. Freudenberger's prepared statement
follow:]
PAGENO="0295"
1979 - l98~ REPORTEb REyES SyNbROME CASES
PAGENO="0296"
PAGENO="0297"
291
198# RE~JE'S JNL~ROME CASES. REPORTEI) TN OBZO
PAGENO="0298"
292
ttfi©Lu~ill Reye'~s Syndrome * ~
* ~ I "a disease that affects the liver and brain.
I 426 N. Lewis, Bryan, OH 43506
419/636-2679
1984 SCHOOL AWARENESS CAMPAIGN
In November of 1984, the National Reye's Syndrome Foundation,
of Bryan, Ohio, sent copies of the `1984 School Awareness
Bulletin" to over 16,000 school superintendents in the country.
The superintendents were asked to make sure that each and
every child in the school district took the information home.
To date, the National Reye's Syndrome Foundation has received
responses from across the country in regard to the information.
The tabulation of the return post cards completed by school
officials indicates that over 6,000,000 homes have received
the information concerning Reye's Syndrome. The. national
office has been inundated with telephone calls from parents
across the United States whose children have brought the
awareness bulletin home. They want additional information
about the syndrome, or they have a sick child who needs
prompt medical treatment.
The general public wants accurate information and is frustrated
by the fact that so little is known about Reye's Syndrome and
is greatly concerned about the aspirin issue.
PAGENO="0299"
293
~dy rT~' I.., f,,,,,~
~Jj BE WISE ABOUT REYE'S
Lt~J® * AWARENESS BULLETIN
The flu or various symptoms identified as influenza occur more frequently during the winter months.
Influenza is a viral infection, and as such, warrants our special attention because a fatal children's disease is
associated with it. The disease, Reye's Syndrome, affects children from infancy through adolescence and
can develop 3 to 5 days after the onset of the chicken pox, an upper respiratory illness, or other viral infec-
tions. It affects the liver and brain, is non-contagious and is often misdiagnosed as encephalitis, meningitis,
diabetes, poisoning, drug overdose, or sudden infant death.
After a viral infection has seemingly run its course and the child is feeling better the following symp-
toms should be treated as serious and as possibly the first indication of Reye's Syndrome. Anti-nausea
medication may mask the symptoms of the disease and because of the possible association of aspirin with
Reye's Syndrome, parents should consult their physician before using these drugs. Watch for these symp-
toms, usually occuring in this order:
* PERSISTENT OR CONTINUOUS VOMITING
* LISTLESSNESS (LOSS OF PEP AND ENERGY, DROWSINESS)
* PERSONALITY CHANGE (SUCH AS IRRITABILITY,
COMBATIVENESS OR SLURRED SPEECH)
* DISORIENTATION (UNABLE TO IDENTIFY WHEREABOUTS,
OR FAMILY MEMBERS)
* DELIRIUM, CONVULSIONS
A child's life can depend on ~ diagnosis. Reye's Syndrome should be suspected in any child with
chicken pox who vomits repeatedly. Phone your physician immediately if these symptoms develop and tell
him you suspect Reye's Syndrome. If your doctor is not available take your child to an emergency room
promptly. Two liver function tests (SGOT/SGPT) can be done to determine the possibility of Reye's Syn-
drome. There is a 90% chance of recovery when the syndrome is treated in its earliest stages by physicians
and nurses experienced in the treatment of Reye's.
Epidemiologic research has shown an association between the development of Reye's Syndrome and the
use of aspirin for treating the symptoms of influenza-like illnesses, chicken pox, and colds. The U.S. Sur-
geon General, the Food and Drug Administration, and the Centers for Disease Control recommend that
aspirin and combination products containing aspirin not be given to children 18 years of age and under
during episodes of these illnesses.
The NRSF is a non-profit, tax-exempt organization with chapters in forty states. The NRSF has
pioneered the movement to disseminate knowledge about the disease in an effort to aid in early diagnosis.
and also provides funds for research into the cause, cure, care, treatment, and prevention of Reve's
Syndrome.
For more information contact the NATIONAL REYE'S SYNDROME FOUNDATION, P0. BOX
829AB, BRYAN, OHIO 43506, OR CALL 419/636-2679, 800/233-7393, OHIO RESIDENTS CALL
800/231-7393.
84.i5 copy,Ight ~i9S4 TOo Natlooot Rays's SyRO~oa,s Fo~nd~tio~, B,yan, Ohio 43506
PAGENO="0300"
294
WINTER 1984
Vol 8, No. 2
t~fi©ro~ll
* `~ ~ - -~
**
P.O. Box 829
________ Bryan, Ohio 43506
419-636-2679
CA disease that affects the liver avd brain
~©d~fi©r~
inthe~
CHILDREN HELPING CHILDREN
THROUGH BALLOON LAUNCH
Elementary school children in Leipsic, Ohio launch 1,000 helium filled balloons
tagged with Reye's Syndrome information to kick off National Reye's Syndrome Week.
PAGENO="0301"
295
PRESIDENTIAL NOTES
Resolutions passed by the Senate
and the House proclaimed November
12-18 as National Reye's Syndrome
Week for 1984. Chapters across the
country held special events, provided
programs and disseminated Reye's
Syndrome information. This has also
helped to provide coverage of Reye's
Syndrome in such publications as
November issues of Women's Day
and McCaHs. Recently we have been
hearing about Reye's Syndrome on tel-
evision shows such as "Good Morning
America" and "Nightwatch."
The new 800 telephone Hot Line is
in operation at the national office! With
funding from the Dana Wigutoff Mem-
orial Foundation, the hot line was
installed in the National Office in
October. The toll-free telephone
numbers will be included in all our
updated brochures and the 1984 school
"Awareness Bulletin." Once the
number is in circulation, we expect to
be inundated with telephone calls. Par-
ents will now have the capability to call
and have all of their questions answered
at no charge to them. We are proud to
be able to offer this service to the public
and are deeply grateful for the grant to
make the existence of the hot line
possible.
The national office has been quite
busy the past few months. In addition to
planning for the 800 hot line, and the
usual flow of requests for information,
the "1984 School Awareness Cam-
paign" was recently completed. This
has been the single largest project
undertaken by the National Reye's Syn-
drome Foundation. Because of this pro-
ject, millions of people across the
country will be more familiar with
Reye's Syndrome and have the 800 hot
line at their fingertips.
As previously mentioned, the
"Because You Need to Know" bro-
chure has been updated and is availa-
ble. A section concerning the use of
aspirin has been added. Our medical
director, Dr. William Schubert, has
approved the information and we feel it
will answer many questions concerning
the aspirin issue.
This year a nationwide fundraising
project was created through the vision
of Val and Bob Carroll, of our East Cen-
tral Missouri Chapter. Foundation
members and friends from across the
United States have sent recipes to the
Carroll's who have typed, catagorized
and forwarded them to the national
office. The "Sunrise Cookbook" will be
available in February at $7.50 with over
400 recipes. Comparable books have
sold for $12.00, so this is a good buy.
The books will be available from the
national office or affiliate chapters.
The Eleventh Annual Meeting will
- be held June 26-30, 1985 at the Long
Island Marriott in Uniondale, New
York. At the banquet, we will be pres-
enting the second annual Elaine J.
Lasky Humanitarian Service Award.
Nominations may be made by submit-
ting a one page biography on a volun-
teer to the national office no later than
April 10, 1985.
Another year is drawing to a close
and we have taken great steps toward
our goal of alerting the public to the
dangers of Reye's Syndrome. But we
still have a long journey ahead of us
because our ultimate goal is the eradi-
cation of the disease. Now is the time to
renew our vengeance against this
iilness and walk forward with a strong,
determined spirit, a spirit dedicated to
the conquest of eliminating Reye's Syn-
drome as a threat to our children.
I would like to express my apprecia-
tion for your continued support of the
Foundation's effort. Without each of
you, our battle would not have gained
the strength it has achieved. Thank you
all. -
We look forward to seeing you in
New York!!
incerely,
E. Freude rger
President
PAGENO="0302"
296
A DECADE OF SERVICE
The Tenth Annual Meeting of the
National Reye's Syndrome Foundation
of Bryan, Ohio was held June 21-22,
1984, at the Hyatt Regency Ohio Cen-
ter, Columbus, Ohio. The meeting
marked a decade of service to the gen-
eral public and the medical community.
The TenthAnnualMeetingwasheld
in conjunction with the Fourth Interna-
tional Conference on Reye's Syndrome
which was conducted by Dr. J. Dennis
Pollack, past Scientific Advisory Board
Chairman of the National Reye's Syn-
drome Foundation. Researchers and
scientists from throughout the world
attended the conference. Representa-
tives from Australia, Japan, England,
and Canada presented research data at
the symposium. One scientistattending
was Dr. Grame Morgan, an Australian
Pediatrician, who co-authored theorigi-
nal report with Dr. R. Douglas Reye,
that appeared in Lancet which pres-
ented their initial findings of the disease
during the 1950's. -
Two doctors from the United King-
dom described the occurrence in Eng-
land and stated that the current
mortality rate w80%. The reasonfor the
high mortality rate in the United King-
dom, the doctors stated, is the fact that
the disease has onlystarted to be recog-
nized there in recent years.
Reye's Syndrome remains a world
problem with cases being reported in
Europe, Asia, Japan, Thailand, Africa,
and India.
Honored guests at the banquet of
the Tenth Annual Meeting included
past Scientific Advisory Board Chair-
man Dr. J. Dennis Pollack, Donald Lan-
thorn of the Ohio American Legion and
John Maynard, District Office Director
of the office of United States Senator
Howard M. Metzenbaum.
The banquet was opened with wel-
coming remarks from Mr. William
Myers, representing the office of
Columbus Mayor Dana Rhinehart. Mr.
Myers, the Health Commissioner for
the city of Columbus, presented a brief
listing of achievements for which the
capitol city of Columbus is known. Wel-
coming the Foundation members and
guests to the state was Dr. David Jack-
son, Director of the Ohio Department
of Health. Dr. Jackson focused his
address on a number of achievements
of the organization, and the work
accomplished in the state during the
last 10 years because of the efforts of
the National Reye's Syndrome
Foundation.
The guest speaker for the banquet
was Dr. Nelson Krause. Dr. Krause is
well known in the Columbus area,
appearing on weekly television and
radio talk shows. He addressed the
audience briefly on preventative medi-
cine, prescription drug usage, and basic
health standards. Audience participa-
tion was engaged and Dr. Krause ans-
wered several questions concerning a
variety of subjects.
Highlighting the two day activity
was the awarding of the Eighth Annual
Research Grant by Dr. Thomas H.
Glick, Chairman of the National Reye's
Syndrome Foundation's Scientific
AdvisOry Board. The 1984 recipient is
Dr. Doris Trauner, Associate Profes-
sor, Department of Neurology and
Pediatrics, University of California at
San Diego, who will be working with
structures within body cells which are
called mitochondria. Dr. Trauner will
be studying the effects of the influenza
B virus, both alone and with aspirin or
acetominophen, on mitochondria
structure and function. Dr. Trauner will
also be working with a natural body
substance called carnitine, presently
thought to be helpful in the treatment of
Reye's Syndrome.
Awards were presented to chapter
presidents in recognition for their out-
standing efforts and accomplishments
during the past year. The first Elaine J.
Lasky Humanitarian Service Award
was presented to Elisabeth M.
Osborne, President of the South Kan-
sas Chapter, Anthony, Kansas. The
award was established in honor of a
longtime Foundation Trustee and Pres-
ident of the Chicago Chapter, Elaine J.
Lasky, who died in 1983. The Humanit-
arian Service Award will be presented
annually to a Foundation member who
has exemplified the work and dedica-
tion displayed by Elaine Lasky.
Dr. Joel Taubin, Vice-President of
the Foundation, on behalf of the Board
of Directors of the National Reye's Syn-
drome Foundation, presented John
and Tern Freudenberger with a special
tribute for their service, effort andcom-
mitment. The Freudenbergers were
honored with a plaque renaming the
annual research grant to be known
hereafter as the Tifinni Freudenberger
Memorial Research Grant. Since 1974,
the Freudenbergers have fought a long
unending battle against Reye's
Syndrome.
Foundation members and guests
viewed a video tape with a personal
message from Senator John Meicherof
Montana. The Senator was instrumen-
tal in introducing S.74 (The Reye's Syn-
drome Act of 1983.) Senator Meicher
stated that prior engagements pre-
vented him from attending the Tenth
Annual Meeting and commended the
Foundation for all the fine work and
effort that has been demonstrated dur-
ing the past decade.
Members of the National Reye's Syndrome Foundation enjoy the banquet of the Tenth
Annual Meeting which was held in Columbus, Ohio, June 22, s984.
PAGENO="0303"
297
Workshops were held Saturday
moming in the meeting rooms of the
Hyatt Regency. The first workshop was
conducted by Gary Honnert, of the
Ohio State University, where he is head
of all television public service
announcements for the school and acts
as news media consultant to the Uni.
versity. Mr. Honnert presented chapter
representatives and members with a
general overview of public appearance
techniques including directional help in
speaking, dressing and preparing mate~
del for a television news interview.
The second workshop of the morn~
ing was conducted by Dr. Charles
Dygert, Ohio State University. An out~
standing motivational speaker, Dr.
Dygert conducts workshops and
seminars nationwide with tremendous
acceptance. Through the workshop
with Dr. Dygert, audience members
learned to recognize their own personal
strengths as Dr. Dygert clarified self
perception, the effect of criticism on
motivation, and the effects of human
chemistry on one's behavior.
The activities concluded Saturday
afternoon with the general business
meeting of the Foundation. It was
announced at the businessmeetingthat
the Foundation had been the recipient
of agrant from iheDana WigutoffMem~
orial Foundation to fund an 800 hot line
number.
The Eleventh Annual Meetingof the
National Reye's Syndrome Foundation
will be held at the Long Island Marriott,
in Uniondale, New York, June 26-30,
1985.
~a Syndrome
*
II'
SEALS AVAILABLE
The blue and white logo of the
NRSF has been made available as a seal
which can be used on note paper, sta-
tionery or as an added touch to sealed
envelopes. You can use them inside
greeting cards to indicate in a subtle,
attractive way your support of the
National Reye's Syndrome Foundation.
Cost is $5.00 per 100 seals, plus a
75~ postage and packaging charge. For
ordering, send checks payable to:
National Reye's Syndrome Foundation,
P. 0. Box 829, Bryan, Ohio 43506.
(Actual size 1" x 1%").
Set a good example by spreading
awareness and use the seals on every-
thing you mail out! -
Mr. Gary Honnert,above center, leads discussion withchapter members during aworknhop
des~gned to help chapter members become more familiar with media techniques and
presentations.
I 8 1994
Mr. John E. Freudeeberger
president
National Reye's Synderave Foundation, Inc.
426 North Lewis
Bryan, Ohio 43506
Dear Mr. Freudenberger,
It gives me great pleasure to send greetings to
everyone attending the Tenth Annual Meeting of the
National Beye's Syndrome Foundation.
The mystery of Reye's syndrone is a threat to the
health and lives of our children. We are heartened
that fewer canes of the disease worm reported in 1982
and 1983 thun in previous years for which figures had
been formally collected. Continuing efforts tq broaden
our knowledge and to educate Americans about this
disease will help protect the health of our children.
I send my congratulations toever yone associated
with your work and my best wishes for its continuation.
Sincerely,
PAGENO="0304"
298
BETH OSBORNE RECEIVES SERVICE AWARD
On June 22, 1984, the National
Reye's Syndrome Foundation was
proud to present the first Elaine J.
Lasky Humanitarian Service Award to
Beth Osborne, President of the South
Kansas Chapter, Anthony, Kansas.
Beth would like to share the following
thoughts with all the members and
friends of the Foundation:
Shocked... numbed... excited...
elated... overwhelmed.., and humbled
are but a few of the many emotions I
experienced a split secondafter hearing
my name announced as the first recip-
ient of the ElaineJ. LaskyHumanitarian
Service Award.
Even now, months later, lam still at
a loss for words. How do I express
those deepest of feelings? For me, it
comes through tears.
Tears have a language all their own.
On June 22, 1984 they spoke louder
than any words could. Their message
was one of deepest gratitude and appre-
ciation to all those responsible for this
special unforgettable moment in mylife.
lf I begin to name the individuals I'd like
to thank, I would risk leaving someone
out, I do not want that to happen. So
many have contributed in varying
degrees. Iwant to thank each of you for
your involvement in this special award.
I especially want to thank the Lasky
family for permitting the establishment
of this award. Although I never had the
opportunity to meet Elaine, I believe
she and I shared the same vision, the
same dream and goal concerning
each fight confronting her with every
ounce of her being. A dear friend of
Elaine told me she did not give up her
dreams and visions when the"goinggot
tough."
I shall always treasure this special
award. It is overwhelming to realize
what it stands for, and very humblingto
gain a glimpse of the high standards
-Elaine achieved. Those of you who
knew Elaine have been especially
blessed. May you share with thoseofus
who did not know her, the special gifts
and qualities she has shared with you.
Beth Osbome
South Kansas Chapter
Anthony, Kansas
HEALTH AND HUMAN
SERVICES ATTACKS
PRO-ASPIRIN AD
The first Elaine J. Lasky Humanitarian Service Award was presented to Beth Osborne,
President of the South Kansas Chapter,Anthony, KansaS. Presenting the awardwereLarry
Lasky, left, President of the Chicago Chapter and Foundation Trustee, and right, Dr. Joel
Taubin, Foundation Vice-President and President of the Washington Metropolitan Chapter.
On Monday, November 5, the Food
and Drug Administration denounced a
television announcement distributedby
the Committee on the Care of Child-
ren, (CCC) as seriously misleading and
accused the organization of undermin-
ing federal efforts towarnparentsof the
suspected link between aspirin and
Reye's Syndrome.
The television spot is preceded by
Reye's Syndrome. This mysterious dis- an announcer's voice saying "Stay
ease wounded both of our hearts. Yet, tuned for a medical bulletin on Reye's
we've both desired to make our expe- Syndrome." The ad does not point out
rience with Reye's Syndrome positive that health officials have been warning
and productive. I envision the day, as that aspirin increases the risk of con-
I'm sure Elaine did, when this dreaded tracting the disease.
stalker of our youth will be forever Joining the FDA in its' criticism of
conquered. the ad were officials of the Centers for
May the Elaine J. Lasky Humanitar- Disease Control, the American
ian Service Award be an inspiration to Academy of Pediatrics and Dr. Edward
every chapter leader, every member of Brandt, Assistant Secretary for Health
the National Reye's Syndrome Founda- and Human Services, who said the ad
lion. May we strive for the highest point `flies in the face of scientific evidence."
of commitment, dedication, and service Dr. Brandt's office is coordinating the
in ourcommunities, states and country. federal study of Reye's Syndrome and
May we NOT become discouraged aspirin. The FDA recommends that
when we are tired, misunderstood and until current studies are completed,
feel alone. May we gain new strength children who are ill with chicken pox or
and encouragement in knowing that flu should not be given aspirin. Since
one woman, Elaine J. Lasky, fought 1982, the FDA has aired television
PAGENO="0305"
299
announcements warning parents to
exercise caution in the administering of
medication.
The disputed ann~incement does
not mention the possible aspirin link.
Instead, it states only that "we do not
know that any medication has been
proven to cause Reye's." Focusing on
that statement, federal officials
as6erted that the Committee on the
Care of Children is supported by the
drug industry. The ad was prepared
and distributed by the CCC, a private
organization that was formed in 1982
when the aspirin studies became
national headlines.
Last year, the CCC brought an
unsuccessful lawsuit against the FDA
to try to stop it from carrying out an
educational programlinkingthedisease
to aspirin. The CCC lawyers also have
threatened legal action against televi-
sion stations that broadcast FDA public
service announcements. The CCC has
threatened drug stores that made use
of voluntary warning labels on aspirin
packages as well.
The Committee on the Care of
Children is headed by Neil Chayet, a
Boston lawyer, who reportedly organ-
ized a similar group about 12 yearsago.
That organization was called the Com-
mittee on the Care of Diabetics and it
fought efforts to tell diabetics that they
might not need drugs to control their
disease. Diet and exercise alone are
capable of controlling many cases of
diabetes. Chayet was unable to be
reached for comment, but his office
referred calls to Camille Oldenberg,
administrator of another Chayetorgan-
ization called the International Science
Exchange. Oldenberg acknowledged
that the Committee on the Care of
Children was launched with pharma-
ceutical industry funds channeled
through the International Science
Exchange.
REYE'S SONG TOUCHES REALITY
When Wayne Hagood told the story
of his daughter Sonya Lee's fight with
Reye's Syndrome, he touched the
hearts of many of his co-workers. Per-
haps touched the most by the tragic
death of the 12 year old Lee was Ed
Stockton, an engineer from Philadel-
phia, who returned to his motel room
after hearing the sad story and wrote
the following song in memory of Mr.
Hagood's daughter. Since that day, the
words have been put to music and
copyrighted by Mr. Stockton.
Thank you, Daddy, flee! okay
I really am much better today.
My cold's all better and I'm
feelin' fine,
I think I'll go out in the bright
sunshine.
Daddy, Daddy, my tummy's sore.
I've never felt this way before.
The room is spinnin' round and
round,
I think I'd better go lie down.
No! Daddy, I won't go
For a ride in the car,
Oh, NO, NO, NO!
Daddy, where are you takin' me?
To a room they call emergency.
Daddy, where did the doctor go?
He hasn't come back for an
hour or so.
He says that he thinks I'm on
drugs -
But I'm not, cause I hate em!
I'd rather eat bugs!
CHORUS:
Won't somebody save the children
from the devil in disguise -
Tell the parents and tell the doctors
that the demon's name is REYE'S.
Just look at your little children -
With their wide bright innocent
eyes.
And let your doctors know and
let your neighbors know -
And maybe we can stamp out
RE YE'S
Daddy, why won't the doctor try
To find out ~f I've really got
REYE'S?
My body's hurtin~ every place
And Daddy, I can't see yourface.
I can't talk Daddy, but please be near.
I'm afraid that soon I won't be here.
Daddy, Daddy, I love you -
Lord Jesus, take me home with you.
I wrote this song for a girl named
Lee whose life ended in tragedy.
Her dad told the doctors he thought
it was REYE'S
But they didn't believe him until
she died.
So, I'm trying to save the children
from the Devil in disguise.
And I'll tell anyone who'll listen
that the Demon's name is REYE'S.
You see, I've looked to my own
little children,
into their deep blue, loving eyes,
and I've prayed to God that
everyone know
arid no more would diefrom RE YE'S.
And let your doctors know,
and let your neighbors know -
That we've got to stamp out REYE'S
That we're gonna stamp outREYE'S
x,py,ightrd 1984 Edoa~d St,okt,,,,
12 year old Sonya Lee Hagood
PAGENO="0306"
MY EMPTY SPACE
by M. Bernice Stengel
Like a summer day without the bril.
liance of the sun.
Like an amusement park without a
merry-go.round.
Like a kiss without a hug.
So is my life without Nicole.
U
Nicole Marie Stengel
Time passes. Things change. I
change. Yet, the empty space stays
stubbornly in place. The void is there,
despite son Scott's embarking upon the
threshold of his manhood. Emptiness
continues as littleAngela talksand talks
and talks in the discovery of her three
year old vocabulary. The void is vast at
times, minuscule at others, but always
present.
Nicole would be ten now. Horror
describes the realization that she has
been dead for more than four years.
Memories of a mature six year old.
Of a child with a bright future. Of a
stubborn little girl determined in her
destinations, unconcerned by discipli-
nary deterrents. Confident in some
situations, Mommy's baby in others.
Always ajoy, even in her stomping, mad
feet and her sassy, pouting mouth.
Paper work. Crafts. Drawing. A
stack of construction paper and a rollof
cellophane tape could fill her day with a
multitude of creations. Writing letters
and presenting pictures to her family
made her face shine with a smile.
Shy in an almost painful way when
outside of her haven home. Many never
heard her sweet voice. Memories of
words she uttered are with me. Oh
God, how I wish I could make my mind
recall the tones she used in her wonder-
ful expressions.
Her presence is near at times. Dis-
tant at times. But always there. A spirit
so special that I can almost... but not
quite see her.
Of all my senses, the one that longs
for the baby girl most is my touch... To
hold her, hug her, kiss her. If Ihad held
her real tight, clutched to me, could I
have enclosed herspirit in that sick little
body and kept her?
No! Nicole is free. Free from the
body that she thought too tall. Free
from the body that had to go to school.
Free from the body that had to be
around others.
Free to be wherever, whatever,
whenever, however... But always pres-
ent to her Mommy in that vacant, hurt-
ful, empty space.
CELEBRITY GOLF
TOURNAMENT
In August of 1983, bright, lively 16
year old Jamie Beth Slavin became a
victim of Reye's Syndrome. In dedica-
tion of her daughter's memory, and in
vengeance of this mysterious disease,
Jill Slavin organized the first Reye's
Syndrome celebrity golf tournament
with the help of professional tour vete-
ran Gail Toushin.
The tournament, co.hosted by Har-
vey Korman and McLean Stevenson,
was the first golf event held in the Uni-
ted States to benefit the National
Reye's Syndrome Foundation. Thirty
celebrities joined one hundred and ten
golfers in a five man scramble at El
Cabellero Country Club, a private well
landscaped course which lies to the
north of Los Angeles, on the fringes of
Laurel Canyon.
NRSF co-founders John and Tern
Freudenberger attended the event
which was held June 17. Among the
celebrities participating in the event
were Jack Lemmon, Jerry Vale, Monty
Hall, Alex Trebek, Jack Carter, Fred
Decordova, Kevin Hagen, Johnny
Yune, Donny Most, Jamie Farr, Tom
Poston, Peter Marshall and Hal Linden.
A banquet was held in the evening
and several of the celebrities enter-
tained the group with a floor show
which was emceed by Korman and
Stevenson. Musician and composer
David Clark lead his 14 piece string
orchestra in a piece of music he com-
posed in the memory of Jamie Slavin.
His tribute, entitled "Adagio for Jamie"
was a very emotional, moving part of
the evening.
Numerous items were raffled off
after the dinner. One of the items on the
auction block was an all expense paid
trip for two to Ceasars Palace in Atlan-
tic City, including limousine serviceand
a deluxe suite, all donated by Buddy
Hackett.
The tournament was backed with a
$10,000 contribution from a corpora-
tion in Los Angeles called Data Pro-
cessing Enterprises. Each golfer
received a matching garment and duffle
bag, calculator, pen, lighter, two golf
balls, golf towel, celebrity golf bag tag,
and a Reye's Syndrome celebrity golf
shirt complete with the NRSF logo.
The tournament was a tremendous
success and plans are underway forthe
2nd annual Celebrity Golf Tournament
which will be held June 18, 1985. Har-
vey Korman and McLean Stevenson
will again co-host the event.
300
McLean Stesenson, Harsey Korman and Jill Slavin
greeting a guest at the Jamie Beth Slavin Memorial Golf Tournament.
PAGENO="0307"
KRISTI
by Bud Shaffer
Kristi Kristi Kristi
Thoughts of you make our eyes
grow misty
A little known disease called
Reye's Syndrome
Took your life and placed you in
God's kingdom
You were a child in years only
You were a very special grown up
young lady
Your absence causes Mom, Dad, Sister
and Brother to be lonely
When you were dressed up you were
a very pretty young lady
AROUND THE COUNTRY
EASTERN DISTRICT
DISTRICT VICE-PRESIDENT
KATHY SPEECE
Reynoldsburg Chapter, Reynolds.
burg, Ohio, held a garage sale in June.
Teresa, Chapter President, received a
contribution from the J.C. Penney
Community Service Award Program.
This is a program for Penney's
employees and she was nominated by
her supervisor.
Baltimore Chapter, Edgewater,
Maryland, is promoting awareness
through brochure distribution. The
Awareness Bulletins are going out with
the aid if the State Health Department.
You touched the hearts of many during
your short life span
You were thoughtful and kind to
the young ~nd old with an
instinct of a mother
We shall never forget your lastsummer
when you were trying to get a tan
You loved to pester, kid and laugh
with Sister and Brother
Kristi Kristi Kristi
Thoughts of you make our eyes
grow misty
A little known disease called
Reye's Syndrome
Took your life and placed you in
God's kingdom
We all prayed and prayed for a miracle
with a bleeding heart
You were a special child in our eye
You have given us many precious
memories that are locked in
our heart
You must have been more of a
special child in God's eye
Our hearts still ache for you
Help us to ease the pain
Please Lord, tell us what to do
And understand her death was not
in vain
Kristi Kristi Kristi
Thoughts of you make our eyes
grow misty
A little known disease called
Reye's Syndrome
Took your life and placed you in
God's kingdom
Delaware Chapter, Wilmington, Del.
aware, reports that area school nurses
are again helping to distribute aware-
ness through the local schools to help
the chapter's educational program.
Washington Metropolitan Chapter,
Potomac, Maryland, held their second
annual square dance and barbeque in
June which helped to raise a whopping
$26,000 for the chapter. JoelandSonya
Taubin planned, organized, and imple.
mented the event which was supported
by many of their friends and family.
Chapter members have been busycon-
ducting awareness in the greater
Washington, D.C. area.
Ocean County Chapter, Toms River,
New Jersey, implemented awareness
programs during observation of
National Reye's Syndrome Week.
Northeast Division Chapter, Phila.
delphia, Pennsylvania, has conducted
several awareness programs. Kathy
Zajkowski received support from the
Mayor of Philadelphia and the Gover-
nor of Pennsylvania in regard to pro-
claiming Reye's Syndrome Week in the
city and state. 1,000 helium balloons
were released by students in two differ-
ent school systems. The balloons con
tamed Reye's Syndrome information
and were sent up during Reye's Syn.
drome Week
Loretta George Memorial Chapter,
Glendale, NewYork, heldanannual tag
sale netting the chapter a profit. They
are in the process of conducting their
annual membership drive along with a
301
Kristi Shaffer
Teresa Murray, center is shown receicing a $100 check
from the Columbus Catalog Center
for the Reynoldsburg Chapter of the National Reyc's Syndrome Foundation.
PAGENO="0308"
Around the Country (Continued)
raffle drawing. This year the prize will
be a choice of either a VCR or $500 in
cash. Awareness presentations are also
being given to area groups.
Virginia Beach Chapter, Virginia
Beach, Virginia, gave a presentation to
a Da~ Care Center with 45 parents of
children attending. The Day Care Cen.
ter made a donation to the chapter and
held a "TrikeAThon" for Reye's Syn.
drome in November. Other speaking
engagements are being given to groups.
Dayton Area Chapter, Dayton, Ohio,
held their eighth annual St. Patrick's
Day Dance which was a huge success
this past March. A raffle was also con
ducted during the dance which helped
to raise over $2,500.
Western Buckeye Chapter, Leipsic,
Ohio, is busy working on the next
celebrity Auction. A sausage and pan.
cake breakfast is planned and presenta-
tions are scheduled for the winter
months to various groups. 1,000 bal.
loons were released by three area
schools in observation of National
Reye's Syndrome Week.
North Central Kentucky Chapter,
Jeffersontown, Kentucky, reports that
last spring a doctor from the State
Department of Health published two
articles about Reye's Syndrome and
included information about the NRSF
slide/tape program. As a result the pro-
gram has been used in at least 10 hospi-
tals, clinics, etc. all over the state. A
Bike.A.Thon was held for the second
year. There were 26 participants and
the local papers gave the event plentyof
news coverage. They recently had a
raffle and booth at an area festival.
Northwest Ohio Chapter, Tiffin,
Ohio, received an annual gift of $2,000
which was presented on behalf of the
employees of the Whirlpool Corpora-
tion. Slide presentation is being utilized
at a number of speaking engagements.
Suffolk County Chapter, Hunting-
ton, New York, has had several garage
sales during the summer raising funds
for the chapter. Members recently held
a Theatre Dinner and Raffle. The chap-
ter hopes to make this an annual affair.
The chapter is continuing to advertise
through the "Pennysaver", which is a
free flyer distributed to the community
door to door, featuring ads from var-
ious stores and area groups. The Hun-
tington Township PTA Council ran an
Awareness Forum during Reye's Syn-
drome Week. Members also conducted
awareness programs for ambulance
attendees during Reye's Syndrome
Week.
Tn-County Chapter, Peekskill, New
York, held a bowling tournament this
past spring. Awareness programs have
been given to PTA's, and Nursing
Schools. Brochures have been distrib-
uted in the libraries throughout the
county.
Michigan Upper Peninsula Chap-
ter, Ishpeming, Michigan, is busydistri-
buting literature to area doctorsoffices.
The local Jaycees will be helping with a
dance that is beingplannedforJanuary.
Canisters were placed in local stores
during Reye's Syndrome Week.
Berks County Chapter, Reading,
Pennsylvania, is giving presentations to
local schools in the area. Several more
are on the schedule.
Rhode Island Chapter, East Green-
wich, Rhode Island, distributed 1,000
Reye's Syndrome flyers in July at a local
festival which also was an opportunity
to set up donation canisters. An aware-
ness program is planned for a "New
Neighbors Club" which consists mostly
of young mothers. A program was
recently given at the local hospital. The
chapters annual spirit raffle raised sev-
eral hundred dollars.
Central New England Chapter,
Fitchburg, Massachusetts, made a
Reyc's Syndrome Float for the Fouith
ot July parade which won second
302
Dayton Area Chapter members enloy their annual St. Patrick's Day Dance along with
National President John Freudenberger and National Secretary Tern Freudenberger.
Members attending included:
Rowone(L-R): Kathy Speece, Cheree VanDyke, Peggy Matthews, and Pat Marlin. Rowlwo:
Dan Cordova, Etma Evans, Jack Matthews, Ginger Brockman, Gene Brockman, Nancy
Eckstein, and Tern Freudenberger. Row three: Bill Eckstein, John Freudenberger, George
Evans, John Van Dyke, Bob Speece and Bob Martin.
Chapter President Bernice Stenget, far left, watches as twenty-sis children peddle the,, wa~
through the second annual Bike-A-Thon.
PAGENO="0309"
SOUTHERN DISTRICT
DISTRICT VICE-PRESIDENT
MARILYN ANKENEY
McDowell Chapter, Columbia, Ten-
nessee, has been keeping busy with
speaking engagements and distributing
awareness literature.
Middle Georgia' Chapter, Warner
Robins, Georgia, recently held a raffle
and raised $1,600 with the help of the
Haygood family who were in charge of
the event. The raffle had miscellaneous
items, prizes and a microwave oven.
During Reye's Syndrome Week, the
chapter attracted media attention by
conducting a balloon release with the
local school children at the courthouse.
Dallas-Fort Worth Chapter, Dallas,
Texas, is presently conducting a solici-
tation mailing in the greater Fort Worth
and Dallas areas.
South Carolina Chapter, Columbia,
South Carolina, is pleased to announce
that the NRSF has been accepted into
the Charleston Combined Federal
Campaign which is the largest local in
CENTRAL DISTRICT
DISTRICT VICE-PRESIDENT
ROBERT CARROLL, JR.
Chicago/DuPage County Chapter,
Chicago, Illinois received support from
the Distributive Education Students of
Lake Park High School who held
another BowlA-Thon in September for
Reye's Syndrome. It is always a suc-
cessful event and helped to raise
$3,700.
East Central Missouri Chapter,
Amold, Missouri, has had its hands full
with new son Robby Carroll, but the
chapter is planning several fundraisers
and have a good schedule of presenta-
tions. The 4th Annual Dance was held
October l9and raisedover$2,800. Sev-
eral hospitals have been contacted for
in-service presentations.
Southwest Illinois Chapter,
Edwardsville, Illinois, reports that a
large schedule of presentations for the
fall campaign are planned. A presenta-
tion to the Lewis and Clark College of
Nursing class on September 14th
marked the fourth time they have
appeared before the group. A
November 10th dance and raffle was
held and raised$1,100. CitySteelTorch
Club made a contribution to the chap-
ter of $1,650.
Southeast Iowa Chapter, Washing-
ton, Iowa, reports that the Theta
Lambda Sorority made a nice contribu-
tion to the chapter. Area awareness
programs were conducted during
Reye's Syndrome Week.
Western North Dakota Chapter,
Dickinson, North Dakota, is busy
promoting Reye's Syndrome aware-
ness in the area. The chapter's local
303
Around the Country (Continued) the state! A brochure distributed by the
place. Two fund raisers are planned; chapter was the key to the alert reac-
the second annual"RunforReye's"and tion of a mother in having her child
the fourth annual dance which will be diagnosed early!
held along with a raffle of donated Greater Lubbock Area Chapter,
prizes. An awareness program will be Lubbock, Texas, held a garage and
given to student nurses and flyers will craft sale. They are busy distributing
be distributed to area doctors' offices, awareness materials.
Maine Chapter, Auburn, Maine, con- Central East Coast Florida Chap.
ducted theirannualsoftballtournament ter, Merritt Island, Florida, recently
in June and raised about $1,000. A had a booth at a Flea Market which
dance last spring helped to raise $1,500 helped to raise funds for the chapter
for the chapter. In late October they and distribute awareness literature.
raffled a Cabbage Patch doll as part of They conducted a Reye's Syndrome
the Maine Mall Community Bazaar. balloon release during Reye's Syn-
Their junior board is planning a dance drome Week and have been working
for the area teens. with pediatricians in the area.
Eastern Lake Erie Chapter, Erie,
Pennsylvania, had a full schedule for
Reye's Syndrome Week. Their annual
Walk-A-Thon was held. Two skating
rinks in Erie, the United Skates of
America and Erie Skating Rink donated
all profits to the chapter from one day
during Reye's Syndrome Week. Allnine
local McDonald's restaurants in the
Erie area displayed Reye's Syndrome
canisters during the week and one local
McDonald's donated one full days prof-
its to the chapter.
Cooperative Education Students from Lake Park High School join together to help fight
Reye's Syndrome during their fall Bowt-A-Thon to benefit the Chicago Chapter.
Wisconsin Lakeshore Chapter, Reye's Syndrome Emergency Line is
Wauwatosa, Wisconsin, participated in quite busy and information is being dis.
the Health Fair in Milwaukee and dis- seminated in this manner.
tributed many Spanish brochures. The Southwest Iowa Chapter, Red Oak,
chapter had a booth at a Health Fair in Iowa, is gearing up for an extensive
October. A fund raising raffle of a Cab-, awareness campaign which was con
bage Patch doll is being held at the Jay. ducted through the schools this fall.
cee Women's Convention. Local health Sac-Ida Chapter, Arthur, Iowa, is
departments have been requesting promoting Reye's Syndrome aware-
more brochures. ness in the area.
PAGENO="0310"
Four State Area Chapter, Fouke,
Arkansas, was the recipient of a slide
projector from the local American
Legion Auxiliary along with a screen
and carrying case. Chapter has distrib-
uted brochures and Emergency Room
posters in New Mexico. Arkansas
Children's Hospital in Little Rock is
maintaining close work relationship
with the chapter. Many requests for
literature have been received lately.
The chapter is planning another Music-
A.Thon with the local Baldwin dealer
this year.
South Central Wisconsin Chapter,
New Lisbon, Wisconsin, is involved
with a two day presentation/meeting to
be held shortly. They hada full schedule
of presentations this fall.
South Kansas Chapter, Anthony,
Kansas. Beth Osborne plans to attend
an all day conference sponsored by the
Kansas Association for the Education
of Young Children, Inc. The chapter's
"Display Racks" featuring poster
boards with brochures have been
requested by the Family Practice Cen.
ter in Wichita. The chapter has been
contacted by many pre-schoolteachers
throughout the state for information.
The Wichita Branch has been doing a
super job promoting Reye's Syndrome
awareness and has held a fund raiser.
They also have a bake sale planned
which will be held at the Wichita court-
house. All the items will be donated.
The group also appeared at the
November 10th 2nd Annual Parent's
Fair which is sponsored by KSN-TV
Channel 3 in Wichita. The chapter
pushed awareness heavy again this
year during Reye's Syndrome Week
and have several fundraisers planned.
PSA's will be distributed to radio sta-
tions. The group is grateful to Tern
Cross who works with them in making
their own PSA's for the Kansas Agricul-
tural Network. The chapter urges
anyone who is interested in finding an
address for the Satellite Station in their
area to contact the national office.
The Elk City Oklahoma Branch of the
South Kansas Chapter has also been
busy. Deanna Sweetin has worked with
the Jaycees on a fundraiser recently.
The "Singing Wilkersons" from Silver
Dollar City provided the entertainment
and the event netted the branch over
$725.
South Central Nebraska Chapter,
Farnam, Nebraska, had a full schedule
of presentations lined up this fall. Some
of the programs are 75-100 miles away.
The chapter is very proud of the fact
that Nebraska became a reportingstate
this past summer.
Southeast Kansas Chapter, Coffey-
yule, Kansas, had a presentation sche-
duled in August with visiting Nurses
Association and reports a good sche-
dule of lectures are booked.
WESTERN DISTRICT
Southern California Chapter,
Hacienda Heights, California is pleased
to announce that Reye's Syndrome is
now a reportable disease in California!
Jim Johnson and George Robeson
spearheaded the effort through letters
and presentations made before various
committees. All the chapters in the
state were contacted and input from
everyone was helpful in making this
possible. Thank you all for a job well
done!! A Skate-A.Thon this past spring
helped to raise funds for the chapter
and was a huge success with many
youngsters participating in the event.
This chapter held their annual Bowl-A-
Thon. This event is sponsored by Foot-
hill Beverage and Budweiser and has
always made a nice profit for the
chapter.
Northern Montana Chapter, Chi-
nook, Montana, received a donation of
30 Charlie Russell (local artist) framed
prints which will be used to help raise
funds for the chapter. They are partici-
pating in a fair and a rodeo. Speaking
engagements are scheduled during the
winter.
Central California Chapter, Clovis,
California, reports that local stations
are interviewing the ChapterPresident,
Greg Pullen and he is pleased to say
that the public service announcements
are still being shown. The flyers will be
sent home through schools this year.
Flathead Lake Area Chapter, Pablo,
Montana, has had many successful
meetings in the last couple of months.
The Health Agency and preschool
groups have shown interest. Also the
Indian groups are schedulingprograms.
The public was invited to attend a town
meeting on Reye's Syndrome in
November.
San Francisco Bay Area Chapter,
Pleasanton, California, will have an
opportunity to appear on a cable televi.
sion network. Chapter President Betty
Mathias was asked to appear on the
program which will focus on Reye's
Syndrome and the aspirin issue.
304
NRSF EXPANSION
The Foundation is encouraged by continued support of individuals
interested in fostering the goals and programs of the organization.
The newest affiliates are:
Greater White River Area Chapter, White River, Arizona,
organized by Ray and Mary Courser.
Carlsbad Chapter, Carlsbad, New Mexico, formed by Gene and
Anita Bryan.
Shawn McClure Tibbetts Memorial Chapter, Montgomery,
Alabama, started by Gary and Sharolyn Tibbetts.
Tn Valley Chapter, Tarzana, California, organized by Nancy
Vaccaro and Jill Slavin.
PAGENO="0311"
305
CUT AND TAPE TO YOUR MEDICINE CHEST
FOR KIDS' SAKE...
BE WISE ABOUT REYE'S!
~ Reye's Syndrome usually appears after a flu-like Infection,
~ upper respiratory infection, or chicken poo.
The early signs are tsu ally Continuous uomiting, listlessness,
loss of pep, aggressiveness, Contusion, and irrational behavior.
Medicines at the very least van mask symptoms.
E~I ~ ~ Child anti-nausea or lever
Phone your doctor immediately.
~ Abnormal Liuer Tests: SOOT and SOPT
___________ strongly sugges: a diagnosis of
__________ Reye's Syndrome.
Time is important' Early diagnosis
is VITAL.
C Copyright, 1983
Naffonat Reyss SyndromeFoandaffon a Brpan0hfo43506 a (419)636-2679
~ National __________
fl~j Reye's Syndrome Nan-PeeRS Org
b*b 11 Foundation U.S. POSTAGE
ilk? P.OBox829 PAID
U.~ Bryan, Ohio 43506 P.m, No. 197
Bryas OH 43506
PAGENO="0312"
306
Mr. WAXMAN. Thank you, Mr. and Mrs. Freudenberger, for being
with us.
Mr. and Mrs. Happle.
STATEMENT OF GAIL HAPPLE
Mrs. HAPPLE. First of all, we lost our child February 6 of this
year.
Mr. WAXMAN. Excuse me, but would you please pull the micro-
phone a little closer.
Mrs. HAPPLE. So this may be real difficult for me, because I am
still not real strong. We have not been able to move back into our
home. We are working. But I feel that it is something that I can do
for her. She was an only child. I have a lot of time on my hands
now. They don't let you put but so many flowers in a mausoleum,
so you can't do much there. But our town is small, and I will spend
this time making sure that the children in our town do not take
aspirin for anything, because our child had not been that sick. She
only had a little cough. We gave her Congesprin, which contains
aspirin, the equivalent to a baby aspirin in each tablet. We had
been doing that all week.
On Thursday she went to school all day. She threw up at school,
but she cleaned it up herself and didn't even tell anyone about it.
When she got home she told us. She continued to throw up. On
Friday we called her pediatrician. He prescribed a suppository be-
cause we could not keep anything in her. There was so much flu
around that he did not want us to bring her to the office. And I
was also sick with the flu. My doctor didn't want me to come out to
the office either. He phoned in my prescription. On Saturday morn-
ing she was still throwing up. She watched TV. She ate some crack-
ers and drank ginger ale. By the time we got to the doctor at 10:30
she was already delirious. So it happens very fast.
They sent us directly to the Medical University in Charleston.
We were there by 1:30. They immediately started treatment, after
doing two of the blood tests, to make sure that that is what she
had. And when I say started treatment, they don't wait and see; by
the time we saw her again, they had already put a probe in her
brain so that they could monitor the pressure to enable them to
keep her fluids in the right proportion, so that her blood pressure
would stay stable as the pressure went up.
On Sunday the pressure went so high that her brain was dam-
aged irreparably then. In fact, the doctor has told us then from
Sunday on she was probably brain dead.
Because of this-and they hyperventilate them, trying to keep
their blood pressure up-her lungs then got a hole in it, and the
air was getting into her body cavities, so then her heart did not
work properly. So then a tube had to be inserted and get rid of the
air. Her kidneys failed. They had to put her on dialysis. And the
kidneys did start to act again, but nothing like it should have been.
On Tuesday night, because we did not leave the hospital except
for brief times to change, and the nights were the times that we
stayed in the room as long as we could with her, because they
didn't limit your time at night. In the daytime they didn't limit
your time, only if they were doing something to her or to another
PAGENO="0313"
307
child, you could not be in there. But on Tuesday night the monitor
quit working. It just would not work at all. We prayed that it
didn't mean what it did.
On Wednesday morning the doctors came to us and they had
done another CAT scan, and they told us that she was brain dead,
and that they felt they should unhook the respirator, which she
had been on from the very beginning, and so we agreed to let them
do that because we had seen her suffer so much. And within just a
matter of minutes all of her body functions ceased.
But it is something that happens so fast, and parents don't know
enough to even recognize the symptoms until it is too late. And it
is not rare, because she went to a very small school, and they lost a
child in that school last year. They have two teachers who have
lost children to Reye's Syndrome as far back as 10 years, and she
had had aspirin. So I feel that if I had another child, I would never
buy aspirin or an aspirin-related product again, because what she
had happened so fast.
Mr. WAXMAN. Thank you very much for sharing that story. How
old was she?
Mrs. HAPpLE. She would have been 7 on Monday.
Mr. WAXMAN. Thank you very much. We would like to hear from
Mr. and Mrs. Dumigan. If you could, please pass the microphone.
STATEMENT OF GEORGE DUMIGAN
Mr. DUMIGAN. Good morning. Thank you very much. My name is
George Dumigan. Our daughter Jill got sick wtih Reye's Syndrome
and still is. On January 3, the same symptoms that you had, just
like lightening it happened. She had the flu, she is getting over
from the flu, she wants to go out and she wants to play, and she
can't go out and she can't play. We take her in to our local doctor.
He rushes her immediately to St. Raphael's Hospital in New
Haven. Within about 10 minute's she is there. She is diagnosed
within about 1½ hours.
She is rushed over to Yale-New Haven Hospital which is the
treatment center locally. She has been in Yale-New Haven-well,
let me give you a little bit of the background too. We go in there
and we have the same anxiety, the same tension, the same every-
thing that you are feeling and anyone else is feeling when they see
their children hurting. We are told 3 to 4 days something is going
to happen, or possibly 6 to 12 days, at the outside chance-16 to 22
days, 16 to 22 days, right?
The first 3 to 4 days we are up all night and all day. Diane is
either up at nights or I am up at nights, or she is up in the day
and I am up in the day. Three to four days pass. We watch the
monitors. We see the brain pressure go up to whatever, forties,
thirties, fifties, whatever it is. We see all the other regulators. We
are watching it. Three to four days pass and that is past. We are
saying to ourselves, well, isn't it supposed to get better? Isn't it sup-
posed to get better?
Six to 12 days pass, the same thing, 6 to 12 days watching the
monitor go up and down, blood pressure go up and down, every-
thing else. After the 12th day passes we are saying, well, it is going
to be 16 to 22 days, hey, you know, that is it. Sixteen to 22 days
PAGENO="0314"
308
pass. What happens still? She is still on the monitor. We are still
watching the brain pressure. We are still watching the blood pres-
sure, and everything else. After 30 days the doctors are saying: We
don't really know what to tell you, because no one has been this
way before.
After 35 days the same thing. After 40 days the same thing.
After 42 days, 43 days, what happens is she starts to come out of it,
and she starts to come off the medication and off everything else.
What is happening with her right now is she is in Newington
Children's Hospital in Connecticut. She has been taken from Yale-
New Haven, and I can gladly report as a parent that at least she is
living. She is in Newington Children's Hospital, and she is talking.
She is walking, one of the other functions that we take for granted.
Let me just tell you one other thing, too, before I finish. More
than likely, in looking around at the ages of people in this room,
you are probably all 25 to 45 or 50 years old. More than likely you
have been brought up with the TV ads: Take two aspirin, fruit
juice, get sleep, and what is going to happen to you is you are going
to get better.
Well, do you know something? In many cases that may be true,
but it is not true in all cases. It is not true in all cases. And it
strikes me that if there is a relationship between the taking, the
ingestion of aspirin and the getting of this dreaded viral disease,
Reye's, if there is some connection then you should know about it.
You should know about it so that your children don't get the same
thing.
Something else. One night about the 20th night, the 25th night
into the whole ordeal Diane was talking with one of the doctors
there and saying what about this, what could we have done differ-
ently. Obviously, feeling as every parent probably would in here,
what did we do wrong. What could we have done differently to
change this.
One of the doctors turned around to her and said, you know, it's
very similar to aspirin poisoning, very, very similar.
We have heard statements from Congressman Waxman this
morning limiting the age to 19. You don't have to be a teen-ager or
an infant to get it. You can be older and still get it. Do you know
something-you can be you and still get it. Right here, right now,
you can be you and get it by taking it. Does it happen in all cases?
No. Can it happen? Yes. Should you be aware of it? Absolutely.
Thank you very much.
Mr. WAXMAN. Thank you very much, Mr. and Mrs. Dumigan and
Mr. and Mrs. Happle. Your children have been affected this year,
this flu season. Of course, you didn't know taking aspirin was any-
thing dangerous. The same was true of the Freudenbergers and
Taubins, although they experienced the same thing some time ago.
You just didn't know.
Now let me ask you-maybe I will address this to Dr. Taubin-
you are not only a parent but a physician. I don't know if you are a
pediatrician or not. Are you?
Dr. TAUBIN. No.
Mr. WAXMAN. What would you recommend to worried parents
when they hear about something called Reye's Syndrome, that they
PAGENO="0315"
309
never heard about before, and they want to protect their children
from Reye's Syndrome? What should they do?
Dr. TAUBIN. I think you have to believe in what you hear
through your pediatricians, through TV now and through PTA
groups. Several years ago we tried, and I became the National Vice
President of Reye's Foundation and John and I have worked
throughout the country for awareness and for research projects in
trying to let family members, not only the pediatricians or family
doctors aware of this disease. It was very difficult 4 or 5 years ago
to have PTA groups hear us.
It was very difficult to have pediatricians hear us because, as you
are so well aware, I had never seen a case. Four or 5 years ago
these were two sentences in a pediatric book saying you will never
see it again.
Mr. WAXMAN. Now that they know about it, people have heard
about it, what should parents be aware of? What do you tell par-
ents?
Dr. TAUBIN. What we tell parents now is if in a symptom com-
plex, if they have a flu or a viral syndrome we know what those
are, the muscles ache, the head aches, a little nausea or chicken-
pox, don't take aspirin or aspirin products. There are many over-
the-counter aspirin products. If the child gets very ill, call your pe-
diatrician.
If he says to you-we tell this on the phone when they call, they
say for the fever, high fever take aspirin, say is this Reye's Syn-
drome. Is there a question? Many parents are aware of it now. We
don't have to treat every symptom; you don't treat every fever or
muscle ache or headache or a sore throat with a drug. Most of
them get better.
The country is so involved in taking medication, this is one case
where you push away and say, gee, don't take it. It will hurt you
rather than help the situation. If there is any question in your
mind, you call your pediatrician. If he doesn't know, and it is possi-
ble he may not know the symptoms, then go to your nearest emer-
gency room and hopefully they will know the symptoms. If you are
not sure at all, don't take it.
Mr. WAXMAN. Mr. Dumigan, when did your child take the aspi-
rin? What date, approximately?
Mrs. DUMIGAN. The first few days of January.
Mr. WAXMAN. The first couple of days of January, around the
time the Secretary was saying she acknowledged the fact this was
a problem and we had to do something about it and started to talk
to the aspirin manufacturers about some voluntary action on their
part to warn people. If you picked up an aspirin bottle and it said
on that label "If you are looking at flu symptoms, consult your
physician," would that have meant anything to you as parents
then?
Mrs. DUMIGAN. I don't know whether I would think about it that
much. If it just said contact your physician if she was sick in the
middle of the night-I mean those things happen. You just give it
to them in the middle of the night.
Mr. DUMIGAN. Can I respond on that too?
Mr. WAx~N. Sure.
PAGENO="0316"
310
Mr. DUMIGAN. Different people respond differently to informa-
tion. If you say to some people, look, hey, you don't take aspirin
period, under these conditions, getting over flu or getting over
chickenpox, that works. That works. With other people it may not
necessarily be the case. You may have to say to them, hey, don't
take aspirin when getting over from these conditions, and here is
the reason why.
We know now in the country the question, the authority that
doctors had 50 years ago when they said, hey, don't do this, is not
always taken by people the same way. So you may have to give rea-
sons for not doing it now.
There is no question about it, that if you put a label on the aspi-
rin, that would work for a lot of people, no question about it. And
pediatricians should still know that, hey, the reason you don't take
it is this. These things can happen from it, and that is why not to
do it.
When our child went in January 3 to Yale-New Haven, you don't
read the newspapers, you don't watch TV or anything else. By Jan-
uary 8, 9, 10 a lot of people were calling up and saying, "How is
Jill', and we're saying, "Well we don't know how Jill is. She is
much the same."
"Did you give her aspirin? Did you give her aspirin?" That was
the question that was echoed over the phone time, and time, and
time again.
And the answer was "Yes; we gave her aspirin. Yes. Is it so dif-
ferent from what you would do? Is it so different from what you
would do?"
"Probably not. Probably not." The awareness that was made
through the TV, the newspapers certainly helped a lot of people, no
question about it, and I think it would have helped us too.
Mr. WAXMAN. Mr. Freudenberger, you are the chairman of the
parents' organization, and later in the hearing today we are going
to receive testimony from a group called the Aspirin Foundation.
They are going to tell us that a Reye's parents' group oppose a
mandatory aspirin label. Do you agree with that statement? Is that
your position?
Mr. FREUDENBERGER. No; that is not my position at all. There are
three parent groups combating Reye's right now, that I am aware
of, the National Reye's Syndrome Foundation in Bryan, OH, the
Reye's Syndrome Society of Michigan, with whom just last week we
agreed to merge, and those are two largest groups.
There is another group based in Denver that is a very weak
group, a small group, and has always yielded to the Aspirin Foun-
dation's. It was last year when the aspirin, or 2 years ago when the
Aspirin Foundation's opinion that there shouldn't be any labeling,
the Denver group thought that there shouldn't be any labeling.
Mr. WAXMAN. So there is evidently a parents' group that seems
to---
Mr. FREUDENBERGER. They are weak and they need the money of
the Aspirin Foundation, I believe.
Mr. WAXMAN. I wasn't aware there was another parents' group,
but you are saying there are other parents' groups. Two of the
groups do support a warning label and for whatever reason the
third one takes a different position?
PAGENO="0317"
311
Mr. FREUDENBERGER. Yes.
Mr. WAXMAN. Some industry spokesmen have criticized this leg-
islation as unnecessary and needlessly frightening to consumers.
Do you agree?
Mr. FREUDENBERGER. No, not at all. We have been faced with
that kind of idea for a long time. From the very beginning, when
we were driving home from the hospital after Tiffinni had just died
and I said to Tern, "We have got to send out letters to doctors and
tell them what Reye's Syndrome is," so that is what I have been
doing for over 12 years now, telling people what Reye's Syndrome
is, and you go into a community and you get resistance.
You go to the school nurse and you say, "Hey, we ought to hand
this out." And she goes to the county health department and talks
to the doctor there, and too frequently we hear, you know, "We
don't want to panic the community." You know what their defini-
tion of "panic the community" is? That doctor is going to get some
phone calls.
You know, there are kids that are going to be sick and they are
going to get a phone call whether to use aspirin or not. And I say
that when you are a doctor you are committed to that. You know,
you are committed to treat people, and ignorance is no way to solve
a problem.
Mr. WAXMAN. Let me say to all of you that in the time that I
have been chairman of this Health Subcommittee, over and over
again I have been impressed by the fact that people who know the
most are the people who have had to live with the consequences of
an illness or disease. More than the doctors and more than the
drug manufacturers and more certainly than the government offi-
cials in charge of protecting the public health, because they have
taken the time through the painful experience they have had to try
to understand why things aren't being done that should be done. I
can't imagine anything more frightening than having a child with
Reye's Syndrome, and I would rather have a warning on aspirin
bottles to warn a parent about this danger, even though it may
scare some people. That is exactly what should happen.
The fact you have been willing to come here today and share
your own personal experiences with us has been very helpful to us.
I know that you have committed yourselves to working to inform
other parents and the medical community and the Secretary of
Health and Human Services and everyone else that this could have
been avoided in your circumstances, and you want to see it avoided
with other families so they don't have to go through what you have
gone through.
Mr. Wyden.
Mr. WYDEN. Thank you, Mr. Chairman.
I want to commend all of you for your great courage and your
tenacity. It seems to me that it shows a special strength, to be out
continually working for changes. I only have one question. You
have all been directly affected by this and you have dealt with gov-
ernment, basically at every level, to get solutions to this situation.
Do you think that, by and large, government has been responsive?
Has government been listening to the concerns of parents?
Mrs. DUMIGAN. No, I don't think government has been respon-
sive enough. I, too, am in the medical profession. I am a nurse, and
PAGENO="0318"
312
I didn't know that much about Reye's Syndrome other than the
name, and I don't think anybody who hasn't experienced it or seen
it in an intensive care unit can imagine it. You just can't imagine
what your child is going through. They have a tube into their
brain. Our daughter had four ventriculostomies into her brain at
different times. They have at least three or four IVs going into
their veins or arteries. They can be on dialysis. They lose weight.
My daughter developed bed sores from the time that she couldn't
be moved because of the terrible pressure in her brain.
I mean, I see patients and it is just devastating when you see
children like this. It is the most intensive therapy I have ever seen,
and I don't think government has been responsive. I think we need
a label warning that says Reye's Syndrome, and people really need
to know what Reye's Syndrome is, not just a name but they need to
know the devastation that this wreaks on a family and the child.
Mr. WYDEN. Would any one else care to comment?
Mr. FREUDENBERGER. If I might comment, I have been working
with government for 10 years, and like some of your comments
today, I don't know why we couldn't have had labeling already at
the start of this flu season, and in those 10 years what I have had
to learn is to be patient. It just takes a long time, and I don't think
it needs to take a long time, and I think I am seeing more and
more response from government, and I think there is still more
needed.
Mrs. FREUDENBERGER. We have been hearing a lot of the com-
ments this morning directed to parents, but in the last few years
we have seen a large increase in the number of Reye's Syndrome
cases that have occurred in late adolescence, and this warning is
very important for the children in this country who are self-medi-
cating. We need that warning on there, because when they are
sick, they are away, they are going to go and put their hands on a
bottle of aspirin as fast as they can. They are not going to ask their
parents if they can take something. They are going to go ahead and
do it. That label has to be on there for them as well.
Last year in Ohio we lost two adults, one 19-year-old and one 27-
year-old man. It is happening in the adult population. We are not
recognizing it in children as well as we should be, and we are cer-
tainly not detecting it in the adults, but it is there, and one day we
will know a lot more about Reye's Syndrome than we know right
now.
Mr. WYDEN. I really appreciate that comment, because it seems
to me that probably this evening millions of Americans of all ages
are going to head home and reach for an aspirin bottle, and what
you have said is that we need a little bit better information before
we make that decision. I think the Federal Government just
dragged its feet.
I am not sure whether it is bureaucratic bumbling or just plain
indifference, but clearly it has got to change, and just the fact that
all of you are here to deliver this information because you have
been directly affected is going to speed up that process, and I thank
you for being here.
Mr. WAXMAN. Thank you very much. Mr. Bates, any questions or
comments?
PAGENO="0319"
313
Mr. BATES. The only question I had is the circumstances that
have occurred and what you members of the panel have had to live
through is hard to even imagine. Certainly everyone would have to
try and empathize and sympathize with the situation. I was curi-
ous, with the Reye's Syndrome organization that you founded, and
that some research is being done, how much do we know in terms
of the conditions or the kind of individual that would be susceptible
to the aspirin.
It seems to me that in terms of the use of aspirin, the tremen-
dous use of asprin, and even if it is not a rare disease, that it seems
to strike only at random or certainly not everyone who takes aspi-
rin gets Reye's Syndrome, I am just curious as to what research
and what more should be done in that area to try and determine
more about it. Anyone who has any knowledge on that?
Dr. TAUBIN. One of the problems we have is it is not a totally
reportable disease. When you get out statistics from the Communi-
cable Disease Center they say there is a certain number of cases.
They are not reported. The disease, if it is classic, you may not
miss it. A pediatrician may not. They take children to the emer-
gency room. During the flu season we talked to an emergency
doctor. Well, he has the flu. It is overwhelming.
The problem we have is that it masquerades as a disease. A teen-
ager who goes into the emergency room screaming and cursing and
yelling, the first thing you think of is not Reye's Syndrome but
they are going to think of a drug overdose.
The pediatrician told us that they develop vomiting and head-
aches and irrational behavior with screaming and lethargy and sei-
zures and you think of a meningitis or infection of the brain, not
Reye's Syndrome.
How many cases in this country are sitting in just hospitals or
small hospitals that are called something else. They are never
called Reye's Syndrome and because of that they are given aspirin
in the hospital. We all know we have been through cases of chil-
dren being tied down in a psychiatric hospital-one in Maryland a
couple of years ago where the child eventually died and the autop-
sy showed Reye's Syndrome. How many physicians have seen this
and are unable to report it?
We have a pediatrician here in the area who tried to report to
CDC approximately a number of 13 or 14 cases about 3 years ago
and was sent back on a CDC form saying document more forms. He
got so disgusted he didn't send it back. You have a listing in our
journals in CDC of Reye's Syndrome. There maybe more and more
unreported cases or cases masquerading as another disease. More
and more because the child may not have all the classic symptoms.
They may say I am not going to bother my physician at 2 o'clock in
the morning.
One of the big things we have to do is better report diseases, a
better way for the physician to send to the CDC or to the local
State department, health department, a means of identifying
known cases of Reye's Syndrome. There are five stages. There is
the now considered stage zero in which there is minimal symptoms
of headache, you get a little vomiting and they get better with this.
How many children who have a cold, a little flu symptoms, you
wouldn't think of calling your pediatrician. Let me call your teach-
PAGENO="0320"
314
er and stay home for a day or two, take a little fluids, a little weak
soda, and maybe some aspirin and you will get better tomorrow.
How many of these cases took the aspirin and developed Reye's
Syndrome in such a mild, mild stage of Reye's Syndrome that could
be totally stopped.
There isn't a member of this board here or other members of the
family life with the rest of their lives knowing we gave something
that our children and the child here-how can you forgive us? I
don't want to be here. None of us want to be here. We have a
rea~~ to be here and hopefully there will be no more parents sit-
ting here.
You have to start now. You have to give a child or the parents a
chance to survive and live because it is the most devastating illness
you are going to see. I will never forget it and our family will not.
The only hope we have and support we have is we as family mem-
bers and our other children say you have got to do something now,
you can't worry about how much money they are going to lose to
the aspirin people and wait for more studies and more studies and
more articles to come out, more letters to the editor. I see in our
field of medicine that you cannot to that. There is a problem, you
stop the problem now, and be aware of it, and if there is a reason
not to give it, why take a chance and wait for 15 journals to come
out.
Thank you.
Mr. WAXMAN. Mr. Scheuer.
Mr. SCHEUER. Well, Mr. Chairman, I want to express my appre-
ciation to these witnesses who have come and tell them how deeply
touched I have been to hear their testimony. It is almost a heart
wrenching-it is a heart wrenching experience, especially for
anyone who is a parent. I raised four kids. I realize how lucky I
was and how lucky my four siblings and I-the five of us-were,
because the principal on which my parents raisd me and I raised
my four kids was if it hurt on the outside you put vaseline on it, if
it hurt on the inside you take a couple of aspirins. How lucky we
were we didn't have a case of Reye's Syndrome in our family.
I am concerned with this notice. I am concerned that it doesn't
tell us enough. It says don't take aspirin if your child has symp-
toms of influenza, chicken pox or flu. I wonder how many Ameri-
can parents at every educational level-I have three university de-
grees, and I have raised four kids-I couldn't tell what the symp-
toms are for influenza, chicken pox or flu. How many parents do? I
think if you stopped a thousand people at the corner of 42nd Street
and Broadway, you would be lucky to find five of them who could
even give you a rough estimate of the symptoms of influenza,
chicken pox, or flu.
So I am sending up an early warning signal, a yellow flag, I don't
think we are telling parents enough. I think we have to tell them
what the symptoms are that they have to watch out for. Normally
we take aspirin when we don't feel very good. That could be a
headache. That could be a little temperature. We have to distin-
guish between these symptoms for we all are used to taking aspirin
as sort of a magic potion for a mild symptom of some kind.
We have to be far more selective and I think there is a real edu-
cational job to do with parents and also with adults apparently,
PAGENO="0321"
315
and I am not at all persuaded that the notice goes far enough. I
would like to see some kind of listing of the kind of symptoms that
we must be aware of and--
Mr. WAXMAN. Would you yield? I think you make an excellent
point. I am interested to hear from the next panel of pediatricians
and other, physicians, what those symptoms are. Also, how the
warning label, was negotiated with the industry by the Secretary of
Health and Human Services. It does not say don't take aspirin for
symptoms of these illnesses, it simply says if you have these illness-
es, consult a physician before taking aspirin. So there is very, very
little information that is there.
But I think you raise a good point-what are those symptoms,
how are they different, how would anybody know if you have a
headache or nausea or a backache or muscle ache whether it is
from flu or--
Mr. SCHEUER. Or a slight temperature.
Mr. WAXMAN. Or a slight temperature, or from a whole range of
possible illnesses. Most likely what you do is pop an aspirin and
hope you get better.
Mr. WYDEN. I happen to agree completely with what you are
saying. It seems to me we have got an enormous education job to
do and this warning is just one piece of the job that we ought to do.
There is a lot of resources out there. For example, we are going to
hear, I understand, from the retail pharmacists, who said that they
feel that there is a role they can play in helping to educate the
public.
So I think the gentleman is right on point. I see this as just one
piece of a very large educational undertaking that we have got to
do in this area.
Mr. SCHEUER. I thank my colleague.
Mr. WAXMAN. Mr. Bates.
Mr. BATES. Well, in trying to react to the comment, I certainly
wouldn't know the symptoms of any of these things either, but
then as I think about this, the more we put on here-I think Hap-
ple's statement is one that I would take, it is overreaction. I would
say I am not going to use aspirin for anything because I don't know
enough about the symptoms, I am not taking any chances. I think
that probably is the reaction of a number of people so that the as-
pirin sales aren't going to drop a little, they are going to drop a lot,
and I think that the idea of consulting a physician may be a good
idea, but I certainly think this warning is minimal.
I think maybe how it should be worded or the extent of the infor-
mation there, that is why I was sort of probing on the research
that has been done on what is it in aspirin that activates or causes
the Reye's Syndrome, and I suppose we will get into that as we go
along.
Mr. WAXMAN. I think these are important issues to explore.
Mr. SCHEUER. The warning does say it is a salicylated product,
which nobody understands, and it doesn't help them very much,
but it doesn't give them the information they need to know when
they can safely take aspirin, and it is a health and comfort in the
overwhelming majority of cases I suppose. But we have got to have
the hard numbers to know when we can take it safely and enjoy its
52-266 0-85--il
PAGENO="0322"
316
health and comfort enhancing effects and when we have to avoid it
like the plague.
And I honestly think that we know all about-we are told about
salicylate, which I am probably pronouncing badly, don't have the
remotest idea what it means. That is not the relevant information
that we need. We have to know what the symptoms are so we can
get the benefits of aspirin for most of the time when we could take
it safely, have that early warning signal for the few times, but the
highly important times when we must avoid it. We must have the
specific knowledge to avoid it.
And probably I think Congressman Bates is right, it probably
can't be done on a label. We have got to crank this into our health
education-and we have improved our health education vastly in
the last decade or so-but this certainly is something we can think
about and I don't think we can stop with the language that is on
that label. To my mind, it is insufficient and leaves out critically
urgently needed information.
Mr. WAXMAN. Thank you, Mr. Scheuer.
Let's hear from other witnesses today what they think ought to
be the appropriate actions to be taken by Congress and then we
will see what legislation we ought to be passing. But I think we all
so far are at least of the opinion that action so far may not be
strong enough, what was negotiated by the Secretary is certainly
inadequate.
Thank you very much, this panel of witnesses, for being with us.
We appreciate your willingness to share your views with us and
your experiences.
I would like to call forward a panel of Dr. Sidney M. Wolfe, di-
rector, Health Research Group, Dr. Albert Pruitt, FAAP, chair-
man, Committee on Drugs, American Academy of Pediatrics, ac-
companied by Dr. Harry Jennison, executive director, American
Academy of Pediatrics.
STATEMENTS OF SIDNEY M. WOLFE, M.D., DIRECTOR, PUBLIC
CITIZEN HEALTH RESEARCH GROUP; AND ALBERT PRUIVF,
M.D., FAAP CHAIRMAN, COMMITTEE ON DRUGS, AMERICAN
ACADEMY OF PEDIATRICS, ACCOMPANIED BY DR. M. HARRY
JENNISON, EXECUTIVE DIRECTOR
Dr. WOLFE. I know I had a great deal of difficulty emotionally
listening to what we have just heard. A number of parent whose
children have died or been brain damaged have called me during
the 3 years since we have started working on it and I guess it is
particularly frustrating to me. We are in the middle, as you know,
of legal action against the Government to require warning labels,
particularly a phrase stating that we are, if not 100 percent, close
to 100 percent certain we have got an identifiable agent-aspirin-
that can prevent a disease. It is a classic preventive medicine, yet
we have got a really unethical, illegal and moral response by the
Federal Government and its partner, the aspirin industry.
Nothing can more clearly highlight the need for this legislation
than the statements by parents whose children died or became
brain damaged as a result of Reye's Syndrome. No parent would
ever give or have given a child aspirin for treatment of chicken pox
PAGENO="0323"
317
or flu had they known of the strong association between the use of
aspirin in these circumstances and the greatly increased rjsk of
contracting Reye's Syndrome.
Especially tragic is the plight of over 610 children, 175 now dead,
who have gotten Reye's Syndrome since the beginning of 1982, sev-
eral months after an October 14, 1981 CDC-Centers for Disease
Control-Advisory Committee recommended that the use of aspirin
"should be avoided" for treatment of chickenpox or flu. Almost all
of these children had been given aspirin. Their deaths and injuries
were thus preventable.
The evidence that aspirin is strongly associated with Reye's Syn-
drome is now based on five studies, four of which were completed
over 3 years ago. Three years ago, Public Citizen Health Research
Group petitioned FDA to require warning labels on all aspirin con-
taining products and later, along with the American Public Health
Association, filed a lawsuit against FDA. In remanding the case
back in the U.S. Federal District Court, the U.S. Court of Appeals
said, of HHS's November 1982 reversal of its earlier plan to require
warning labels:
The record evidence indicating that industry pressure precipitat-
ed this reversal is parti~ularly troubling in that the pace of agency
decision making may jeopardize the lives of children. . . . The cur-
rent record strongly suggests that the pace of agency decision
making is unreasonably dilatory. All scientific evidence in the
record points to a link between salicylates and Reye's Syn-
drome. .
Over 2 months ago, HHS Secretary Heckler asked the aspirin
makers to voluntarily:
First, immediately remove any labels which recommend that as-
pirin products be used to treat flu or chicken pox in children or
teenagers;
Second, further label all aspirin products to indicate that there is
a possible association between the use of aspirin and the onset of
Reye's Syndrome in children and teenagers, and that aspirin prod-
ucts should not be used in those cases unless a physician is first
consulted.
That subset of aspirin makers who belong to the Aspirin Founda-
tion later "voluntarily" agreed to put warning signs in drugstores.
First, child and adult aspirin products with labels still recom-
mending flu as an indication for aspirin use.
As of this week, the following nationally distributed aspirin prod-
ucts were found in drugstores with labels recommending use for
treatment of flu:
Children's aspirin: St. Joseph's, Bayer.
Adult and therefore teenage aspirin: maximum strength Anacin;
regular, maximum and arthritis strength Bayer; regular and extra
strength Bufferin; Excedrin.
Thus, Secretary Heckler's first request for immediate removal of
such labels is not being taken seriously since it is voluntary.
Second, relabeling all aspirin products to warn against use of
chicken pox, or flu, because of the increased risk of Reye's Syn-
drome:
PAGENO="0324"
318
Secretary Heckler's second request has been met with equal en-
thusiasm by the aspirin industry. A survey by phone of 53 drug-
stores in 31 States found that no store had aspirin products with
labels. The voluntary promise by the Aspirin Foundation to label
newly manufactured products has not yet showed up in the stores,
nor when it does, will the labels mention Reye's Syndrome.
Third, the Aspirin Foundation promise to voluntarily put warn-
ing signs in stores:
Of the 53 stores surveyed this week, only 17 had posters, many of
which had come from the American Pharmaceutical Association,
the pharmacist organization which sent members a warning poster
1½ months ago. In other words, over two-thirds of the stores had
no warning poster.
In summary, the voluntary program is a cruel disaster. During
this heavy flu and chicken pox season, no aspirin purchased in this
country has warning labels and some of the biggest selling products
actually recommend use for treatment of flu.
Because HHS has failed to require mandatory warning labels,
the introduction and passage of H.R. 1381 is very important. By
taking into account interim warning labels, advertising, signs in
the stores and the labels for future manufactured products, it
covers four crucial areas which have been left largely unimple-
mented as a result of the voluntary approach. H.R. 1381 also recog-
nizes that many people don't have a doctor to go to and that many
who do, don't consult her/him for chicken pox or flu. Thus, the
straightforward language that "this product should not be given,"
rather than "consult your doctor" is quite appropriate.
In conclusion, there is little doubt that many of the hundreds of
children and teenagers who have died or suffered brain damage
from Reye's Syndrome would be alive and healthy today if the
Reagan administration had not yielded to pressure from the drug
industry 2½ years ago and canceled its plan for mandatory aspirin
warning labels.
Thank you.
I would like to make a couple of comments concerning the kinds
of things that at least are likely to be said, because we have seen
the people from the industry and the apologies from the govern-
ment testifying and talking over and over again for 3 years on this
issue.
I am getting sick and tired of hearing from the aspirin industry
and from the government that there are flaws in the studies. If
there are flaws they are minor. The main flaws are in the people
who have stopped the government from issuing warning labels 2½
years ago. There are flaws in terms of the health of what the gov-
ernment has not done. There are flaws in the morals and ethics of
Dras and anyone else who participated in any way to block some-
thing that could have saved the lives of many children and pre-
vented a lot of brain damage.
The studies that have been done, particularly the last two, the
one that was completed, the first part of which was completed a
few months ago, and the one completed over 3 years ago, will go
down as landmarks in the ability to use case control studies to de-
termine the cause of illnesses.
PAGENO="0325"
319
I think one of the most frightening things, as recently as 1984,
the beginning of this year-last year-about 40 to 45 percent of the
parents were still giving their children aspirin for treatment of
chicken pox or flu or similar symptoms. That is the proof that the
voluntary, the educational approach as opposed to automatic warn-
ing labels, that we need the full scope of every kind of possible way
of reaching these parents.
Thank you.
Mr. WAXMAN. Thank you very much.
Dr. Pruitt.
STATEMENT OF ALBERT PRUITT, M.D., FAAP
Dr. PRurrr. Mr. Chairman, members of the House Energy and
Commerce Health Subcommittee, I am Dr. Albert Pruitt, chairman
of the Department of Pediatrics at the Medical College of Georgia,
and chairman of the Committee on Drugs of the American Acade-
my of Pediatrics. I represent more than 27,000 pediatricians who
today comprise the Academy.
Our interest in the relationship between aspirin and Reye's Syn-
drome dates from 1981, when we published a notice in our newslet-
ter apprising the membership about the possible association be-
tween the administration of aspirin to children with influenza and
chicken pox and the subsequent development of Reye's Syndrome.
In February 1982, we issued in our newsletter a similar warning to
all members. In June 1982, after further data became available on
studies in Ohio, Michigan and Arizona, all showing an association
between aspirin and Reye's Syndrome, a special report was pub-
lished in "Pediatrics." This statement said in part:
Aspirin should not be prescribed under usual circumstances for chidren with van-
cella or those suspected of having influenza on the basis of clinical or epidemiologi-
cal evidence. . . Inasmuch as salicylates are over the counter preparations, educa-
tion of parents to their avoidance in influenza and varicella requires a total commu-
nity effort. We urge that the appropriate governmental agencies undertake appro-
priate review and necessary action to inform the public at large. We also believe
that manufacturers of salicylates should cooperate in informing prospective users of
the relationships detailed in this report.
Since 1982 when that statement was published, and to a degree
at the urging of the American Academy of Pediatrics, a carefully
designed research study was undertaken by the United States
Public Health Service to ascertain whether the administration of
aspirin would continue to show association with Reye's Syndrome.
With the advice, of a committee of the Institute of Medicine, Na-
tional Academy of Sciences, chaired by Dr. Floyd Denny, a distin-
guished pediatrician and Fellow of the Academy, with expertise in
infectious diseases research, a protocol for a multicenter study was
developed by the Centers for Disease Control, and the pilot study
began in February 1984. The results of that pilot study have now
been presented.
Mr. Chairman, we believe that there is today more reason than
ever to warn the public, and especially young adolescents, about
the association between aspirin and other pediatricians and Reye's
Syndrome. A surprising number of Reye's Syndrome patients in
the pilot study were young adolescents who presumably took adult
strength aspirin without physician advice. Aspirin can no longer be
PAGENO="0326"
320
regarded as an appropriate medication for flu for a child or young
adult, nor should it be taken for an illness which might be chicken
pox.
Because aspirin is largely self-medicated by young adults, it is
important that the labeling read by the consumer be unambiguous
on this point.~ The American Academy of Pediatrics supports label-
ing which provides current information about the relationship be-
tween aspirin and Reye's Syndrome, and we therefore support the
intent of this legislation.
Also, as a scientific organization, the appropriate Academy com-
mitteés have been asked to review the complete data and make a
determination if those data are sufficient to warrant immediate
steps by the Federal Government. We are undertaking that review
now. Please recognize that the data review is a different proposi-
tion from taking every precaution to protect our children now. We
are here testifying to the latter.
The Academy was asked for comment on HHS Secretary Marga-
ret Heckler's announcement of the voluntary labeling approach.
We supported that. Yet we remain deeply concerned that the mes-
sage about aspirin and Reye's Syndrome get to the consumer, and
this has caused us to question the effectiveness of voluntary label-
ing. Accordingly, we have met recently with representatives of the
Food and Drug Administration to press for progress in this area.
We recognize the urgency of definitive actions, and would hope this
hearing will serve as the necessary catalyst to encourage a suitable
response by FDA and the industry. Ideally, we feel this would
happen without legislation, but as a practical matter, it may not.
Outside of the labeling issue at hand, research in this area must
be continued and a full PHS study must follow. In the interim, the
Academy will continue to state its position that aspirin not be pre-
scribed for children or young people with varicella or influenza. It
is our intention to work with you, Mr. Chairman, in the speedy res-
olution of this issue. When our children are at risk, they most cer-
tainly deserve the benefit of any doubt, and we are confident that
through your leadership, appropriate public policy will be forth-
coming.
I appreciate the opportunity to address the committee, and I
would be glad to answer questions.
Mr. WAXMAN. Thank you very much, Dr. Pruitt.
Dr. Pruitt, Dr. Jennison, Dr. Wolfe, let me commend each of you
and your organizations for the strong stand you have taken with
regard to trying to prevent this particular disease and others as
they affect children and to press for effective action that will ac-
complish that goal.
Let me ask you, Dr. Pruitt-the question came up earlier about
symptoms-if I were a teenager and I got a headache or felt nau-
seous or felt muscle aches, or if I were a parent and heard my child
complaining about, these kinds of symptoms, how would I know if it
is chicken pox or a virus-flu-or something else? Under what cir-
cumstance would I be able to make a decision that aspirin would be
appropriate?
Dr. PRurrr. I think it is important to note that there are really
no specific symptoms for the diagnosis of influenza. We all know
that with influenza, one might have low grade fever, usually have
PAGENO="0327"
321
muscle aches, and/or have a headache, but it does not necessarily
mean that every time you have those symptoms that you have flu,
a virus infection. There are numerous other respiratory viruses
that can cause similar symptoms.
Chicken pox is a bit of a different matter. Once the lesions, the
rash occurs, then the diagnosis is obvious. Prior to the development
of the rash, however, it is very nonspecific. There is usually some
low grade fever. Oftentimes there is a history of exposure to other
children with chicken pox, which can be a help to you.
But it is not possible to make an absolute diagnosis of influenza
simply by examining the patient. It is very helpful if you know
there is influenza in the community. Then there is a reasonable
epidemiologically to suspect that influenza infections are around.
Mr. WAXMAN. Is there a simple over-the-counter medication that
I could give my child when he has some of these symptoms, other
than aspirin?
Dr. PRUITT. I think Dr. Taubin made a very important point, and
that is that we need to be careful not to over-medicate children.
There are many, many times with most infectious illnesses, that
are nonbacterial, the child probably doesn't need any medication.
We overtreat fever. We overtreat other symptoms. I think this also
provides us an opportunity to evaluate whether or not a medication
is actually needed.
Mr. WAXMAN. Dr. Wolfe, if the child is just uncomfortable and
you want to do something to relieve the pain, maybe to lower the
fever, what could a parent do?
Dr. WOLFE. Well, as you know, there is really no evidence what-
soever that there is an association between acetaminophen, which
is the active ingredient in Datril or Tylenol and Reyes. I would
agree with Dr. Pruitt that this country and many others are over-
medicated societies, whether it is tranquilizers or pain killers or
fever lowerers or whatever. I think in many or most of the circum-
stances no medication is indicated.
I would agree with Dr. Pruitt that if one wants to make a defini-
tive diagnosis as a pediatrician or anybody else, of influenza, there
isn't any specific set of symptoms. You are really in a sense asking
the other question, what kinds of things that might be i'~iiuen-
za--
Mr. WAXMAN. I appreciate the statement that we most likely can
forego any medication with children and they will get well and we
are certainly taking minimal risk of a side effect from a drug if we
don't give a child--
Dr. WOLFE. That is the active ingredient in Tylenol, Datril, and it
is the nonaspirin. In fact, the companies that were the biggest sell-
ers of children's aspirin several years ago, anticipating that eventu-
ally as hard as they would try, they would lose this battle-a lot of
dead children in the interim-started selling very vigorously nona-
spirin products. So that you have children's products, Bayer and St.
Joseph's nonaspirin. I think nonaspirin has become a more famil-
iar word than acetaminophen. What it is is another ingredient or
chemical that can lower fever and treat pain, which is not aspirin,
which is not linked in any way to Reye's Syndrome.
Mr. WAXMAN. Are there nonaspirin pain killers?
PAGENO="0328"
322
Dr. WOLFE. And fever lowerers. Like Kleenex and Jello it is be-
coming a generic name.
Mr. WAXMAN. A nonaspirin pain killer, fever reducer is it less
available, can I buy it? I know this kind of risk is a possibility.
Dr. WOLFE. One of the issues that has been raised-I think it is
something to think about-but it affects such a small number of
children, juvenile rheumatoid arthritis, a severe form of arthritis,
which starts at a young age, the best treatment for this is aspirin.
However, even when these children are getting an illness like this,
if they were to call their pediatrician and they would probably be
told to discontinue it.
So I think that the answer to your question is that even though
we can't make the definitive diagnosis of influenza a lot of times,
for reasons Dr. Pruitt that by adding a very tiny amount to the
label or to the thoughts and to the educational campaign that
would include, for example I mentioned colds, coma, fever, head-
ache, intestinal problems as examples of symptoms, any one of
which might indicate something that really is the flu, we would be
more communitative.
I think it is interesting that a poster that was to be sent out a
month ago to 47,000 junior highs, high schools and 2 year colleges
by the Food and Drug Administration, was canceled, destroyed at
the request of the aspirin industry because it had a phrase in it
"other viral illnesses." The Government wanted to go beyond
chicken pox and flu and include a phrase which would have at
least broadened the scope and terms of people looking at the
poster. That was destroyed. It has now been replaced and now, I
am told, sent out in the last few days.
There was an effort to make more communicative what the Gov-
ernment was doing, which has, as you pointed out, a number of
other flaws. The industry didn't like it, therefore, it was canceled.
Mr. WAXMAN. Let me ask a very straightforward, simple ques-
tion of you, Dr. Pruitt. You are a pediatrician, patients want to
know from you as a pediatrician. If my kids get sick during this flu
season, should I give them an aspirin?
Dr. PRUITT. No, sir.
Mr. WAx~N. Mr. Bates.
Mr. BATES. No uestions.
Mr. WAx~N. Let me-one point I was impressed by-we always
think of children. We are talking about teenagers, up to 21 years
old, who are self-medicating. These are people being conditioned by
all the ads we have seen on television over the years, got a pain,
take an aspirin. Is the advice that you would give to a college stu-
dent under the age of 21 with some of these symptoms, to avoid as-
pirin as well?
Dr. PRurrr. I am not really comfortable placing an age limit on
it. If we had been discussing this matter several years ago, we
would have thought, well, Reye's Syndrome is very uncommon in
the older adolescent, therefore, the older adolescent probably is not
at risk. Now, as we look at more recent data I think the older ado-
lescent is at risk. So I don't know that we can establish an upper
age limit.
Dr. WOLFE. There has been much more success because the typi-
cal Reye's patient has been portrayed of someone 5, 6, 7, 8, 9, in
PAGENO="0329"
323
reducing the number of cases of Reye's in the younger age group. It
has fallen off considerably. In the 10 and above age group there
has been almost no change at all because those people did not get
the message. So I think I would agree. I think in the national sur-
veillance data, 2 percent of the cases were over the age of 20, but
certainly putting an age limit may mislead one person and that
would be one too many taking aspirin for treating of influenza or
chicken pox.
Mr. WAXMAN. I didn't want to get into questions on the science
in terms of the strong feelings whether it is scientifically proven or
not, that there is this link between aspirin and Reye's Syndrome
because I gather you are all satisfied that there is enough of a
link-as the Secretary was satisfied-there is enough of a link for
us as prudent people to make some judgment to warn parents and
others not to take aspirin for these flu and chicken pox symptoms.
Is that a correct statement?
Dr. PRuIrr. Certainly we don't believe that aspirin is a sole cause
of Reye's Syndrome. There are a number of factors which play a
role in the development of Reye's Syndrome.
Mr. WAXMAN. You feel satisfied with the science about the link-
age between aspirin and Reye's Syndrome that you would recom-
mend obviously to avoid taking aspirin for these symptoms?
Dr. PRuIrr. That is correct. We are recommending two things.
One is that, and the other is that this other study proceed, the
study which has already been planned by illS.
Mr. WAXMAN. Absolutely.
Now, the American Academy of Pediatrics supported the volun-
tary effort by the Food and Drug Administration and the Secretary
of Health and Human Services because you wanted something. You
got it. Is it adequate?
Dr. JENNISON. Let me tell you what we have had. We were asked
very shortly after the Secretary announced the volunteer labeling
programs what our opinion was and our office at the academy re-
sponded, yes, that is a step obviously in the right direction.
Since that time, our technical committees have been trying very
hard to understand the more recent data and have advised us that
they are deeply concerned about how the labeling process will pro-
ceed. On that basis, you heard Dr. Pruitt describe the meeting we
had with Assistant Secretary of Health, Dr. Mason and FDA repre-
sentatives just a little over a week ago to express that concern.
Mr. WAXMAN. You are concerned about it and you have ex-
pressed that to the Department of Health and Human Services rep-
resentatives. Of course, we would rather people do what they ought
to be doing and what is best calculated to inform the public rather
than have to pass legislation. But I don't feel that this voluntary
negotiated settlement is adequately reaching most people.
Dr. JENNISON. Could I add an additional comment, if I may, be-
cause several of our committee members may have raised the ques-
tion of the improved public education and the parent group spoke
very eloquently to this. I would have to say the Reye's Foundation
folks have probably done the best job of trying to get information
out. We in the academy have made a strong effort. We would like
to work with them, but I want to point out this group is sophisti-
cated.
PAGENO="0330"
324
We have been labeling cigarettes for 25 years and there are quite
a few people in the room that haven't found it made them stop
smoking. Labeling is not enough, and I hope in your deliberations
you will keep clearly in mind that it is the responsibility of the
Federal Government, the responsibility of the volunteer agencies,
and it is certainly the responsibility of the academy, as a scientific
medical organization, to be on the forefront of public education.
Mr. WAXMAN. Dr. Wolfe, what do you think about the other as-
pects of the administration's attempt to educate the public aside
from the labeling part?
Dr. WOLFE. No one has ever advocated one means of educating
the public on anything, this included. I think we have certainly
always supported every possible creative thing being done, whether
it is signs in stores, supermarkets, whatever. The problem is, that
to the extent that they are voluntary, some will do them and some
will not. That is why I think 3 years ago when the evidence was
strong enough-and we are not talking about perfect evidence be-
cause there is rarely perfect evidence-when it was strong enough
for a Government advisory committee to say October 18, avoid use
of aspirin.
As soon as that threshold was reached, everything should have
been done possible to educate people, including mandatory warning
labels. The separation out of it is enough evidence to tell people not
to do it, but it is not enough evidence to put warning labels is a
ridiculous dicotomy. So we believe that even though labels alone
might not do the trick, labels alone are absolutely necessary for
many people who don't go to a doctor-it is an over the counter
drug-most people will not call a doctor, many tens of millions, as
the Census Bureau points out, don't have health insurance and
may not have doctors.
Mr. WAXMAN. It is inadequate in your opinion, based on what is
being said under this voluntary agreement and on what your own
survey indicates. Is it because the approach is voluntary, that more
is not being done?
Dr. WOLFE. Not only is it not being done, when you have it on a
voluntary basis you sort of come begging, as Secretary Heckler and
FDA and take whatever you can get.
The label that the Aspirin Foundation agreed to doesn't mention
Reye Syndrome. One of the parent's eloquently stated that the
more explicit it is, the more they would pay attention to it. If there
is no mention of Reye Syndrome, let alone Reye Syndrome is often
fatal, people would pay less attention to it and yet, they have
agreed because it is voluntary to let the industry put-there have
been too many instances where pamphlets were burned a year or
two ago, these posters were destroyed last month-that indicate
that as long as it is voluntary, as long as the Government doesn't
take the thing seriously enough to require warning labels, even
their public education campaign is flawed. The statements aren't
strong enough, as you pointed out.
Mr. WAXMAN. In other words, the Secretary of Health and
Human Services has given the aspirin industry a veto over the
most effective way to inform the public because they have to be
satisfied before they would permit the Government to go forward?
PAGENO="0331"
325
Dr. WOLFE. That is right. There are two instances. The one with
the posters being destroyed last month and another I believe was
1½ year ago where a huge number of hundreds of thousands of
pamphlets were too strong to please the aspirin industry and were
recalled, not sent out, and reprinted with a more watered down
version.
You are right. Not only have they vetoed mandatory labels, they
vetoed some of the stronger elements in the educational campaign.
The words "strongly associated" was in this poster. It was taken
out.
Mr. WAXMAN. Dr. Pruitt, we are going to hear later from a group
called the Committee on the Care of Children. Are you familiar
with that group and do you associate yourself either with their
views or are you in any way affiliated with them?
Dr. PRurn~. I personally am not affiliated with the Committee on
the Care of Children.
Mr. WAXMAN. And Dr. Jennison, how about you?
Dr. JENNISON. No affiliation. We are a group of 27,000 members
and I am well aware there are those out--
Mr. WAXMAN. Are you aware of their views on this issue?
Dr. JENNI5ON. Oh yes, very clear.
Mr. WAXMAN. Do you associate yourselves with their views?
Dr. JENNISON. Not in the slightest.
Mr. WYDEN. Just one for either you, Dr. Pruitt or Dr. Jennison.
Is there any tangible scientific evidence which would indicate that
the Administration's approach thus far is sufficient to protect the
public health?
Dr. JENNISON. Well, I can say to you that in the meeting that we
had with Dr. Mason and representatives of FDA, there was out-
lined before us a rather comprehensive sort of monitoring program
which I am told is to commence at some future time. I am sure
someone will comment on that later, but you are asking for tangi-
ble evidence?
Mr. WYDEN. I think you two have been very careful in saying
that the voluntary program is only the beginning, but from all you
have seen in the Administration. Is any credible scientific evidence
which supports their position that what they have done thus far is
sufficient?
Dr. JENNISON. I don't know how you could comment on terms of
scientific evidence. I can only say to this date we have made our-
selves available to help with the development of language or label-
ing or things like that and we haven't been asked to examine any
particular products.
Mr. WAXMAN. Thank you very much, gentlemen. We appreciate
very much your testimony. We will look forward to working with
you on this issue and the legislation as we move it forward.
Thank you very much for being with us.
I would now like to call forward Dr. Frank Young, Commission-
er, Food and Drug Administration, accompanied by Dr. Dowdle,
Mr. Scarlett, and Mr. Michels, representing the Department of
Health and Human Services. We want to welcome you to the sub-
committee meeting today. We are looking forward to your testimo-
ny. Your full statement we will make part of the record in its en-
tirety. We would like to ask you to summarize that statement.
PAGENO="0332"
326
STATEMENT OF FRANK E. YOUNG, M.D., Ph.D., COMMISSIONER,
FOOD AND DRUG ADMINISTRATION, PUBLIC HEALTH SERVICE,
DEPARTMENT OF HEALTH AND HUMAN SERVICE, DANIEL
MICILELS, DIRECTOR, OFFICE OF COMPLIANCE
Dr. YOUNG. Thank you very much, Mr. Chairman. I appreciate
the opportunity to be here and to listen to the concerned comments
of the parents.
I believe that you share, as I do, the concern that this dread sym-
drome is met and met vigorously. It is a tragedy, and as both a
parent and physician, I can identify clearly with their concerns
and great pain that was felt in listening to these discussions.
Let me begin by emphasizing two key points. We feel that we
have under the leadership of Secretary Heckler forged a significant
degree of public/private sector cooperation that addresses both the
short-term and the long-term considerations.
I would like to raise the two points that we feel are very key for
this hearing. First, the definitive scientific data are still not avail-
able, as you know. The existing data were derived largely from pre-
vious state epidemiological studies which demonstrated a possible
association between aspirin and Reye's Syndrome and the signifi-
cance of which was uncertain, and from a more recent limited
Public Health Services pilot study.
The pilot study compared the aspirin by 30 cases of Reye's Syn-
drome with that of 140 controls. The pilot study found nearly all
the Reye's Syndrome cases had aspirin exposure. That is compared
to only about 45 percent of controls. While highly suggestive and
consistent with previous studies, procedural changes and the rela-
tively small size of the pilot project means that its findings should
not be considered definitive. The larger and more positive full scale
study is now underway. Accordingly, the evidence needed to sup-
port the mandatory labels is not in our view available at this time.
Second, there is a voluntary labeling and extensive public educa-
tion program underway, and I will describe that more fully in just
a few moments. I will skip the chronology of the events only to
point out two things:
The first public health announcement that I made was made in
the fall of this year at the onset of the flu season and was made on
Reye's Syndrome. Your 5-minute time does not allow that to be
shown, but I do have the tape here if you wish to see that.
Second, the meeting that was first approach and raised by the
American Academy of Pediatrics, in which they were first exposed
to the data, was started when I was in the Naval Bethesda Hospi-
tal with a temperature of 104°. I felt constrained, though not being
able to be there, started the conversation by phone personally, and
have stayed and remained committed to dealing with this very im-
portant medical problem.
These are the things that were undertaken in regards to dealing
with this disease:
First, the pilot study was to be released and was released, and
very rapidly we saw the program appear in Morbidity and Mortali-
ty Weekly Reports and followed subsequently in the Journal of the
American Medical Association. We felt it extremely important to
get out posters, and I have some displays of some of these that
PAGENO="0333"
327
were put out on Reye's Syndrome very, very early, as well as send-
ing letters to doctors, to consumers, to consumer groups, to phar-
macists, and other people that might be able to influence bringing
this view to the American public.
We have also published recent information of the pilot study in
the current issue of the FDA Consumer magazine. To ensure coop-
eration from the media, the Secretary took the unusual step of con-
tacting the heads of the major media asking their assistance in in-
forming the public of the pilot study results. She also wrote to
health professional organizations, hospital administrators, and
some 173,000 physicians about the new data.
In this regard we consider the professional community, especially
those in pediatrics, to be the most important vehicles in conveying
this type of information. We felt that although the data was not
conclusive at this time, it was imperative to inform, even at this
stage, the American public and follow the approach that we are de-
scribing here.
We reasoned, therefore, that because the data was not complete,
that it was not appropriate to develop a mandatory requirement
for labels. I am pleased to inform you that two events have oc-
curred:
First, we have put out a large number of posters, letters, and in-
formation, as I described and as my full testimony shows.
Second, we have assurances from members of the Aspirin Foun-
dation that the labels will be in place as of the next flu season.
As you know, we do have a labeling from Plough and St. Joseph's
Aspirin, and they did withhold shipment and put a sticker on im-
mediately on those bottles, on those boxes, while the changes in la-
beling was occurring. As you know, it takes a while for labeling
and artwork to be put in place and that period of time would
exceed the time that would be required for this flu season to pass,
and we felt that it should be out as rapidly as possible and if label-
ing isn't .ready for this flu season, that we must have the public
education brought forward. But I did want to show you this for one
change that was made so far.
Finally, we have sent a letter to the aspirin making firms
throughout the country, whether or not they are members of the
Aspirin Foundation, with a questionnaire. I submit this as well as
all other information that we have put forward for the record, so
that we wish to be able to get-the direct input about what they
plan and to close the loop, the very important loop that was men-
tioned here, namely reaching all of the aspirin firms through this
volunteer effort.
I would be most interested, as an educator, to learn of your
thoughts as to ways that we might be able to better influence the
public. We are monitoring this-this is the first time that a volun-
teer effort has been monitored. We not only have taken early
points, as Dr. Wolfe mentioned-but also these posters were just
sent out within the last month to month and a half. We want to
find out how long it takes for penetration, how long it takes for
shelf life and I would be delighted to share these results with you
and receive any suggestions that you or your staff or your subcom-
mittee members have in determining best how to educate and
inform the American public.
PAGENO="0334"
328
I have also with me, Daniel Michels, who is the Associate Direc-
tor for Compliance in the Center for Drugs and Biologics, Mr. Tom
Scarlett, who is our Chief Counsel, and Dr. Walter Dowdie, from
the Centers for Disease Control, who was instrumental in discuss-
ing and determining this study.
I would be glad to answer questions or have you direct questions
to any of the members of the administrative panel.
Thank you.
[Testimony resumes on p. 345.]
[Dr. Young's prepared statement follows:]
PAGENO="0335"
329
STATEMENT BY
FRANK E. YOUNG, M.D., Ph.D.
COMMISSIONER
FOOD AND DRUG ADMINISTRATION
PUBLIC HEALTH SERVICE
DEPARTMENT OF HEALTH AND HUMAN SERVICES
W. Chairman:
I am pleased to be here today to discuss with you H.R. 1381, the
"Emergency Reye's Syndrome Prevention Act of 1985." As part of my
testimony, I will also describe what steps the Food and Drug
Administration (FDA) has taken as well as address, in general terms,
the questions you raised in a recent letter to Secretary Heckler
concerning the voluntary progran being undertaken by leaders in the
aspirin industry. I will be glad to provide a more specific response
to those questions, either *here today or as a submission to the
record.
I am accompanied by Dr. Walter Dowdie, Director, Centers for
Infectious Diseases, Centers for Disease Control, Mr. Tom Scarlett,
General Counsel of the Food and Drug Administration, and Mr. Dan
Michels, Director, Office of Compliance.
Let me begin by emphasizing two key points. The first is that, under
Secretary Hecklers leadership, we have successfully forged a
significant degree of public-private sector cooperation thataddresses
both short-term and long-term considerations. Second, as a physician
and parent, I can assure you that I have not rested, nor will I rest,
until I have convinced myself that we are taking all the appropriate
steps. In fact, the first public service announcement that I made
after becoming Comissioner was on Reye syndrome. Our efforts include
an intensified nationwide program for alerting American parents and
teenagers of the possible association, focusing efforts on teenagers
PAGENO="0336"
330
who self-medicate and therefore are in a different risk group, and
arranging a longer term effort to make appropriate revisions in the
labeling of aspirin and other salicylate-containing products.
Here I would note that this effort augments our prior educational
program for this year's flu season which had been in effect since
November 1984. As has been our practice for the last three flu
seasons, we have tried to plan our public awareness campaigns to
coincide with National Reye Syndrome Week and the beginning of the flu
season. Results have occurred as exemplified by a decline in sales of
single entity aspirin products for children during the flu-season for
the last several years. Also doctor recomendations for the use of
aspirin for the treatment of flu and chicken pox in young children
declined 72 percent between 1980 and 1983. These trends probably
suggest that our public education efforts have succeeded in reaching
consumers and health care providers.
Before describing the specifics of the voluntary precautionary
program which has been initiated, I will first address the bill which
you recently introduced.
H.R. 1381
As you know, H.R. 1381 would require that the labeling of any drug
which contains a salicylate include a warning that that product should
not be given to individuals who have `chicken pox, influenza, or flu
symptoms" because of the association between salicylate and the
development of Reye syndrome. Under the bill, a drug containing a
PAGENO="0337"
331
salicylate which did not bear this warning on its labeling would be
misbranded under the Federal Food, Drug, and Cosmetic Act. The drug
would also be misbranded if manufacturers, packers or distributors
(including retailers) failed to include the warning in any
advertisements or other printed and descriptive matter about the
drug.
We agree wholeheartedly that the American people, and especially
parents and teenagers, should be made aware of the dangers of Reye
syndrome, its possible association with aspirin use, and the fact that
early detection and intervention is critical to the process and
treatment of this condition. We believe, however, that the proposed
legislation is unnecessary for two reasons.
First, the definitive scientific data are still not available. As
you know, the existing data were derived largely from previous State
epidemiological studies which demonstrated a possible association
between aspirin and Reye syndrome, the significance of which was
uncertain, and from a more recent, though limited, Public Health
Services (PHS) pilot study. The pilot project compared aspirin use by
30 cases of Reye syndrome with that in 140 controls. The pilot study
found that nearly all Reye cases had aspirin exposure, as compared to
only about 45 percent of controls. While highly suggestive and
consistant with previous studies, procedural changes made and the
relatively small size of the pilot project means that its findings
should not be considered definitive. The larger, and more dispositive,
full scale PHS study is now underway. Accordingly, the evidence needed
to support mandatory labeling is not, in our view, available at this
time.
PAGENO="0338"
332
Second, there is currently a voluntary labeling and extensive public
education program underway. There are strong indications that this
effort will be fully successful in protecting the public health. There
has been a dramatic reduction in the number of cases of Reye syndrome
at the same time that there has been a significant decline in the sales
of single entity aspirin products for children. We do not know whether
these are casually related events or caused by changes in physician
practicing patterns such as giving different parental advice, earlier
detecton of adverse sypmtoms during flu or chicken pox, or other
unknown factors. Whatever the reason, however, this decline has
occurred without any legislation. Furthermore, if the voluntary effort
continues to succeed, and we are confident that it will, a mandatory
approach will not be warranted.
CHRONOLOGY
First Public Awareness Campaign
In May 1982, based on the results of several epidemiological studies,
the Department of Health and Human Services concluded that there was
sufficient evidence of a possible association between the use of
salicylate-containing products, such as aspirin, and Reye syndrome to
warrant notifying physicians and parents. Reye syndrome is
characterized by vomiting and lethargy which may progress to delirium
and coma and, in some instances, death in children and teenagers who
are recovering from flu or chicken pox. In past years, approximately
600 to 1,200 cases occurred annually in the United States, mostly in
children and teenagers. Death results in 20 to 30 percent of the
cases, and brain damage has been reported in many of the children who
survive.
PAGENO="0339"
333
To disseminate this information, Secretary Schweiker directed the FDA
to undertake an educational campaign to inform consumers of this
finding. However, because there was considerable scientific
controversy in the medical community over the studies, we determined
that additional research to identify more. definitively this
relationship was needed before we could conclude that a warning label
should be required. While these new research efforts have been
underway, we have continued as in past years with our public awareness
campaign to alert consumers of this important public health
information.
The Public Health Service Study
To investigate the possible relationship between Reye syndrome and
various exposure factors, including the use of aspirin and other
salicylate-containing products, former Secretary Schweiker directed the
Public Health Service to develop a plan for further research in this
area. Under the plan, the study would be conducted by the Public
Health Service Reye Syndrome Task Force. The study and the data
generated would be reviewed, critiqued and monitored by the Institute
of Medicine of the National Academy of Sciences.
This new study called for a pilot phase to determine the study
feasibility and establish methodology; to be followed by a full-scale
investigation. The pilot study phase has now been completed, and the
data have been reviewed and analyzed by the Institute of Medicine.
The results of the study, although not conclusive, appear to show an
PAGENO="0340"
334
association between ~the use of~ salicylate and the onset of Reye
syndrome in children and teenagers.
The Secretary~ s Actions
Upon receiving the Institute of Medicines report, Secretary Heckler
issued a statement on January 9, 1985 strongly urging parents to follow
the advice of the Surgeon General and consult a physician before using
aspirin in children or teenagers in cases of flu or chicken pox. She
also emphasized the need to vigorously pursue the full..scale study in
light of the results of the pilot study. That work is now
underway.
To ensure that all children continue to be given the fullest
protection while we await final scientific conclusions, the Secretary
announced four additional steps to be taken.
First, the pilot study was to be released for review and analysis.
As noted, the results of the study were sumarized and published
that same week in the Morbidity and Mortality Weekly Report, and
republished in the Journal of the American Medical Association on
February 8, 1985.
Second, FDA would vigorously pursue expanding and extending its
public education efforts. Specific steps would be taken as soon
as possible to inform teenagers who often self-medicate.
* Third, the Secretary would contact media leaders throughout the
country, asking them to use every possible resource to help
broadcast this message.
PAGENO="0341"
335
Fourth, aspirin manufacturers would be asked to voluntarily revise
the labeling of their aspirin products to further alert consumers
about the advisability of using aspirin products to treat flu or
chicken pox in certain age groups.
On January 11, 1985, the Secretary announced that representatives of
the major aspirin manufacturers had agreed to cooperate with the FDA to
develop new labeling for aspirin products. Details of this voluntary
effort are described further below.
IMPLEMENTING THE SECRETARY'S CHARGE
At that point, we moved as quickly as possible to implement the
Secretary's charge, involving both our own public education efforts and
discussing with leaders of the aspirin industry what steps they would
be taking.
Our efforts were intensified because of the time of year these new
scientific data became available. Knowing we were already at or
apprQaching the height of the flu season, we felt it imperative that we
take steps to alert parents and teenagers as soon as possible,
including the large number that already had aspirin or
aspirin-containing products in their medicine cabinets at home. We
therefore adopted a two-pronged approach:
First, we increased consumer awareness campaigns, involving both
FDA and the industry. This includes public service announcements,
special mailings, and special posters. Particular emphasis was
placed on getting the industry and retailers to use `shelf
PAGENO="0342"
336
posters" because it is expeditious and eye-catching; we have used
this approach in the past in the device area for educating
consumers about the risk of toxic shock syndrome in connection
with the use of tampons. Moreover, we knew that a considerable
period of time (longer than was available to us this flu season)
would be necessary to make available relabeled aspirin products,
and of course not even that would affect already-purchased
medicines.
Second, we pursued voluntary labeling changes to the products
themselves. This involves both deletion of the "flu" indication
for children's products and warning against use of the product in
children and teenagers with flu or chicken pox without medical
advice. Our goal is to have these changes in place prior to the
comencement of next year's flu season.
Let me now describe each of these efforts for you in more
detail.
Consumer Awareness Efforts
The Government's expanded public education program ordered by
Secretary Heckler has included newspaper columns, radio public service
announcements, posters and newspaper advertisements. The newspaper
columns were in English and Spanish and were sent to more than 10,000
newspapers. The radio announcements were used by at least 1,000
stations from coast to coast. Moreover, 43,000 posters have been sent
to all junior and senior high schools and colleges, this being in
PAGENO="0343"
337
addition to the 120,000 posters sent out in November 1984. Because
the results of the pilot study had implications for older teenagers not
observed in the previous studies, special emphasis was placed on
targeting this specific group in our educational efforts, whenever
feasible.
An article providing updated information with regard to the results
of the pilot study was also published in the current issue of the FDA
Consumer magazine.
To ensure cooperation from the media, the Secretary took the unusual
step of contacting the heads of the major media asking their assistance
in informing the public of the pilot study results. She also wrote to
health professional organizations, hospital administrators and some
173,000 physicians (internists, pediatricians, familypractitioners and
emergency medical doctors) on the new data. In this regard, we
consider the health professional community, especially pediatricians,
to provide one of the best vehicles for conveying this type of
information, especially to parents.
I have also provided background information on the recent pilot study
to the major health professional organizations and have asked them to
share the information with their membership. I should note here that
the Mierican Pharmaceutical Association has initiated a Reye syndrome
warning campaign. They have issued-a Dear Pharmacist letter enclosing
a poster to its 50,000 members. We greatly appreciate their
disseminating this important information.
PAGENO="0344"
338
In addition, through our consumer outreach program, we are providing
updated educational materials which reflect the results of the pilot
study. The organizations within this network have the capability to
reach over 20 million people.
The Aspirin Foundation has also coordinated the activities of its
member companies and has developed its own educational program. Its
nationwide campaign includes television and radio public service
announcements which make reference to the possible association of
aspirin use and the development of Reye syndrome.
The campaign also includes a Reye syndrome poster in two sizes,
developed by the Aspirin Foundation, to be placed in retail
establishments throughout the United States during the 1985 flu
season.
We especially encouraged the use of this poster as an efficient and
effective mechanism for comunicating this important public health
message. A major attraction of this approach is that one generic shelf
poster can provide a uniform health message coverin9 virtually all the
aspirin products being sold in that particular area of the store. In
this way, shelf posters are extremely efficient and cost-effective. It
can also be implemented expeditiously, given that members of the
Aspirin Foundation have volunteered to use their considerable sales
forces to visit major grocery stores and pharmacies throughout the
nation and seek to have the posters prominently displayed.
PAGENO="0345"
339
I have included copies of the relevant documents of both Government
and industry efforts to disseminate the information for inclusion in
the record.
At this point, I think it only appropriate to note a special thanks
to Giant Foods for taking the lead among retail establishments and
producing their own posters and shelf labeling. The Giant materials
have been in place since late January and include a main poster and
tear-off literature attached to the shelves which gives more detailed
information. These efforts have been followed by other retailers such
as Safeway, Walgreen, Thrift, Osco, and People's Drug Stores. We
applaud this excellent public service effort.
We believe that this private sector effort together with the
Government's educational campaigns for the last three years and the
recent publicity generated by the release of the pilot study results
will be an effective vehicle for making the general population aware of
the possible association between Reye syndrome and aspirin.
I have with me today the video public service announcements prepared
by the Aspirin Foundation and the FDA which I would like to show at
this time.
Labeling Revisions
In conjunction with the educational materials which have already been
disseminated, the major aspirin manufacturers have agreed to revise the
labeling of their aspirin products. A warning statement will appear on
PAGENO="0346"
340
all medicines containing aspirin by fall 1985. Specifically, all
such products will bear the statement: "Warning: Consult a physician
before giving this medicine to children, including teenagers, with
chicken pox or flu.' In addition, the labels for children's aspirin
products will be revised to delete all references to flu.
Plough, Inc. of Memphis, Tennessee, maker of St. Joseph aspirin and
non-aspirin products for children, which is not a member of the Aspirin
Foundation, has developed its own voluntary precautionary labeling
program. A part of its program includes the labeling revisions for
children's products which will bear the following warning
statement:
"Warning: Reye Syndrome is a rare but serious disease which can
follow flu or chicken pox in children and teenagers. While the
cause of Reye Syndrome is unknown, some reports claim aspirin may
increase the risk of developing this disease. Consult a doctor
before use in children or teenagers with flu or chicken
pox."
Plough, Inc. has also begun placing an abbreviated warning sticker on
all stocks shipped from its plant and intends, in addition, to include
in its packages an insert bearing information which identifies the
symptoms of Reye syndrome. This program was begun on January 9, 1985.
In addition, those products manufactured since that date will bear the
revised labeling.
PAGENO="0347"
341
In an effort to reach other manufacturers of aspirin and
salicylate-containing drug products to advise them of these voluntary
initiatives, we have written to all drug manufacturers registered with
FDA. The purpose of this letter is also to update our drug listing
files and ascertain whether, and to what extent, these firms intend to
join in this nationwide campaign. We fully expect the rest of the
industry to follow the type of responsible and public spirited labeling
revisions being instituted by members of the Aspirin Foundation and
Plough, Inc. A copy of this letter will be submitted for the
record.
FOLLOW-UP EFFORTS
To determine whether the efforts 1 have just described have been
effective, we will monitor compliance of the voluntary program and the
success of our combined educational campaigns.
We plan to conduct a telephone survey of U.S. households on consumer
awareness of this issue. Survey results will be representative of
telephone households in the United States which have children 19 years
of age and younger. A parent or responsible adult will be interviewed
as to their knowledge of a possible association between aspirin and the
development of Reye syndrome in children with flu or chicken pox.
Information will be obtained on their awareness of this association,
how they became aware (i.e., source of information) and whether they,
in effect, believe the message. Data will be analyzed by age of
respondent, household income groups, education level and race.
PAGENO="0348"
342
The Agency has a contract which will enable it to start collecting
information as soon as the appropriate clearances are obtained for the
questionnaire. We anticipate that we will have data within 30 to 40
days of the beginning of data collection.
I would caution that this survey should be viewed as a preliminary
attempt to get early feedback on the effect of our educational efforts
and to obtain valid baseline data for future survey work. However, I
will gladly share with the Subcomittee our~ results in monitoring the
true effectiveness of our current educational effort and its effect on
use of the product.
I would also appreciate learning from you your thoughts about the
types of programs that may be most helpful in determining the
educational value of our programs.
Second, we are prepared to conduct a more definitive survey later
once these educational efforts have become fully operational if we deem
that further feedback will help us.modify our informational and
educational programs.
As an educator I am concerned that we establish as rapidly as
possible what programs are most effective in reaching the public.
VOLUNTARY LABELING
I know, Mr. Chairman, that in your letter of January 11, 1985 to
Secretary Heckler, the Subcommittee expressed its concern that we had
reached a decision to rely on a voluntary approach rather than
requiring mandatory labeling. I would like to try to put our decision,
and the reasons for it, into perspective.
PAGENO="0349"
343
When the State studies suggested a possible association with
salicylates, we concluded that physicians and parents should be
informed. As attention focused on the details of the studies, we
determined that new studies were necessary to resolve the scientific
dispute over whether the studies did in fact demonstrate an association
between Reye syndrome and salicylate-containing drugs. Also, we
concluded that although public information efforts were justified, the
evidence was sufficiently questionable to warrent more stringent
action.
Now the pilot phase of the new study has been completed. Although
the pilot phase is not conclusive and must be considered preliminary,
its findings may indicate an association between the use of aspirin and
the onset of Reye syndrome in children and teenagers. Because we
continue to believe that it is important that consumers receive the
most up-to-date information, we have intensified our educational
campaign and asked the aspirin industry to undertake voluntary
initiatives to amplify the message. However, both the Institute of
Medicine and the Public Health Service have concluded that the full
study should be completed before drawing more definitive conclusions
about an association between Reye syndrome and salicylates.
Our deliberations have been careful and thoughtful. We have tried to
base our public statements and our decisions on the most accurate and
complete analysis of the scientific evidence available to us. The
resolution of the scientific dispute which has surrounded this
PAGENO="0350"
344
extremely complex issue is crucial, and we are hopeful that the study
underway as well as other basic research on Reye syndrome will provide
us with the additional information to definitively resolve this
controversy. Nevertheless, even in the face of this uncertainty, we
have acted quickly to take steps we felt appropriate to protect
children during their most vulnerable years.
CONCLUSION
Let me conclude by saying that I do understand your concern, and I
truly believe that we are striving to reach the same goal. We must
protect the health and safety of our children. They are our
future.
Our t~tmost concern is *that the actions we take be in the best
interest of these children and their parents who will be affected by
our decisions. We believe that the steps we have already taken to
inform the public of the dangers of Reye syndrome and its possible
association with salicylate use as well as the voluntary labeling and
public education initiatives undertaken by the private sector
responsibly addresses this important public health problem.
Thank you Mr. Chairman. This concludes my prepared testimony. I
will be happy to answer any questions you may have.
PAGENO="0351"
345
Mr. WAXMAN. Thank you very much, Dr. Young.
Let me see if I understand the situation. You don't feel you had
enough data to say conclusively that there is a link between aspi-
rin and Reye's Syndrome, and, therefore, you didn't want to re-
quire mandatory labels. Is that correct?
Dr. YOUNG. That is correct. We did not feel that we had the evi-
dence at this time to unequivocally establish a link and go toward
mandatory labeling.
Mr. WAXMAN. You felt that there is a strong enough public
health danger that the public should be informed of the probable
link between aspirin and Reye's Syndrome?
Dr. YOUNG. That is correct, and I felt that in November, upon
coming into FDA, and felt similarly and more definitively, as this
additional pilot study came forward.
Mr. WAXMAN. Because you didn't want to go with a mandatory
label, you pretty much left the aspirin industry to control what
would be on that label, because they had to agree. They didn't
want to agree to anything that would hurt their sales, so therefore,
you have a warning label that simply says if you have these symp-
toms, talk to your doctor about them. How would anybody know
that has anything to do with Reye's Syndrome?
Dr. YOUNG. I was trying to summarize my statement. I will use
two other points from that.
Mr. WAXMAN. You don't really need a statement for that. How
would you expect anybody, how would you expect anybody as a pa-
tient or grandparents, to know if you weren't the Commissioner of
FDA, that a label that doesn't say don't use this aspirin product for
flu or chicken pox syndromes-how would you know that you
shouldn't use aspirin if it simply says consult your physician if you
have the flu or chicken pox symptoms?
Dr. YOUNG. Surely. First--
Mr. WAXMAN. Do you think anybody would know from that in-
formation that they shouldn't use aspirin?
Dr. YOUNG. I think labeling is only part of the total program and
that was brought forward very clearly by the representatives of the
American Academy of Pediatrics and by others. I went back to look
at this issue and tried to compare some other events that have oc-
curred by both congressional hearings-and this is related to the
study on Premarin that I will introduce for the record. It shows the
effect of a congressional study, a Senate hearing, physician label-
ing, and the Patient Package Insert Labeling. The drop in use was
not necessarily completely related to labeling, and the same was
true in saccharin.
We felt that by getting out a variety of educational programs
and these types of hearings, we will make a big impact on the
public.
[Testimony resumes on p. 361.]
[The study referred to follows:]
PAGENO="0352"
346
Reprinted from Banbury Report 6: Product Labeling and Health Risks
© 1980 Cold Spring Harbor Laboratory
Estrogenic Drugs -
Patient Package Inserts
LOUIS A. MORRIS
Food and Drug Administration
Rockville, Maryland 20857
Prescription drugs are among the most carefully controlled consumer products.
The consumer must visit one highly trained professional to receive a prescription
and a second to receive the actual product. The government closely reviews
pharmaceutical development, testing, and manufacturing; .all pharmaceutical
industry labeling and promotional materials undergo federal scrutiny.
Of course, itis no accident that this amount of societal control is directed
towards prescription rugs. Their therapeutic potential is phenomenal, as are the
consequences of theIr misuse. Yet, with all the potency of pharmaceuticals, the
consumer receives little in the way of labeling information about these products.
The name and some brief directions for use are provided in a small label typed
by the pharmacist. Warnings, precautions, side effects, and other important
information are rarely provided (L. Morris, unpubl. results) and frequently
forgotten if orally conveyed (Ley and Spelman 1965).
These considerations prompted the Food and Drug' Administration (FDA)
to require that patient.oriented labeling (also known as patient package inserts
[PPIs]) be dispensed with certain prescription drugs, the most notable being
oral contraceptives and estrogen drugs. Data regarding the effectiveness of PPIs
for these drugs may serve as an important source of information for determining
the impact of labeling for other prescription drugs and other consumer products.
The Institute of Medicine (IOM) of the National Academy of Sciences
recently reviewed data on PPI effectiveness derived from a number of sources,
such as consumer and professional preference surveys and clinical studies of
prototype patient leaflets (IOM 1975). This paper will focus solely on evalua-
tions of the federally required oral contraceptive (OC) and estrogen PPIs. This
limited focus provides the most concrete and generalizable information on the
effects of a government-required label for a consumer product. Those interested
in a more thorough review should consult the IOM report.
ORAL CONTRACEPTIVE PPIs
In the late 1960s evidence began accumulating about the dangers of OC use,
especially the risk of possibly fatal blàod clots. In addition to revising labeling
PAGENO="0353"
347
24 / L. A. Morris
directed toward health professionals, FDA required that specially prepared
labeling be made available to OC users. The rationale for the OC PPI was one of
patient consent (Schmidt 1973). The purpose of the information was to allow
consumers to make an informed choice about their birth control method. The
PPI was deemed necessary because OCs are used by healthy women for non-
therapeutic purposes and are associated with serious risks. There are alternative
means of contraception without such risks. In light of these special circum-
stances, written information directed to the consumer was seen as a method to
assure that decisions about birth control methods could be made on the basis of
accurate, information regarding the effectiveness of various methods and their
risks.
The original r'~quirement specified that two types of printed materials be
made available to patients: a relatively brief insert to be distributed with birth
control pifis and a longer brochure to be distributed by the physician upon
patient request. The insert was delivered to the patient in the drug container.
Manufactuiers of each brand printed their own version of the inserts which
differed in shape, size, and extensity of information. However, for all brands,
there were nine required sentences of information, set off in a box that preceded
all other material. This boxed material summarized the important precautions
about OCs. It contained information about the blood clot warnings, referred
women to their physician and to the brochure, and cautioned that OCs were
of no value for venereal disease.
The basic brochure was printed by the American Medical Association
(AMA) and distributed to physicians. It contained 22 paragraphs of information
about possible adverse reactions, the risk of blood clots, what to do about
missed periods, other considerations, and a summary. Manufacturers printed
longer brochures, with additional material about the menstrual cycle, fertiliza-
tion, and directions for use that followed the basic 22 paragraphs of information.
In 1975, FDA completed a national survey of OC users to evaluate the
effects of this PPI and brochure (Morris et al. 1977; Mazis et al. 1978). This
survey constitutes the most detailed knowledge to date on the effects of a FDA-
required PPI. Since the purpose of the PPI was to increase informed decision-
making, the questionnaire solicited information about receipt, readership, use,
and effects of the insert and brochure. Women, aged 18.44, currently using
the pill were eligible to be interviewed. Over 23,000 households were contacted
in a national probability sample to complete interviews with 1720 OC users.
Only female interviewers were used and several call-backs were made to assure
acceptable response rates. Completed interviews or patient ineligibility was
determined at 86% of the households where contact was attempted.
Each respondent was asked if she received the insert or brochure and if so,
whether it was read. In a previous regional survey of OC users `(Fleckenstein et
al. 1976) only 64% of the respondents filling out questionnaires said they
52-266 O-85----12
PAGENO="0354"
348
Patient Package Inserts / 25
received a copy of the PPI. In the present survey, respondents were shown
copies of the PPI and brochure for their brand of birth control pill with the
contents made illegible. When asked in this fashion, 93% of the respondents said
they had received a copy of the PPI, but only 35% said they received a copy of
the brochure.
If respondents received the brochure and insert, the great majority said
they read the insert (95%) and brochure (94%). As shown in Table 1, most
reported that they read the information when they first took the pifi. This
trend was more pronounced for the brochure compared to the insert. About
one-fifth recounted that they read the insert when stimulated to do so by some
event, such as receipt with a refill, a missed pifi, or when they did not feel right
(presumably to discern if their discomfort was due to the drug).
Although a substantial majority reported reading the PPI, it is not clear
how carefully the material was read or how well it was remembered. Women
may have merely glanced at the material and tossed it away. To determine
knowledge transmitted, respondents were shown the insert for their brand of
birth control pills with the boxed information made illegible. They were asked
to recall what information was contained in the box.About half (54%) correctly
recalled that the insert mentioned risks of clots, which was the most serious
warning at that time. However, 87% said that the box contained directions for
use of information, which appeared in most inserts but did not appear in the
box. Thus, people tended to remember what they considered the most impor-
tant information about OCs, but they were not able to identify the contents of
specific sections of the insert. One may speculate that people extract infor-
mation from the PPI and fit it into their own existing cognitive structure.
When asked to describe specific sections, they reconstruct the answer based
upon their memory. The site for specific material may be of little value to
Table I
When OC Information is Read
.
Reade
rs (%)
insert
brochure
First took pill
78
88
Each refill
11
6
Missed pill
*
6
2
Don't feel right
4
3
Can't reach MD
1
2
Other
14
13
Don't know
1
*
2
No response
3
2
PAGENO="0355"
349
26 I L. A. Morris
consumers and, therefore, may not be retained. People may believe that dosage
directions are important and, thus, believe that this material is located in the
important sections of the insert.
To discern how the inserts may have affected patients' behavior, respond-
ents were asked if the insert or brochure increased or decreased the frequency of
physician contacts. About three quarters said there was no change in the pattern
of contact, 10% reported a decrease, 5% an increase, and 9% did not answer or
said they did not know. Interestingly, PPIs have been criticized both for decreas-
ing physician contacts (and thereby interfering with the provision of physician
services) (R. Lanzillotti and R. Blair, unpubl. results) and for increasing physi-
cian contacts (and thereby increasing the costs of health care) (Gross 1978).
Thus, not only are the behavioral results of interest, but it is important to
understand the reasons for observed patterns of results. In the present survey,
OC users were also asked if the insert or brochure contained information that
led to contacting their physicians. Twelve percent of the insert readers and 6%
of the brochure readers said it did. Many of the questions directed to the physi-
cian were prompted by effects not mentioned in the patient information but
experienced by the respondent; for example, spotting, bleeding, breast sore-
ness, weight gain, and what to do about missed pills.
These results, combined with data on readership and knowledge about
OCs, suggest that the PPI serves two basic functions. First, the PPI is initially
read by most people to obtain a general knowledge of content. At this time
some important information may enter the patients' memory and augment
existing knowledge stores. For drugs like OCs, women may already have a set
of beliefs about use and effects. For other drugs, especially those not used
before by the patient, the PPI may help formulate a more complete set of
impressions. However, there is incomplete memory for details and the patient
may then use the PPI for its second function, that of a reference sheet. The
reference function appears to be an infrequently utilized but extremely impor-
tant aspect of PPI usage. One may speculate that as one first begins using the
pill, side effects may occur that need to be put in perspective. Other events,
such as missed pills or less frequent (but more serious) side effects, may occur
after longer usage of the pifi. For these events the individual may again consult
the insert.
Finally, women were asked to compare the insert and brochure and state
which was their preferred source of drug information. The brochure was pre-
ferred to the insert by an 89% to 3% margin. Longer inserts and brochures were
preferred to shorter ones. In addition, respondents said they would like more
information in the insert and the brochure, especially information about risks
of using the pill. Only 16% of the women receiving the AMA brochure said they
kept it for future use compared to about half of those receiving the longer
manufacturer's brochure.
PAGENO="0356"
350
Patient Package Inserts / 27
The results of this survey were utilized by FDA to revise its policy regard-
ing the OC PPI. The brochure and insert were lengthened to include new infor-
mation about cardiac and cancer risks. In addition, distribution of the brochure
was changed. Rather than distributing it through the physician upon patient
request, FDA required that it be distributed along with the insert at the time the
drug was dispensed to patients. The implications of this survey must be carefully
interpreted. Women overwhelmingly preferred the longer brochure to the insert.
When asked which type of information they would prefer included with other
drugs, 67% cited the brochure and 20% the insert. In addition, there are some
indications that lack of information, rather than conclusions about listed
material, causes confusion for OC users. The sample was composed of younger
and more highly educated women than representative in the female population.
Thus, we cannot be certain that sick, older individuals share these preferences
with respect to drugs used to treat disease conditions. Yet, even if they did,
patient preferences may not fully predict how people will react to and utilize
information on other drugs. It is necessary to obtain patient responses to various
forms of information. Knowledge and behavioral differences attributable to
various forms of information that was stated as related to individual preferences
would allow more meaningful interpretations. A study by Rand Corporation
to collect this type of information is currently underway.
ESTROGEN PPIs
In 1977, FDA required manufacturers of estrogenic drugs to distribute PPIs.
The requirement was prompted by epidemiological studies indicating an
increased risk of endometrial cancer withprolonged usage of the drug. In addi-
tion, estrogen usage is often quasi-elective, in that many women take the drtig
for menopausal symptoms where it is not therapeutically necessary or necessary
for only short periods of time. FDA estimated that in the mid-1970s several
million unnecessary patient-years worth of treatment were being dispensed
(Burke et al. 1977). The PPI was part of a larger information campaign directed
at professionals and patients to reduce the use of estrogen in treating conditions
where it was neither effective nor medically justified (FDA 1979).
The PPI written for estrogens was 35 paragraphs long and frankly dis-
cussed the risks of estrogen use. The insert contained information about symp-
tOms of the menopause, the use of estrogens to prevent swelling of the breasts
after delivery, the dangers of estrogens (such as~cancer of the uterus, other
cancers, gall bladder disease, and abnormal blood clotting), a warning about
birth defects from estrogen use during pregnancy, side effects of estrogens, and
a summary. The PPI has been criticized for its tone and comple)dty. Critics
maintain that it serves merely to frighten women without improving the quality
of care or patient decision-making. Several authors-have estimated reading levels
PAGENO="0357"
351
28/ L. A. Morris
at 8th grade to college level (Liguori 1978; Pryczak 1978; Smith and Adams
1978).
Data on the effects of the estrogen PP! is presently limited to several small
studies and market research data on pharmacy sales. A larger evaluation of the
estrogen PPI is currently underway as part of the Rand study previously men-
tioned. In that study the current estrogen PPI is compared to rewritten versions
to discern how changes in writing style affect patient knowledge and other
behavioral effects.
MARKETING DATA
Oral Premarin®, the largest selling brand of estrogens, has maintained a constant-
ly high percentage of the estrogen market throughout the past several years.
Figure 1 displays pharmacy sales for this drug for a 6-year period. Data is derived
from the National Prescription Audit, a monthly survey of 800 pharmacies con-
ducted by IMS America of Ambler, Pennsylvania. Events that might be expected
to influence drug usage are identified. This graph denotes some of the difficulties
3 DECEMBER 975
1W CANCER STUDIES PUBLISHED
\ ~ I
JANUARY-MARCH 1576
SENATE HEARINS5; FDA DRUG BULLETIN WARNING
/ NEW PHYDICIAN LABELING REDUIRED
I OCTOBER 1971
PATIENT PACKAGE INSERT REQUIRED
0
I I I I I I I I I I I I I I I I I I
* "~* ~ ~ "~* ~
QUARTERS
Data from IMS America's National Prescription Audit
Figure 1
Oral Premarin®: Total retail prescriptions dispensed at 1.25 mg-strength. (Data from IMS
America's National Prescription Audit.)
PAGENO="0358"
352
Patient Package Inserts /29
that face researchers in discerning the effects of various information programs.
The PPI requirement followed a number of events that appear to have initiated
a decrease in sales of the most popular dosage of the drug. It is impossible to
discern the independent influence of the PPI. Is the apparent leveling of the
decreasing sales trend in the summer and fall of 1977 (prior to PPI requirement)
due to a spurious fluctuation, part of a seasonal variation in sales, or is it due to
the decreasing influence of previous informational influences? The data suggest
that the PPI may have contributed towards this downward trend. One has no
way of knowing what sales levels would have been without the PPI.
PATIENT STUDIES
In addition to marketing data, studies have been conducted on the distribution,
understandability, and other effects of the estrogen PPI. The first question of
interest is whether patients actually receive a PPI when they fill a prescription.
The oral contraceptive PPI is prepackaged by manufacturers in consumer-
sized containers. Estrogen PPIs are delivered to pharmacies as separate leaflets,
thus requiring dispensers to place a leaflet in each package given to patients.
Recently FDA completed a survey of 271 pharmacies in 20 cities (Morris
et al. 1980). Observers filled prescriptions for conjugated estrogens and
requested a PPI if none was delivered spontaneously. Results indicated that the
PPI was spontaneously delivered 39% of the time. Observers were more apt to
receive the PPI in larger-volume chain stores (59% of these stores) compared to
independent pharmacies (30% of these stores). If requested, 94% of the stores
dispensed a PPI. The most frequently offered reason for not spontaneously
dispensing the PPI was that it was forgotten. The 39% rate for spontaneous
delivery of the PPI is disappointingly low. It is doubtful that many women
would request the PPI.
Thus, this survey suggests that in the absence of prepackaging, some
efforts reinforcing the health professional's role in PPI dispensing are needed.
Although we may assume there is approximately a 4 in 10 chance of any individ-
ual receiving a PPI for estrogens when a new prescription is filled, we do not
know the cumulative probability that an individual taking estrogens would have
received a copy of the PPI at some time during the course of treatment.
Assuming that the PPI is delivered at some point to the patient, it must
be understood to some degree for it to have its desired effects. The ability of
the PPI to communicate important messages was examined in a study of 117
pharmacy college freshmen (Russel et al. 1978). Written and oral instructions
about estrogens were compared. People receiving either oral or written instruc-
tions scored better than controls (receiving no information) and slightly better
than a group receiving both oral and written instructions. Contrary to most
research showing increased effectiveness of drug communications when both
PAGENO="0359"
353
30 I L. A. Morris
oral and written modalities are used (Morris and Halperin 1979), this study
indicated that simultaneous presentation could produce distraction and less
effective information transfer. Most subjects receiving the PPI said the material
was easy (87%), very clear (8 1%), and that they understood most or all of the
information (94%). The PPI had higher scores on clarity measures compared to
verbal or combination presentations, although the difference between oral and
written presentations was not significant. There were also no significant differ-
ences between groups on questions relating to concern about taking estrogens.
All three groups receiving information did better than controls on a knowledge
test.
In a second study of the estrogen PPIs, outpatients were given the PPI,
asked to read it and told they would be interviewed in 2 weeks (N. Ferencz,
unpubl. results). Of the 112 subjects questioned, 90 said they read the PPI
carefully, 10 said they glanced at it, and 12 said they did not read it. Relevant
dangers of estrogens appeared to be remembered by most patients. Sixty percent
remembered information about the uses of estrogens, 86% remembered informa-
tion about its dangers, 67% about its side effects, and 2% remembered to avoid
estrogen use during pregnancy. Data on patient compliance were also gathered.
Twelve of the 100 people reading the PPI said they did not follow the physi-
cians' directions, whereas five of the 12 women not reading the PPI were not
compliant. The author did not define his measure of noncompliance.
A third study of the estrogen PPI focused on responses of 154 patients
offered the drug as treatment for postpartum breast engorgement (Udkow et al.
1979). Most women (79%) received the PPI at the time of delivery (in the labor
or delivery room) or soon after delivery, about 13% received it in the physician's
office, and 8% never received the PPI. The questionnaire was left with women
after delivery.
Women who read the insert attempted and correctly answered more
questions about estrogens. Readers generally judged the insert as easily readable
(78%), not unnecessary (91%), and not too detailed (72%). About half (45%)
felt the PPI was too long and 17% felt it was too short. Comparing readers to
nonreaders, the PPI did not appear to affect the risk-benefit assessment of
estrogens nor did it lead people to refuse to take the medication.
These latter three studies suggest that patients judge the estrogen PPI
as easier to understand than reading tests and professional judgments. Perusal
of the estrogen PPI suggests that there are many multisyllabic words and long
sentences, elements that would lead to high reading-level estimates. It is also
evident that many of the concepts are difficult to understand. Yet most women
tested judged the material to be useful and understandable.
One may postulate that the people in these studies may have been more
motivated to read the PPI than women who were not going to be questioned
about it. However, motivation to read is not necessarily directly related to
PAGENO="0360"
354
Patient Package Inserts / 31
patient understanding (although one could postulate a higher degree of informa-
tion processing for high motivation materials). Another possibility is that reading
tests may lack reliability and predictive validity (Morris êt a!. 1980). Thus, it
may be difficult for people to understand many of the specifics, but upon
reading they retain global impressions and an understanding of some key issues.
A third possibility is that the studies undertaken so far have not been conducted
on representative samples and, therefore, are not generalizable to most of the
women taking estrogens.
DISCUSSION
In reviewing these data elements it is clear that judgments about the success or
failure of PPIs as warning labels will be dependent upon the criteria chosen. To
ascertain objective criteria for success or failure, one must be cognizant of the
purpose of the PPI. The oral contraceptive PPI was intended to inform women
of risks and benefits to aid in informed decision-making. The FDA surveys
suggest high levels of reported receipt and readership. However, the degree or
manner in which PPIs affected decision-making is unknown and awaits further
study.
Results for the estrogen PPI are more heterogenous and controversial. The
estrogen PPI was written to dissuade inappropriate drug use. It was one of
several interventions undertaken to accomplish this objective. On a gross
measure of retail sales, there is a decreased use of this drug. However, it is not
known if those dissuaded from use of the drugs are the individuals most at risk
from cancer. Interestingly, Jick reports evidence that endometrial cancer fell
27% nationwide from 1975 to 1977 (Jick et al. 1979). However, even if correla-
tional evidence exists regarding the benefits of decreased estrogen use, the role
of the PPI in influencing this effect is unknown.
The OC and estrogen data suggest some interesting applications and
directions for future research. The most important communications problem for
PPIs is getting patients exposed to the information. Packaging inserts with the
drug is one effective method. Other cost effective methods need to be examined
to increase exposure rates.
It is clear that only a small proportion of information presented on the PPI
is actively remembered by patients. One can speculate that people remember
what they think is most important. Perceived importance is apt to be determined
by the patient's existing needs, goals, knowledge, and beliefs. It is also apt to be
influenced by the label itself. With products like specific drug entities, people
may have a relatively low initial knowledge base. The manner in which the PPI
is structured can help formulate perceptions about the relative importance of
various pieces of information. Thus, labels should be written with a few clear
objectives in mind so that the most important information will be effectively
PAGENO="0361"
355
32 / L. A. Morris
stressed. Furthermore, we need to understand more about what patients cur-
rently know about drugs. Important information should be presented in a
fashion that will be assimilated into the patient's memory.
Future research is also needed to clarify some of the inconsistencies that
appear to have grown from this literature. For example, why does the PPI score
fairly well when people are asked to rate its value and clarity, but reading tests
indicate it is difficult to understand? If the PPI does at least contribute toward
a downward sales trend, how does it do this if it is dispensed to only about 4 of
10 people filling prescriptions? It is possible to generate numerous hypotheses
to account for these data - Certainly evaluations are necessary to further test the
impact of PPIs. The estrogen data points toward the need to utilize multiple
methods of assessment so that a more complete overview of PPI impact can be
obtained.
Finally, one may speculate how data on PPIs might be generalized to
products other than prescription drugs. Certainly there are some similarities;
PPIs seek to communicate technical information via a written channel. However,
there are some important differences. Patients (individuals who delegate product
selection to a physician) rather than consumers (who make their own product
choices) are the recipients of the information. The risk-benefit nature of
prescription drugs make side-effect and warning information important aspects
of the communication. Thus, patients may be more motivated to read this
information (although I know of no data to support this) but may necessarily
be exposed to fear-arousing information.
Given these important differences, perhaps the most generalizable set of
results would be those pertaining to the communication value of PPIs. An
understanding of the ability of different types of PPIs to generate desired levels
of knowledge would ii:icrease our understanding of how information is processed.
Behavioral and attitudinal effects of PPIs are probably much less generalizable,
given the unique aspects of prescription drugs compared to other consumer
products.
ACKNOWLEDGMENTS
The author gratefully acknowledges the assistance of Ivan Barofsky, Mike Mazis,
and lloyd Millstein for their suggestions on an earlier draft. The views expressed
here are solely those of the author and do not necessarily reflect the policies of
the Food and Drug Administration.
REFERENCES
Burke, L., D. Crosby, and C. Lao. 1977. "Estrogen prescribingin menopi~use."
Paper presented at American Public Health Association, Washington, D.C.,
November.
PAGENO="0362"
356
Patient Package Inserts / 33
Fleckenstein, L., P. Joubert, R. Lawrence, B. Pastner, J. Mazullo, and L. Lasagna.
1976. Oral contraceptive patient information: A questionnaire study of
attitudes, knowledge, and preferred information: sources. J. Am. Med.
Assoc. 235:1331.
FDA (Food and Drug Administration). 1979. Update on estrogens and uterine
cancer. FDA Drug Bulletin 9:2.
Gross, A. 1978. Assessing the value of information for patients-letter to the
Editor. J. Am. Med. Assoc. 23:240.
IOM (Institute of Medicine). 1979. Evaluating patient package inserts. (79-05),
August. National Academy of Sciences, Washington, D.C.
Jick, H., R. Watkins, J. Hunter, B. J. Dinan, S. Madsen, K. J. Rothman, and
A. M. Walker. 1979. Replacement estrogens and endometrial cancer.
N. Engl. J. Med. 300:218.
Ley, P. and M. S. Spelman. 1965. Communications in an outpatient setting.
Br. J. Soc. Clin. Psychol. 4:114.
Liguori, S. 1978. A quantitative assessment of the readability of PPIs. Drug
Intell. Clin. Pharm. 12:7 12.
*Mazis, M., L. Morris, and E. Gordon. 1978. Patient attitudes about two forms of
printed oral contraceptive information. Medical Care 16:1045.
Morris, L. and J. Halperin. 1979. Effects of written drug information on patient
knowledge and compliance: A literature review. Am. J. Public Health
69:47.
Morris, L., M. Mazis, and E. Gordon. 1977. A survey of the effects of oral con-
traceptive patient information. 1. Am. Med. Assoc. 238:2504.
Morris, L., A. Myers, and D. Thilman. 1980. Application of the readability
concept to patient-oriented drug information. Am. J. Hosp. Pharm.
(in press).
Morris, L., A. Myers, P. Gibbs, and C. Lao. 1980. Estrogen PPIs-An FDA
survey. Amer. Pharm. NS2O :318.
Pryczak, F. 1978. Applications of some principles of readability in the prepara-
tion of patient package inserts. Center for the Study of Drug Develop-
ment, Rochester, New York.
Russel, W., R. Roberts, D. Bradley, J. Marshall, and H. Glazer-Waldman. 1978.
"Patient package inserts: A study of communication techniques." Paper
presented at the American Association of Hospital Pharmacy Meeting,
San Antonio, Texas, December.
Schmidt, A. 1973. "Dimension of changes in the FDA." Paper presented at the
Pharmacy Advertising Seminar, Chicago, Illinois, September 13.
Smith, T. and R. Adams. 1978. Readability levels of patient package inserts.
Am. J. Hosp. Pharm. 35:1034.
Udkow, G., L. Lasagna, M. Weintraub, and Z. Tamoshunas. 1979. The safety
and efficacy of the estrogen patient package insert: A questionnaire study.
J. Am. Med. Assoc. 242:5 36.
PAGENO="0363"
357
34/ L. A. Morris
COMMENTS
SCHULTZ: Was a patient supposed to get the brochure from the doctor?
MORRIS: Doctors were supposed to give out the brochure upon patient
request. We believe that some doctors may have handed it out routinely,
others may have given it only upon request, and other doctors may not
have given it out at all. Some doctors never even knew it existed. Another
possibility is some women may have gotten their pifis from clinics where
they are dispensed from bulk packages.
McGUIRE: Did you check that 93% for false alarm recognition by holding up
a phony labeling also and asking "Did you get this one?"
MORRIS: No, we didn't go that far. In an earlier survey people were asked
"Did you get a copy of it?" By that survey only 66% said they ever
received a copy of the insert. The difference between surveys may be due
to recall and recognition testing, or it could be that people didn't know
what was being referred to in the recall test. If we were to have only the
recall data, it would have led to totally different conclusions. Luckily,
we had recognition data which we feel is more accurate. I don't know the
extent to which people may have over-remembered or tended to say "yes."
RHEINSTEIN: The brochure was simply made available to outside salesmen
to give to doctors, like any other service item, wasn't it?
MORRIS: Yes. I think most companies did print the brochure. Also, the
AMA distributed millions of them to doctors.
WALDEN: Well, FDA required the companies to print and distribute them but
we couldn't require the doctors to give them out.
SCHULTZ: During what period of time was the brochure distributed to
doctors?
MORRIS: From 1970 to 1977.
FABRO: The brochure actually was a part of the information that the patient
was given in the early `70s when discussing alternative methods of contra-
ception. Now everybody discusses the benefits and risks. In 1980, this is
a big issue.
PAGENO="0364"
358
Patient Package Inserts /35
SCHULTZ: Why did you change the distribution point of the brochure?
MORRIS: FDA now requires that the brochure be distributed with the drug
rather than available upon request. The only authority we have in terms of
requiring labeling is if it's dispensed with the drug. Also, people over-
whelmingly preferred the brochure to the insert.
WALDEN: Lou, are you saying that labeling is working then?
MORRIS: From looking at the recent data, my impression is that the PPI
seemed to influence the trend but there's no way of knowing to what
extent.
This is aggregate data. What we want to do with estrogen labeling is
dissuade usage for people who don't need the drug, or are on it for long
periods of time.
We don't know who's not using the drug. We also don't know the
mechanism. PPIs may have influenced the doctor rather than the patient.
Maybe the doctors don't want their patients to see it. We don't have a
good feeling for how the information is working. I think we need to know
more about that.
SCHULTZ: Is the use of estrogens for engorgement reduction an approved use?
MORRIS: Yes. In the JAMA study (Udkow et al. 1979) women were offered
estrogens and given the insert the day after delivery for postpartum breast
engorgement. Twenty-four hours later they were asked if the wanted to
take th~ drug. Only five or six people refused it-two refused it because
they read the PPI. It really wasn't the best of circumstances for an evalua-
tion study. This study has lots of problems with it. However AMA cited
that study as a reason for opposing PPIs.
RHEINSTEIN: All of the ifi effects that the insert talks about have to do with
long-term use of estrogen, so it's not surprising that the AMA came out
and said that "this doesn't change behavior, therefore it's not useful."
It didn't change behavior because nothing in it was relevant to that
situation.
MORRIS: One of the problems with PPIs is that all drugs are used with differ-
ent indications in different ways.
WALDEN: You've got to study some other kinds of drugs and PPIs because
you've got a terrific bias here. Oral contraceptives have to do with improv-
ing sex, and estrogens, by and large, have to do with sex after menopause
and how to improve it. That provides a tremendous bias, don't you think?
PAGENO="0365"
359
36/L.A.Morris -
MORRIS: Yes. I presented the data on estrogens and oral contraceptives
because that's where we've done our regulations.
We've done some clinical studies using prototypes and our next
step is to acquire about ten PPIs that vary in uses and populations, and
reasons for PPIs and study them.
SCHULTZ: I'd be interested in learning more about the experience with giving
the brochures out in the doctor's office for diethystilbestrol (DES). Do
you know any more about that?
MORRIS: Unfortunately, that regulation was never enforced because the
company that manufactured that pill issued PPIs only for DES used as
the "morning after" pill.
SCHULTZ: It never was enforced?
WALDEN: That's right. FDA invited marketing of the "morning after" pill
with DES, but nobody ever did it. I always had the impression-I am
certainly no expert-that it doesn't matter all that much, that an estrogen
is an estrogen is an estrogen. DES was used because it was synthesized
and therefore a low-cost estrogen.
FABRO: It appears at the present time that estrogenic activity may not always
be associated with neoplastic activity, and vice-versa.
References
Udkow, G., L. Lasagna, M. Weintraub, and Z. Tamoshunas. 1979. The safety
and efficacy of the estrogen patient package insert: A questionnaire
study. J. Am. Med. Assoc. 242:536.
Patient Information on
CAFERGOT®
(ergotamine tartrate and caffeine) tablets, NF
(KAF-er-got)
PLEASE READ BEFORE TAKING CAFERGOT
PAGENO="0366"
* ORAL PREMARIN
TOTAL RX'S DISPENSED, BY STRENGTH
SEMIANNUALLY-~-4973 THROUGH 1980
1ST CANCER STUDIES PUBLISHED
SENATE HEARINGS; FDA DRUGBULL~11JN WARNING
NEW PHYSICIAN LABELING REQUIRED
PPI REQUIRED
S
5,
1'
r
SIX MONTH PERIODS
Legend
L~ 0.3 MG
X 0.63 MG
0 125 MG
~ 2.5 MC
PAGENO="0367"
361
Mr. WAXMAN. That is why we are holding this hearing, because I
don't think we are going to have much available to the public by
way of Government action that would inform them of the dangers
if understood. Labeling does have some significance in the overall
information to the public and this label that you have as part of a
voluntary effort is about as meaningless a label as I could possibly
imagine.
Dr. YOUNG. The labels will vary. Some of the labels from Plough
are very strong in the descriptions of Reye's Syndrome. Others are
not as strong and merely say contact your physician. I agree there
is a variability. If we try a volunteer program, the government is
not, as you rightly pointed out, requiring specific language at this
point.
Mr. WAXMAN. Should the Government require specific language?
If you can't say there is a definitive link, there is probably a link,
you feel comfortable with that?
Dr. YOUNG. I have no problem with the possible association, that
is correct.
Mr. WAXMAN. It seems to me that in every way possible we
ought to inform the public. Labels are one opportunity. When a
person is reaching for the aspirin, the label should have the words
Reye's Syndrome, don't use it. But instead, it simply says if you
have these symptoms talk to your doctor.
You have other ways of communicating information. The poster I
probably won't stop to read. The other one mentions flu or chicken
pox. I think that is real nice. You have to read the fine print there.
I haven't had a chance to read all those posters. But whatever you
do is better than nothing. I am wondering how much better than
nothing we have in terms of the voluntary effort by the adminis-
tration. Can you tell us-you're monitoring it-what information
you have? First, let's talk about the labels that you agreed to.
What percentage of aspirin products on the market had warning
labels as of February 28, 1985? Do you know how many complied
with what you voluntarily agreed to?
Dr. YOUNG. Because of pipeline issues and the fact that there
was not a recall, only 1 percent would be expected to comply by
that time.
Mr. WAXMAN. One percent. What percentage of aspirin products
still identified influenza or chicken pox as indications for aspirin as
of February 28?
Dr. YOUNG. Similarly, because of the pipeline and that these
were used in the beginning of the flu season, we have the product
labeling as described. Those indications will not be there in the
next flu season. About 99 percent would have those because it is a
pipeline issue.
Mr. WAXMAN. Well, you are being awfully nice to the aspirin in-
dustry if you are concerned about their making sure they can sell
the aspirin during the flu season without disturbing their profit
picture. What do you care about their pipeline if there is a product
that is still going to have on the label to go ahead and use this for
these symptoms, that aspirin is appropriate for these symptoms.
Isn't that the wrong kind of information?
Dr. YOUNG. The only way to get those out would be to recall all
of those products from the shelf. That is exactly what I meant by
PAGENO="0368"
362
the pipeline issue. A recall was not even contemplated at this
point.
Mr. WAXMAN. A recall is one way, another label on those prod-
ucts could be slapped on, which you say one company is already
doing?
Dr. YOUNG. One company stopped shipment.
Mr. WAXMAN. A mandatory sign at the point where those prod-
ucts are sold certainly would be another way to inform them. I
assume there was no mandatory sign imposed by the Department
on retail establishments?
Dr. YOUNG. That is correct.
Mr. WAxM~. Do you know how many retail establishments
have any kind of sign that indicates that people ought to be aware
of the potential risk of Reye's Syndrome by taking aspirin.
Dr. YOUNG. Yes; we have conducted a study to look at this within
the early weeks of March. We studied 115 retail drug and 115 gro-
cery pharmacies.
I will ask Mr. Michels to comment on that study, and describe
this, but I emphasize that this is very early in the process of get-
ting it out, and we fully intend to follow this and find out how long
it takes to get these on the shelves.
The answer is that it is approximately 12 percent, but I would
like him to describe how the study was done.
Mr. WAXMAN. I don't want to know about the study. The result
is 12 percent of the establishments you monitored have some kind
of warning sign up.
Mr. MICHELS. Of the 230 chain drug stores and chain grocery
stores we looked at, a total of 28 stores had posters in them.
Mr. WAXMAN. And what do those posters say? Or do they vary?
Mr. MICHELS. There were a variety. There was the Aspirin Foun-
dation posters.
Mr. WAXMAN. What does the Aspirin Foundation poster say?
Mr. MICHELS. If I can find it here, sir.
Dr. YOUNG. We will get that directly for you.
Mr. WAXMAN. I am sorry, I thought you might have that avail-
able. I would be curious if there are varying signs and the Aspirin
Foundation has a sign I would be interested in knowing what they
say, but I gather you have varying signs, because it is all volun-
tary.
Dr. YOUNG. Yes.
Mr. WAXMAN. Whatever anybody wants to do to inform the
public, it is fine with you. There is no uniform sign agreed to.
Dr. YOUNG. That is correct, and there are also some that were
put out by some of the pharmaceutical corporations, I am sorry,
some of the retail corporations.
Giant, for example, very early put a shelf peeler on, and was ex-
tremely helpful, because that was right at the point of purchase,
and would not only apply to one particular brand of aspirin, but
would apply to all on the shelves.
These were requested to be displayed very prominently where we
have the analgesics.
Mr. MICHELS. Here is a copy of the Aspirin Foundation poster. I
understand it is identical to that in their 60-second public service
announcement.
PAGENO="0369"
363
Mr. WAXMAN. Is that announcement saying there is no connec-
tion proved between Reye's Syndrome and aspirin?
Dr. YOUNG. We have this available, Mr. Chairman, if you would
like to see it. We have both the 30-second and 60-second.
Mr. WAXMAN. No, just the text.
Mr. MICHELS. Not this poster, no.
Mr. WAXMAN. I would like to see all of those for the record. I
would like to receive the full studies and monitoring reports that
you have for the record as well. Also, we sent a letter specifically
to Secretary Heckler asking for certain data as well, and we would
like to have that answered for the record.
Dr. YOUNG. We certainly will supply that.
[Testimony resumes on p. 413.]
[The information requested follows:]
PAGENO="0370"
364
Aspirin Foundation of America
Reye Syndrome Public Service Announcements
Text of 30-Second Announcement
"An important message for parents of children and teenagers with chicken pox
or flu.
A rare but serious childhood disease called Reye Syndrome may develop in
children who have chicken pox or flu.
Although the cause of Reye Syndrome is not know, some studies suggest a
possible association with medicines containing salicylate or aspirin. So it
* is prudent to consult a doctor before giving these medicines to children and
teenagers with chicken pox or flu.
A public service announcement brought to you by the American Reye's Syndrome
Association, the Reye' S Syndrome Society and the National Reye `5 Syndrome
Foundation."
Text of 60-Second Announcement
"An important message for parents of children and teenagers with chicken pox
or flu.
A rare but serious childhood disease called Reye Syndrome may develop in
children who have chicken pox or flu.
Although the cause of Reye Syndrome is not known, some studies suggest a
possible association with medicines containing salicylate or aspirin. So it
is prudent to consult a doctor before giving these medicines to children and
teenagers with chicken pox or flu.
Remember, Reye Syndrome occurs even in children and teenagers who take other
medicines or no medicines. It's important to be aware of the early signs and
symptoms. If your child shows unusual behavior, such as severe tiredness,
belligerence, or excessive vomiting after appearing to recover from chicken
pox or flu, get medical help irsnediately. Give no medications.
A public service announcement brought to you by the American Reye's Syndrome
Association, the Reye's Syndrome Society and the National Reye's Syndrome
Foundation."
Doc. 3258F, Disk Oll2A
PAGENO="0371"
365
DEPARTMENT OF HEALTH & HUMAN SERVICES Public Health Service
Food and Drug Administration
Rockville MD 20857
April 11, 1985
`The Honorable Henry A. Waxman
Chairman, Subcomittee on Health
and the Environment
Cormiittee on Energy and Cormterce
House of Representatives
Washington, D.C. 20515
Dear Mr. Waxman:
This is in response to ynur letter of January 11, 1985, addressed to
Secretary Heckler, regarding the ongoing voluntary progran to revise
the labeling for aspirin and salicylate-containing drug products to
reflect the possible association bett~en the use of these products and
the development of Peyn syndrome in children and teenagers who have flu
or chicken pox. As ynu know, this voluntary progran also includes art
extensive public education canpaign.
Recently, in appearing before the Subcornitittee t~ responded to some of
the questions posed in ynur letter. We are now submitting the enclosed
written responses to all of these questions to complete the record.
If t~ can be of any further assistance, please let us know.
Sincerel yours,
Frank . o , h.D.
* Commissioner o Food nd Drugs
Enclosure
PAGENO="0372"
366
RESPONSES TO QUESTIONS IN CHAIRMAN WAXMAN'S
LETTER OF JANUARY 11, 1985
1. The percent of aspirin products on the market with adequate warning
labels as of February 28, 1985, and projections as to the date when
all products will be in full compliance.
Answer
Less than 1 percent. Based on FDA's own experience, which was
confirmed by discussions with aspirin manufacturers who are members of
the Aspirin Foundation of America, it was concluded that relabelino
products would not be feasible during this flu season because, by
mid-January, the flu season was already half over and would last only
about three additional months. Instead, FDA concluded that an
intensified public education caiipaign, combined with shelf posters,
would be the most expeditious and effective mechanism of communicating
this information to the consuming public in so short a period of
time.
FDA has, however, strongly encouraged the industry to relabel
individual products prior to the beginning of next year's flu season.
The Agency has recently been in contact with representatives from the
Aspirin Foundation of America, whose eight member companies plan to
voluntarily relabel their aspirin-containing drug products. These
revisions would entail: (a) a warning statement which reads:
"Warning: Consult a physician before giving this medicine to children,
including teenagers, with chicken pox or flu" and (b) deletion of all
references to flu on the labels of children's aspirin products. Our
understanding is that all eight firms are currently revising their
labeling.
The industry members have indicated to us that the first stock with
revised labeling will be available for distribution as early as June or
July 1985. The goal is to have these changes in place prior to the
commencement of next year's flu season.
Plough, Inc. of Memphis, Tennessee, maker of St. Joseph aspirin and
nxn-aspirin products for children, which is not a member of the Aspirin
Foundation, has developed its own voluntary precautionary labeling
progrmn. Beginning on January 9, 1985, Plough placed an abbreviated
warning sticker on all stocks shipped from its plant. The sticker
reads: "Consult doctor before use in children or teenagers with flu or
chicken pox." Plough will also include in all packages which contain
an insert information which identifies the syiiptoms of Reye syndrome.
Few, if any, of these stickered packages wore likely to reach retail
shelves by February 28, 1985.
In addition, Plough intends to relabel all its children's
aspirin_rontaifling products to include the followinq warning
statements:
"Warning: Reye Syndrome is a rare but serious disease which can
follow flu or chicken pox in children and teenagers. While the
cause of Re~ Syndrome is unknown, some reports claim aspirin may
increase the risk of developing this disease. Consult a doctor
before use in children or teenagers with flu or chicken pox."
As with the Aspirin Foundation members, the goal is to have the new
label ing in place prior to the commencement of next year's flu season.
PAGENO="0373"
367
2. The percent of aspirin products on the market that continue to
identify influenza, "flu" or chicken pox as indications for the use
of aspirin, as of February 28, 1985.
Answer
We are aware that some aspirin products on the market identify
influenza, "flu," as an indication for use while others do not. We
believe few, if any, are indicated for chicken pox per se. However,
accurate percentage figure information is not available at this time.
Efforts are underway to detennine this type of information fran the
responses received from the 3,264 "Dear Drug Establishment Registrant"
letters describing the voluntary label inq progran which were mailed
March 8, 1985 (copy enclosed).
As stated in response to the first question, FDA believed that shelf
posters and public education, rather than relabeling of individual
products, would be possible to accomplish immediately. Also as noted
in our answer to question #1, however, the Aspirin Foundation members
do intend to relabel their products to delete reference to flu in the
labeling of children's aspirin products, prior to the commencement of
the next flu season. I should note that apart from children's aspirin,
some aspirin products will continue to be labeled for use to treat
influenza. Rut, as yu know, the warning statement that will appear on
all aspirin-containing products specifies that a physician should be
consulted before giving the product to children or teenagers with flu
or chicken pox.
PAGENO="0374"
368
3. Evidence that parents and physicians are becoming aware of the
risks of using aspirin and are in fact avoiding the use of that
drug in cases of chickenpox or influenza, and a description of
plans the Department has for monitoring parental information and
behavior.
Answer
The Agency is seeking approval through appropriate channels to conduct
a telephone survey to assess constziier awareness of the issue. A
questionnaire desiqned to query individuals about drug use patterns and
knowledge about the use of aspirin during episodes of flu or chicken
pox will be utilized. Data will be collected using a sample size of
1500 eliDible households to be identified by screening 3000 telephone
households.
The survey, as currently envisioned, however, does not include
physicians. In an effort to get the survey underway, FDA decided that
because these products are, for the most part, taken without consulting
a physician, it would be appropriate and logical to target the survey
towards the general consinier to ascertain awareness in our initial
survey. The Agency is prepared to conduct an expanded survey after
these educational efforts have become fully operational if we feel that
further feedback will help modify and improve the informational and
educational programs underway.
It is worth notinq here that we have bequn to see some indication that
the public awareness campaigns are having an effect. Sales of single
entity aspirin products for children have declined notably during the
flu-season for the last several years. Also, data show that doctor
recommendations for the use of aspirin for the treatment of flu and
chicken pox in yeung children declined 72 percent between 1980 and
1983. These trends probably suggest that public education efforts have
succeeded in reaching consumers and health care providers.
PAGENO="0375"
369
4. Actions that the Department and aspirin manufacturers have taken to
distribute new warning labels to be placed on aspirin products
already in people's homes as well as on inventories already in
distribution.
Answer
As noted earlier, FDA felt that relabeling products already in
distribution channels, or mailings to provide labels for individual
home use, was not feasible at this time. Instead, the Agency expanded
its public education caiipaign, with some modifications to update the
information as a result of the pilot study, as the most practical way
of informing the public during this flu season with respect to products
already on store shelves or in people's homes. The progra~
specifically included public service announcements, posters in schools
and doctor's offices, newspaper columns, and special mailings to
various health and consimier organizations.
The private sector has also launched public education efforts. The
Aspirin Foundation has prepared public service announcements for
television and radio. In addition, the Aspirin Foundation members, as
well as retailers and trade associations, have distributed shelf
posters to be placed at the point of purchase in grocery stores and
pharmacies to cover current inventories.
PAGENO="0376"
370
5. The degree of compliance of each specific aspirin manufacturer or
distributor with your voluntary program.
Ans wer
FDA does not have data on each specific aspirin manufacturer. The
Agency did, however, do a sampling of major retail establishments to
assess the deqree of compliance with this aspect of the voluntary
program.
Specifically, during March 4 to 6, 1985, FDA conducted a nationwide
inspection of 115 randomly selected major chain grocery stores and 115
randomly selected major chain drup stores to determine the
effectiveness of voluntary compliance with respect to the placement and
display of posters containing a warning statement of the possible
association of Reye syndrome with aspirin-containing drug
products.
As of March 6, 1985, of the 230 combined retail outlets visited, only
28 had Reye syndrome warning posters displayed. A total of 38 posters
were displayed in these 28 retail outlets. Nine posters were supplied
by members of the Aspirin Foundation of America and 29 posters wore
supplied by corporate offices of various retail outlets (e.g., t~iant
Foods) or by the American Pharmaceutical Association (APhA).
The majority of posters that were available were prominently displayed
in the analgesic sections of the stores in such a manner that a
consumer purchasing these products would readily see the warning
statements. Some retail outlets have displayed the poster near the
checkout cash register.
rn addition, 5 retail outlets surveyed had had Reye syndrome warning
posters supplied to them but had not displayed them at the time of
FDA's visit. Our inspectors encouraged store managers and pharmacists
to make use of these posters to convey this important public health
information.
Overall, results of the inspection indicate that posters supplied by
all sources wore displayed as early as February 1, 1985, and as
recently as March 6, 1985.
There are a number of possible explanations or contributory factors as
to why such a limited number of industry-sponsored posters have
appeared in retail establishments. For example, industry sales force
personnel often made posters available to wholesalers and distributors
rather than to retail outlets. In addition, in some instances, there
has been a reluctance on the part of retailers to display the posters
due to the past controversy surrounding this issue. Finally, the time
period was fairly short and may not have been sufficient to make a
proqram of this magnitude fully operational.
PAGENO="0377"
371
Nevertheless, the Agency did find these initial results of the poster
campaign to be disappointing. Therefore, FDA officials met with the
Aspirin Foundation on March 13 regarding the level of voluntary
compliance observed. The Aspirin Foundation offered assurances that
additional efforts, such as direct mailinos to pharmacies and grocery
stores, and more vigorous canvassing by the industry sales forces are
being undertaken to ensure as complete coverage as possible. We intend
to perform a second inspection of retail establisirents in the next
several weeks to measure the effectiveness of the Aspirin Foundation's
renewed efforts with respect to posters.
As you know, this private sector voluntary labeling campaign is
respresentative of the eight members of the Aspirin Foundation of
~n~erica and Plough, Inc., maker of St. Jospeh's aspirin and non-aspirin
for children, which is not a member of the Aspirin Foundation. As was
mentioned above in responding to ouestion #2, in an effort to reach
other manufacturers of aspirin and salicylate-containing drug products
to advise them of these voluntary initiatives, we have written to all
drug manufacturers registered with FDA. The purpose of this letter is
also to ascertain whether, and to what extent, these firms intend to
join in this nationwide campaign. We will also be assessing the
results of this additional effort.
Attachment
PAGENO="0378"
372
Retail Survey--Reye Syndrome Warning Statement Posters
On March 1, 1985, the Office of Compliance, CDB, FDA issued an all FDA
District Office and Station assignment to determine the effectiveness
of the industry voluntary informational program on Reye Syndrome.
Each District Office and Station was instructed to randomly select and
visit five major chain drug stores and five major chain grocery stores
for a total of 230 establishments within their Standard Metropolitan
Servicing Area to determine whether any Reye Syndrome posters or
placards were displayed. In addition to reporting whether posters were
present, the size and placement of the posters was reported. If the
posters differed from those of the Aspirin Foundation of America, the
Districts were instructed to report the exact language of the warning
posters and to determine the source of supply.
The survey was conducted during the week of March 3, 1985, and all data
were received at FDA Headquarters on or before Friday, March 8, 1985.
REYE SYt~1E RETAIL SURVE
P&uther of Stores with Poster
_______ Sub~t~.
DrUg 7 2 14 16 23
Grocery 2 1 2 3 5
1~ta1 9 3 16 19 28
PAGENO="0379"
373
DEPARTMENT OF HEALTH & HUMAN SERVICES Pubtc Health Servlte
Food and Drug Administration
Rockville MD 20857
March 8, 1985
Dear Drug Establishment Registrant:
On January 9, 1985, the Secretary of the Deparbnent of Health and Human
Services requested the aspirin industry to undertake a voluntary program
to warn parents and teenagers about the possible association between the
use of aspirin and the onset of Reye Syndrome. As a consequence, the
Comissioner of Food and Drugs met with representatives of the Aspirin
Foundation of America, Inc., and Plough, Inc., at which time both
organizations announced they vould launch voluntary Reye Syndrome
precautionary programs. The purpose of this letter is to inform you of
the voluntary labeling progress being undertaken by the Aspirin
Foundation and Plough, Inc. and to. ascertain whether, and to what extent,
your firm intends to join in this nationwide program.
As a part of its voluntary program, the Aspirin Foundation has proposed
labeling revisions for aspirin and aspirin-containing products, which
include:
(1) Indications for use in ~flu5 will be resoved from products
packaged only for use in children (pediatric products).
(2) All such products will bear the statement; "Warning: Contact a
physician before giving this medicine to children, including
teenagers, with chicken pox or flu."
Plough, Inc. of Wasphis, Th, maker of St. Joseph aspirin and non-aspirin
products for children, which is not a meniDer of the Aspirin Foundation,
has developed its own voluntary precautionary program. A part of its
program includes the labeling revisions for children's products proposed
by the Aspirin Foundation with the, following expanded warning statement:
PAGENO="0380"
374
"Warning: Reye Syndrome is a rare but serious disease
which can follow flu or chicken pox in children and
teenagers. While the cause of Reye Syndrome is
unknown, some reports claim aspirin (or salicylates)
may increase the risk of developing this disease.
Consult a doctor before use in children or teenagers
with flu or chicken pox."
Plough, Inc. also intends to include in its packages an insert bearing
information which identifies the symptoms of Reye Syndrome.
The ~DA supports these voluntary precautionary programs of the Aspirin
Foundation and Plough, Inc. and the labeling revisions proposed by them
and urges that they be applied to all aspirin and salicylate-containing
drug products intended for use in the treatment of flu or chicken pox,
and/or likely to be used by children or teenagers in the treatment of
symptoms coxmnonly associated with flu or chicken pox (e.g., fever, cough,
headache, sore throat, sneezing, nasal congestion, rhinitis). For more
information, please refer to the attached HHS Press Releases and FDP~ TALK
PAPER.
Should you elect to participate in this voluntary program, we would
reconmend that a warming statement appear on all c~irtons, container
labels, and other printed materials as the first warning for products with
multiple warning statements, and that the labeled directions for use refer
to the warning statement, such as "For Chicken pox or Flu see Warnings."
This is consistent with the agency's position in the advance notice of
proposed rulemaking that was issued on December 28, 1982 (47 FR 57886).
In an effort to update our files under the drug listing regulations, we
request that you answer the questions on page 3. of this letter:
PAGENO="0381"
375
(1) Establishment Name Address City/State/Zip
________ ____________ ( )
(2) Respondent's Name Title Telephone No.
(3) Is your firm currently involved th the manufacturing,
repackaging, relabeling, and/or distribution of products
containing aspirin or salicylates?
Yes No
If yes, please attach specimens or ~ of each
container label, carton label, and accompanying
labeling. Mark on each specimen or copy whether the
product is manufactured (M), repackaged (RP), relabeled
(RL), repackaged and relabeled (RP/RL), or distributed
only (D).
(4) Does your firm intend to relabel its aspirin or
salicylate-containing products in conformance with the
voluntary initiatives d~veloped by the Aspirin
Foundation or Plough, mc?
Yes No
Not Applicable -
* If yes, please attach specimens or copies of each
container label, carton label, and accompanying labeling
showing changes to be made.
(5) If yes to items 3 and 4, what is your anticipated date to
begin using the new labeling?
* * Date_________
(6) If yes to items 3 and 4, what is your anticipated date
for such newly labeled products to reach the retail
market place?
Date_________
Please return using enclosed envelope by 3/29/85 to;
Food and Drug Administration
* HFN-3l2
5600 Fishers Lane
Rockville, ~5) 20857
Attn: Reye Syndrome Labeling
PAGENO="0382"
376
As indicated above, we request that, whether or not you decide to
participate, you submit one copy of each label, carton label, and
accompanying labeling for each aspirin or salicylate-containing product
currently manufactured, repackaged, relabeled and/or distributed by you.
Should you agree to participate in this program, we ask that you also
submit a copy of each label, carton label, and accompanying literature for
each such product showing the revisions to be made. With regard to
questions 5 and 6, we request that you identify the anticipated dates for
using such revised labeling and when products, bearing revised labeling,
will reach the retail market place.
Please return page 3 of this letter and any pertinent labeling, as
requested, using the enclosed envelope, by March 29, 1985. Should you have
any questions you may contact Kevin M. Budicn, Assistant to the Director,
Division of Drug Labeling Compliance, Office of Compliance, Center for
Drugs and Biologics at (301) 443-7283.
Thank you for your prompt attention in this matter.
Sincerely,
(7~-) Y2i
Harry M. fr~yer, Jr., M.D.
Director
Center for Drugs and Biologics
Enclosures (3):
Secretary's Press Statemant, 1/9/85
rIBS Press Release, 1/23/85
FD~ Talk Paper, 1/25/85
PAGENO="0383"
377
YPe*C*ETAaY O~ H(ALTh ANO NLUAN ISSV$cU
~ assi
Statement by
Margaret N. Heckler
Secretary of Health and Human Services
Nothing is more important to Americans than the health and safety
of their children and, as Secretary of Health and Human Services, I
feel a special responsibility to protect the health of our nation's
children during their most vulnerable years.
That is why I ordered special steps to resolve the scientific
dispute when some early studies showed an association between Reye
syndrome and the use of aspirin for children suffering from chicken
pox, influenza and flu-like illnesses. That is also why I instructed
the Food and Drug Administration to pursue a vigorous public education
campaign to ensure that parents were made aware of the possible link.
In particular, I ordered the Centers for Disease Control a year
ago to undertake a new study of aispirin and Reye syndrome. The study
had two parts a one-year pilot study followed by a full-scale
investigation.
The Centers for Disease Control have now completed the pilot
study. This study is not completely conclusive - but its findings do
show an association between the use of aspirin and the onset of Reye
syndrome in children and teenagers.
These results make it urgent that CDC vigorously pursue the full-
scale study. That work was begun last month and is now fully underway.
In the meantime, I strongly urge parents to follow the advice of
the Surgeon General: in all cases involving children, inclndi~q
teenagers~ a physician should be consulted before using aspirin in
cases of fIü~or chicken pox.
It is significant that fewer children are now being struck by Reye
syndrome - 190 known cases in the year ending November 1984 - while
reported cases in previous years were as high as 548 (in 1980). But
this does not mean we can be complacent. The disease is deadly, with a
fatality rate of 26 percent last year. In addition, those who suffer
from the disease are increasingly older children and teenageri, as well
as young children: According to the pilot study, some 50 percent of
all cases were in those over age 10, and 15 percent were in those aged
15 and older.
In order to ensure that all children continue to be given the
fullest protection, even while we await final scientific conclusions, I
am today taking four additional steps:
First, I am ordering CDC to release the pilot study immediately,
and I am instrutting that it also be published as soon as possible in
CDC's journal Morbidity and Mortality weekly Report. This information
along with other scientific evidence will appear~in a refereed
scientific journal.
Second, I am asking the Food and Drug Administration to extend and
expand its public education efforts -- parents must understand the need
to consult a physician before using aspirin to treat flu or chicken
pox. Likewise, FDA will take steps to inform teenagers - who often
treat themselves -- of the possible link between aspirin and Reye
syndrome.
PAGENO="0384"
378
Third, I am contacting media leaders throughout the country asking
them to use every possible resource to help broadcast the message. I
am telegraphing the presidents of the three television networks as well
as the American Newspaper Publishers Association, the National
Association of Broadcasters, the Association of Independent Television
Stations, and the National Cable Television Association. I will also
send letters to the owners of newspapers as well as television and
radio stations throughout the country.
I will re-emphasize the importance of the public service
announcements we've already supplied to them. And I will urge them to
take additional steps to convey this important message: for example,
special news coverage, new public service announcements, messages
specially designed to reach teenage audiences, or other appropriate
steps.
Finally, I will ask the makers of aspirin products to take two
steps voluntarily: first, to immediately remove any labels which
recommend that aspirin products be used to treat flu or chicken pox in
children or teenagers; and second, to further label all aspirin
products to indicate that there is a possible association between the
use of aspirin and the onset of Reye syndrome in children and
teenagers, and that aspirin products should not be used in those cases
unless a physician is first consulted.
I would ask the industry to voluntarily retain this expanded
labelling until the results of the full-scale CDC study have been
reported and thoroughly analyzed.
I want to emphasize that this step does not mean that aspirin is
unsafe for other uses. Aspirin is, in fact, a tremendously valuable
and effective analgesic and anti-inflammatory drug that has, will and
should continue to be used by tens of millions of Americ~ans safely.
But, as with any other drug, it is crucial that aspirin be administered
appropriately.
I am confident that both aspirin manufacturers and the American
media will take the steps needed to ensure the best possible protection
for our children.
These are useful first steps. I believe they are entirely in the
spirit of the recommendations we have received from the National
Academy of Sciences' Institute of Medicine. In addition, the data now
available in the pilot study will be reviewed further with great care,
as will all independent comments and recommendations, to determine
whether further steps may be warranted.
PAGENO="0385"
379
HHS
U.S. D~PARTMCNT O~ HCALTH AND HUMAN SERVICES
FOR IMMEDIATE RELEASE Claire del Real -- (202) 245-6343
Jan. 23, 1985
HHS Secretary Margaret M. Heckler announced today that the nation's
major aspirin manufacturers have agreed to her call for voluntary action
concerning the rare but serious Reye syndrome. A new program by the
manufacturers will include television announcements, s'ore posters and label
changes and warnings regarding the rare but serious Reye syndrome.
Secretary Heckler had called for such voluntary action Jan. 9 and
today applauded the Aspirin Foundation of America for "its prompt and
responsible action, which will be getting the message to Americans within a
week." The program was worked out in a series of meetings between the
foundation and the Food and Drug Administration over the past two weeks.
The Secretary's request for information and labeling was made following
a review by the Institute of Medicine of the National Academy of Sciences
of a pilot study supporting a link between use of aspirin to treat childhood
flu and chicken pox and the subsequent development of Reye syndrome.
Public service announcements and store posters and signs will be
distributed next week by the manufacturers' sale representatives and the
Advertising Council, Secretary Heckler said. She asked the media and store
managers to use the materials widely, "because we will rely on these
materials to notify people buying aspirin products with the old labels -- or
already having such products in their homes."
Some of the label changes and warnings may be in place as early as this
summer, and will thus appear well in advance of the next winter's flu and
chicken pox seasons. Warning stickers on store shelves will appear in some
areas as early as this week.
The posters and radio-TV public service announcements say, in part:
"A rare but serious childhood disease called Reye syndrome may develop
in children who have chicken pox or flu. Although the cause of Reye
syndrome is not known, some studies suggest a possible association with
medicines containing salicylate or aspirin. So it is prudent to consult a
doctor before giving these medicines to children and teenagers with chicken
pox or flu."
The posters and announcements also note that Reye can occur without a
link to medications. The materials list the symptoms -- lethargy,
belligerence or excessive vomiting -- and recommend quick medical help.
The labeling changes are twofold:
--Suggestions for use in flu will be deleted from the labels of
children's aspirin.
-- The following warning will be added to labels of aspirin-containing
products for adults as well as children: "Consult a physician before giving
this medicine to children, including teenagers, with chicken pox or flu."
Reye syndrome is a rare condition, with only several hundred reported
cases a year. Last year there were 190 cases reported. But 20-30 percent
of reported cases are fatal, and many of the surviving youngsters suffer
brain damage.
-MORE-
52-266 O-85---13
PAGENO="0386"
380
Pour state studies initially made possible associations between Reye
and aspirin's use for childhood chicken pox and flu. A larger federal study
to confirm or negate the link will continue through next winter's flu and
chicken pox seasons.
A pilot for this larger epidemiological case review found 96 percent of
cases had the common thread of aspirin use for flu-like illnesses or chicken
pox. After a review, the Institute of Medicine of the National Academy of
Sciences advised that the federal government should alert parents and
physicians now and not await the full study's results. The institute
recommended that the full study continue, however. A task force of Public
Health Service employees is overseeing the study.
First to respond to the new information was Plough Inc. of Memphis,
Tenn., manufacturer of St. Joseph products. for children. Plough is making
label changes and is placing stickers on products already produced but not
yet distributed.
The Aspirin Foundation represents such major aspirin manufacturers and
distributors as Sterling, Bristol-Myers, Miles, Burroughs Wellcome, Merrell
Dow and Procter & Gamble.
Retailers such as Giant Foods, with offices in the Washington area,
plan their own posters and shelf signs on Reye syndrome and aspirin in the
nonprescription drug sections of their pharmacies and food stores. FDA has
been working with these retailers. Giant Foods plans to have their posters
in place tomorrow.
Secretary Heckler emphasized that warnings on Reye syndrome ~do not
mean aspirin is unsafe for other uses. Aspirin is, in fact, a tremendously
valuable and effective analgesic and anti-inflammatory drug that has, will
and should continue to be used by tens of millions of Americans safely. But
as with any other drug it is crucial that aspirin be administered
appropriately."
HI'
PAGENO="0387"
381
FDA
,.Ru < J34\J)[J~, FOOD AND DRUG ADMINISTRATION
U.S Department of Health and Human Services
Public Health Service 5600 Fishers Lane Rockvile, Maryland 20857
FDA Talk Papers are prepared by else Offlee ci Public Affairs to guide FDA personnel in responding with consistency and accuracy
to questions from the public on subjects c(current interest Talk Papers are subject to change as move information becomes
available. Talk Papers are not intended for general distribution outside FDA. but all information in them a public, and full tests
are releasable upon request.
T85-7 Bill Grigg
Jan. 25, 1985 (301) 443-4177
RECENT ACTIONS ON REYE SYNDROIcE/ASPIRIN LINK
The FDA has held a series of meetings to carry forth HHS Secretary
Margaret M. Heckler's Jan. 9 call for voluntary labeling changes on aspirin
products. The changes were requested to reflect a recent federal pilot study
supporting earlier state studies linking aspirin's use in teen and childhood
flu and chicken pox to the subsequent development of the rare but serious Reye
syndrome (see Talk Paper T85-3).
Secretary Heckler announced the results of these meetings -- agreement
with the major manufacturers for label changes, store posters and radio-TV
announcements -- on Jan. 23. The following may help answer questions on
the warning labels and broadcast announcements pledged:
The labeling agreed to by members of the Aspirin Foundation of America --
such major manufacturers as Sterling, Bristol-Myers, Miles and Burroughs
Wellcome, Squibb, Whitehall and Procter & Gamble -- and found acceptable by
FDA will add to the warning section of the labels:
"Contact a physician before giving this medicine to children, including
teenagers, with chicken pox or flu."
In addition, recornendations for use in flu will be removed from
children's products.
Als~as part of the agreement, the Aspirin Foundation has produced 60-
and 30-second TV and radio public service announcements to be distributed to
the media in the next few days. The shorter version says:
"A rare but serious childhood disease called Reye Syndrome may develop in
children and teenagers who have chicken pox or flu. Although the cause of Reye
Syndrome is not known, some studies suggest a possible association with
medicines containing salicylate or aspirin. So, it is prudent to consult a
doctor before giving these medicines to children or teenagers with chicken
pox or flu.'
The longer version adds to the above:
"Remember, Reye Syndrome occurs even in children and teenagers who take
other medicines or no medicines. It's important to be aware of the early
signs and symptoms. If your child shows unusual behavior, such as severe
tiredness, belligerence, or excessive vomiting after appearing to recover from
chicken pox or flu, get medical help imediately. Give no medications.'
Plough Inc. of Memphis, Tenn., maker of St. Joseph aspirin and non-
aspirin products for children, is not a member of the Aspirin Foundation but
was the first to announce it would comply with the Secretary's request (even
though company officials said they did not feel aspirin had been established
as a cause of Reye syndrome). Its program is different from the foundation
members. The corporation met with FDA Jan. 15 and later announced that it:
-MORE-
PAGENO="0388"
382
-- would begin next week to print packages for its aspirin-containing
products with changes suggested by the Secretary and FDA in the labeling,
eliminating any recommendation for use in childhood or teen flu or chicken
pox, and adding a warning against such use, with an explanation of Reye
syndrome; and
-- was adding warning stickers on the boxes of aspirin products already
produced but still under its control. Consumers may begin to see the stickers
soon.
The stickers say, "Consult doctor before use in children or teenagers
with flu or chicken pox." The Plough label warning will say:
"WARNING: Reye Syndrome is a rare but serious disease which can follow
flu or chicken pox in children and teenagers. While the cause of Reye
Syndrome is unknown, some reports claim aspirin may increase the risk of
developing this disease. Consult doctor before use in children or teenagers
with flu or chicken pox."
Plough will also insert in packages information to read: "The symptoms
of Reye Syndrome can include persistent vomiting, sleepiness and lethargy;
violent headaches; unusual behavior, including disorientation, combativeness
and delirium. If any of these symptoms occur, especially following chicken
pox or flu, call doctor immediately, even if your child has not taken any
medication. REYE SYNDROME IS SERIOUS, SO EARLY DETECTION AND TREATMENT ARE
VITAL."
FDA Commissioner Frank E. Young wrote Plough commending the company's
speed and cooperation.
Giant Foods and other retailers have contacted FDA about producing their
own posters and shelf labeling. The Giant materials will be in all of the
chain's food and drug stores tomorrow, Jan. 26. The main poster says, "The
U.S. Food and Drug Administration recommends that parents check with a doctor
before giving aspirin or products containing aspirin to children or teenagers
who have the flu or flu-like symptoms or chicken pox."
Below the posters, Giant is attaching to the shelves tear-off literature
giving more details about the warning and about Reye syndrome.
FDA has reviewed the wording used by Giant and supports it.
FDA has conducted public education campaigns cautioning about the use of
aspirin in childhood flu and chicken pox for three winters and is now updating
those materials. Since the pilot and last year's case reports indicate about
half the cases of Reye syndrome to be in teens and children over 10, who may
self-medicate, the campaign will shift emphasis toward this older group. A
new radio announcement and a column for weekly newspapers is being given
priority. Secretary Heckler has sent letters, on the pilot study to
pediatricians and family doctors, as well as to newspapers and broadcast
outlets.
PAGENO="0389"
383
INDUSTRY INITIATIVES OTHER THAN ASPIRIN FOUNDATION
ON REYE SYNDROME WARNINGS
cc~s
Waigreen Drug Stores
Letter Walgreen/Lampkin Dated March 11, 1985
Mamorandum, Reye Syndrome Signs
Waigreens News Flash, Reye Syndrome Signs Dated February 4, 1985
Reye Syndrome Sign
Giant Feod
Reye Syndrome Warning Poster
Consumer Leaflets
Thrift Drug Company
Letter Thrift/Lampkin Dated March U, 1985
Thrift Drug Bulletin Dated February 1, 1985
Reye Syndrome Warning Poster
Peoples Drug Stores
Bulletin on Reye Syndrome Sign
Osco Drug Stores
Letter Osco/Lampkin Dated March 8, 1985
Daily General Bulletin on Aspirin Warning Signs
"Shelf Talker" on Reye Syndrome
Safeway Stores, Incorporated
Letter Safeway/Lampkin Dated March 8, 1985
Inter-Office Coninunication, Reye Syndrome
Food Marketing Institute
American Pharmaceutical Association
Apharmacy Weekly Dated February 1, 1985
Reye Syndrome Warning Poster
Plough, Incorporated
Letter Schering-Plough/Lampkin Dated March 12, 1985
Labeling for St. Joseph Cold Tablets for Children
Package Insert
Labeling for St. Joseph Cold Tablets for Children
Package Insert
Labeling for St. Joseph Aspirin for Chi1drej~
Package Insert
Bottle Label for St. Joseph Aspirin for Children
Bottle Label for St. Joseph Cold Tablets for Children
PAGENO="0390"
384
Walgreen Drug Stores
200 Leermond Road
Deerfield, Illinois
On February 4, 1985, sent out Reye Syndrome warning statment posters and
instructions to over 1100 Waigreen Stores. Waigreen also will be sending
out bulletins to all store managers requesting an effectiveness check to
see if the posters have been displayed and are still in place. Walgreen's
will not allow other posters to be placed in their stores. They feel that
additional posters will cause clutter on the shelves and confusion to the
customer. Walgreen's stated that the State of Illinois had proposed a
State law requiring a Reye Syndrome warning statment and poster but this
bill has died.
PAGENO="0391"
385
Wa~teei~~
Walgreen Co.
Corporate Offices
200 Wilmot Road
Deerfield, Illinois 60015
March 11, 1985
Win. Lampkin
FDA
5640 Nicholson Lane
Room 26
Rockville, MD 20852
Dear Mr. Lampkin:
Enclosed please find the information that we discussed on the telephone.
As I mentioned to you earlier, the Waigreens News Flash was originally
sent nationwide to all Waigreen store managers - over 1,050 drug stores.
I am in the process of distributing the follow-up memo from Mr. G.S. Kraiss,
Senior Vice President of Store Operations, to our Pharmacy Supervisors. As
you can tell from the memo, the Pharmacy Supervisors will verify that the
Reye's Syndrome notice has been provided to our aspirin buying consumers.
Sincerely,
Dr~iI1
Jill Leslie Drell
Senior Attorney
Governmental and Public Affairs
JLi~/pr
Enclosure
PAGENO="0392"
386
W~94~a1cL
look Tide:
i
i
"T"T"
i
i
i
.
Subject: REYE'S Syndrome Signs
From: C. S. Kraias
To: AU Pharmacy Supervisors
Attached is a copy of a Nevaflash that went to all Store Managers
requesting the posting of Reye's Syndrome signs in the analgesic depart-
ments of our stores.
On your next visit to the stores within your District, insure that the
signs have been posted in the appropriate locations. Included are extra
notices for use in those stores that have lost the original signs sent to
them. For additional signs, contact the Governmental and Public Affairs
Department.
It is very important that our atores provide this notice to buyers of
aspirin products. -
GSK:btm
cc: F. F. Canning
V. A. Brunner
V. 0. Shank
K. C. Atlas
K. L. Cudworth
K. A. Daniels
V. L. Earnest
G. C. Eilers
.1. B. Karlin
P. E. Eanifen
V. C. Thien
K. K. King
All District Managers
V. K. Hatfield
.1. L. Drell
I
I
~ ~
PAGENO="0393"
tV~z4jr,teei~1~ ~ News Flash
Subject REYE `S SYNDROME SIGNS
From T. A. Braun - Drug Merchandising Division
To All Store Managers
Date February 4, 1985
The Aspirin Council, which represents proprietary manufacturers of aspirin
and aspirin compounds, has voluntarily agreed to provide consumer
information on Reye's Syndrome. This voluntary program will be implemented
in all Walgreen stores in the form of signs that will be placed in the
analgesic department.
Accompanying this letter are two signs, 3 1/2 X 5 1/2, that are to be
displayed in the analgesic department and inserted into the appropriate
chrome sign holder.
THESE SIGNS ARE THE ONLY SIGNS APPROVED FOR DISPLAY IN WALGREEN STORES.
It is our recoimnendation that if you have a 12 foot department that two
signs be used, and if you have a 9 foot department, one sign should be
utilized. Irregardless of department location, the signs are to be placed
on the third shelf from the bottom since childrens' products are on this
shelf or nearby. They are to remain until further notice.
All manufacturers of aspirin products are implementing a warning on
their packages and the signs will be removed when all packaging is
revised.
If there are any further questions concerning this program, please
do not hesitate to call me on X312O.
Drug Merchandising Division
387
copies: Mr. F. F. Canning Mr. W. D. Cavanaugh
Mr. V. A. Brunner Mr. W. C. Thien
Mr. C. S. Kraiss Mr. W. H. Hatfield
Mr. W. 0. Shank Health Service Representatives
Mr. R. C. Atlas Mr. E. H. King
Mr. E. L. Cudworth Ms. J. L. Drell
Mr. R. A. Daniels Mr. T. L. Mammoser
Mr. W. L. Earnest Ms. M. T. Kari
Mr. C. C. Eilers Mr. A. F. Tuhy
Mr. J. B. Karlin Mr. N. D. Smith
Mr. P. E. Hanifen
File this N Iash1wjthstore bulletins
Fo~O6 Re~1O181
PAGENO="0394"
388
The Shopper's Center
CONSUMER INFORMATION
"Reye Syndrome is a rare but serious disease
which can follow flu or chicken pox in children
and teenagers. While the cause of Reye Syndrome
is unknown, some reports claim aspirin may in*
crease the risk of developing this disease.
Consult doctor before use in children or
teenagers with flu or chicken pox"
-Post in analgesic Dept.-
PAGENO="0395"
389
Giant Food
Landover, MD
Giant prepared and sent out 11 inch by 14 inch yellow and red posters and
3 1/2 inch by 3 inch consumer leaflets with the Reye Syndrome warning
statement. The posters and slips were sent out on January 22 to
approximately 132 stores in Virginia, Maryland and the District.
1
a doctor before
giving aspirin OF
products containing
apirin to child~en
or teenagers whO
have the flu, flu-like
symptoms or
óhlcken pox.
See shelf sign below.
Giant Food Inc.
PAGENO="0396"
390
PLEASE TAKE ONE
DRUG ALERT
Rsye syndroms
Recent medical studies show a Nnk
between the use of aspirin and a
rare, serious and sometimes fatal
condition known as Reys Syndrome.
This condition can develop when
children or teenagers are recovering
from the flu, flu-like symptoms, or
chicken pox and In many cases have
been taking aspirin. UntU more Is
known, the U.S. Food and Drug
Administration recommends that
parents Check with a doctor before
giving aspirin or products
containing aspirin to children or
teenagers who have the flu, flu-Ilk.
symptoms, or chicken pox.
Se other ~de for sympfoms.
Reye Syndrome usually occurs when
the child or teenager appears to be
recovering from the original Illness
and then develops the following
symptoms:
* Persistent vomiting
* Fatigue
* ConfusIon and Irritability
IF YOUR CHILD DISPLAYS ANY OF
THE ABOVE SYMPTOMS, CONSULT
YOUR DOCTOR IMMEDIATELY
ANNE HARTNETT
CONSUMER AFFAIRS SPECIALIST
GIANT FOOD INC. P. 0. BOX 1804
WASHINGTON. DC 20013
PHONE (301) 341-4373
PAGENO="0397"
391
Thrift Drug Company
Pittsburgh, PA
Thrift Drug send out Reye Syndrome warning bulletins and posters in the
first week of February to approximately 375 stores.
TRUST THRIFT
DRUG ,./tt3flW ~ PHYLLIS PATTERSON
March 11, 1985
Mr. Lampkin:
As requested, please find enclosed the bulletin
and sign that was sent to all of our stores regarding
the Reyes Snydrome.
If I can be of any further assistance, please
do not hesitate to contact me.
erely,
yl Patterson
P c Affairs Coord.
Attachment
PAGENO="0398"
392
,4Tt Drug Bulletin
February 1, 1985 Bulletin No. 2/1 *
Mail To All Stores Retain Until February 1, l98~
Copies To IA
SECTION I - DRUG DEPARTMENT
A. OPERATIONAL
1. Reyes Syndrome Warning
In keeping with our company's tradition of working in
the best interest of the consumer, we are voluntarily
cooperating in warning the public of the potential hazards
of using aspirin in children and teenagers with the
flu or chicken pox.
Attached to this bulletin you will find (2) Warning
Signs. One sign must be placed in your Pain Relief
Department and the other in the Cough & Cold Department
on the top shelf where it is visible to the consumers.
2. Fill Every Prescription
Our Mail Order Pharmacy is in need of the following
product:
Essence of Pepsin manufactured by Lilly.
Should you have this item, please notify:
Express Pharmacy Services
100 Delta Drive
Pittsburgh, PA 15238
Attention: Janet Rukas
SECTION II - GENERAL INFORMATION
A. OPERATIONAL
1. March Tabloid Items Update
The following items are still on division from the servicing
Distribution Center indicated. All other items should
be in your hands by this date. Check your March Advertising
Bulletin for a complete list of all items.
ITEM DESCRIPTION ITEM # LANG. ATL. PGH.
Happy Ending Books Asst. 968826 X X X
Woodtone Plaques 974964 X X X
PAGENO="0399"
WARNING: REYE'S SYNDROME
*REYE'S SYNDROME IS A RARE BUT SERIOUS
DISEASE WHICH CAN FOLLOW FLU OR
CHICKEN POX IN CHILDREN AND TEEN-
AGERS.
*WHILE THE CAUSE OF REYE'S* SYNDROME
IS UNKNOWN, SOME REPORTS CLAIM
ASPIRIN MAY INCREASE THE RISK OF
DEVELOPING THIS DISEASE.
*CONSULT YOUR DOCTOR BEFORE USING
I ASPIRIN IN CHILDREN OR TEENAGERS
WITH FLU OR CHICKEN POX.
PAGENO="0400"
394
Peoples Drug Stores
Alexandria, VA
Peoples sent out Reye Syndrome warning bulletins to approximately 330
stores in Maryland, Virginia, West Virginia, Pennsylvania, North Carolina,
and the District during the middle of February 1985. -
J Bulletin No.
TO: Wash. Area Only ____________
Mid-Atlantic Division xxx
Mid-West Division ____________
SUBJECT: REYES SYNDROME SIGN
Distribution was recently made to all stores on Reyes Syndrome (copy below).
Please post this sign in a sign holder in the OTC Section where the aspirin-
containing products are located.
Any stores not receiving the Reyes Syndrome sign shown below should contact the
Advertising Department.
We have also been advised that Norrell Services are distributing to stores in
the Washington Metro area a similar sign on Reyes Syndrome provided by the
Aspirin Foundation. This sign may also be placed in the area of the aspirin-
containing products or placed on the wall by the pharmacy drug wrap counter.
t4CS:mlt
RE YE'S SYNDROME
Notice to Parents
A rare but serious childhood
disease called Reye's Syndrome may
develop in children and teenagers who
have chicken pox or flu. Although the
cause of Reye's Syndrome is not known,
some studies suggest a possible
association with medicines contaIning
Salicylate or Aspirin. So, it Is prudent to
consult a doctor before giving these
Medicines to children or teenagers with
chicken pox or flu.
PEO~I~~fl~i?RUG
PHARMACY
PAGENO="0401"
395
Osco Drug Stores
Wheaton, Illinois
Osa~ sent out two-sided "Shelf Talkers." ~ielf Talker is a two-sided
bufletin printed with Reye Syndrome warning statments. Osco sent these
shelf talkers to a~roximately 330 stores during the last week of January
1985.
OscoDrua
SubsidIary of Jewel Companie~ ln~
EXPRESS MAIL
March 8, 1985
WRITER'S DIRECT LINE
(312)887-5237
ExecutIve Offics
l8l8SwiftDr)ve
Oak Brook IllinoIs 60521
(312) 887-
Food and Drug Administration
Room 326
5640 Nicholson Lane
Rockvifle, MD 20852
Attention: Mr. Willias Lampkin
Re: Reye Syndrome
Dear Mr. Lenpkin:
The enclosed materials are being sent in response to your telephone
conversation today with Ms. Paula Dahlquist of our company.
You will note that the memo sent to the Osco Drug Stores referenced a sign
statement which eventually was changed. The sign enclosed contains the
actual statement used.
If you have any further questions regarding this, please contact me.
Very truly yours,
OSCO UG, INC.
Vice President
and General Counsel -
LAM: 1mg: 1 79X4
Copy to: P. Dahlquist
PAGENO="0402"
396
DAILY GENERAL BULLETIN
1k Zfl" ~
AU. $T0A$
PAGE N STORE ~ ~$TA'~U71OU
0GB DAN
TO: ALL STORES FROM: SEROMIECKI SUBJECT: ASPIRIN WARNING SIGNS
Within the next week, all stores will receive three aspirin warning signs with their
ad signing package. These signs will state, `Consult doctor before giving aspirin
to children or teenagers with flu or chicken pox.' These signs will be printed on
both sides and should be put into the special sign clips that hold then perpendicular
to the shelf. Please place these sl~s In front of the following Items In the analgesic
section - St. Joseph Aspirin For Children, Bufferin Tablets Regular Strength 165's and
Osco Thin Coated Aspirin Tablets 300's.
In the near future all aspirin products will provide the following type label, `Warning:
Reye Syndrome Is a rare but serious disease which can follow flu or chicken pox In
children and teenagers. While the cause of Reye Syndrome is unknown, some reports claim
aspirin ~y Increase the risk of developing this disease. Consult doctor before use In
children or teenagers with flu or chicken pox.' Additionally, children's products will
contain an insert which will give the symptoms of Reye Syndrome.and the vital Importance
of early detection and treatment. This Information will read: `The symptoms of Reye
Syndrome can include persistent vomiting, sleepiness and lethargy, violent headaches,
unusual behavior, including disorientation, cothatlveness and dellrliai. If any of these
symptoms occur, especially following chicken pox or flu, call doctor imediately, even
If your child has not taken any medication. REYE SYNDROME IS SERIOUS, SO EARLY DETECTION
AND TREAThENT ARE VITAL.'
Aspirin is, In fact, a tremendously valuable and effective analgesic and antl-lnflamator~
drug that has, will and should continue to be used by tens of millions of Americans safel~
But as with any other drug, It Is crucial that aspirin be administered appropriately.
02570C ~ READ REACT TOSS
PAGENO="0403"
397
PAGENO="0404"
398
Safeway Stores, Incorporated
Oakland, California
Sent a bulletin dated January 30, 1985 to their 17 independent
United States retail divisions requesting that they post Reye Syndrome
warning statements in the pharmacy section by the children's aspirin.
Safeway had no idea as to how many divisions actually posted the signs but
will collect the information and relay it to us next week (week of
March 18-22). -
Eoecutiue Offices
(C~ SAFEWAY
P( ~ STORES INCORPORATED
201 Fourth St reef. Oakland, CA 94660
March 8, 1985
Mr. William Lampkin
Food & Drug Administration
5640 Nicholson Lane #326
Rockville, MD 20852
Dear Mr. Lampkin:
Per your telephone request I am attaching a copy of the
bulletin that I issued to our 17 independent U.S. retail
divisions. As I mentioned, I do not have information on which
of our divisions actually used it, but I am trying to collect
that information now and will call you next week.
Unfortunately, our Washington, D.C. division did not use the
signs and our San Francisco division has no samples available
since all their signs are posted. Maybe the Food Marketing
Institute will be able to obtain a sample sign.
I hope the attached is helpful. Thanks for calling.
Sincerely,
C~fo
Felicia del Campo, Manager
Public Affairs Department
FdC:pat
016 6U
PAGENO="0405"
399
4
TO Robert E.
INTER-OF
Bradford
FICE
COMMUNIC
FROM
ATION~?J~~
FeliCia de Campo
for U.S.
Public Relations
Mgrs
.
LOCATION
Public Affairs
Dept. Manager
LOCAT ION
DATE
January 30, 1985
SUBJECT
REYE
SYNDROME
The Aspirin Foundation released information last week to the media
concerning their proposed labeling on children's aspirin. They also
mentioned that supermarket retail outlets would be provided with
shelf stickers and labels to cover the time period before new
container labels appeared on the shelves.
You may want to post signs in your pharmacy sections by the
children's aspirin. If you do post the signs, you should not forget
any aspirin displays in the baby section, also.
The aspirin package warnings will read as follows:
`Reye syndrome is a rare but serious disease which can
follow flu or chicken pox in children and teenagers.
While the cause of Reye Syndrome is unknown, some reports
claim aspirin may increase the risk of developing this
disease.
Consult doctor before use in children or teenagers with
flu or chicken pox.
If you do elect to use signs, your wording should coincide with the
above which has been developed by the aspirin industry.
FDC: jas/0091U
Attach.
cc: P. DiGrazia
Everything you want from a stote % and a little bit more
F Ho. 45$ (~io. 4-5*)
PAGENO="0406"
400
Food Marketing Institute
Food Marketing Institute is an organization which serves food stores in
the United States. Safeway is one of their largest customers. The
Institute has not developed any Reye Syndrome warning posters of their own
but they have been contacted by the Aspirin Foundation to distribute their
posters. As of March 8, 1985, the Institute has not received the posters
from the Aspirin Foundation. They indicated that once the posters have
been received that they will be distributed by the Institute to their
member organizations.
PAGENO="0407"
401
American Pharmaceutical Association (APhA)
Washington, D.C.
APhA inserted a warning poster approximately 17 inches by 11 inches in their
weekly newsletter dated February 1, 1985. The newsletter was mailed on
January 25, 1985 to over 36,000 pharmacists. A smaller version of the same
poster was reproduced and printed in the March 1985 issue of the APhA Journal
which was mailed to over 50,000 members on March 3, 1985.
APha also received a request from Long's Drug Stores in Walnut Creek, CA, for
400 extra copies of the APhA poster.
PAGENO="0408"
402
February 1,1985 apharmacy 15
weekly
©
Dear Pharmacist:
In the words of the National Academy of Sciences' Institute of
Medicine (IOM), a pilot study done by the Centers for Disease Con-
trol shows "a strong association between the Reye syndrome and
the use of aspirin." The IOM committee added, "considering that
data from previous studies also show an association of use of aspi-
rin and Reye syndrome. . steps should be taken to protect the
public health before the full study is completed."
What the investigation had shown was that 97% of Reye's
syndrome cases had received some sort of salicylates during a bout
of the flu or chicken pox, whereas only slightly more than half of a
group of control children, with similar antecedent illnesses, had
gone on to develop Reye's. Statistically, this meant that the use of
aspirin.in these illnesses in children or teen-agers involved a 12-26
greater risk than notgiving aspirin (depending on which statistical
model was assumed).
Therefore, APhA has prepared a poster to warn parents about
this possible danger. We urge pharmacists to display it
prominently, at least for the duration of the flu season, as a public
health service to your patients.
PAGENO="0409"
403
Themessageprintedbelowshouldberensovedandplaced na prominentposltlon Inyour
pharmacyasa publkhealth servicetoyourpatients. Permission to reproducetheir message is
granted.
~u~o
A study by the Federal government's Centers
for Disease Control has found a strong
association between the use of aspirin in
children with flu orchicken pox and the
development of the potentially fatal illness
Reye's Syndrome.
Symptoms of Reye's Syndrome include
vomiting, fever, lethargy, and convulsions.
The symptoms generally appear as the child
seems to begetting better.
* Do not use aspirin for children or
teenagers with the flu or chicken pox without
first consulting a physician.
* If symptoms of Reye's Syndrome appear,
immediate medical attention is required.
For additional information, consult your pharmacist.
The American Pharmaceutical Association
The national professionalsociety of pharmacists
PAGENO="0410"
404
Shering Plough, Incorporated
Memphis, ¶L~J
Stopped shipping unstickered product on January 9, 1985. Started stickering
children's aspirin on January 9, 1985. Stickered all existing inventory in
warehouses. Stickered product available for shipoent late January 1985. All
products manufactured after January 9,. 1985 have Reye's Syndrome warning
statement. All products which contained an insert has the Reye Syndrome
warning statement printed on the insert. Firm has no plans for unstickered
product on market. Firm plans no market withdrawal. Firm has not prepared
public service announcements. Firm will not give projection on when remaining
unstickered stock on market will be exhausted.
PAGENO="0411"
405
~ Schering-Plough
Schering-Plough Corporation Telephone 901/320-2011
3030 Jackson Avenue Telex 53861
P. o. Box 377
Memphis, TN 38151-0001 U.S.A.
March 12, 1985
SENT BY FEDERAL EXPRESS
Mr. William Lampkin
Office of Compliance
Food and Drug Administration
5640 Nicholson Lane
Room 326
Rockville, MD 20852
Dear Mr. Lampkin:
Pursuant to your request, enclosed are representative samples
(2 each) of Plough aspirin-containing products bearing either a
sticker or printed warning label concerning Reye Syndrome. They
are as follows:
AVAILABLE FOR
BRAND LOT WARNING SHIPMENT
1. St. Joseph 4HlOl Stickered late January
Aspirin for 1985
Children
2. St. Joseph 4G279 Printed early March
Aspirin for 1985
Children
1. St. Joseph 4C177 Stickered late January
Cold Tablets 1985
for Children
2. St. Joseph 4C178 Printed early March
Cold Tablets 1985
for Children
Please note that the cartons bearing the printed warning also
contain a package insert with a printed, detailed statement
regarding Reye Syndrome.
January 9, 1985, the very day Secretary Heckler requested
aspirin manufacturers to comply with the voluntary program,
Plough immediately stopped shipment of such products from our
warehouses and distribution centers pursuant to oral instructions
to appropriate personnel. These instructions were confirmed in
writing the next day. Since that date, Plough has shipped no
aspirin-containing product without a Reye Syndrome warning.
It is our pleasure to cooperate with the Agency and we hope
that the enclosed information is beneficial.
Respectfully yours,
Gary ~7Wi1kerson
Legal Director
PAGENO="0412"
PAGENO="0413"
1!
F
1
PAGENO="0414"
PAGENO="0415"
0
LU
0
* 0
* Lt~
PAGENO="0416"
0
PAGENO="0417"
h
1111111
k~
~ n
a
PAGENO="0418"
412
PAGENO="0419"
413
Mr. WAXMAN. Before I recognize my colleagues, I just want to
say that what I think the administration did was to take precau-
tions not to offend the aspirin industry, and in doing that, I think
you did a disservice to the American people, and children particu-
larly, who may come down with Reye's Syndrome.
I know you don't like to fight with any of the industry groups. I
know it is better to do things voluntarily than to have to require it.
But when you rely on the good will of people who have a profit to
make and a product to sell, they are going to be more interested in
that profit, and if you are going to let them be more interested in
it, they are going to take advantage of you.
And I think they already have, because I don't think what you
have agreed to is going to reach the American people. Even your
own statistics indicate that I don't think there is much of a hope
even in the next flu season that people are going to be aware of
this danger, and that they should, when it comes to a child, avoid
the use of aspirin for one of the most common symptoms for which
we are all conditioned to think aspirin is appropriate.
Mr. Wyden.
Mr. WYDEN. Thank you, Mr. Chairman.
Dr. Young, you do not look like a callous man to me.
Dr. YOUNG. I hope not.
Mr. WYDEN. But the effects of these actions in my view are very,
very callous. I see a huge gap between the concerns that you have
professed to have in this area, concerns everybody shares, and the
actions that the Department has actually taken.
I wanted to start my questioning by asking you to read the
Plough label out loud, if you would.
Dr. YOUNG. Surely. The label that I showed you here is the one
that was put on in regard to the immediate withholding of ship-
ment at that time, and I will also read the label changes to give
you the complete portion.
Mr. WYDEN. Read the long-term label, not the short-term one.
Dr. YOUNG. Fine, let me just get it here for you.
Warning: Reye's Syndrome is a rare but serious disease which can follow flu or
chickenpox in children and teenagers. While the cause of Reye's Syndrome is un-
known, some reports claim aspirin may increase the risk of developing this disease.
Consult doctor before use in children or teenagers with flu or chickenpox.
The symptoms of Reye's Syndrome can include persistent vomiting; sleepiness and
lethargy; violent headaches; unusual behavior, including disorientation, combative-
ness and delirium. If any of these symptoms occur, especially following chickenpox
or flu, call your doctor immediately, even if your child has not taken any medica-
tion. REYE'S SYNDROME IS SERIOUS, SO EARLY DETECTION AND TREAT-
MENT ARE VITAL.
Mr. WYDEN. Doctor, that strikes the subcommittee as a strong,
dramatic label.
Dr. YOUNG. Yes, it does, and I worked in a number of meetings
with a wide variety of industry, and I am pleased to see that label.
Mr. WYDEN. Why wouldn't that be preferable in terms of policy
than the one that you agreed to with the Aspirin Foundation? You
agreed to a substantially weaker one with the Aspirin Foundation.
Why wouldn't the stronger label have been preferable to protect
the public?
Dr. YOUNG. This is an excellent question. We made widely-known
the Plough decision, and we fully discussed this with each of the
PAGENO="0420"
414
corporations and the Aspirin Foundation, and any of the others
that came to see us, or that we invited in.
We feel that if we are maintaining a voluntary effort, it is not
for us to prescribe the exact makeup of the label, but to encourage,
in the sense of voluntarism those types of labeling activities.
We feel that that is an excellent label. We are still in the early
phases of the voluntary efforts.
Mr. WYDEN. I want to yield to the chairman in just a second, but
Plough is just a small percentage of the aspirin market?
Dr. YOUNG. That is correct.
Mr. WYDEN. And they have developed something that would
really help the public. And yet, whether it was because you didn't
want to rock the boat or because you were looking at obscure scien-
tific arguments, you wouldn't go with something that really would
help the public. I think that is unfortunate.
I think that the public needed that kind of strong, aggressive
action. You know, I hear a lot from various administration spokes-
persons about being pro-family and taking profamily positions on
the issues.
Well, here is a chance where the administration could have done
something that really would help the families of this country, and
you let them down. I think that the country is owed more than
that.
The chairman wanted me to yield, and I have another question
or two.
Mr. WAXMAN. You have got two values here, doing things volun-
tarily and doing what is necessary to protect the public health. You
think the label on this children's aspirin is more calculated to pro-
tect the public health.
Why do you think voluntarism is so important? Aren't you en-
trusted not with doing things voluntarily with the industry, but
doing what is helpful to protect the public from dangers?
Dr. YOUNG. Mr. Chairman, that is exactly why I listed the two
points in the order that I did. I think that the first issue to be em-
phasized is that the information that we are working on at this
point is not completely definitive, and therefore, though not defini-
tive, as a physician and public health official, I feel that we must,
still in the face of uncertainty, bring as much information as we
possibly can to the American public. That is why the actions were
undertaken.
Mr. WAXMAN. But you don't have to be definitive in your state-
ment. You don't have to say taking aspirin absolutely will cause
Reye's Syndrome. You can say, taking aspirin has been determined
by the Institute of Medicine, the Centers for Disease Control, every
scientific organization including the American Academy of Pediat-
rics, may cause Reye's Syndrome.
Isn't that sufficient, a responsible warning that you could order?
Dr. YOUNG. This is exactly what we have done in our public edu-
cation, and as you would see on the tape, I have tried to make very
clear these type associations, and these types of warnings to the
American public, and I still contend that warning labels on pack-
ages are only one of many parts.
Mr. WAXMAN. I know, but you are throwing away one of the
most important ways to reach people at the time when they are
PAGENO="0421"
415
about to use the product that may kill their kids. It seems to me
you are throwing away an effective vehicle to communicate, be-
cause you don't want to offend the aspirin industry, and I am just
astounded by that.
Mr. Bates.
Mr. WYDEN. Could I ask one more question, Mr. Chairman?
Mr. WAXMAN. Certainly.
Mr. WYDEN. Dr. Young, let me read to you from a letter from the
FDA dated February 22, 1985. It has got a Dear Consumer at the
top.
I quote:
The purpose of this letter is to alert you to the link between Reye's Syndrome and
the use of aspirin-containing products as treatment of children and teenagers with
flu or chickenpox.
It goes on to say:
A pilot study recently completed at the Department substantially strengthens ear-
lier evidence of the association between the use of aspirin-containing drugs and the
development of Reye's Syndrome. While the results of the pilot study are only pre-
liminary, we are making them public because of their clear importance to protect-
ing the health of children and teenagers.
Now, it seems inconsistent at best to hear you make these kinds
of strong statements on the one hand, and then to look at the con-
clusion of this letter, which states that the Surgeon General advise,
and I quote here, "People should consult their physician before
using aspirin for children with chickenpox or flu."
It is inconsistent at best, and you are going to confuse some
people. I can't figure out why you want to have it both ways. At
one point, you are trying to tell people it is very serious.
At the other point, you tell them people ought to consult a physi-
cian before using aspirin. Again, it is symptomatic in my view of
this kind of "don't rock the boat" way of thinking. You are taking
very cautious steps, when in fact what the public really needs is
aggressive action along the lines of the plough label or something
similar.
How do you think this campaign is going to work if you send out
those kinds of messages, which at best are confusing, and show
that you want to have it both ways. How is that going to help to
get your message across?
Dr. YOUNG. We don't want to have it both ways, and we want to
articulate clearly.
Mr. WYDEN. Does that letter do that?
Dr. YOUNG. I think the point of the letter, or where I would in-
terpret it as not doing it is that we wanted to point out what the
facts were as we knew them today. We wanted to add the addition-
al point of replaying the Surgeon General's message, and point out
that he advised in all cases involving children, including teenagers,
a physician should be consulted before using aspirin in cases of flu
or chickenpox.
I think that is pretty clearly the same message.
Mr. WYDEN. I just tell you my reading of that letter is a very
strong warning in the beginning, a completely different message at
the end. Here we need a clear, direct, educational campaign.
PAGENO="0422"
416
All our witnesses have said this, and they represent a variety of
different professions. You aren't performing that function. I think
you have already written off this year's flu season.
I don't see any evidence that what you are doing today is going
to mean we have got a good plan in place for next year's flu
season, and I think it is too bad.
Thank you, Mr. Chairman.
Mr. WAXMAN. Thank you.
Mr. Bates.
Mr. BATES. Thank you, Mr. Chairman. I appreciate the chance to
participate in this hearing, and particularly to ask the person
charged with this responsibility of carrying out the warning of
Americans of the possible association between aspirin and Reye's
Syndrome. I have been trying to talk to someone who maybe has a
different point of view, because most of the panelists that we have
heard today are very concerned, and feel very strongly.
And the impression I got is that the warning would be a good
idea. Just to clarify the record, do you support Congressman Wax-
man's legislation?
Dr. YOUNG. I do not believe that legislation is necessary at this
time.
Mr. BATES. Why?
Dr. YOUNG. I think that we are very early in the understanding
of two points. First of all, I would like to, in response to Mr.
Wyden's question, give the sequence of the educational materials,
and I will introduce this for the record.
On January 9, 1985, there was a statement by the Secretary;
January 11, the CDC Morbidity and Mortality Weekly Report; Jan-
uary 11, 1985, the Secretary's telegram to TV executives; January
17, the Secretary's letter to the general managers of radio stations;
the 23rd of January, letters to editors; the 23rd of January, Miller's
letter from FDA to the Public Service Directors with 30- and 60-
second radio spots; the 28th of January, the letter of the Secretary
to hospital administrators; the 28th of January, the Secretary's let-
ters to doctors; the 28th of January, the Commissioner's letter to
the testing council; the 28th of January, the Commissioner's letter
to store managers, the variety of newspaper articles in English and
Spanish that were sent forward as columns; in February, on the
8th, Myers' letter to drug registrants; and the 11th of March, the
poster that you see there.
Those are the educational activities.
In regards to the data, we did not expect the pilot study to come
forward with the degree of association that it revealed. We felt that
the pilot study was designed to see if the definitive study would be
correct.
When the code was broken, we were surprised by the association
and felt that it was not appropriate, even though the flu season
had started, to do nothing.
It would be wrong to do nothing, and therefore, we studied
whether the data was available to go with a mandatory labeling at
this time.
We concluded not at this point, and therefore, embarked upon
the information that I just read to you, sir. You can see our educa-
tional campaign and how we have worked very vigorously.
PAGENO="0423"
417
As I mentioned earlier, the saccharin labeling only added a little
bit to the total program, and I felt, as an educator, that the first
thing to do was rapidly get the information out to the American
public.
[Testimony resumes on p. 457.]
[The information follows:]
PAGENO="0424"
418
REYE SYNDROME PUBLIC EDUCATION MATERIALS
January 9, 1985 - Statement by Secretary Margaret M. Heckler
January 11, 1985 - CDC Morbidity and Mortality Weekly Report
January 11, 1985 - Secretary Telegram to TV Executives etc.,
with list of addressees
January 17, 1985 - Secretary letter to General Managers of Radio
and TV Stations
January 23, 1985 - Secretary letter to Editors
January 23, 1985 - Miller letter to Public Service Directors
with 30-second and 60-second Radio spots
Undated - Radio Station PSA comment card
January 28, 1985 - Secretary letter to Hospital Administrators
January 28, 1985 - Secretary letter to Doctors
January 28, 1985 - Commissioner letter to The Advertising
Council
January 28, 1985 - Commissioner letter to Store Managers
February/March - Newspaper column English version
February/March - Newspaper column - Spanish version
March 8, 1985 - Meyer letter to Drug Establishment Registrants
March 11, 1985 - Miller letter to School and Colleges with
Poster
PAGENO="0425"
I
419
/
ThSSSC*(TAAY OF P$ti TN AND N(~AN $5NVIU~S
WAN*NSTON.DC. ~S*
JAN 91985
Statement by
Margaret N. Heckler
Secretary of Health and Human Services
Nothing is more important to Americans than the health and safety
of their children and, as Secretary of Health and Human Services, I
feel a special responsibility to protect the health of our nation's
children during their most vulnerable years.
That is why I ordered special steps to resolve the scientific
dispute when some early studies showed an association between Reye
syndrome and the use of aspirin for children suffering from chicken
pox, influenza and flu-like illnesses. That is also why I instructed
the Food and Drug Administration to pursue a vigorous public education
campaign to ensure that parents were made aware of the possible link.
In particular, I ordered the Centers for Disease Control a year
ago to undertake a new study of aspirin and Reye syndr~. The study
had two parts - a one-year pilot study followed by a full-scale
investigation.
The Centers for Disease Control have now completed the pilot
study. This study is not completely conclusive - but its findings do
show an association between the use of aspirin and the onset of Reye
syndrome in children and teenagers.
These results make it urgent that CDC vigorously pursue the full-
scale study. That work was begun last month and is now fully underway.
In the meantime, I strongly urge parents to follow the advice of
the Surgeon General: in all cases involying children, including
teenagers, a physician should be consulted before using aspirin in
cases of flu or chicken pox.
It is significant that fewer children are now being struck by Rey.
syndrome - 190 known cases in the year ending November 1984 - while
reported cases in previous years were as high as 548 (in 1980). Hut
this does not mean we can be complacent. The disease is deadly, with a
fatality rate of 26 percent last year. In addition, those who suffer
from the disease are increasingly older children and teenagers, as wall
as young children: According to the pilot study, some 50 percent of
all cases were in those over age 10, and 15 percent were in those aged
15 and older.
In order to ensure that all children continue to be given the
fullest protection, even while we await final scientific conclusions, I
am today taking four additional steps:
First, I amoz~dering CDC to release the pilot study immediately,
and I am instructing that it also be published as soon as possible in
CDC's journal Morbidity and Mortality Weekly Report. This information
along with other scientific evidence will appear ii~ a refereed
scientific journal.
Second, I am asking the Food and Drug Administration to extend and
expand its public education efforts -- parents must understand the need
to consult a physician before using aspirin to treat flu or chicken
pox. Likewise, FDA will take steps to inform teenagers - who often
treat themselves -- of the possible link between aspirin and Reye
syndrome.
PAGENO="0426"
420
Third, I am contacting media leaders throughout the country asking
them to use every possible resource to help broadcast the message. I
am telegraphing the presidents of the three television networks as well
as the American Newspaper Publishers Association, the National
Association of Broadcasters, the Association of Independent Television
Stations, and the National Cable Television Association. I will also'
send letters to the owners of newspapers as well as television and
radio stations throughout the country.
I will re~enphasize the importance of the public service
announcements we've already supplied to them. And I will urge them to
take additional steps to convey this important message: for example,
special news coverage, new public service announcements, messages
specially designed to reach teenage audiences, or other appropriate
steps.
Finally, I will ask the makers of aspirin products to take two
steps voluntarily: first, to immediately remove any labels which
recommend that aspirin products be used to treat flu or chicken pox in
children or teenagers; and second, to further label all aspirin
products to indicate that there is a possible association between the
use of aspirin and the onset of Reye syndrome in children and
teenagers, and that aspirin products should ~ be used in those cases
unless a physician is first consulted.
I would ask the industry to voluntarily retain this expanded
labelling until the results of the full~scale CDC study have been
reported and thoroughly analyzed.
I want to emphasize that this step does not mean that aspirin is
unsafe for other uses. Aspirin is, in fact, a tremendously valuable
and effective analgesic and anti'inflammatory drug that has, will and
should continue to be used by tens of millions of Americans safely.
But, as with any other drug, it is crucial that aspirin be administered
appropriately.
I am confident that both aspirin manufacturers and the American
media will take the steps needed to ensure the best possible protection
for our children.
These are useful first steps. I believe they are entirely in the
spirit of the recommendations we have received from the National
Academy of Sciences' Institute of Medicine. In addition, the data now
available in the pilot study will be reviewed further with great care,
as will all independent comments and recommendations, to determine
whether further steps may be warranted.
PAGENO="0427"
421
CB~4TB~$ FOR DSEASE CONTROL
M~NP
MORBIDITY AND MORTALITY WEEKLY REPORT
Reye Syndrome - United States, 1984
For the 1984 surveillance year,' 190 cases of Reye syndrome (RS) meeting CDC's case
definitiont were reported. Although delayed reports will increase the number of cases for
1984 somewhat, the 1984 total is presently among the lowest annual totals reported
through the National Reye Syndrome Surveillance System (NRSSS) since its initiation in
December 1973 (Table 1).
`For the purposes of surveillance, Reye syndrome years extend from December 1 to November 30 (i.e.
the 1984 year runs from December 1, 1983. to November. 30, 1984). The data for 1984 are preliminary
and include cases reported as of January 8, 1985.
tThe CDC case definition is (1) acute noninflammatory encephalopathy documented by the clinical pic-
ture of alteration in the level of consciousness and, if available, a record of cerebrospinal fluid containing
eight teukocytes or less per mm3, or histologic sections of the brain demonstrating cerebral edema with-
out perivascular or meningeal inflammation; (2) fatty metamorphosis of the liver diagnosed by either
biopsy or autopsy or a threefold or greater rise in the levels of either the SGOT, SGPT, or serum ammo-
nia; and (3) no known more reasonable explanation for the cerebral or hepatic abnormalities.
PAGENO="0428"
422
Cases were reported from 42 states. The sex and race distributions were similar to previ-
ous years. Of patients for whom this information was reported, 51% were male; 94%, white;
3%, black; and 3%, of Asian or American Indian extraction. Most AS patients were school-aged
children; 38% were 10-14 years of age; 29%, 0-4 years of age; 18%, 5-9 years of age; 13%,
15-19 years of age; and 2%, 20 years of age or older.
For 179 (94%) of the patients, a prodromal illness occurring within 2 weeks before the
onset of vomiting or neurologic symptoms of AS was reported. This prodromal illness was
characterized by respiratory symptâms (76%), varicella exanthem (15%), diarrhea without re-
spiratory symptoms (2%), or other signs and symptoms, including fever alone (7%).
Most patients were hospitalized in the first 6 months of the surveillance year (Figure 1).
This winter and spring seasonal distribution primarily reflected the incidence of respiratory
virus infections among children, particularly influenza types A(H1 NI) and B, the predominant
influenza isolates during 1984. In addition, the small number of varicella-associated AS pa-
tients were hospitalized primarily during this period.
The largest percentages of patients were admitted to hospitals in the three precomatose
stages of AS: stage I-38%; stage 11-36%; or stage 0-8% (1). Of these, 56% progressed to
coma. The short-term outcomes were reported for 173 (91%) of the AS patients; 45 died, for
a case-fatality ratio of 26%.
Editorial Note: The NRSSS is useful in providing crude annual comparisons of AS activity, al-
though the number of cases reported is recognized to be an underestimate of the true inci-
dence of AS. During 1982-1984. the annual incidence of AS was the lowest reported since
the initiation of national surveillance. The incidence of AS in previous years has reflected, at
least in part, the intensity and/or type of influenza activity. However, the influenza activity in
1984 appeared to be much greater than in the 2 previous years. with widespread school out-
breaks of both influenza types A(H1 Ni) and B (2).
When analyzed by 10-year age groups, the decline in reported cases from 1981 to 1984
is accounted for by a consistent decline in the number of cases reported each year among
children under 10 years of age. No such decrease has occurred in the number of patients
10-19 years of age; in 1984, the number of cases reported in this age group increased, con-
sistent with the increased influenza activity.
Varicella-associated AS cases show an even larger decline (from 77 in 1981 to 26 in 1984)
in the number of cases reported each year among children under 10 years of age. However,
annual varicella activity in the United States remained relatively stable during this period. The
TABLE 1. ~icldence of Reys syndrome, by year - thilted States, 1974 and 1977-1984
ye-
(D.c. 1-
Nov 30)
Major
Influenza activity
No. cases
kicidence'
Death/caset ratio (%)
1974~
B
379
0.58
157/379(41)
1977
B
454
0.71
156/373 (42)
1978
A(H3N2),(H1NI)
237
0.37
66/225 (29)
1979
A(H1N1)
389
0.62
113/349 (32)
1980
B
548
0.88
114/516(22)
1981
A(H3N2),(H1N1)
313
0.49
89/296 (30)
1982
B
222
0.35
73/208 (35)
1983
1984
A(H3N2).(H1N1)
A(H1N1),B
198
1901
0.32
0.30
57/181 (31)
45/173(28)
Cases/100.000 population under 18 years of age.
tW1th known outcome.
§For the period December 15. 1 973-June 10, 1974.
1Preliminary count; reported cases as of January 8. 1985.
PAGENO="0429"
423
reasons for the decline in incidence among children under 10 years of age is unclear, although
it does not appear to be solely the result of annual differences in the incidence of either in-
fluenza or varicella.
One possible, explanation for the reduced incidence among children under 10 years of age
is that there has been a decline in the use of salicylates among younger children in recent
years.
In 1982, the Surgeon General of the Public Health Service (PHS) advised against giving sa-
licylates and salicylate-containing medicati,,,-c to children with influenza and chickenpox (3).
This advice was based on the review of results of case-control studies that showed a statisti-
cally significant association of AS with the ingestion of salicylates during the antecedent ill-
ness (4-6). Because of concerns regarding methodologic issues and the limitations of these
studies, the Secretary of Health and Human Services appointed a PHS Task Force comprised
of members of the National Institutes of Health, Food and Drug Administration, and CDC to
design and implement a new epidemiologic study concerning the nature of the possible rela-
tionship between AS and medications.
A pilot study was conducted between February and May 1984 to determine the study
feasibility and establish methodology. The pilot study included 29 AS cases and 143 controls
consisting of children admitted to the same hospital (lP) or emergency room (ER), attending
the same school, or identified by random-digit dialing (ADD). Ninety-seven percent of case
children were reported to have received salicylates during the respiratory or chickenpox illness
before a clinically defined onset of AS, compared with 28% (ER), 23% (P), 59% (school), and
55% (ADD) at any time during their matched illnesses. The risk defined in the pilot study was
comparable to or greater than that determined in the previous studies. The Institute of Medi-
cine (lOM). National Academy of Sciences, served to advise and critique the protocol, monitor
the study progress, and review study analysis and results. Following a review of the data cot-
FIGURE 1. Reye syndrome cases, by month of onset - United States, December 1,
1 983-November 30, 1984
60
50
40
0 Nonvaric.II. prodrom*
30 ~ Varicells prodrome
U
20
10
0 r~fl
DEC JAN FEB MAR APR MAYJUN JUL AUG SEP OCT NOV
1533 1934
ONSET
PAGENO="0430"
424
lection methodology in July 1984 and the data analysis In December 1984, the tOM. on Janu-
ary 8, stated:
1. The PHS Task Force should proceed with the full study.
2. Results of the pilot study should be released promptly to the public end to scientists
for review and analysis.
3. Analysis of the pilot study data reveals a strong association between the Reye syn-
drome and the use of aspirin; considering data from previous studies also show an
association of use of aspirin and Reye syndrome, the Committee recommends that
steps should be taken to protect the public health before the full study is completed.
4. Although it is impossible to know with certainty whether the release of the pilot study
data will harm the full study, the Committee suspects the effects of the attendant pub-
licity will be no more damaging than the current climate of public opinion, which ap-
pears not to have impeded conduct of the pilot study.
A report of the pilot study is currently being prepared for publication. In view of these prelimi-
nary findings, physicians, parents, and older children who self-medicate should continue to be
advised of the probable increased risk of RS associated with the use of salicylates for child-
ren, including teenagers, with influenza-like illness or chickenpox.
Reported by Div of Viral Diseases, Center for Infectious Diseases, CDC; the Reye Syndrome Task Force,
consisting of members from U.S. Food and Drug Administration, National Institutes of Health. Office of
theAssistant Secretary of Health, and CDC.
References
1. Hurwitz ES, Nelson DB, Davis C, Morens D, Schonbergar IS, National Surveillance for Reye syn-
drome: a five-year review. Pediatrics 1 982;70:895-900.
2. CDC. Influenza-United States, 1983-1984 season. MMWR 1 984;33:41 7-8.
3. CDC. Surgeon General's advisory on the use of salicylates and Reye syndrome. MMWR
1982;31 :289-90.
4. Starko KM. Ray CG, Dominguez LB. Stromberg WL Wodall DF. Reye's syndrome and salicylate use.
Pediatrics 1 980;66:859-64.
5. Waldman RJ, Halt WN, McGee H, Van Amburg G: Aspirin as a risk factor in Reye's syndrome. JAMA
1 982;247:3089-94.
6. Halpin TJ. Holtzhauer FT. Campbell RJ, et al: Reye's syndrome and medication use. JAMA
1 982;248:687-91
PAGENO="0431"
425
January 11, 1985
Telegram to:.
W. Frederick Pierce, thief Executive Officer
Mer1~an Broadcasting Coaianles, Inc.
1330 Avenue of the Americas
lew York, NY 10019
I am writing to ask your help in reaching the Americanpeople with an
1n~ortant message concerning the health of our children..
A pilot study recently completed for the Departh~ent of Health and Hianan
Services materially strengthens earlier evidence suggesting that
children and teenagers who take aspirin~containing medicines during a
bout of flu or chicken pox are at increased risk of developing Re)e
syndrome, a rare disease that causes death in 20 to 30 percent of its
victims.
While the results of the pilot study are only preliminary, I believe it
is important that parents, children, teenagers and the health care
coninunity be made aware of this evidence and be urged to obtain medical
advice before using aspirin to treat the symptoms of flu or chicken
pox. Here are the salient facts that have been provided to us:
The Institute of Medicine of the National Academy of Sciences has
carefully analyzed the results of a pilot study conducted b, the U. S.
Public Health Service involving 29 children and teenagers who developed
Reye syndrome following a case of flu or chicken pox and 143 other
children (controls) who had flu or chicken pox but did not develop Reye
syndrome. The study Shuwed that 28 of the children, br 96 percent of
those who developed Reye syndrome, had recently taken or been given
aspirin. Fewer than half of the controls (those who did not have Reye
syndrome) had had aspirin or an asp1rin~conta1ning drug during their
illness.
It is also significant that those who suffer from the disease are
increasingly older children and teenagers as well as young children;
according to the pilot study some 50 percent of all cases were in those
over age 10 and 15 percent were in those aged 15 and older.
This finding does not prove that aspirin causes Reye syndrome or that
aspirin is not a safe and effective drug for other purposes. It does,
however, strengthen existing evidence suggesting an association between
aspirin and Reye syndrome. We have reason to believe that the public
educatiorrcampaign conducted for the past several years by the Public
Health Service has helped to reduce the number of cases of Reye
syndrome, particularly in young children who receive medication from
their parents. The increase in Reye cases among older children and
teenagers may result from their tendency for self treatment at the
onset of flu symptoms. Therefore, it is necessary to redouble our
efforts to Inform the public of this health risk, and I am asking for
your help in doing that.
PAGENO="0432"
426
Radio, television, and print media public service announcanents have
beers distributed throughout the country to inform the American people
thout the possible association of aspirin and Reye s~idrone. I urge
)VU to make use of these announcenents-to give than the widest
possible circulation and to cooperate In publicizing the known facts
about this situation. It ~uld be particularly helpful for additional
eophasis to be placed on public service announcenents durThg
progranning that has a target audience of older children and teenagers.
In a separate mailing, I en sending you additional information that can
be used to get this important health message to the American people.
In the meantime, however, please help us by giving this preliminary
message the wide distribution it clearly warrants.
Thank you for your assistance.
Merger N. Heckler
Secretary
Department of Health and
Human Services
Washington, DC
PAGENO="0433"
427
Frederick Pierce, Chief Izeciative Officer
Amarican Broadcasting Coi~,anies, Inc.
1330 Ave. of the Americas
1ev York, BY 10019
Grant A. tinker, Chief Executive Officer
National Broadcasting Co.
30 lockefeller Plaza
1ev York, BY 10020
Thomas B. Wyman, Chief EzecuticS Officer
CBS, Inc.
51 West 52nd St.
New York, 1! 10019
National Association of Broadcasters
Edward 0. Pritts, President and CBO
1771 N St., N.W.
Washington, D.C. 20036
National Cable TV Association
James P. Mooney, President
1724 Massachusetts Ave., LW.
Washington, D.C. 20036
Association of Independent TV Stations Inc.
Herman N. Land, President
1200 18th St., 1.1.
Suite 502
Washington, D.C. 20036
American Newspaper Publisher! Associatioj~
Jerry Friedheim, President
11600 Sunrise Valley Dr.
Reston, VA 22091
PAGENO="0434"
428
mz SEC~ETA*Y O~ $tALTh *110 llt~*N a~viczs
.~Ø~STO~O~ asvsi
JAN 17 ~85
~Dear General Manager:
I am writing to ask your help in reaching the American people
with an important message concerning the health of our children.
A pilot study recently completed for the Department of Health
and Human Services materially strengthens earlier evidence
suggesting that children and teenagers who take aspirin-containing
medicines during a bout of flu or chicken pox are at increased risk
of developing Reye syndrome, a rare disease that causes death in 20
to 30 percent of its victims.
While the results of the pilot study are only preliminary, I
believe it is important that parents, children, teenagers and the
health care community be made aware øf this evidence and be urged to
obtain medical advice before using aspirin to treat the symptoms of
flu or chicken pox. Here are the salient facts that have been
provided to us:
The Institute of Medicine of the National Academy of Sciences
has carefully analyzed the results of a pilot study conducted by the
U.S. Public Health Service involving 29 children and teenagers who
developed Reye syndrome following a case of flu or chicken pox and
143 other children (controls) who had flu or chicken pox but did not
develop Reye syndrome. The study showed that 28 of the children, or
96 percent of those who developed Reye syndrome, had recently taken
or been given aspirin. Fewer than half of the controls (those who
did not have Reye syndrome) had had aspirin or an aspirin-containing
drug during their illness.
It is also significant that those who suffer from the disease
are increasingly older children and teenagers as well as young
children; according to the pilot study some 50 percent of all cases
were in those over age 10 and 15 percent were in those aged 15 and
older.
This finding does not prove that aspirin causes Reye syndrome
or that aspirin is not a safe and effective drug for other purposes.
It does, however, strengthen existing evidence suggesting an
association between aspirin and Reye syndrome. We have reason to
believe that the public education campaign conducted for the past
several years by the Public Health Service has helped to reduce the
number of cases of Reye syndrome, particularly in young children who
receive medication from their parents. The increase in Reye cases
among older children and teenagers nay result from their tendency
for self-treatment at the onset of flu symptoms. Therefore, it is
necessary to redouble our efforts to inform the public of this
health risk, and I am asking for your help in doing that.
PAGENO="0435"
429
Page 2 General Managers
Radio, television, and print edia public service announcanents
bays been distributed throughout the country to Inform the ~mer1cw
people about the possible association of aspirin and Re)e syndrome. I
urge you to make use of these announcenents~..to give than the widest
possible circulation and to cooperate in publicizing the known facts
about this situation. It ~uld be particularly helpful.for additional
emphasis to be placed on public service announcements during
prograimning that has a target audience of older children and teenagers.
In a separate mailing, I an sending you additional information that can
be used to get this important health message to the American people.
In the meantime, however, please help us by giving this preliminary
message the wide distribution it clearly warrants.
Thank you for your assistance.
Sincerely,
1~ ~
Margarf N. Heckler
SecretI~ry
PAGENO="0436"
430
T~~$5CUTA*V OF NIA%.ThNID HUMAN *mvicu
M~HSNST~.OC. *I
`JAN 23 ~35
Dear Uitorz
I am writing to ask your help in reaching tbe~Americ*fl people
with on important message concerning the hóalth of our children.
A pilot study recently completed for the Department of ~ea1th
and Human Services materially strengthens earlier evidence
suggesting that children and teenagers who take aspirin~containthg
medicines during a bout of flu or chicken pox are at increased risk
of developing Reye syndrome, a rare disease that causes death in 20
to 30 percent of its victims.
While the results of the pilot study are only preliminary, I
believe it is important that parents, children, teenagers and the
health care community be made aware of this evidence and be urged to
obtain medical advice before using aspirin to treat the symptoms of
flu or chicken pox. Here are the salient facts that have been
provided to us:
The Institute of Medicine of the Wational Academy of Sciences
has carefully analyzed the results of a pilot study conducted by the
U.S. Public Health Service involving 29 children and teenagers who
developed Reye syndrome following a case of flu or chicken pox and
143 other children (control!) who had flu or chicken pox but did mmt
develop Reye syndrome. The study showed that 28 of the children, or
96 percent of tlfo!ewho developed Reye syndrome, had recently taken
or been given aepirin. Fewer than half of the controls (those who
did not have Reye syndrome) had had aspirin or an aspirin~cOntaining
drug during their illness.
It is also significant that those who suffer from the disease
are increasingly older children and teenagers as well as young
children; according to the pilot study some 50 percent of all cases
were in those over, age 10 and 15 ~ercent were in those aged 15 and
older.
This finding does not prove that aspirin causes ReyeayndrOme
or that aspirin, is not a safe and effective drug for other purposes.
It does, howeyer, strengthen existing evidence suggesting an
association between aspirin and Reye syndrome. We have reason to
believe ~bat the public education campaign conducted for the past
severaijears by the public Health Service has helped to reduce the
number of cases of Reye syndrome, particularly in young children who
receivd medication from their parents. The increase in Reye cases
among older children and teenagers may result from their tendency
for self-treatment at the onset of flu symptoms. Therefore, it i5
necessary to redouble our efforts to inform the public of this
health risk, and I am asking for your help in doing that.
PAGENO="0437"
431
Radio, television, and print media public service announcements
have been distributed throughout the meuntry to inform the American
people about the possible association of aspirin and Reye syndroime.
I urge you to make use of these announcements....to give than the
widest possible circulation and to cooperate in publicizing the
known facts about this situation. It would be particularly helpful
for additional emphasis to be placed on public service announcements
during programming that has a target audience of older children and
teenagers. In a separate mailing, I am sending you additional
information that can be used to get this in~ortant health message to
the American people. In the meantime, however, please help us by
giving this preliminary message the wide distribution it clearly
warrants.
Thank you for your assistance.
Sincerely,
14argaj~t N. Heckler
Secretary
PAGENO="0438"
432
DEPARTMENT OF HEALTH & HUMAN SERVICES Public Health Service
Food and Drug Administration
Rockville MD 20857
January 23, 1985
Dear Public Service Director:
A new scientific study has strengthened existing evidence
linking the use of aspirin to treat flu or chicken pox and
the development of a rare but dangerous condition known as
Reye syndrome. Because of that new evidence, the Food and
Drug Administration has prepared the accompanying public
service announcements to urge people not to use aspirin or
aspirin-containing products for flu or chicken pox.
The new evidence was in a pilot study done for the U.S.
Public Health Service. Of 29 Reye syndrome cases studied,
28 had been treated with aspirin.
It has long been realized that Reye syndrome, which is fatal
in about one out of four cases, strikes mostly children.
However, the new study indicated that teenagers up to the age
of 19 are also likely victims, and the 60-second taped spot
provided is aimed directly at the teen listener.
Also provided is copy for a 30-second spot.
We hope you are able to use them. By broadcasting them, you
may help to avert tragedy.
Sincerely,
Roger W. Miller
Director
Communications Staff
Food and Drug Administration
PAGENO="0439"
433
DEPARTMENT OF HEALTH & HUMAN SERVICES PuMa Health Service
Food and Drug Administration
Rockville MD 20857
Teenagers/Aspirin/Reye syndrome
:60 Radio PSA
(The voice in parentheses is that of a teenage girl.)
Young people often get the flu.
(So do adults.)
Sometimes a rare but dangerous condition called Reye syndrome
develops from the flu or chicken pox.
(Thank goodness it's only sometimes.)
Children, including teenagers, are most often the victims of
Reye syndrome.
(That's not fair!)
Reye syndrome usually occurs just when the child seems to be
recovering.
(How weird!)
The symptoms of. Reye include persistent vomiting, fatigue,
confusion and belligerence.
(Sounds bad. Can it be prevented?)
The cause of Reye syndrome is unknown but studies
suggest a link between the development of Reye and the use of
aspirin.
(So shouldn't I take ~ medicine?)
It's a good idea to check with a doctor before treating the
flu or chicken pox with aspirin or any product containing
aspirin.
(But how will I get well?)
Flu and chicken pox are usually self-limiting. Time will
cure them. Take it easy. Get plenty of rest.
(Oh, I'm really good at that.)
A message from the U.S. Department of Health and Human
Services.
PAGENO="0440"
434
DEPARTMENT OF HEALTH & H~MAN SERVICES Public Health Sertoce
Food and Drug Administration
Rockville MD 20857
Reye syndrome PSA
30-seconds
HERE S SOME ADVICE WE WANT TO PASS ALONG TO YOU FROM THE U. S.
SURGEON GENERAL ABOUT REYE SYNDROME AND THE USE OF ASPIRIN.
REYE SYNDROME IS A RARE BUT DANGEROUS CONDITION THAT MAY
DEVELOP FROM FLU OR CHICKEN POX. IT OFTEN STRIKES JUST WHEN
AN INDIVIDUAL APPEARS TO BE RECOVERING. CHILDREN, INCLUDING
TEENAGERS, ARE MOST OFTEN THE VICTIMS. STUDIES
SUGGEST A LINK BETWEEN THE USE OF ASPIRIN TO TREAT THESE
ILLNESSES AND THE DEVELOPMENT OF REYE SYNDROME. SO, THE
SURGEON GENERAL URGES YOU TO CHECK WITH YOUR DOCTOR BEFORE
USING ASPIRIN OR PRODUCTS THAT CONTAIN ASPIRIN TO TREAT FLU
OR CHICKEN POX.
Contact:
Louise Patterson
Office of Communications, HFW-40
Food and Drug Administration
5600 Fishers Lane
Rockville, MD 20857
(301) 443-3210
PAGENO="0441"
435
Your PSA's have been rcelved In ________ condition. I
PLANNED USE: (IA? a ~ ~
COMMENTS:
NAME:___________ TffL~ P ~
CALL LIRS: J(~1t') ~... ! ~ `AM____ FM____
ADDRESSe ~ t«='7
CI1Y: ~ STATE.~ (4
PAGENO="0442"
436
THE SECRETARV OF HEALTH AND HUMAN SERVICES
Dear Hospital Administrator:
Results obtained in the pilot phase of a case-control study
conducted by the U.S. Public Health Service provide strengthened
evidence of an association between aspirin and Reye syndrome.
Enclosed with this letter is detailed information about the study
methodology and findings and about steps which I have called for
to protect children and teenagers, the groups most clearly at
risk.
I am providing this information to you and your colleagues so that
you can be familiar with these recent findings and take
appropriate action to reduce the risk of Reye syndrome.
As you know, on the basis of earlier studies, the U.S. Public
Health Service has for the past several years conducted an
education campaign to alert the public to the symptoms of Reye
syndrome and to call attention to preliminary findings suggesting
that the use of aspirin-containing drugs to treat flu-like
illnesses or chicken pox in children appears to be associated with
increased risk of developing Reye syndrome. The pilot study
described in the enclosed MNWR article strengthens the evidence
for such an association and clearly warrants increased efforts to
warn the public -- parents, teenagers, and health care providers --
of the potential risk involved in using aspirin-containing drugs
to treat childhood chicken pox or flu.
We have taken steps to bring this information to the attention- of
the American people. Some of those steps are outlined in the
enclosed statement I issued on January 9. In addition, I hope that
you and your colleagues will carefully consider the implications of
these new Reye syndrome findings and join in translating them into
improved protection against this serious disease.
Your cooperation will be deeply appreciated.
Sincerely,
i~
Margar~M. Heckler
Secret'ary
Enclosures
PAGENO="0443"
437
Tht$~CRCTAsV o~ .~Aa.m NiB iS.N*N VNV$ctS
y. ~ ama
JAN 28 1985
Dear Doctars
Results obtained in the pilot phase of a case-control study
conducted by the U.S. Public Health Service provide strengthened
evidence of an association between aspirin and Reye syndrome.
Enclosed with this letter is detailed information about the study
methodology and findings and about steps which I have called for
to protect children and teenagers, the groups most clearly at
risk.
I am providing this information to you and your colleagues so that
you can be familiar with these recent findings and take
appropriate action to reduce the risk of Reye syndrome.
As you know, on the basis of earlier studies, the U.S. Public
Health Service has for the past several years conducted an
education campaign to alert the public to the symptoms of Rsye
syndrome and to call attention to preliminary findings suggesting
that the use of aspirin-containing drugs to treat flu-like
illnesses or chicken pox in children appears to be associated with
increased risk of developing Reye syndrome. The pilot study
described in the enclosed *IWR article strengthens the evidence
for such an association and clearly warrants increased efforts to
warn the public -- parents, teenagers, and health care providers
of the potential risk invoJ~ved in using aspirin-containing drugi
to treat childhood chicken pox or flu.
We have taken steps to bring this information to the attention of
the American people. Some of those steps are outlined in the
enclosed statement I issued on January 9. In addition, I hope that
you and your colleagues will caref~ully consider the implications of
these new Reye syndrome findings and join in translating them into
improved protection against this serious disease.
Your cooperation will be deeply appreciated.
Sincerely,
Marg~t H. Heckler
Secr~tary
Enclosures
PAGENO="0444"
438
DEPARTMENT OF HEALTH & HUMAN SERVICES PIM~ *4Mth $sivics
- Food and Dw~ Admi~strodon
Rodmil, MD 20357
January 28, 1985
The Advertising Council
1730 Rhode Island Avenue, N.W.
Washington, D.C. 20036
Dear Sirs:
The Food and Drug A&ninistration has reviewed public service announcements
prepared by the major aspirin manufacturers with the cooperation of the
Advertising Council.
These materials are responsible and clear. They have the support of F~.
They were prepared in response to the request of U.S. Health and Human
Services Secretary Margaret P1. Heckler. Store posters and announcements are
also being distributed.
Thank you for your work in distributing these public service announcements.
trust that the broadcast media will air these vital messages promptly, during
this flu season.
Sincerely,
FrankE.Y ,
Comissioner of Fo and ugs
PAGENO="0445"
439
( DEPARTMENTOF HEALTh & HUMAN SECVICES H~Ic I~iaI SaMoa
Feed and Drug AdmW~medon
m~~vIP. MD 30557
January 28, 1985
Dear Store Manager:
The Food and Drug Ackninistration has reviewed posters and buBetin board
announcements prepared by the major aspirin manufacturers with the cooperation
of the Advertising Council.
These materials are responsible and clear and have F1's support. They have
been prepared in response to a request of U.S. Health and Human Services
Secretary Margaret H. Heckler. Television and radio announcements are also
being distributed.
Sincerely,
Comissloner of Fo and ugs
PAGENO="0446"
440
FOR IMMEDIATE RELEASE William Grlgg
Feb. - March 1985 (301) 443-3285
In the midst of the flu season, important new information has become
available about the development In teens and children with flu -~ of Reye
syndrome, a rare but serious condition that kIlls 20 to 30 percent of Its
young victims and leaves many survivors brain damaged.
The new information comes from a U.S. Public Health Service pilot study
of a possible link seen in four earlier state studies between the use of
aspirin in treating flu or chicken pox and an Increased risk of Reye
syndrome.
The Institute of Medicine of the National Academy of Sciences has
reviewed the pilot study and found Nstrong supportw for the link.
Although personnel from the Food and Drug Administration, the National
Institutes of Health and the Centers for Disease Control will contiune the
study through next winter, the Institute of Medicine advised that the federal
government not wait to inform and protect the public.
As a result, Health and Human Services Secretary Margaret M. Heckler has
asked manufacturers to remove any~recommended use in flu and chicken pox from
aspirin-containing products aimed at children -- and to add a warning to all
aspirin-containing products against use for flu and chicken pox in children
and teens.
The pilot study looked at the histories of drug treatments and other
factors of 29 young people who got Rey~ syndrome last year. Use of aspirin
for flu or chicken pox symptoms was the common thread shown in 28 of the 29
MORE
PAGENO="0447"
441
REYE/ASPIRIt4 page 2.
(whereas ordinarily less than half the young people with flu or chicken pox
would be expected to take aspirin.)
U.S. Surgeon General C. Everett Koop, M.D., has said that most childhood
illnesses are self-limiting and ususally don't require any medication at all.
Doctors often suggest that a child with fever simply be made comfortable with
cool compresses.
Of course, physicians continue to find aspirin Useful and safe for adult,
teen and childhood arthritis and other conditions.
Reye syndrome is a rare condition a few hundred cases a year. It was
named in 1963 for an Australian pathoiogist who described it as a swelling of
the brain, combined with liver malfunction and blood chemistry disorders
leading In most cases to death.
Improved recognition and early treatment of the disease has helped reduce
the death rate, but still about one out of four reported cases are fatal.
It is crucial to take action quickly if Reye's symptoms occur whether
or not aspirin or an aspirin-containing product has been used. The first sign
is generally persistent vomiting. The young person may be sleepy and
lethargic, but still responsive. Within half a day, he or she can become
disoriented, combative and delirious.
Untreated, the teenager or child can go into a coma and die.
Thus, Reye is a medical emergency. A child with Reye syndrome symptoms
must be taken immediately to a hospital, where blood andbody fluids can be
monitored and a respirator used if breathing fails. Surgery may be needed, in
some cases, to relieve pressure on the swoflen brain. Therefore, act promptly
If you suspect Reye syndrome.
ft.,'
PAGENO="0448"
442
Feb.-March 1985
Reye
Ahora que estamos en piena ~poca de ia influenza, nueva e
iinportante inforrnaci6n se ha dado a conocer acerca del desarroilo
del s~ndrome de Reye, una condicic~n poco comun pero muy seria que
ocasiona la muerte del 20 al 30 por ciento de Bus v~ctimas -~ ni~os
y adolescentes -- y serios daftos en el cerebro de los que ia
sobrevi yen.
La nueva informaci6n fue el resuitado de un estudio lievado a
cabo por el Servicio P6blico de Salud de los Estados Unidos, sobre
la posibilidad observada en cuatro estudios preliminares -- de
una asociacic~n entre el uso de la aspirina para el tratamiento de
influenza o varicela y un auinento en el riesgo de contraer ci
s~ndrome de Reye.
El Instituto del4edicina de la Academia Nacional de Ciencias,
despu~s de analizar el estudio mencionado, ha liegado a la
conclusic~n de que existe una "marcada posibilidad" de que la
mencionada asociaci~n entre la aspirina y ci srndrome de Reye
sea una realidad.
Aunque ci personal de la Adininistracic~n de Drogas y Alimentos,
(FDA), los Institutos Nacionales de Salud (NIH) y los Centros de
Control de Enfermedades (CDC) continuar~n el estudio durante ci
prccximo invierno, ci Instituto de Medicina ha aconsejado al
gobierno federal no esperar para informar y proteger ai pi~biico.
Como resuitado, Margaret M. Heckier, Secretariadei
Departamento de Salud y Seryicios Humanos, ha pedido a los
PAGENO="0449"
443
laboratorios manufactureros de drogas, abstenerse de recomendar el
uso de medicarnentos para el tratamiento de influenza y varicelas
que contengan aspirina, y m~s bien a~adir una advertencia que
prevenga ci uso de tales productos en niftos y adolescentes.
El estudio principal examinc«= las historias m~dicas, las drogas
usadas en los tratamientos, y otros factors de 29 jóvenes vi~ctixnas
del sindrome de Reye durante el aflo pasado. El uso de la aspirina
contra los sintomas de influenza o varicela, fué ci factor
predominante en 28 de los 29 casos.
El Cirujano General de Los Estados Unidos, C. Everett Koop,
M.D., ha manifestado que la mayori'a de las enfermedades en los
niftos generalmente son leves, y no requieren medicamentos. Los
in~dicos usuaimente sugieren tratar un caso de fiebre conuin con
compresas de agua fr~a; desde luego, ellos contintcan recetando
aspirina a ni~os y adultos para aliviar otras dolencias, tales. como
la artritis.
El s«=ndrome de Reye as una condici6n ~oco com~n -- unos pocos
casos se presentan cada a~o. Fue llamado Reye, como ci pat~iogo
Australiano que en 1963 10 describio como una infiaTnacidn del
cerebro, en combinaciä'n con defectos en ci funcionamiento del
h(gado y desc~rdenes en la composici6n qu«=mica de la sangre,
generalmente resultando en la muerte.
Diagnc~sticos acertados y r~pido tratamiento m~dico de ~sta
condici6n han ayudado a reducir la mortalidad, pero todavia, uno de
cada cuatro casos reportados es fatal.
52-266 0-85-15
PAGENO="0450"
444
Es de decisiva. importancia actuar con rapidez, ~i los srntomas
del s«=ndrome de Reye se presentan -- haya el paciente o no tornado
aspirina o algi~n otro medicamente conteniendo aspirina.
Generalmente, el primer scntoma es un v6mito persistente. El
nifto aparenta estar so?~oliento y letárgico, pero todav~a responde.
En pocas horas, puede encontrarse desorientado, agresivo o
delirante, y de no recibir asistencia m~dica inmedlata, puede
entrar en estado de coma y morir.
El si'ndrome de Reye es una emergencia médica. Un ni~o enfermo
debe ser ilevado inmediatamente a un hospital, en donde la sangre y
los fluidos del cuerpo pueden ser observados y corregidos; se puede
alli usar un aparato respiratorio si la respiracic~n est~ fallando
y Si es necesario, se le puede someter a una operaci~n para
disminuh la presi~n del cerebro inflamado.
No lo olvide. Act~e con rapidez ante la menor indicaci~n del
s«=ndrome de Reye.
PAGENO="0451"
445
DEPARTMENT OF HEALTH & HUMAN SERVICES Public Health Service
Food and Drug Administration
Rockville MD 20857
March 8, 1985
Dear Drug Establishment Registrant:
On January 9, 1985, the Secretary of the Department of Health and Human
Services requested the aspirin industry to undertake a voluntary program
to warn parents and teenagers about the possible association between the
use of aspirin and the onset of Reye Syndrome. As a consequence, the
Conanissioner of Food and Drugs met with representatives of the Aspirin
Foundation of America, Inc., and Plough, Inc., at which time both
organizations announced they weuld launch voluntary Reye Syndrome
precautionary programs. The purpose of this letter is to inform you of
the voluntary labeling programs being undertaken by the Aspirin
Foundation and Plough, Inc. and to. ascertain whether, and to what extent,
your firm intends to join in this nationwide program.
As a part of its voluntary program, the Aspirin Foundation has proposed
labeling revisions for aspirin and aspirin-containing products, which
include:
(1) Indications for use in `flu' will be renewed from products
packaged only for use in children (pediatric products).
(2) All such products will bear the statement: `Warning: Contact a
physician before giving this medicine to children, including
teenagers, with chicken pox or flu.'
Plough, Inc. of Wasrçthis, W, maker of St. Joseph aspirin and non-aspirin
products for children, which is not a nner~er of the Aspirin Foundation,
has developed its nwn voluntary precautionary program. A part of its
program includes th~ labeling revisions for children's products proposed
by the Aspirin Foundation with the foll~eing expanded warning statement:
PAGENO="0452"
446
"Warning: Reye Syndrome is a rare but serious disease
which can follow flu or chicken pox in children and
teenagers. While the cause of Reye Syndrome is
unknown, some reports claim aspirin (or salicylatas)
may increase the risk of developing this disease.
Consult a doctor before use in children or teenagers
with flu or chicken pox."
Plough, Inc. also intends to include in its packages an insert bearing
information which identifies the symptoms of Reye Syndrome.
The FDA supports these voluntary precautionary programs of the Aspirin
Foundation and Plough, Inc. and the labeling revisions proposed by them
and urges that they be applied to all aspirin and salicylate-containing
drug products intended for use in the treatment of flu or chicken pox,
and/or likely to be used by children or teenagers in the treatment of
symptoms cosmonly associated with flu or chicken pox (e.g., fever, cough,
headache, sore throat, sneezing, nasal congestion, rhinitis). For more
information, please refer to the attached HHS Press Releases and FDA TALK
PAPER.
Should you elect to participate in this voluntary program, we would
recoirmend that a warning statement appear on all cartons, container
labels, and other printed materials as the first warning for products with
multiple warning statements, and that the labeled directions for use refer
to the warning statement, such as "For Chicken pox or Flu see Warnings."
This is consistent with the agency's position in the advance notice of
proposed rulemaking that was issued on December 28, 1982 (47 FR 578~6).
In an effort to update our files under the drug listing regulations, we
request that you answer the questions on page 3 of this letter:
PAGENO="0453"
447
(1) Establishment Name Address City/State/Zip
________ ___________ ( )
(2) Respondent's Name Title Telephone No.
(3) Is your firm currently involved in the manufacturing,
repackaging, relabeling, and/or distribution of products
containing aspirin or salicylates?
Yes No
If yes, please attach specimens or ~ of each
container label, carton label, and accompanying
labeling. Mark on each specimen or copy whether the
product is manufactured (N), repackaged (NP), relabeled
(RL), repackaged and relabeled (RP/RL), or distributed
only (D).
(4) Does your firm intend to relabel its aspirin or
salicylate-containing products in conformance with the
voluntary initiatives developed by the Aspirin
Foundation or Plough, mc?
Yes No
~ot Applicable
If yes, please attach specimens or copies of each
container label, carton label, and accompanying labeling
showing changes to be made.
(5) If yes to items 3 and 4, what is your anticipated date to
begin using the new labeling?
Date__________
(6) If yes to items 3 and 4, what is your anticipated date
for such newly labeled products to reach the retail
market place?
Date_________
Please return using enclosed envelope by 3/29/85 to:
Food and Drug Administration
HFN-3l2
5600 Fishers Lane
Rockville, MD 20857
Atth: Reye Syndrome Labeling
PAGENO="0454"
448
As indicated above, we request that, whether or not you decide to
participate, you submit one copy of each label, carton label, and
accompanying labeling for each aspirin or salicylate-containing product
currently manufactured, repackaged, relabeled and/or distributed by you.
Should you agree to participate in this program, we ask that you also
submit a copy of each label, carton label, and accompanying literature for
each such product showing the revisions to be made. With regard to
questions 5 and 6, we request that you identify the anticipated dates for
using such revised labeling and when products, bearing revised labeling,
will reach the retail market place.
Please return page 3 of this letter and any pertinent labeling, as
requested, using the enclosed envelope, by March 29, 1985. Should you have
any questions you may contact Kevin M. Budich, Assistant to the Director,
Division of Drug Labeling Compliance, Office of Compliance, Center for
Drugs and Biologics at (301) 443-7283.
Thank you for your prompt attention in this matter.
Sincerely,
(7~-~7 /2i
Harry M. fr~yer, Jr., M.D.
Director
Center for Drugs and Biologics
Enclosures (3):
Secretary's Press Stateirmnt, 1/9/85
tillS Press Release, 1/23/85
FDP~ Talk Paper, 1/25/85
PAGENO="0455"
449
ThE$LCSET**Y OF H(ALTW aso wusas sr.sv.cts
Statement by
Margaret N. Heckler
Secretary of Health and Human Services
Nothing is more important to Americans than the health and safety
of their children and, as Secretary of Health and Human Services, I
feel a special responsibility to protect the health of our nation's
children during their most vulnerable years.
That is why I ordered special steps to resolve the scientific
dispute when some early studies shoved an association between Reye
syndrome and the use of aspirin for children suffering from chicken
pox, influenza and flu-like illnesses. That is also why I instructed
the Food and Drug Administration to pursue a vigorous public education
campaign to ensure that parents were made aware of the possible link.
In particular, I ordered the Centers for Disease Control a year
ago to undertake a new study of aspirin and Reye syndrome. The study
had two parts - a one-year pilot study followed by a full-scale
investigation.
The Centers for Disease Control have now completed the pilot
study. This study is not completely con~lusive - but its findings do
show an association between the use of aspirin and the onset of Reye
syndrome in children and teenagers.
These results make it urgent that CDC vigorously pursue the full-
scale study. That work was begun last month and is now fully underway.
In the meantime, I strongly urge parents to follow the advice of
the Surgeon General: in all cases involving children, includi~~q
teenagers,~_physician should be consulted before using aspirin in
cases of flu or chicken pox.
It is significant that fewer children are now being struck by Reye
syndrome - 190 known cases in the year ending November 1984 - while
reported cases in previous years were as high as 548 (in 1980). But
this does not mean we can be complacent. The disease is deadly, with a
fatality rate of 26 percent last year. In addition, those who suffer
from the disease are increasingly older children and teenagers, as wall
as young children: According to the pilot study, some 50 percent of
all cases were in those over age 10, and 15 percent were in those aged
15 `and older.
In order to ensure that all children continue to be given the
fullest protection, even while we await final scientific conclusions, I
am today taking four additional steps:
First, I am ordering CDC to release the pilot study immediately,
and I am instructing that it also be published as soon as possible in
CDC's journal Morbidity and Mortality Weekly Report. This information
along with other scientific evidence will appear in a refereed
scientific journal.
Second, I am asking the Food and Drug Administration to extend and
expand its public education efforts -- parents must understand the need
to consult a physician before using aspirin to treat flu or chicken
pox. Likewise, FDA will take steps to inform teenagers - who often
treat themselves -- of the possible link between aspirin and Reye
syndrome.
PAGENO="0456"
450
Third, I am contacting media leaders throughout the country asking
them to use every possible resource to help broadcast the ssage. I
am telegraphing the presidents of the three television networks as well
as the American Newspaper Publishers Association, the National
Association of Broadcasters, the Association of Independent ?elevisior*
Stations, and the National Cable Television Association. I wiU also
send letters to the owners of newspapers as well as television and
radio stations throughout the country.
I will re~emphasize the importance of the public service
announcements we've already supplied to them. And I will urge them to
take additional steps to convey this important message: for example,
special news coverage, new public service announcements, messages
specially designed to reach teenage audiences, or other appr~riate
steps.
Finally, I will ask the makers of aspirin products to take two
steps voluntarily: first, to immediately remove any labels which
recommend that aspirin products be used to treat flu or chicken pox in
children or teenagers; and second, to further label all aspirin
products to indicate that there is a possible association between the
use of aspirin and the onset of Reye syndrome in children and
teenagers, and that aspirin products should not be used in those cases
unless a physician is first consulted.
I would ask the industry to voluntarily retain this expanded
labelling until the results of the ful]~-scale cDC study have been
reported and thoroughly analyzed.
I want to emphasize that this step does not mean that aspirin is
unsafe for other uses. Aspirin is, in fact, a tremendously valuable
and effective analgesic and anti~inflammatory drug that has, will and
should continue to be used by tens of millions of Americans safely.
But, as with any other drug, it is crucial that aspirin be administered
appropriately.
I am confident that both aspirin manufacturers and the American
media will take the steps needed to ensure the best possible protection
for our children.
These are useful first steps. I believe they are entirely in the
spirit of the recommendations we have received from the National
Academy of Sciences' Institute of Medicine. In addition, the data now
available in the pilot study will be reviewed further with great care,
as will all independent comments and recommendations, to determine
whether further steps may be wArranted.
PAGENO="0457"
451
HHS ~
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
FOR IMMEDIATE RELEASE Claire del Real -- (202) 245-6343
Jan. 23, 1985
HHS Secretary Margaret M. Heckler announced today that the nation's
major aspirin manufacturers have agreed to her call for voluntary action
concerning the rare but serious Reye syndrome. A new program by the
manufacturers will include television announcements, store posters and label
changes and warnings regarding the rare but serious Reye syndrome.
Secretary Heckler had called for such voluntary action Jan. 9 and
today applauded the Aspirin Foundation of America for Uits prompt and
responsible action, which will be getting the message to Americans within a
week. U The program was worked out in a series of meetings between the
foundation and the Food and Drug Administration over the past two weeks.
The Secretary's request for information and labeling was made following
a review by the Institute of Medicine of the National Academy of Sciences
of a pilot study supporting a link between use of aspirin to treat childhood
flu and chicken pox and the subsequent development of Reye syndrome.
Public service announcements and store posters and signs will be
distributed next week by the manufacturers' sale representatives and the
Advertising Council, Secretary Heckler said. She asked the media and store
managers to use the materials widely, because we will rely on these
materials to notify people buying aspirin products with the old labels -- or
already having such products in their homes. U
Some of the label changes and warnings may be in place as early as this
summer, and will thus appear well in advance of the next winter's flu and
chicken pox seasons. Warning stickers on store shelves will appear in some
areas as early as this week.
The posters and radio-TV public service announcements say, in part:
UA rare but serious childhood disease called Reye syndrome may develop
in children who have chicken pox or flu. Although the cause of Reye
syndrome is not known, some studies suggest a possible association with
medicines containing ealicylate or aspirin. So it is prudent to consult a
doctor before giving these medicines to children and teenagers with chicken
pox or flu. U /
The posters and announcements also note that Reye can occur without a
link to medications. The materials list the symptoms -- lethargy,
belligerence or excessive vomiting -- and recommend quick medical help~
The labeling changes are twofold:
--Suggestions for use in flu will be deleted from the labels of
children's aspirin.
-- The following warning will be added to labels of aspirin-containing
products for adults as well as children: UConsult a physician before giving
this medicine to children, including teenagers, with chicken pox or flu. U
Reye syndrome is a rare condition, with only several hundred reported
cases a year. Last year there were 190 cases reported. But 20-30 percent
of reported cases are fatal, and many of the surviving youngsters suffer
brain damage.
-MORE-
PAGENO="0458"
452
Four state studies initially made possible associations between Reye
and aspirin's use for childhood chicken pox and flu. A larger federal study
to confirm or negate the link will continue through next winter's flu and
chicken pox seasons.
A pilot for this larger epidemiological case review found 96 percent of
cases had the common thread of aspirin use for flu-like illnesses or chicken
pox. After a review, the Institute of Medicine of the National Academy of
Sciences advised that the federal government should alert parents and
physicians now and not await the full study's results. The institute
recommended that the full study continue, however. A task force of Public
Health Service employees is overseeing the study.
First to respond to the new information was Plough Inc. of Memphis,
Tenn., manufacturer of St. Joseph products for children. Plough is making
label changes and is placing stickers on products already produced but not
yet distributed.
The Aspirin Foundation represents such major aspirin manufacturers and
distributors as Sterling, Bristol-Myers, Miles, Burroughs Wellcome, Merrell
Dow and Procter & Gamble.
Retailers such as Giant Foods, with offices in the Washington area,
plan their own posters and shelf signs on Reye syndrome and aspirin in the
nonprescription drug sections of their pharmacies and food stores. FDA has
been working with these retailers. Giant Foods plans to have their posters
in place tomorrow.
Secretary Heckler emphasized that warnings on Reye syndrome "do not
mean aspirin is unsafe for other uses. Aspirin is, in fact, a tremendously
valuable and effective analgesic and anti-inflammatory drug that has, will
and should continue to be used by tens of millions of Americans safely. But
as with any other drug it is crucial that aspirin be administered
appropriately."
tilt
PAGENO="0459"
453
FDA
`PjJ ( E~AJ'E1~ FOOD AND DRUG ADMINISTRATION
U.S. Department of Health and Human Seivices
Public Health Service 5600 Fishen Lane Rockvile, Maryland 20857
FDA Talk Papers are prepared by the Office ci Public Affairs to guide FDA personnel in responding with consistency and accuracy
to questions from the public on subjects of current interest. Talk Papers are subject to change as more information becomes
available. Talk Papers are not intended for general distribution onnide FDA, but all information in them I, public, and full tests
are releasable upon request.
185-7 Bill Grigg
Jan. 25, 1985 (301) 443-4177
RECENT ACTIONS ON REVE SYNDROIE/ASPIRIN LINK
The FDA has held a series of meetings to carry forth HHS Secretary
Margaret N. Heckler's Jan. 9 call for voluntary labeling changes on aspirin
products. The changes were requested to reflect a recent federal pilot study
supporting earlier state studies linking aspirin's use in teen and childhood
flu and chicken pox to the subsequent development of the rare but serious Reye
syndrome (see Talk Paper T85-3).
Secretary Heckler announced the results of these meetings -- agreement
with the major manufacturers for label changes, store posters and radio-TV
announcements -- on Jan. 23. The following may help answer questions on
the warning labels and broadcast announcements pledged:
The labeling agreed to by members of the Aspirin Foundation of America --
such major manufacturers as Sterling, Bristol-Myers, Miles and Burroughs
Wellcome, Squibb, Whitehall and Procter & Gamble -- and found acceptable by
FDA will add to the warning section of the labels:
`Contact a physician before giving this medicine to children, including
teenagers, with chicken pox or flu.'
In addition, reconmendations for use in flu will be removed from
children's products.
Also as part of the agreement, the Aspirin Foundation has produced 60-
and 30-second TV and radio public service announcements to be distributed to
the media In the next few days. The shorter version says:
`A rare but serious childhood disease called Reye Syndrome may develop In
children and teenagers who have chicken pox or flu. Although the cause of Reye
Syndrome Is not known, some studies suggest a possible association with
medicines containing salicylate or aspirin. So, it Is prudent to consult a
doctor before giving these medicines to children or teenagers with chicken
pox or flu.'
The longer version adds to the above:
`Remember, Reye Syndrome occurs even in children and teenagers who take
other medicines or no medicines. It's important to be aware of the early
signs and symptoms. If your child shows unusual behavior, such as severe
tiredness, belligerence, or excessive vomiting after appearing to recover from
chicken pox or flu, get medical help Immediately. Give no medications.'
Plough Inc. of Memphis, Tenn., maker of St. Joseph aspirin and non-
aspirin products for children, is not a member of the Aspirin Foundation but
was the first to announce it would comply with the Secretary's request (even
though company officials said they'did not feel aspirin had been established
as a cause of Reye syndrome). Its program is different from the foundation
members. The corporation met with FDA Jan. 15 and later announced that it:
-MORE-
PAGENO="0460"
454
-- would begin next week to print packages for its aspirin-containing
products with changes suggested by the Secretary and FDA in the labeling,
eliminating any recommendation for use in childhood or teen flu or chicken
pox, and adding a warning against such use, with an explanation of Reye
syndrome; and
-- was adding warning stickers on the boxes of aspirin products already
produced but still under its control. Consumers may begin to see the stickers
soon.
The stickers say, `Consult doctor before use in children or teenagers
with flu or chicken pox." The Plough label warning will say:
"WARNING: Reye Syndrome is a rare but serious disease which can follow
flu or chicken pox in children and teenagers. While the cause of Reye
Syndrome is unknown, some reports claim aspirin may increase the risk of
developing this disease. Consult doctor before use in children or teenagers
with flu or chicken pox."
Plough will also insert in packages information to read: "The symptoms
of Reye Syndrome can include persistent vomiting, sleepiness and lethargy;
violent headaches; unusual behavior, including disorientation, combativeness
and delirium. If any of these symptoms occur, especially following chicken
pox or flu, call doctor immediately, even if your child has not taken any
medication. REYE SYNDROME IS SERIOUS, SO EARLY DETECTION AND TREATMENT ARE
VITAL."
FDA Commissioner Frank E. Young wrote Plough commending the company's
speed and cooperation.
Giant Foods and other retailers have contacted FDA about producing their
own posters and shelf labeling. The Giant materials will be in all of the
chain's food and drug stores tomorrow, Jan. 26. The main poster says, "The
U.S. Food and Drug Administration recommends that parents~ check with a doctor
before giving aspirin or products containing aspirin to thildren or teenagers
who have the flu or flu-like symptoms or chicken pox."
Below the posters, Giant is attaching to the shelves tear-off literature
giving more details about the warning and about Reye syndrome.
FDA has reviewed the wording used by Giant and supports it.
FDA has conducted public education campaigns cautioning about the use of
aspirin in childhood flu and chicken pox for thre~ winters and is now updating
those materials. Since the pilot and last year's case reports indicate about
half the cases of Reye syndrome to be in teens and children over 10, who may
self-medicate, the campaign will shift emphasis toward this older group. A
new radio announcement and a column for weekly newspapers is being given
priority. Secretary Heckler has sent letters on the pilot study to
pediatricians and family doctors, as well as to newspapers and broadcast
outlets.
PAGENO="0461"
455
DEPARTMENT OF HEALTH & HUMAN SERVICES Pubbc Health Service
Food and Drug Administration
Rockville MD 20857
March 11, 1985
Dear Madam or Sir:
The flu is a common ailment, and usually self-limiting --
particularly for children. Not 80 common and not so easy' to treat
is Reye syndrome, which may develop in children who, have had the
flu or chicken pox. Reye syndrome can result in brain damage and
is fatal in about one case out of four. Some scientists have
suspected that Reye syndrome develops mainly in children who have
been treated with aspirin when they have had those illnesses.
Recently, a U.S. Public Health Service study confirmed evidence
linking Reye syndrome with the use of aspirin. Equally
significant was that the study found a number of Reye syndrome
cases among teenagers. Previously, it had been thought that the
disease was found almost exclusively in children under 16.
The Public Health Service, through the Food and Drug
Administration, is taking a number of steps to warn teenagers
about the suspected association between Reye syndrome and aspirin.
Messages, such as the enclosed poster, are aimed directly at these
youths, many of whom do their own medicating.
When Reye syndrome strikes, fast action is required to forestall
its dire consequences. But the fastest action is to prevent its
occurrence. This poster is designed to make that point. We hope
you find a suitable place to display it.
Roger W. Miller
Director
Communications Staff
PAGENO="0462"
456
R~for Flu c~ Chicken Pox: Kindness
Be good to yourself when you'vegot the fluorchicken pox. Take
it easy. Get plenty of rest.
Viral illnesses such as these are usually self~limiting. Time will
cure them.
Check with yourdocsorahoutusing medications to treat flu or
chicken pox. For children-including teenagers-medications
such as aspirin and aspirincontaining products may not be a
good idea. A rare but dangemuscnnditioncalled Reye syndrome
may develop in young people just when they appear to be re
covering. Studies suggest a link between the development of
Rcye and the use of aspirin to treat the flu or chicken pox.
So, treat yourself tight when you've got the flu!
cs. DepavxrvsnfHeslth riot Hsxas Snxim * PvblicHnfth Srswr * Fssdrod DxgAdicixi,msiss * Scot) rot Lair. Rsdi,itk. Md. 2)057 * HHSPnblicaisv No. (ODA)t5.0)49
PAGENO="0463"
457
Mr. BATES. Thank you.
Let me just follow that logic that the legislation is not needed.
Evidently, we live in an imperfect world.
Dr. YOUNG. Yes, sir.
Mr. BATES. Science is constantly changing our facts or knowledge
about the effects of drugs or other medicines, so there is a margin
of error.
Dr. YOUNG. Yes.
Mr. BATES. And if we err, which way do we err? Do we err on the
side of the public, or do we err on the side of the aspirin manufac-
turers?
Let me ask you, because I think this is the fundamental ques-
tion, and you could say you are being cautious in one sense, but
you also said that you are not being cautious in another sense.
Dr. YOUNG. Sure.
Mr. BATES. So I would ask this question: Do we have any evi-
dence to suggest that children or adolescents or adults have died
from not taking aspirin?
In other words, does aspirin prevent death in flu or something
that someone may have? Would aspirin keep them alive?
Dr. YOUNG. It is very clear, as stated by Dr. Wolfe and the testi-
mony from the American Academy of Pediatrics, that we do over-
medicate. I think that is unquestionable in many cases.
Many of these infectious diseases, particularly nonbacterial, will
resolve spontaneously. In the event that one has a very high fever,
and the fever is not brought down either by antipyretics or cooling,
a young child, particularly a young child could die, I must have to
say, in my own case, when my fever hit 105, 105.5, my wife got ap-
prehensive, and I was equally apprehensive.
One has, in the case of high fever, a chance of having complica-
tions of death due to the fever itself, and in that circumstance, as-
pirin and salicylates and other antipyretics are designed primarily
to lower fever. In those cases where fever is not lowered, death
could occur. It must also be stated that there are other ways of low-
ering fever besides aspirin, and even besides drugs.
Cool bath is one.
Mr. BATES. And is there any indication or any evidence at all to
demonstrate that there is an association between aspirin and
Reye's Syndrome?
Dr. YOUNG. I think there is an association with aspirin and
Reye's Syndrome, as shown in the variety of studies, and I have
said that clearly on both TV and the other media that are there.
We do not know the exact etiology or the magnitude. There is a
very tight link. But there are other factors; we felt at this time
there was not sufficient information to warrant mandatory label-
ing, but felt because of the association that a very vigorous pro-
gram should not only be instituted, but we must monitor how effec-
tive it is.
Mr. BATES. So, you do think that whether it is mandatory or vol-
untary, that at this time a vigorous public education program is
warranted?
Dr. YOUNG. Absolutely.
Mr. BATES. And the posters-I personally would like 300 of those
today delivered to my office.
PAGENO="0464"
458
Dr. YOUNG. Would you please, Joe, arrange for that?
Mr. BATES. And I intend to take your letter, which I think was a
strongly worded letter, and include it in my next newsletter.
Dr. YOUNG. How many copies would you like, sir?
Mr. BATES. I will have it reprinted. I will start with one copy.
Have you done any television, public service announcements?
Dr. YOUNG. Yes; could I please show the public---
Mr. WAXMAN. We are not really going to have time. I don't know
how long this thing is, but let's just have questions now.
Dr. YOUNG. Fine. I do have that, and if you would like?
Mr. BATES. I would like copies of that.
Dr. YOUNG. I could provide you with a reel that you might be
able to send out to your constituents as well, and we will provide
that.
Joe, will you please be sure that that is available to the Con-
gressman, and we will have a reel that will be sent. If you would
like, we can provide the radio announcement that went out as well.
Mr. BATES. Send 50 of those.
[The following material was submitted for the record:]
PAGENO="0465"
459
DEPARTMENT OF HEALTH & HUMANSERVICES Pubbc Health Service
Food end Drug Administration
Rockvilhe MD 20857
Rbye syndrome PSA
30-seconds
HERE' S SOME ADVICE WE WANT TO PASS ALONG TO YOU FROM THE U.S.
SURGEON GENERAL ABOUT REYE SYNDROME ~ND TEE USE OP ASPIRIN.
REYE SYNDROME IS A RARE BUT DANGEROUS CONDITION THAT MAY
DEVELOP PROM FLU OR CHICKEN POX. IT OFTEN STRIKES JUST WHEN
AN INDIVIDUAL APPEARS TO BE RECOVERING. CHILOREN, INCLUDING
TEENAGERS, ARE MOST OFTEN THE VICTIMS. STUDIES SUGGEST A
LINK BETWEEN THE USE OP ASPIRIN TO TREAT THESE ILLNESSES AND
THE DEVELOPMENT OF REYE SYNDROME. SO, THE SURGEON GENERAL
URGES YOU TO CHECK WITH YOUR DOCTOR BEFORE USING ASPIRIN OR
PRODUCTS THAT CONTAIN ASPIRIN TO TREAT FLU OR CHICKEN POX.
Contact:
Louise Patterson
Office of Communications, HFW-40
Food and Drug Administration
5600 Fishers Lane
Rockville, MD 20857
(301) 443-3210
PAGENO="0466"
460
DEPARTMENT OF HEALTH & HUMAN SERVICES Pubic Health
Food and Drug Ad sat at on
Rockvilla MD 20857
Teenagers/Aspirin/Reye syndrome
:60 Radio PSA
(The voice in parentheses is that of a teenage girl.)
Young people often get the flu.
(So do adults.) -
Sometimes a rare but dangerous condition called Reye syndrome
develops from the flu or chicken pox.
(Thank goodness it's only sometimes.)
Children, including teenagers, are most often the victims of
Reye syndrome.
(That's not fair!)
Reye syndrome usually occurs just when the child seems to be
recovering.
(Bow weird!)
The symptoms of Reye include persistent vomiting, fatigue,
confusion and belligerence.
(Sounds bad. Can it be prevented?)
The cause of Reye syndrome is unknown but studies suggest a
link between the development of Reye and the use of aspirin.
(So shouldn't I take any medicine?)
It's a good idea to check with a doctor before treating the
flu or chicken pox with aspirin or any product containing
aspirin.
(But how will I get well?)
Flu and chicken pox are usually self-limiting. Time will
cure them. Take it easy. Get plenty of rest.
(Oh, I'm really good at that.)
A message from the U.S. Department of Health and Human
Services.
PAGENO="0467"
461
Mr. WYDEN. Would the gentleman yield?
Mr. BATES. Yes.
Mr. WYDEN. I think you asked a very good question. I would like
to know, is there any evidence that anyone has died or suffered se-
rious injury as a result of not taking aspirin?
Dr. YOUNG. There is evidence that people have died or suffered
serious injury from not having their temperature lowered, and the
primary focus of aspirin in its use is to lower temperature.
A second area is the anti-inflammatory actions that are there,
and that is trivial. By and large, one does not die of inflammatory
reactions that would be prevented by aspirin, but the lowering of
temperature and the subjective relief of symptoms has been what
the drug has been used for, amongst other purposes.
Mr. WYDEN. But we have already been talking about the alterna-
tives, and I don't want to have it on my conscience that aspirin
stock went down as a result of this hearing, but I think we do want
to make it clear that there is no evidence that anybody has died or
suffered serious injury as a result of not taking aspirin.
I haven't heard anything to the contrary.
Dr. YOUNG. Just so your conscience is clear, the sales on aspirin
have gone down between 1980 and 1983 by 72 percent. It might not
go down by another 72 percent as a result of today's hearing, so I
think we have already seen a big drop, and that is one of the em-
phases that I made in my testimony, to indicate that the campaign
has been working.
Mr. WYDEN. I don't want to prolong this, and you have been very
patient. We know that some of that reduction is due to the fact
that there is evidence that people who take aspirin may have stom-
ach problems and the like, isn't that correct?
Dr. YOUNG. I think there is a variety of factors contributing. I
wouldn't want to claim any one.
Mr. WYDEN. I appreciate that.
Mr. WAXMAN. In your calculations as to how best to inform the
public, did you figure that there are thousands of people, I don't
know how many, maybe tens of thousands, buying aspirin bottles
right now, with all the information that you warn people about,
that will say, "Use aspirin for flu and chickenpox"?
Dr. YOUNG. We tried to deal with that, Mr. Chairman. I think
that is the most troubling problem that we faced. We felt that the
best way to get this out, actually, is the public media, the media
that we see here, television, the evening media broadcasts and the
radio and newspapers.
Mr. WAXMAN. Have you purchased any media on television,
radio or the newspapers?
Dr. YOUNG. We have sent out a newspaper ad. We have already
sent out the radio-and of the 6,600 stations that were contacted,
1,000 have played this.
Mr. WAXMAN. These are all public service announcements?
Dr. YOUNG. Yes, sir.
Mr. WAxM~. That are played during the time they play public
service announcements, and we all know what time that is?
Dr. YOUNG. Sometimes it is 2 in the morning.
Mr. WAx~.N. Usually not the same time the advertisements are
on to take aspirin?
PAGENO="0468"
462
Dr. YOUNG. But I think the prime-time coverage that we got with
the announcement of the Secretary and the prime-time coverage by
radio and newspapers in the announcement was very effective.
Mr. WAXMAN. Dr. Young, I have already expressed my position
to you. I hope you will rethink your position.
Let me just ask you this: You are the head of the Food and Drug
Administration, you are Commissioner of the Food and Drug Ad-
ministration. You are a physician, aren't you?
Dr. YOUNG. Yes, sir.
Mr. WAXMAN. If I asked your advice as a patient, should I give
my children aspirin or let my children have aspirin for flu or
chickenpox, what would you tell me?
Dr. YOUNG. My advice would be similar to that of the American
Academy of Pediatrics. I would say that at this time, although
there is not an absolutely proven association between aspirin and
Reye's Syndrome, that it would be prudent to take all precautions
and to not use that.
Mr. WAXMAN. You feel comfortable making that statement, don't
you?
Dr. YOUNG. Yes.
Mr. WAXMAN. Wouldn't you feel comfortable having that on a
label?
Dr. YOUNG. I think we depart there, sir.
Mr. WAXMAN. Why? Do you think that is an inaccurate state-
ment, that factually it is irresponsible to make?
Dr. YOUNG. No. I think that at this point, that we can accom-
plish this in the current flu season with a voluntary educational
program, and to get the information in place for next flu season.
Mr. WAXMAN. Thank you very much for being with us. We ap-
preciate your testimony. We will look forward to working with you,
because I think legislation is going to be necessary.
Dr. YOUNG. I certainly appreciate, sir, your genuine concern, and
I know that it is heartfelt, and I look forward to working with you
on this.
Mr. WAXMAN. We will now call forward Dr. Joseph White, presi-
dent of the Aspirin Foundation; James Cope of the Proprietary As-
sociation; and Neil Chayet, Committee on the Care of Children.
Gentlemen, we want to welcome you to this hearing. We have
your prepared statements, which we will place in the record in
their entirety.
What we would like to ask you to do is to summarize your state-
ments in no more than 5 minutes.
Dr. White, why don't we start with you?
STATEMENTS OF JOSEPH M. WHITE, M.D., PRESIDENT, ASPIRIN
FOUNDATION OF AMERICA, ACCOMPANIED BY R. BRUCE DICK-
SON, COUNSEL; JAMES D. COPE, PRESIDENT, THE PROPRIE-
TARY ASSOCIATION; AND NEIL L. CHAYET, LEGAL COUNSEL,
COMMITTEE ON THE CARE OF CHILDREN
Dr. WHITE. Good morning, Mr. Chairman, and members of the
subcommittee. I am Dr. Joseph M. White, I am a physician, phar-
macologist. I am appearing before you today as president of the As-
pirin Foundation of America.
PAGENO="0469"
463
With me is R. Bruce Dickson, the counsel to the foundation.
The Aspirin Foundation is a trade association of the aspirin in-
dustry. Its members include all producers of bulk aspirin and all
the major producers of finished aspirin products in the United
States.
I appreciate this opportunity, and I would like, first, to ask you
to consider just two things. First, I urge you to listen to the scien-
tific data. It is important in this situation, because Reye's is such a
terrible condition.
It has occurred in many children who have never been given as-
pirin, and it is a danger that if we think we have solved the prob-
lem, and it really isn't solved, that this terrible disease will go on,
and we will have to start out all over again and reinstitute the
search for what is the real cause.
In addition t~ that, the voluntary program is in it~ early stages
and has been quite successful. It is unfair at this time to say volun-
tary programs will never work because we just learned that this
one is working well.
Some parts of that program, as a matter of fact, went in the mail
just last night, so that we have to wait until that filters out, and
there are a lot of stories people have about postal deliveries and so
forth these days, that tell us that we have to give the distribution
channels a chance to deal with it, and we think that even the early
indications that we have now are that there is an upward trend in
the awareness of the American public.
It was said sometime back as being around 50 percent of mothers
were aware of aspirin as being possibly associated with Reye's syn-
drome.
We have data just available now that indicates that that is ap-
proaching 80 percent now. So the combined effort of what the Sur-
geon General is doing, what the Public Health Service is doing,
what the members of the industry are doing, is actually beginning
to have an effect.
Mr. WAXMAN. Would you repeat that percentage again? I want
to see if I understand it.
Dr. WHITE. Seventy-nine as we now read it.
Mr. WAXMAN. Seventy-nine percent?
Dr. WHITE. Are now aware, that is mothers who have children
between the age of 2 and 15, that was the category that happened
to be questioned, and that 79 percent of them were aware of Reye's
syndrome and the possibility that aspirin had something to do with
it.
Mr. WAXMAN. Who did this study?
Dr. WHITE. I can get you those names.
Mr. WAXMAN. I would like the names and the study for the
record.
Dr. WHITE. Yes, we will be glad to supply it.
[Testimony resumed on p. 489.]
[The following material was submitted for the record:]
PAGENO="0470"
464
PAUL. HASTINGS. JANOFSKY & WALKER
April 10, 1985
The Honorable Henry A. Waxman
Chairman
House Energy and Commerce
Subcommittee on Health and the Environment
House Office Building, Annex 1
300 New ~Tersey Avenue, S.E.
Washington, D.C. 20515
RE: H.R. 1381
Dear Mr. Chairman:
Enclosed herewith are materials requested during the
hearing on the above-referenced bill on March 15, 1985. Speci-
fically, the materials include:
o Reye Syndrome Awareness Research --
* Final Report (March 28, 1985)
o Supplementary Report on Aspirin
Foundation Voluntary Reye Syndrome Pre-
cautionary Program (April 10, 1985)
If you or any member of the Subcommittee has any questions about
the enclosed, please do not hesitate to call.
* Respectfully submitted,
R. Bruce Dickson
Counsel to the Aspirin Foundation of America
RBD : cs
Enclosures
PAGENO="0471"
465
REYE SYNDRCI4E AWARENESS RESEARCH
F~NAL REPORT
PURPOSE AM) METH0DOL~Y
Purpose
The purpose of this research was to determine relative awareness of Reye
Syndrome associated with aspirin along with three other "child oriented"
product/safety Issues. This information was obtained to ascertain the
impact of the aspirin industry's current effort to Inform the public of the
potential danger of children or teenagers using aspirin with flu or chicken
pox combined wit~. prior publicity about the issue from other sources.
Methodology
This research was conducted among 300 women with at least one child between
2-15 years of age. These interviews were done via telephone using a
national probability sample. All interviews were conducted between March
11-13, 1985. A total of 210 natIonally dispersed sampling points were
utilized to complete the final sample.
The presentation of the four Issues evaluated was rotated to avoid position
bias.
The cost of tttis study was $4,850.
Research Supplier
The fieldwork for this research was conducted by Joseph Ramos Inc.
Joseph Ramos Inc.
114 East 32rd Street
New York, New.York 10016
(212) 685-5101
Method Of Analysis
While the major issue of concern is "aspirin being associated with Reye
Syndrome," awareness of three other "child oriented" product/safety issues
was obtained to provide a basis for comparison: "asbestos being associated
with health problems in schools," "adult safety belts in cars being unsafe
for children," and "children's toys being unsafe." The final report
reviews awareness of each Issue by the total sample of 300 women with at
least one child between 2-15 years of age. In addition, awareness levels
for each issue have been reviewed by the following sample characteristics:
PAGENO="0472"
466
Total Sample: 300 Women
Ag~ of Respondent: 18-34 (139)
35+ (157)
Education: Completed High School
or Less (140)
Some College or More
(157)
Total Number
QLQhild~ren: 2-7 Years Old (172)
8-15 Years Old (195)
One Child Householdn: 2-7 Years Old (58)
8-15 Years Old (77)
Note: Not all respondents were willing to respond to the age question (4-
no response). Also, three respondents attended "business or special
school" but were not included in the two educational attainment groups.
PAGENO="0473"
467
cc*iciusicti
Overall1 mothers appear to be relatively familiar with the association QL
~spir1n and Reye Syndro~.
Specifically:
* About 8 out of 10 respondents indicated that they were familiar with the
asplrin/Reye Syndrome Issue (79%). This compares favorably with the
indicated levels of awareness for the other three "child oriented"
product/safety issues included in the survey:
Adult safety belts in cars being unsafe for children: 63%
Asbestos being associated with health problems in schools: 85%
Children~s toys being unsafe: 95%
* Among the respondent sub-groups examined, familiarity with the asplrin/Reye
Syndrome issue did vary somewhat - from 75% to 83%. However, awareness of
the other three issues also varied across sub-groups:
Adult safety belts in cars being unsafe for children: 60-75%
Asbestos being associated with health problems in schools: 81-90%
Childrèn's toys being unsafe: 92-98%
Among each of the sub-groups, asplrin/Reye Syndrome awareness was within the
range of awareness of the other three issues.
PAGENO="0474"
468
SUMMARY OF FIt1)INGS
1. Overall Awareness Leve1~
Respondents were quite familiar with the four "child oriented"
product/safety issues included In this study. The issue which
respondents were ]~.ost familiar with was "adult safety belts in cars
being unsafe for children" (63%). "ChIldren's toys being unsafe" (95%)
obtained the highest awareness level followed by "asbestos being
associated with health problems in schools" (85%) and aspririn being
associated with Reye Syndrome" (79%).
AWARENESS OF SELECT "CHILD ORIENTED!~
PRODUCTJSAFETY ISSL1E~
Total
Awareness
Base: (Women With a Child 2-15) (300)
I
"Have You Ever Heard or Read
Anything About"....
Childt~en's Toys Being Unsafe 95
Asbestos Being Associated With
Health Problems In Schools 85
Aspirin Being Associated with
Reye Syndrome 79
Adult Safety Belts In Cars Being
Unsafe For ChIldren 63
2. ~.sr.eness Levels By Select Sample Characteristics
A. ~g~: Women "35+" years of age were more likely than women "18-34"
years of age to be aware of three "child oriented" product/safety
issues:
Age Groups
("35+" vs. "18-34")
3.5± Pt. DIHI.
Asbestos Being Associated With
Health Problems In Schools 81% 89% +8
Aspirin Being Associated With Reye
Syndrome 75% 82% +7
Children's Toys Being Unsafe 92% 98% +6
PAGENO="0475"
469
Women "18-34" years of age, however, were somewhat more aware of "adult
safety belts in cars being unsafe for children" ("18-34," 66% and "35+,"
60% -- +6 points).
B. Education: Women who had a "some college or more" level of education were
more likely to be aware of two "child oriented" product/safety issues:
Educational Attainment
"Some College +" vs. "High
School Or Less")
High School Some
OrJess College Pt. Diff.
Asbestos Being Associated With
Health Problems In Schools 81% 90% +9
Aspirin Being Associated With
Reye Syndrome 75% 83% +8
Awareness levels show minimal differences by education attainment levels
for the remaining two issues.
C. Ageof Children: The 300 mothers in this research had a total of 367
children -- 172 "2-7" years old and 195 "8-15" years old. Women with a
child "~-15" were more aware of "asbestos being associated with health
problems in schools" than mothers with a child " 2-7" (89% versus 82%,
respectively). No other issue had a meaningful difference in awareness by
age of child.
Among those households with only one child, those households with one
child "8-15" years old were more aware than households with one child
"2-7" years old of "adult safety belts in cars being unsafe for children"
(75% vs. 62%, respectively). No other "child oriented" product/safety
Issue had a meaningful difference by age of child among one child
households.
(Please note the following table for additional details.)
PAGENO="0476"
`Have You Ever Beard Or
Head Anything About'....
Ø~fl~so's Sbys Being Unsafe 95
Asbestos Being Associated With
Health Problese In Scbools 85
Aspirin Being Associated With
Haye Syndrc~ 79
Adult Hafety Belts In Cars
Being Unsafe For Children 63
470
A~8362E83 LEVELS ~ SELEC'F ~1HSR
thildren
Sbtal Me High Sch. Hens AnyThild_ Une Child 83.
Base: (Intel Hespordents) 6eo~1i Or Less Oalleoe± 21 91~ ...2~1 9.15
(300) (139) (157) (140) (157) (172) (195) (58) (77)
% C t ~ I I I I
92
98
94
96
95
97
98
96
81
89
81
90
82
89
86
90
75
82
75
83
79
81
78
75
66
60
61
- 65
62
62
62
75
PAGENO="0477"
471
JOSEPH RAMOS INC.
114 East 32nd Street Job # 0395
New York, New York March, 1985
PUBLIC ISSUES STUDY
Hello my maine is ________________________ from JRI Research, a national
marketing research~ganizatjon. We ar~conducting a survey on public
issues and I'd like to ask you a few questions.
1. Are you the female head of the household?
Yes 1
No 2.......+(ASK TO SPEAK TO FEMALE HEAD OF HOUSEHOLD)
2. Do you have any children from two to fifteen years of age?
Yes 1
No 2.....~(TERMINATE)
3. We would like to ask you about the following health issues. (START
AT ~XtdW ITEM).
START
HERE:
Have you ever heard or read anything about asbestos being associated
with health problems in schools?
Yes 1
No 2
Have you ever heard or read anything about adult safety belts
in cars being unsafe for children?
Yes 1
No 2
~ Have you ever heard or read any~thing about aspirin being associated
with Reye Syndrome?
Yes 1
No 2
Have you ever heard or read anything about childrens' toys
being unsafe?
Yes 1
No 2
PAGENO="0478"
472
4, And just for statistical purposes, what is your age? (DO NOT READ LIST)
18-24 1
25-34 2
35-49 3
50-64 4
65 plus 5
5. What was the last grade of school you completed? (DO NOT READ LIST).
Grade school or less.. .1
Some high school 2
Completed high school. .3
Some college 4
Completed college 5
Post graduate 6
Business or special
school 7
6. How many children do you have in the following age groups? (READ
LIST, RECORD NUMBER BELOW).
2 to 4 years
5 to 7 years
8 to 10 years
11 to 13 years
14 to 15 years
Thank you for your cooperation.
RESPONDENT'S ~ZAMP..
CITY:
AREA CODE:________________
INTERVIEWER:
TIME STARTED:
DATE:
STATE: ZIP:_______
TELEPHONE NUMBER: . -
TIME ENDED:___________________
PAGENO="0479"
JOSEPH RAMOS, INC. TABLE- 1 QUESTIOH- 3
PUBLIC ISSUES STUDY
HO. 0395 MARCH, 1985 HEARD OF OR READ ABOUT
ASBESTOS BEING ASSOCIATED WITH HEALTH PROBLEMS IN SCHOOLS
CHILDREN
EDUCATION * I CHILD IH
HOUSEHOLD
COMPLE-
TED ANY ANY 1 CHILD 1 CHILD
A 0 E HIGH SOME CHILD CHILD OHLY OHLY
SCHOOL COLLEGE 2-7 8-15 2-7 8-15
TOTAL 18-34 35 + OR LESS OR MORE YEARS YEARS YEARS YEARS
BASE-TOTAL 300 139 157 140 157 172 195 58 77
RESPONDENTS 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0
YES 256 112 140 113 141 141 173 50 69
85.3 80.6 89.2 80.7 89.8 82.0 88.7 86.2 89.6
NO 44 27 17 27 16 31 22 ~ 8
14.7 19.4 10.8 19.3 10.2 18.0 11.3 13.8 10.4
DON'T KNOW/NO ANSWER
PAGENO="0480"
JOSEPH RINDS, INC. TABLE- 2 QUESTION- 3
PUBLI.C IS'~JES STUDY
NO. 0395 `RCH, 1985 HEARD OF OR READ ABOUT
ADULT SAFETY BELTS BEING UNSAFE FOR CHILDREN
CHILDREN
EDUCATION * 1 CHILD IN
HOUSEHOLD
COMPLE-
TED ANY ANY 1 CHILD 1 CHILD
A 0 E HIGH SOME CHILD CHILD OHLY ONLY
SCHOOL COLLEGE 2-7 815 2-7 8-15
TOTAL 18-34 33 + OR LESS OR MORE YEARS YEARS YEARS YEARS
BASE-TOTAL 300 139 157 140 157 172 195 58 77
RESPONDENTS 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0
YES 189 92 94 86 102 106 121 36 58
63.0 66.2 59.9 61.4 65.0 61.6 62.1 62.1 75.3
NO 111 47 63 54 55 66 74 22 19
37.0 33.8 40.1 38.6 35.0 38.4 37.9 37.9 24.7
DON'T KNOW/NO ANSWER
PAGENO="0481"
Ii
JOSEPH RAMOS, INC. TABLE- 3 QUESTION- 3
PUBLIC ISSUES STUDY
NO. 0395 MARCH, 1985 HEARD OF OR READ ABOUT
ASPIRIN BEING ASSOCIATED WITH REYE SYNDROME
CHILDREN
EDUCATION 1 CHILD IN
HOUSEHOLD
COMPLE-
TED ANY ANY 1 CHILD 1 CHILD
A G E HIGH SOME CHILD CHILD ONLY ONLY
SCHOOL COLLEGE 2-7 8-IS 2-7 8-15
-TOTAL 18-34 35 + OR LESS OR MORE YEARS YEARS YEARS YEARS
BASE-TOTAL 300 139 157 140 157 172 195 58 77
RESPONDENTS 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0
YES 236 104 128 105 130 136 157 45 58
78.7 74.8 81.5 75.0 82.8 79.1 80.5 77.6 75.3
NO 64 35 29 35 27 36 38 13 19 -.1
21.3 25.2 18.5 25.0 17.2 20.9 19.5 22.4 24.7 Cli
DON'T KNOW/NO ANSWER
PAGENO="0482"
JOSEPH RAMOS, INC. TABLE- 4 QUESTION- 3
PIBLIC ISSUES STUDY
HO. 0395 MARCH, 1985 HEARD OF OR READ ABOUT
CHILDREN'S TOYS BEING UNSAFE
CHILDREN
EDUCATION 1 CHILD IN
HOUSEHOLD
- COMPLE-
TED ANY ANY 1 CHILD 1 CHILD
A 0 E HIGH SOME CHILD CHILD ONLY ONLY
SCHOOL COLLEGE 2-7 8-15 2-7 8-15
TOTAL 18-34 35 + OR LESS OR MORE YEARS YEARS YEARS YEARS
BASE-TOTAL 300 139 157 140 157 172 195 58 77
RESPONDENTS 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0
YES 286 128 154 132 151 163 189 57 74
95.3 92.1 98.1 94.3 96.2 94.8 96.9 98.3 96.1
NO 14 11 3 8 6 9 6 1 3
4.7 7.9 1.9 5.7 3.8 5.2 3.1 1.7 3.9
DON'T KNOW/HO ANSWER
PAGENO="0483"
JOSEPH RAMOS, INC. TABLE- 5 QUEStION- 4
PUBLIC ISSUES STUDY
NO. 0395 MARCH, 1985 AGE
CHILDREN
EDUCATION 1 CHILD IN
` HOUSEHOLD
COMPI E-
TED ANY ANY 1 CHILD 1 CHILD
A G E HIGH SOME CHILD CHILD ONLY ONLY
SCHOOL COLLEGE 2-7 8-15 2-7 8-15
TOTAL 18-34 35 + OR LESS OR MORE YEARS YEARS YEARS YEARS
BASE-TOTAL 300 139 157 140 157 172 195 58 77
RESPONDENTS 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0
18-24 14 14 10 4 14 10
4.7 10.1 7.1 2.5 8.1 17.2
25-34 125 125 60 64 103 56 35 9
41.7 89.9 42.9 40.8 59.9 28.7 60.3 11.7
35-49 145 145 60 83 50 125 11 58
48.3 92.4 42.9 52.9 29.1 64.1 19.0 75.3
50-64 10 10 7 3 3 8 2 7
3.3 6.4 5.0 1.9 1.7 4.1 3.4 9.1
65PLUS 2 2 1 1 1 2
.7 1.3 .7 .6 .6 1.0
NOANSWER 4 2 2 1 4 3
1.3 1.4 1.3 .6 2.1 3.9
MEAN... 36.42 28.64 43.31 36.01 36.77 33.18 39.26 31.35 41.90
STANDARD 8.29 2.56 4.75 9.01 7.61 7.81 7.48 8.05 6.34
DEVIATION
STANDARD .48 .22 .38 .77 .61 .60 .54 1.06 .74
ERROR
PAGENO="0484"
JOSEPH RAMOS, INC. TABLE- 6 QUESTION- 5
PUBLIC ISSUES STUDY
NO. *3~5 MARCH, 1985 EDUCATION
EDUCATION 1 CHILD IN
HOUSEHOLD
COMPLE-
TED ANY ANY 1 CHILD 1 CHILD
A 0 E HIGH SOME CHILD CHILD ONLY ONLY
SCHOOL COLLEGE 2-7 8-15 2-7 8-15
TOTAL 18-34 35 + OR LESS OR MORE YEARS YEARS YEARS YEARS
300 139 157 140 157 172 195 58 77
110.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0
8 3 5 8 4 6 3
2.7 2.2 3.2 5.7 2.3 3.1 3.9
28 13 14 28
9.3 9.4 8.9 20.0
104 54 49 104
34.7 38.8 31.2 74.3
69 32 36
23.0 23.0 22.9
63 32 30
21.0 23.0 19.1
25 4 21
8.3 2.9 13.4
3 1 2
1.0 .7 1.3
CHILDREN
BASE-TOTAL
RESPONDENTS
GRADE SCHOOL
OR LESS
SOME HIGH
SCHOOL
COMPLETED
HIGH SCHOOL
SOME COLLEGE
COMPLETED
COLLEGE
POST GRADUATE
BUSINESS OR
SPECIAL SCHOOL
17 17 8 8
9.9 8.7 13.8 10.4
60 67 20 26
34.9 34.4 34.5 33.8
69 43 47 14 16
43.9 25.0 24.1 24.1 20.8
63 35 36 15 15
40.1 20.3 18.5 25.9 19.5
25 11 20 1 8
15.9 6.4 10.3 1.7 10.4
2 2 1
1.2 1.0 1.3
NO ANSWER
PAGENO="0485"
JOSEPH RAMOS, INC. TABLE- 7 QUESTIOH- 6
PUBLIC ISSUES STUDY
HO. 0395 MARCH, 1985 NUMBER OF CHILDREN IN FOLLOWING AGE GROUP
2 - 4 YEARS
CHILDREN
* EDUCATION 1 CHILD IN
` HOUSEHOLD
CO1PLE-
TED ANY ANY 1 CHILD 1 CHILD
A 0 E HIGH SOME CHILD CHILD ONLY ONLY
SCHOOL COLLEGE 2-7 8-15 2-7 8-15
TOTAL 18-34 35 + OR LESS OR FIORE YEARS YEARS YEARS YEARS
BASE-TOTAL 300 139 157 140 157 172 195 58 77
RESPONDENTS 100~0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0
NONE * 176 47 125 85 89 50 157 17 77
58.7 33.8 79.6 60.7 56.7 29.1 80.5 29.3 100.0
1 105 75 30 45 60 105 33 41
35.0 54.0 19.1 32.1 36.2 61.0 16.9 70.7
2 14 13 1 8 5 14 3
4.7 9.4 .6 5.7 3.2 8.1 1.5
3 * 3 2 1 2 1 3 2
1.0 1.4 .6 1.4 .6 1.7 1.0
4
5.
7 OR MORE
NO AHSLJER 2 2 2
.7 1.4 1.3
MEAN... . .48 .78 .22 .48 .47 .83 .23 .71
STANDARD .63 .67 .47 .66 .59 .63 .51 .45
DEVIATION
STANDARD .03 .05 .03 .OS .04 .04 .03 .05
ERROR
PAGENO="0486"
~IOSEPH RAPIDS, INC. TABLE- 8 QUESTION- 6
PUBLIC ISSUES STUDY
NO. 0395 MARCH, 1985 NUMBER OF CHILDREN IN FOLLOWING AGE GROUP
5 -7 YEARS
CH IL DR EN
EDUCATION - - 1 CHILD IN
HOUSEHOLD
COMPLE-
TED ANY ANY 1 CHILD 1 CHILD
A 0 E HIGH SOME CHILD CHILD ONLY ONLY
SCHOOL COLLEGE 2-7 8-15 2-7 8-15
TOTAL 18-34 35 + OR LESS OR MORE YEARS YEARS YEARS YEARS
BASE-TOTAL 300 139 157 140 157 172 195 58 77
RESPONDENTS 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0
NONE 203 76 124 95 106 77 152 41 77
67.7 54.7 79.0 67.9 67.5 44.8 77.9 70.7 100.0
1 81 55 25 39 41 81. 36 17
27.0 39.6 15.9 27.9 26.1 47.1 18.5 29.3
2 13 5 8 6 7 13 6
4.3 3.6 5.1 4.3 4.5 7.6 3.1
3 1 1 1 1 1
.3 .7 .6 .6 .5
4
S
6
7 OR MORE
NOANSWER 2 2 2
.7 1.4 1.3
MEAN... .37 .50 .26 .36 .37 .64 .26 .29
STANDARD .58 .60 .54 .56 .60 .64 .53 .45
DEVIATION
STANDARD .03 .05 .04 .04 .04 .04 .03 .06
ERROR
PAGENO="0487"
JOSEPH RAMOS, INC. TABLE- 9 QUESTION- 6
PUBLIC ISSUES STUDY
HO. 0395 MARCH, 1905 NUMBER OF CHILDREN IN FOLI.OWING AGE GROUP
8 - 10 YEARS
CH IL DR EN
EDUCATION 1 CHILD IN
` HOUSEHOLD
COHPLE-
TED ANY ANY 1 CHILD 1 CHILD
A G E HIGH SOME CHILD CHILD ONLY DIlLY
SCHOOL COLLEGE 2-7 8-15 2-7 8-15
TOTAL 18-34 35 + OR LESS OR MORE YEARS YEARS YEARS YEI~RS
BASE-TOTAL 300 139 157 140 157 172 195 58 77
RESPONDENTS 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0
HONE 206 100 103 97 107 126 103 58 61
68.7 71.9 65.6 69.3 68.2 73.3 52.8 100.0 79.2
1 83 33 49 41 41 40 83 16
27.7 23.7 31.2 29.3 26.1 23.3 42.6 20.8
2 9 4 5 2 7 6 9
3.0 2.9 3.2 1.4 4.5 3.5 4.6
7 OR MORE
NO ANSWER 2 2 2
- .7 1.4 1.3
MEAN...* .34 .30 .38 .32 .35 .30 .52 .21
STANDARD .53 .51 .54 .49 .56 ~53 .58 .40
DEVIATION
STANDARD .03 .04 .04 .04 .04 .04 .04 .04
ERROR
PAGENO="0488"
JOSEPH RAPIDS, INC. TABLE- 10 QUESTIOH- 6
PUBLIC ISSUES STUDY
NO. 0395 MARCH, 1985 NUMBER OF CHILDREN IN FOLLOWING AGE GROUP
11 - 13 YEARS
CHILDREN
EDUCATION 1 CHILD IN
` HOUSEHOLD
COMPLE-
TED ANY ANY 1 CHILD 1 CHILD
A G E HIGH SOME CHILD CHILD ONLY ONLY
SCHOOL COLLEGE 2-7 8-15 2-7 8-15
TOTAL 18-34 35 + OR LESS OR MORE YEARS YEARS YEARS YEARS
BASE-TOTAL 300 139 157 140 157 172 195 58 77
RESPONDENTS 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0
NONE 206 114 90 102 101 148 103 58 46
68.7 82.0 57.3 72.9 64.3 86.0 52.8 100.0 59.7
1 81 19 61 29 52 22 81 31
27.0 13.7 38.9 20.7 33.1 12.8 41.5 40.3
2 9 2 6 7 2 1 9
3.0 1.4 3.8 5.0 1.3 .6 4.6
3 2 2 2 1 2
.7 1.4 1.4 .6 1.0
4.
5
7 OR MORE
NO ANSWER 2 2 2
.7 1.4 1.3
MEAN... .35 .21 .46 .35 .36 .16 .54 .40
STANDARD .57 .53 .57 .64 .50 .42 .63 .49
DEVIATION
STANDARD .03 .04 .04 .05 .04 .03 .04 .05
ERROR
PAGENO="0489"
JOSEPH RAMOS, INC. TABLE- 11 QUESTION- 6
PUBLIC ISSUES STUDY
NO. 0395 MARCH, 1935 NUMBER OF CHILDREN IN FOLLOWING AGE GROUP
14 - 15 YEARS
CHILDREN
EDUCATION 1 CHILD IN
, HOUSEHOLD
COMPLE-
TED ANY ANY 1 CHILD 1 CHILD
A 0 E HIGH SOME CHILD CHILD ONLY ONLY
SCHOOL COLLEGE 2-7 8-15 2-7 8-15
TOTAL 18-34 35 + OR LESS OR MORE YEARS YEARS YEARS YEARS
BASE-TOTAL 300 139 157 140 157 172 195 58 77
RESPONDENTS 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0
NONE 223 127 94 105 117 153 120 58 47
74.3 91.4 59.9 75.0 74.5 89.0 61.5 100.0 61.0
1 72 10 60 33 37 18 .72 30
24.0 7.2 38.2 23.6 23.6 10.5 36.9 39.0
2 3 3 2 1 1 3
1.0 1.9 1.4 .6 .6 1.5
3
4
5
7 OR MORE
NO ANSWER 2 2 2
- .7 1.4 1.3
MEAN... : .26 .07 .42 .26 .25 .12 .40 .39
STANDARD .46 .26 .53 .47 .44 .33 .52 .48
DEVIATION
STANDARD .02 .02 .04 .04 .03 .02 .03 .05
ERROR .
PAGENO="0490"
484
Aspkmn Foundation of America, Inc.
1075 Central Park Avenue. Scarsdale, N.Y. 10583 * (914)725-1492
ASPIRIN FOUNDATION OF AMERICA
VOLUNTARY PRECAUTIONARY PROGRAM
PROGRESS REPORT
April 10, 1985
This Progress Report is being filed with the House
Energy and Commerce Subcommittee on Health and the Environment in
response to questions raised at the Subcommittee's March 15, 1985
hearing on H.R. 1381, the "Emergency Reye's Syndrome Prevention
Act of 1985."
The Aspirin Foundation of America has responded to
Secretary of Health and Human Services Margaret Heckler's request
for voluntary efforts to advise the public about Reye Syndrome
with a three-part precautionary program. This program has been
undertaken in the absence of scientifically sound data showing a
link between aspirin and Reye Syndrome, but in a spirit of coop-
eration with the Department of Health and Human Services, while
the underlying scientific questions remain unanswered.
The program encompasses three elements: label warnings
and other label modifications, public service announcements and
posters. Substantial progress has been made in each area.
A. Label Revisions
All members of the Foundation and major producers of
private label aspirin either have changed or are in the process
of changing their labels.
PAGENO="0491"
485
In addition to the label changes discussed in testimony
filed with the Subcommittee (2.2.' the new warning and the dele-
tion of the flu indication for children's aspirin), producers
will also "flag" the new label in accordance with the Proprietary
Association guidelines.
A large number of label changes are required by the
program. One company alone is making approximately 75 discreet
label changes. Among the steps being taken is the destruction of
old labeling by several companies, in order to expedite the
shipment of the new labels.
Companies are moving expeditiously to implement the
changes. Several producers have already made the modifications.
For others the changes are in progress. For some products,
shipment with old labels will end in April or May, 1985. Because
of shipment and purchasing schedules, some products will be
shipped with revised labels in the early fall 1985. By the start
of the flu season, however, all new products shipped will bear
the new labels.
B. Public Service Announce ents
The Foundation, with the ~~SS9~ of the American
Reye's Syndrome Association, the Reye's Syndrome Society and the
National Reye's Syndrome Foundation, produced and distributed two
television public service announcements (PSA's) and two radio
PSA's. More than 1,000 copies have been distributed to televi-
sion and radio stations nationwide.
PAGENO="0492"
486
The Foundation has specifically surveyed usage of the
television PSA's and found an extremely high success rate. Calls
were made to 168 television stations in the top 50 markets.
These calls revealed that in every market at least one TV station
(and in most cases several) is airing or has plans to air a Reye
Syndrome PSA. The following responses were received:
TABLE A
Actual No. % of Total
Responses of Stations Responding
Currently airing or plan
to air PSAs *120 72%
Will review and consider
airing 15 9.8%
Cannot locate spots (Foundation
has re-mailed) 18 11.76%
Will not air PSA5 due to
controversy 10 6.5%
Will not air PSAs due to
scheduling load 5 3.27%
* Includes 3 stations producing their own version of the PSA5.
It is highly unusual to experience a success rate as
high as 72% for the airing of PSA5. The Foundation believes that
its PSA program, supplementing the already extensive government
program, has been remarkably successful.
C. Posters
To supplement the initial distribution of 100,000 pos-
ters, the Foundation used a national information network called
PAGENO="0493"
487
Pharm/alert to mail the poster to 60,000 pharmacists on March 9,
1985. In addition, the Foundation mailed the poster to 35,000
supermarkets on March 12, 1985.
When combined with posters prepared by FDA and private
parties, the Foundation's posters are achieving extremely wide
visibility.
D. Success of Education Program
To measure the success of these ongoing efforts, an
independent New York-based research firm conducted a "consumer
awareness" survey in early March 1985.
A national probability sample of 300 women with at least
one child between 2 and 15 years of age was identified. The
respondents were interviewed by telephone.
The major issue of concern for the study was awareness
of "aspirin being associated with Reye Syndrome." However, to
provide a basis for comparison, three other issues were presented,
with the order of presentation rotating among all four questions.
The other issues included: "asbestos being associated with
health problems in schools," "adult safety belts in cars being
unsafe for children," and "children's toys being unsafe." The
following table summarizes the survey results:
PAGENO="0494"
488
AWARENESS OF SELECT "CHILD ORIENTED"
PRODUCT/SAFETY ISSUES
Total
Awareness
Base: (Women With a Child 2-15) (300)
%
"Have You Ever Heard or Read
Anything About"....
Children's Toys Being Unsafe 95
Asbestos Being Associated with
Health Problems In Schools 85
Aspirin Being Associated with
Reye Syndrome 79
Adult Safety Belts In Cars Being
Unsafe For Children 63
It should be apparent that the education program is
working well. The 79 percent awareness for aspirin and Reye
Syndrome raaks along with other "high visibility" issues, such as
asbestos in schools. Clearly, the public is aware of the
reported association.
Conclusion
The purposes of H.R. 1381 -- to obtain warnings on
aspirin labels and to educate the public to a possible associa-
tion between aspirin and Reye Syndrome -- are already being
accomplished. Labels are being revised expeditiously. In the
meantime, the public is acquiring widespread general awareness of
the possible association. Clearly, H.R. 1381 is unwarranted.
Respectfully submitted,
THE ASPIRIN FOUNDATION OF AMERICA, INC.
By: ~
Jc~'ephfr1. White, .D.
P~es ident
Of Counsel:
R. Bruce Dickson
Paul, Hastings, Janofsky & Walker
1050 Thomas Jefferson Street
Washington, D.C. 20007
(202) 333-8500
PAGENO="0495"
489
Mr. WAXMAN. Excuse me for interrupting.
Dr. WHITE. But I think that this is a valuable thing. The reason
why we started a three-pronged program is because we are con-
cerned that not any one of them might be sufficient, and I think
that the Commissioner shares that concern, that not everybody
reads the label on the bottle every time one picks it up.
There are also many other warnings that are very important,
and we wouldn't want to totally eclipse that, so maybe they need to
be kept in some level of equality.
In the meantime, you can isolate attention to Reye's Syndrome
by going through the public service announcements and going
through posters at the point of sale.
The advantage of the public service announcements is that PSA's
get right to the person who is going to make the choice and make
the decision, and if you get them to hear and get them to under-
stand it, they will make an intelligent choice.
The advantage of the poster is it is at the point of sale. It is at
the point of sale, and it is in big print instead of somebody having
to stand and read through all the fine print that might be on vari-
ous packages.
We also would like to indicate that there are a number of people
who need to take aspirin. The question was raised, just don't give
aspirin to children.
Children who suffer from juvenile rheumatoid arthritis take as-
pirin and they take it in high quantities, and they have to take it
for many, many years. It is interesting to know that those children
have no more Reye's Syndrome than any other children.
The other thing that has happened is that the flaws `in all of the
previous studies that have been done, all were found in the raw
data, and how that was interpreted and how that was gathered.
And we are still concerned that, for example, the pilot study, we
have not seen that raw data, so that we have really no way of eval-
uating how valid that study might be, and we ask again that we
get that opportunity.
We also know that this pilot study was meant to be a prelimi-
nary study, that they made changes in the study during the oper-
ation.
It was really a feasibility study to try to learn how to do the
major study, and I think that from a scientific point of view that
major study is extremely important now, because we really need to
know whether there is a connection.
And if there is, to deal with it appropriately. If there is not a
connection, then we know we have to go back and try to find out
what the connection might be, with something else or perhaps this
is a spontaneous event in these children.
It is interesting, too, that the original position of the Institute of
Medicine, who is the monitoring committee, specifically said that
the pilot study will in no way be interpreted as being conclusive
evidence, and that the chairman of that committee, whose name
has already been mentioned here today, Dr. Floyd Denney, advised
the FDA that the pilot study did not provide a basis for mandatory
labeling.
PAGENO="0496"
490
They do not feel that they have learned what they need to learn
in order to demand that a mandatory labeling procedure be carried
out.
Because mandatory labeling was not supported, Secretary Heck-
ler called for voluntary action. This call for voluntary action was a
surprise to us, too, and I thought it was interesting that every
member agreed to do it. There was hardly a hesitation. It went to
the management and they were back again immediately, saying
yes, go see the people, see what they want, and see what we can do
to answer their questions.
And we feel that we have done that. We have a three-phase pro-
gram. We have gone to public service announcements, we have
gone to postering, and we have instituted the label changing.
We were not asked, there was not to be a recall. We were not
asked to reach the shelf. The way to reach the shelf is to put the
poster in the store, and the way to reach even beyond that is to put
the public service announcements in the ears and eyes of the con-
sumers, so that they have the message already.
You don't have to depend on their getting it by chance. During
the past week we have made another effort beyond the original
posters.
In the original poster program, 100,000 of them were sent out
through various channels. Just the other day, there were 95,000
more posters sent out directly to pharmacists and to food stores.
And one of the things we did was to take advantage of an organi-
zation which is called Pharmalert, and ohe of the things which
they do is to call attention to the pharmacist when there is some-
thing that he needs to know to advise the customers, and so forth,
and it says here, on the envelope: "Special Reye's Syndrome Alert
From the Aspirin Foundation of America."
We had 95,000 of these sent out just the other day, again an indi-
cation we have to read this as we go along, and see what the pene-
tration is, and what the accomplishment is.
I am happy to be here and to have this opportunity to comment.
I feel that the scientific justification for passing a law is just not
there at this time. We do have a program. We do believe it will
work.
We hope it will be measured, and an opportunity given to maybe
learn better ways of doing it, if there are better ways to do it in the
future, and we do ask your support. We volunteer to report to you
and give any any additional information you would want to know
from what we may gather as time goes by, and as we see this pro-
gram actually bloom and come to full fruition.
Thank you very much.
[Testimony resumes on p. 518.]
[The prepared statement of Dr. White follows:]
PAGENO="0497"
491
STATE~NT OF
JOSEPH M. WHITE, M.D.
P RES I DENT
ASP IRIN FOUNDATION OF A~ RI CA
Good morning Mr. Chairman and members of the Subcommit-
tee. My name is Dr. Joseph M. White. I am a physician and a
pharmacologist and I am appearing before you today as President
of the Aspirin Foundation of America. With me is R. Bruce
Dickson, counsel to the Foundation.
The Aspirin Foundation is the trade association of the
aspirin industry. Its members include all the producers of bulk
aspirin and all the major producers of finished aspirin products
in the United States. The Foundation was organized several years
ago to facilitate and encourage an understanding of the benefits
and potential health effects of aspirin based upon sound data and
good science.
During the past three years, the Foundation has taken a
leading role in urging that a sound epidemiology study be con-
ducted into the etiology of Reye Syndrome and that regulatory
decision-making on this matter, if it is needed, be based upon
good science.
We are here today to urge this Subcommittee to listen to
the scientists, who tell us that there is not sufficient scien-
tific justification for mandatory labeling. We are also here to
ask you to take a fair look at the voluntary industry program and
to give it a reasonable chance to accomplish its objectives
before passing judgment.
Mplrln In Perspective
To put this matter in the proper perspective, the Sub-
committee must first consider the background of aspirin use.
PAGENO="0498"
492
Since the late 19th century, or for over one hundred years,
acetylsalicylic acid, which acquired the trade nane ~aspirin,~
has become widely used to reduce fever and to relieve pain and
inflammation. Aspirin is now by far the most widely used over-
the-counter medication ingredient in the United States and in the
world. Nearly 19 billion dosage units are sold annually.-21
The efficacy of aspirin has been soundly established
through its long history of use. As an antipyretic, aspirin has
no equal in terms of its many years of safe and effective use
around the world. The Internal Analgesic Monograph cited forty-
three studies showing the effectiveness of aspirin in reducing
pain. It noted that aspirin is often used as the standard
against which new drugs are compared for efficacy.
With regard to safety, the Internal Analgesic Panel
stated:
[A]spirin is the most widely used single drug
in the United States. The Panel believes that
in light of this extensive use and long mar-
keting history and the relatively low mci-
*dence of serious toxic effects associated with
short term use of presently recommended doses,
the safety of aspirin has been well-estab--
lished for the majority of the ~opulation and
the risk benefit ratio is low."...1
1/ Establishment of a Monograph for OTC Internal Analgesic,
- Antipyretic and Antirhetm~atic Products ("Internal Analgesic
Monograph"), 42 . ~ 35346, 35382 (July 8, 1977).
~J Id. at 35383.
PAGENO="0499"
493
Before considering legislation, then, the Subcommittee
must recognize the impressive record that aspirin has created
through its long and widespread use as a safe and effective drug
for the relief of pain and inflammation and the reduction of
fever.
SUMMARY OF ASPIRIN FOUNDATION'S POSITION ON H.R. 1381
The Aspirin Foundation opposes H.R. 1381. The bill is
without scientific support, and, in view of the ccmprehensive
efforts of the Secretary of Health and Hwnan Services, the Food
and Drug Administation, Reye Syndrane parents groups, the news
media and the Aspirin Foundation, it is entirely unnecessary.
First, H.R. 1381 must be viewed in the
context of our current knowledge of Reye
Syndrane and medications. While the bill
is purported to be based upon several
Reye Syndrane studies, in fact it was
prompted by the preliminary field work
(the ~pilot~ study) performed in prepara-
tion for the upcoming national Reye
Syndrome study. Thus, we really do not
yet have any scientific data upon which
to base mandatory regulation.
PAGENO="0500"
494
-- Second, in view of the limited nature of
the available information, the Secre-
tary's call for voluntary action was the
most appropriate and the most expeditious
way to obtain label warnings and an
* industry-sponsored public education
program without first having to complete
a comprehensive epidemiology study. As
you know, the industry responded promptly
to the Secretary's callfor voluntary
action.
-- Third, the voluntary precautionary pro-
gram represents a responsible industry
effort to minimize possible risk while
the underlying question of a possible
medication link with Reye Syndrome is
being studied, and in fact goes well
beyond what could have been mandated if
sufficient data existed.
-- Fourth, the proposed legislation would
result in a warning statement that is
seriously false and misleading, that will
scare the public away fran a valuable
PAGENO="0501"
495
medication and that will lead parents to
ignore the early symptoms of Reye Syn-
drane.
A. There is Insufficient Scientific Justification
for Mandatory Label Warnings.
At the present time, there are no sound epidemiology
studies which provide evidence linking aspirin use for chicken
pox or flu with Reye Syndrome. Early state surveys, which were
etmunarized by the American Academy of Pediatrics Redbook Commit-
tee, were severely discredited by scientists from P~, academia,
the medical community, and industry. Because of the flaws in
those surveys, the Secretary of Health and Htznan Services decided
to conduct a new, comprehensive study. That new study was pre-
ceded by preliminary methodologic research, which has now been
completed and which cannot possibly provide a basis for the
conclusion that aspirin is in fact associated with Reye Syndrome.
1. The early state surveys were flawed.
Reye Syndrome is an extremely rare childhood condition
that can follow chicken pox or influenza. Because of its low
incidence, possible causes can be identified only through the
case-control method of epidemiologic research. Case-control
studies are extremely difficult to design and, if not properly
planned, can produce an ~association" that is merely a function
of the study design. Such a ~false association" will, of course,
PAGENO="0502"
496
be repeated in any subsequent study that incorporates the faulty
design.
The early state surveys were challenged because of
design flaws that could have caused the reported aspirin associa-
tion. FDA scientists reviewed the raw data from the state sur-
veys and identified serious flaws in each survey. They rejected
nearly all of the data because of basic flaws commonly found in
poorly designed case-control studies.
FDA recently summarized its view of the state surveys
and their many flaws in a document filed in federal court. It
stated:
~The uncertainty about the adequacy of
the four epidemiologiCal studies on Reye
Syndrome is reflected not only in the dis-
agreement among prominent and qualified
experts, but also in the scientific studies
themselves. While the agency emphasizes that
it does not consider all of the studies to be
scientifically invalid, there are deficiencies
in the design and implementation of the
studies that lessen the confidence that can be
placed in the results of the studies. These
prominent deficiencies include the following:
(I) lack of formal protocols defining the
study rules;
(2) lack of comparability between cases and
controls as to time between illness onset
and interview;
(3) lack of consistent and comparable verif i-
cation of medication brand names and
recording information from labels;
(4) lack of data collection and analysis in
such a way as to be confident that the
medications were being used for the
treatment of the antecedent illness
rather than Reye Syndrome;
PAGENO="0503"
497
(5) lack of sufficient characterization of
the antecedent illnesses to demonstrate
that the controls had illnesses of sever-
ity comparable to that of the antecedent
illnesses in the cases;
(6) reliance on school absentee lists to
generate matched controls with the conse-
quent underrepresentation of pre-school
children and chickenpox associated cases
(which has peak incidence in late spring
and summer); and
(7) lack of adequate precision in disease
diagnosis to be confident that all cases
truly had Reye's Syndrome.
The agency is also aware that the reported
association between Reye Syndrome and salicy-
lat'~s might be explained by the use of salicy-
lates for treatment of the symptoms of Reye
Syndrome. Although this hypothesis has not
been proven, neither has it been ruled out.~
Defendants' Answers to Plaintiffs' Interroga-
tories and Document Production Request, ERG V.
Young, Civil Action No. 82-1346 (D.D.C.,
October 30, 1984).
The PDP~ list of flaws in the studies is a catalogue of errors,
any of which would be grounds for totally rejecting the studies.
These flaws did not go unnoticed in the medical commun-
ity. In November 1982 the American Academy of Pediatrics trans-
mitted the following statement from its Executive Board to the
Assistant Secretary for Health:
`In June, 1982, the American Academy of Pedi-
atrics published a statement by the Committee
on Infectious Diseases alerting pediatricians
to the possible association of aspirin admin-
istration and Reye's Syndrome. We stated
them, and continue to believe, that there
should be cautious use of any antipyretic
medication in the treatment of influenza or
chicken pox. However, at the present time, we
PAGENO="0504"
498
do not feel that labeling aspirin-containing
preparations as being contraindicated in these
illnesses is in the best interest of children
or the practice of pediatrics. We believe
labeling should be delayed until more conclu-
sive evidence of the association of aspirin
administration and Reye's Syndrome is shown by
further investigation. We urge that support
be provided as soon as possible for appro-
priate investigators, including government
agencies, to address this important question."
Thus, before the new study was begun, there was vir-
tually unanyinous agreement ~nong the scientific and medical
experts who reviewed the state surveys: The surveys could not be
used to justify mandatory label warnings.
2. The preliminary field work for the
new national Reye Syndrome study cannot
support mandatory label warnings.
Because of the inadequate data base, the Departhent
created a Task Force of scientists from the Centers for Disease
Control, FDA and the National Institutes of Health ("PBS Task
Force") to design and conduct a nation-wide study of Reye Syn-
drane and its possible link with medications. To provide over-
sight for the study, the Public Health Service engaged the Insti-
tute of Medicine ("IOM") of the National Academy of Sciences.
tOM created a committee of pediatricians, epidemiologists and
other professionals to review the protocol and the results.
The PBS Task Force initially proposed to begin the new
study in November 1983. The IOM Committee rejected this sugges-
tion, however, noting that
PAGENO="0505"
499
the task force is not sufficiently prepared
to start an epidemiologically sound investi-
gation by the suggested November 1983 date.
It is recommended that the present proposal
and questionnaires be revised and resubmitted
for review by this Institute of Medicine
committee. When the proposal is final, ~
liminar field work should be undertaken to
resolve the uncertainties of study design and
feasibility. Only upon completion of the
preliminary studies will the task force be
prepared to embark on a national study of ~.
* * *
RGeneral Level of Preparedness
It is the committee's judgment that the
task force will be unable to begin the study
in November 1983 as proposed. The reasons for
this conclusion are as follows. There remain
a number of unresolved study design issues
that call for further exploration and planning
by the Task Force. . . . Whether or not
outside personnel are recruited to carry out
the study, there will need to be a period of
training of staff members in the procedures of
case ascertainment, control, and interview-
ing. The committee recommends strongly that a
preliminary, or pilot, study be conducted to
determine the feasibility of control selection
and data collection and to pre-test the ques
tionnaires. It is not conceivable that these
activities cm be completed satisfactorily in
time for a November 1983 study commencement
date.R (An Initial Evaluation of the PES
Study of the Reye Syndrome, Institute of
Medicine, September 1983, at 10, 24-25;
emphasis added.)
The IOM Committee thus concluded that preliminary field
work .had to be completed before the study could begin. What
began in November 1983 was not the new national study that had
been proposed. Indeed, that national study did not begin until.
this winter. The study that began in November 1983 and that
produced the 29 cases cited by proponents of fl.R. 1381 was merely
PAGENO="0506"
500
the preliminary field work or feasibility study recommended by
TOM prior to the start of the new national study.
In its second report, TOM reiterated the need for a
separate investigation in preparation for the proposed national
study. It stated:
"Pilot Study
The Task Force has responded appropri-
ately to the Committee's earlier suggestion by
recognizing the necessity of conducting a
p~lot study in preparation for the proposed
investigation. The committee's general recom-
i~èndation now is that, during the pilot study,
the investigators should focus their greatest
efforts on establishing the feasibility of the
various case ascertainment and control selec-
tion mechanisms, and on developing a valid and
reliable questionnaire. The principal product
of the pilot study should be a report that
describes and summarizes the relative
strengths and weaknesses of the various
options for case detection, control selection,
questionnaire administration, and data collec-
tion. Such a document will serve as the
objective basis for the decisions that are
made about the final study protocol." The PHS
Study of the Reye Syndrome: Ccmntents on the
Revised PHS Protocol, Institute of Medicine,
March 1984, at 2-3; esphasis added.
In its third report, following the completion of the
pilot work, the TOM Committee recommended that the national study
be started, importantly with several significant protocol
changes. Specifically, the TOM Committee recommended that the
study sample be increased to about 250 case-control sets, in
order to evaluate various subgroups. (The PBS Study of the Reye
Syndrome: Comments on the Revised PBS Protocol as a Result of the
Pilot Study, Institute of Msdicifle, September 1984 at 3.) The
PAGENO="0507"
501
Committee recommended that that the Task Force derive indices of
severity f or three types of prodranal illnesses to ensure that
cases and controls are matched in terms of the severity of their
illness. The Committee also recommended several other changes
and, with regard to the medication results, stated:
`It should be emphasized, however, that the
pilot study results of comparisons of me~T~a-
t[on use between cases and controls will in no
way be interpreted as conclusive evidence for
or against an etiologic role of medication use
on the risk of RS.' (Id. at 10; emphasis
added.)
Following the release of this report, Westat, the prin-
cipal contractor for the PBS study, released its final report on
the pilot study. It confirmed the limited purpose for which the
pilot work was conducted:
`This pilot test was conducted to deter-
mine if a larger study to assess the possible
relationship between medications and Reye
Syndrome was methodologically feasible.' (Reye
Syndrome Pilot Study Final Report, Westat, at
13-1.)
Finally, in January 1985, the IOM Committee issued its
most recent report, which has been cited as the basis for H.R.
1381. While the Cctnmittee recommended that precautionary steps
be taken before the full study is completed, it also recognized
the limitations in the preliminary study. It stated:
`[Ms the committee has noted in previous
reports, pilot studies generally are not used
f or drawing conclusions but rather for giving
direction and assessing the feasibhity of
PAGENO="0508"
502
carrying out a larger study. Most important,
all objectives of the proposed PBS study have
not been met in the pilot effort; important
public health questions remain to be con-
si dered.
"Questions can and will be raised by some
observers about the pilot study findings. The
pilot study data suffer from changes in met-
hods during its conduct and the limitation of
a small and geographically limited sample.
Data fran the full study are needed to deter-
mine if the pilot study findings are reli-
able. Because of uncertainties characteristic
of observational studies, ideally a number of
studies should be available to corroborate
scientific findings. More information on RS
and use of medication is required to guide
both clinical practice and public health
measures." (The PBS Study of the Reye Syn-
drome: Recommendations Based on a Review of
the Pilot Study Data, Institute of Medicine,
January 1985, at 3.)
Since the release of the IOM January 1985 report, it has
been revealed that FDA was advised by Dr. Floyd Denny, Chairman
of the tOM Committee, that the pilot data did not provide a basis
for mandatory labeling. At the deposition of Dr. Harry Meyer,
Director of FDA's Center for Drugs and Biologics, BRG's attorneys
asked about an FDA meeting in January 1985 with the American
Academy of Pediatrics and Dr. Denny, as a representative of the
tOM Committee. Dr. Meyer testified:
"So, I was rather suprised when tDr. Denny]
then followed that by saying that he wanted to
be sure that people knew where he was because
he certainly didn't feel that the data was a
basis for mandatory labelling. Which is an
example of what I give as the ambivalence of
the scientific community on this matter."
(BRG v. Youj~g, Civil Action No. 82-1346,
Dè~sition of HarryM. Meyer, Jr., M.D.,
February 12, 1985, at 111.)
PAGENO="0509"
503
When the pilot study is viewed, as it must be, as merely
the preliminary field work in preparation for the national Reye
Syndrome study now being commenced by the Public Health Service,
it becomes clear that the pilot study cannot be used as the basis
for a regulation requiring aspirin label warnings. It should be
clear to this Subcommittee that, the preliminary field work also
cannot be used as the basis for legislation.
B. Because. of the Limited Nature of the Data, the
Call for Voluntary Action Was the Only Course
Realistically Available to the Secretary.
The proposed legislation is premised on the claim that
FDA should have regulated, but has neglected to do so. In fact,
FDA has cccmtenced a regulatory proceeding to determine whether
label warnings should be required.V In conjunction with that
proceeding, FDA has concluded that conducting a well-designed
study is necessary in order to provide a scientific basis for
deciding whetheradoption of mandatory label warning requirements
is warranted. In short, a regulation requiring label warnings
could not be supported by the current information base. There-
fore, voluntary action was the only course realistically
available to the Secretary.
~ See 47 Fed. ~g. 57886 (December 28, 1982). In addition, a
petitiorEy `~Tii Public Citizen Health Research Group
requesting that advertisements for aspirin products be required
to contain a warning concerning Reye's Syndrome is currently
pending before the Federal Trade Ccmmission. The FTC staff has
indicated it will review the content of current aspirin
advertising.
PAGENO="0510"
504
A major proponent of H.R. 1381, Health Research Group
("HRG"), filed a lawsuit in 1982 seeking to compel FDA to impose
a warning requirement on aspirin. Judge John Garrett Penn, of
the United States District Court for the District of Columbia,
dismissed the case, stating:
[I3t appears that there are sufficient
questions so that further consideration of the
issue cannot be held to be an unreasonable
delay. Moreover, the Secretary is on record
that careful and expedited consideration of
the issue is necessary. In short, there is
sufficient support in the record to conclude~
that a further study is necessary provided it
be taken as expeditiously as possible." (HRG
V. Haye~, Men. Op. at 5 (D.D.C., March l4,
l983T~
HRG appealed the dismissal of its complaint and urged
the Court of Appeals to compel FDA to regulate. That court also
refused to interfere with FDA's decision, but remanded the case
to the district court to evaluate the pace of the agency deci-
sional process. The matter is i~w before the district court,
which has set a briefing schedule for HRG's promised motion for
summary judgment next month. The question whether FDA is obli-
gated to require label warnings will soon be presented to the
court a second time.
The Foundation believes that not only is FDA not under
an obligation to regulate, but, more importantly, FDA could not
justify such a regulation on the basis of the preliminary work
generated to date. Had the agency proposed a regulation on the
basis of the preliminary field work, it would undoubtedly have
PAGENO="0511"
505
faced objections that such action lacked scientific support. C
Indeed, a regulatory finding linking aspirin use and Reye Syn-
drone based upon a study whose purpose was limited to determining
the feasibility and the best methodology to use in a national
study would be subject to attack as arbitrary and capricious.
Particularly in view of the advice of the Chairman of the IOM
Conmittee that mandatory labeling is not justified, FDA could not
have supported such a rule.
Clearly, the voluntary route was the most expeditious
way for the Secretary to have obtained the label warnings and the
industry assistance in a continuing public education program that
she wanted. In view of the limited nature of the pilot data, it
was entirely appropriate for Secretary Heckler to have called for
voluntary action.
C. The Voluntary Precautionary Program
Renders Legislation Unnecessary
Despite the severe limitations in the preliminary data,
the Foundation's member companies responded to Secretary
Heckler's request with a ccxnprehensive program of label warnings,
public service announcements and store posters to supplement the
ongoing Reye Syndrane public education program of the Depart-
ment. The Aspirin Foundation Reye Syndrome Precautionary Program
was designed to help the Department alert the public to the
possible association claimed to have been observed in the feasi-
bility (pilot) study, while aspirin labels are being revised to
include a warning statement.
PAGENO="0512"
506
There are two relevant label changes that will be made
in aspirin products. First, the "~RNING" section of all aspirin
product labels will be revised to add the following:
"Consult a physician before giving this medi-
cine to children, including teenagers, with
chicken pox or flu."
Second, the labels of children's aspirin products will be revised
to delete all references to flu.
These label modifications are designed to ensure that
aspirin is used for these conditions only upon the advice of a
physician. The new labels will not be designed to proscribe
absolutely the use of aspirin or to frighten the public into
avoiding the medication. There are certain conditions, such as
juvenile rhei.znatoid arthritis, for which the medical consequences
of withdrawing or denying aspirin treatment must be fully
considered before medical regimens are changed. A physician may
believe that the health risks known to arise from the denial of
medication outweigh any possible risk of Reye Syndrome. The
decision, therefore, to use aspirin in medicating a child or
teenager with chicken pox or influenza requires the advice of a
physician.
As a result of these label changes, it would be in
violation of label warnings for the population assumed to be at
risk to be given aspirin for chicken pox or flu without the
advice of a physician first being sought.
PAGENO="0513"
507
The new warnings are entirely consistent with warnings
and caution statements that are widely used to reduce other
potentially hazardous uses of children's drugs. For example, the
risk of aspirin overdose in children is the subject of a caution
statement: "For larger or more frequent doses, or for children
under 2, consult physician."
Members of the Foundation have already begun the process
of revising their labels. Art work has been completed or is in
process. Materials are being purchased, and actual printing has
begun for many products. It is expected that new products will
have revised labeling by the next flu season.
Because not all aspirin producers are members of the
Foundation, a major effort has been undertaken to advise non-
members of the voluntary program. The Foundation has mailed
information concerning its program to companies who produce
virtually all bulk aspirin sold in the United States. As a
result, virtually every aspirin producer in the country has been
invited to join the program. Because all the major aspirin
producers are already taking part in the program, we believe that
these other companies will join them. Thus we expect that the
entire United States aspirin industry will be included in the
labeling program.
In addition to the labeling, the Foundation offered to
use Its resources to supplement the already extensive public
education efforts that have been undertaken by the Food and Drug
52-266 0-85-17
PAGENO="0514"
508
Administration, the Department of Health and Human Services, the
Surgeon General, the Centers for Disease Control, the American
Academy of Pediatrics, the Reye Syndrome parents organizations
and others. While the government's education campaign has been
in progress for several years, it was most recently augmented by
the following:
a January 23, 1985 letter from Secretary
Heckler to the general managers of the
6,000 radio and 900 television stations
in the country;
a January 23, L985 letter from Secretary
Heckler to the editors of the 1,750 daily
newspapers;
a January 23, 1985 letter from FDA to
public service directors of the 6,000
radio stations, enclosing two public
service announcements;
-- a letter from Secretary Heckler to
173,000 physicians and 8,000 hospital
admini strators;
-- a January 11, 1985 telegram to the major
television networks and various tele-
vision and newspaper trade associations;
PAGENO="0515"
509
-- a January 1985 letter from FDA to the
10,000 weekly newspaper editors, accom-
panied by an article.
To supplement this extensive public education effort,
the industry volunteered to use its contacts with broadcast media
and its extensive sales forces in the retail outlets. The
Foundation has produced two television public service announce-
ments and two radio public service announcements. The following
language appears in both sets of announcements:
30 Second Public Service Announcement
An important message for parents of children
arid teenagers with chicken pox or flu.
A rare but serious childhood disease called
Reye Syndrome may develop in children and
teenagers who have chicken pox or flu.
Although the cause of Reye Syndrome is not
known, sane studies suggest a possible asso-
ciation with medicines containing salicylate
or aspirin. So, it is prudent to consult a
doctor before giving these medicines to
children or teenagers with chicken pox or flu.
A public service announcement supported by the
American Reye's Syndrome Association, the
Reye's Syndrome Society and the National
Reye's Syndrome Foundation.
60 Second Public Service Announcement
An important message for parents of children
and teenagers with chicken pox or flu.
A rare but serious childhood diseasecalled
Reye Syndrome may develop in children and
teenagers who have chicken pox or flu.
Although the cause of Reye Syndrome is not
known, some studies suggest a possible asso-
ci ation with mcdi cines containing salicylate
or aspirin. So, it is prudent to consult a
PAGENO="0516"
510
doctor before giving these medicines to child-
ren or teenagers with chicken pox or flu.
Remember, Reye Syndrome occurs even in child-
ren and teenagers who take other medicines or
no medicines. It's important to be aware of
the early signs and symptoms. If your child
shows unusual behavior, such as severe tired-
ness, belligerence, or excessive vomiting
after appearing to recover from chicken pox or
flu, get medical help immediately. Give no
mcdi cations.
A public service announcement supported by the
American Reye's Syndrome Association, the
Reye's Syndrome Society and the National
Reye's Syndrome Foundation.
Over a thousand copies of these announcements have been
distributed to networks, television stations and radio sta-
tions. A letter from Commissioner Frank Young supporting the
announcements accompanied the tapes. A copy of the Commis-
sioner's letter is attached as Appendix A. The endorsement and
support of the three major organizations of parents of Reye
Syndrome victims was also obtained to ensure the acceptance and
use of the announcements by the media. In addition, the Adver-
tising Council issued a Special Supplement to its Bulletin, which
wassent as a cover letter with the announcements. A copy of the
Special Supplement is attached as Appendix B.
Preliminary inquiries to local stations reveal that
these materials have already reached 137 of the 198 television
stations in the top 50 television markets in the country. A
total of 107 of these stations are already airing or planning to
PAGENO="0517"
511
air one or more of these Reye Syndrome public service announce-
ments.!/ At least one station, and often several stations, in
each of the top 50 television markets is currently airing or
plans to air these public service announcements.
The third element of the Precautionary Program involves
the use of the combined sales forces of Foundation members to
distribute posters in pharmacies arid food stores, and also to
distributors and wholesalers, around the country. The posters
contain the same message as the 60 second public service
announcements, with the addition of the caption BEYE SYNDRO!'T in
bold print. There are two sizes of posters -- 8 1/2 x 11 inches
and 5 1/4 x 7 inches. To encourage the use of the posters, the
Commissioner has also provided a letter of support for this
element of the program. A copy is attached as Appendix C. In
the brief time since the campaign began, 100,000 posters,
together with copies of Commissioner Young's letter, were
distributed to sales forces.
The Foundation has found that several large chain stores
have designed their own posters arid have therefore not allowed
the Foundation's posters to be displayed. Some of these stores,
such as Peoples' Drug in the Washington area, have copied the
language from the Foundation's posters into a sign bearing the
store's logo. Others are distributing the posters internally to
each of their stores for display. The corporate office of Dart
4/ This figure includes 3 stations which are producing their own
versiOn of the public service announcements.
PAGENO="0518"
512
Drug, for example, has distributed the posters to Dart's district
managers for delivery to, and posting in, each of Dart's 71
stores.
In an effort to increase the use of the Eosters beyond
those distributed by sales forces, the Foundation has recently
sent additional copies of the poster and Caitinissioner Young's
letter, by direct mail to over 60,000 pharmacists and 35,000 food
stores, with a wSpecial Notice" cover letter requesting that the
poster be displayed pranptly. Member canpany sales staffs have
also been asked to redouble their efforts to post the signs in
retail stores.
We believe that these combined efforts to educate the
public to the possible association are i~precedented. Despite
the preliminary nature of the pilot study information, the public
is being provided with warnings in print and electronic media and
in posters within retail outlets. The level of public awareness
-- already quite high before the preliminary feasibility work was
released will probably soon have reached the saturation
point. The public is rapidly becoming fully informed on the
possible association.
D. H.R. 1381 Would Require a Misleading
Statement on Aspirin Products, in
~spirin Advertising and in Stores.
The proposed legislation would require that all salicy-
late products, advertising and places of sale, bear a prescribed
warning statement that is seriously misleading and would result
in substantial public confusion.
PAGENO="0519"
513
First, the claim that aspirin and other salicylates have
been "strongly associated with the developnent of Reye's Syn-
drome" cannot be made unless arid until a sound epidemiologic
study has been completed. The statement will be interpreted by
the public as a statement that aspirin causes Reye Syndrome and
that aspirin avoidance will prevent Reye Syndrome. The prelimi-
nary feasibility work that has been referred to as the pilot
study provides no basis whatsoever to conclude that aspirin use
causes Reye Syndrome. As noted above, the IOM Committee stated
categorically:
"It should be emphasized, however, that the
pilot study results of comparisons of medica-
tion use between cases arid controls will in no
way be interpreted as conclusive evi~ince for
~ against an etiologic role of medication use
óii~the risk of PS."
P.R. 1381 would use the preliminary feasibility work to support a
conclusion that was specifically ruled out by IOM. The warning
statement is devoid of scientific support and is therefore
seriously misleading.
Second, the statement, as well as the very title of the
bill, suggests that Reye Syndrome can be prevented by the
avoidance of aspirin. Such a representation is grossly unfair
and can be dangerous to the population at risk for Reye Syn-
drome. It is undisputed that children can develop Reye without
having taken aspirin. By suggesting that aspirin avoidance will
PAGENO="0520"
514
"prevent" Reye, H.R. 1381 would lead parents who have not used
aspirin to the false belief that their children are not at risk
for developing Reye.
Medical experts agree that prompt diagnosis and treat-
ment will save lives and reduce morbidity from Reye Syndrome.
Parents must be alert to the symptoms of Reye and be prepared to
take quick action. This legislation would remove or diminish the
caution that all parents should have when their children have
chicken po~c or flu. The resulting false sense of security may
result in a return to the high mortality rate that recent educa-
tional efforts have reduced.
Finally, the warning is also incorrect in referring to
"individuals under the age of 21 years" as being at risk for Reye
Syndrome. Recent studies have found Reye Syndrome only in
children and teenagers.
CON~LT~ ION
H.R. 1381 must be viewed in light of the limited nature
of the available data on Reye Syndrome and in light of the coin-
prehensive voluntary relabeling and consisner education program
being undertaken by the industry, in cooperation with the Depart-
ment of Health and Nissan Services. In that light, the proposed
legislation is devoid of scientific justification and would
require a misleading warning.
The voluntary program, on the other hand, when combined
with the extensive efforts of the Depar~nent and others, is
clearly the only practical way to communicate a precautionary
statement to the public without the necessity of first completing
a sound epidemiology study. The voluntary program merits your
support. H.R. 1381 is not a viable alternative to that program.
I thank the Subcommittee for the opportunity to present
the views of the Aspirin Foundation.
PAGENO="0521"
515
APPENDIX A
DLVARTMI'.I ii~ iii ; TI~ a Ilk %5~\%ERVI(1'. PubhcMeltthSv~.c,
coou s~a D.g nc.~ ~ ~n
Rock,lIe MD 2080
January 28, 1985
The Advertising Council
1730 Rhode Island Avenue, N.W.
Washington, D.C. 20036
Dear Sirs:
The Food and Drug Administration has reviewed public service announcements
prepared by the major aspirin manufacturers with the cooperation of the
Advertising Council.
These materials are responsible and clear. They have the support of FDA.
They were prepared In response to the request of U.S. Health and Human
Services Secretary Margaret M. Heckler. Store posters and announcements are
also being distributed.
Thank you for your work in distributing these public service announcements.
trust that the broadcast media will air these vital messages promptly, dur~np
this flu season.
Sincerely,
Conrissioner of Fo and ugs
PAGENO="0522"
516
APPENDIX B
v -~ ~
~ -~
~S*~V~%~ -~-~ .~ ~ ~ ~
~ ~4A ~
SUPPLEMENT TO THE ADVERTISING COUNCIL'S JANUARY-FEBRUARY
PUBLIC SERVICE ADVERTISING BULLETIN
This is to send you information about the Reye Syndrome threat to children
and teenagers. The request for Ad Council assistance was received t~o late
for inclusion in the January-February, 1985, issue of the Ad Bulletin.
Reye Syndrome
Aspirin Foundation of America, American Reye's Syndrome Association,
Reye's Syndrome Society and National Reye's Syndrome Foundation.
Parents of children and teenagers with chicken pox or flu should be alerted
that a rare but serious childhood disease could affect both groups. Although
the cause of Reye Syndrome is unknown, some studies suggest a possible
association with medicines containing salicylate or aspirin. Therefore it
is extremely important that parents consult a doctor before giving these
medicines to children with chicken pox or influenza.
Reye Syndrome can also occur in children and teenagers who take other
medicines or no medicines at all. So it's vital that parents are aware
of its early signs and symptoms. If a child shows unusual behavior --
severe tirec~ness, belligerence, or excessive vomiting after appearing to
recover from chicken pox or influenza -- get medical help immediately.
And give no medications.
The enclosed spots have been produced by the Aspirin Foundation of America
under the joint sponsorship of the American Reye's Syndrome Association,
the Reye's Syndrome Society and the National Reye's Syndrome Foundation.
They have been reviewed by the U.S. Food and Drug Administration and by
the Advertising Council and have the whole-hearted support of both organ-
izations. Dr. Frank Young, Commissioner of Food and Drugs, has written
the enclosed letter to support urging the broadcast media to "air these
vital messages promptly, during this flu season,"
For further information please contact: Carl Byoir & Associates, Inc.,
380 Nadison Avenue, New York, N.Y. 10017 (212) 986-6100.
PAGENO="0523"
517
* APPENDIX C
DEPARTMENT OF HEALTH & HUMAN SERVICES PuMic HeatthServ~:
FoodadD gAd t
Rockville MD 20857
January 28, 1986
Dear Store Manager:
The Food and Drug A&uinistratiofl has reviewed posters and bulletin board
announcements prepared by the major aspirin manufacturers with the cooperation
of the Advertising Council.
These materials are responsible and clear and have F~'s support. They have
been prepared in response to a request of U.S. Health and Human Services
Secretary Margaret M. Heckler. Television and radio announcements are also
being distributed.
Sincerely,
Commissioner of Fo and ugs
PAGENO="0524"
518
Mr. WAXMAN. Thank you very much, Dr. White.
Mr. Cope.
STATEMENT OF JAMES D. COPE
Mr. COPE. I am Jim Cope of the Proprietary Association. With
me is Dan O'Keefe, our senior vice president, general counsel, and
secretary. I will abbreviate my written statement, and request if
possible that it be included in the record in its entirety.
Mr. WAXMAN. All the statements will be in the record.
Mr. COPE. Thank you, Mr. Chairman.
Our association represents the manufacturers of all over-the-
counter medicines, and therefore, we have an interest in this bill.
I would like to emphasize at the outset that we share the con-
cern that has been expressed by other witnesses about Reyes syn-
drome.
I will not discuss the scientific issues on Reye's Syndrome, nor
will I cover the voluntary efforts of the Aspirin Foundation. The
Proprietiary Association has not been involved in those matters,
and we defer to the foundation and to the Government on those
points.
I would like to address some broader issues which the bill raises,
specifically, the enactment of legislation at this time which would
put warnings in advertising, which is our basic and major concern
with the bill.
I would like to make four points in my testimony. First is, we
really wonder whether congressional action at this stage is neces-
sary. We think it may be premature, because there is disagreement
among scientists as to this question.
There is an important study underway as we have heard this
morning, and, of course, it is not yet completed, and there are
broad educational programs already underway.
The Food and Drug Administration, as you know, is considering
the issue, and the Federal Trade Commission is, as well. We be-
lieve, as a matter of sound decisionmaking regarding warnings in
advertising and labeling, that Government action should be based
on generally accepted scientific data.
This bill would decide the issue now by legislation. We believe it
would be premature for the Congress to act on its own judgment,
particularly in an area of honest scientific dispute, while the agen-
cies with the expertise-and which have been assigned the respon-
sibility by the Congress-are still considering the matter.
My second point is that we doubt there is any need for legislated
labeling warnings. The aspirin manufacturers agreed to put the
warnings on themselves, and there is adequate authority in the
Food and Drug Act for the Food and Drug Administration to re-
quire label warnings, if and when they are scientifically justified.
This bill, however, would require a bracketed or boxed 48-word
warning on aspirin and other salicylates, with color-coded symbols
and no permitted flexibility.
A couple of questions, if I may. Would the prominence and space
required for this warning obfuscate other necessary label informa-
tion and warnings? And would the use of symbols, required for no
PAGENO="0525"
519
other label information, lead consumers to believe that this pro-
posed label warning is the only one they should read?
A typical aspirin-containing product, a sinus medicine, contains
the following warnings, Mr. Chairman:
Warning: Individuals with high blood pressure, heart disease, diabetes, thyroid
disease, high fever or glaucoma should use only as directed by physician. Do not
drive or operate heavy machinery as this preparation may cause drowsiness.
Caution: As with any drug, if you are pregnant or nursing a baby, seek the advice
of a health professional before using this product.
Those are some of the important warnings, in our judgment,
which may be superseded and overlooked by the consumer, if this
warning is overlaid on them with the force that is proposed.
We submit that these questions, and indeed, the issue of impos-
ing the special warning is best handled first by the Food and Drug
Administration, which it is currently doing.
Third, advertising simply cannot do the job this bill would re-
quest of it. This bill would require that all advertising, broadcast,
print, transit, point of purchase, any and all advertising contain a
48-word warning.
It thus fails to take into account the function and limits, and the
operative word here is "limits," of product advertising.
The function of advertising is three-fold. But before you can get
to any of them, you have to do one other thing, and that is, get the
attention of consumers, and advertising is not a high-involvement
media for consumers.
But assuming you can get their attention, it has three functions.
First, tell consumers that there is a product on the market for a
particular condition, so that in case they have it, they can use the
products safely by reading the label;
Second, attempt to implant a positive image in the mind of the
consumer about that product, and one of its attributes;
Third, very importantly, try to impress consumers with the name
of the product so that when or if they do have a need for it, they
will remember that product.
Believe me, this is most difficult to do. We use advertising heavi-
ly. We try to improve its effectiveness. We would like to very
much, but we find meeting those three simple objectives very, very
difficult.
There is one other important thing to know about advertising. It
is extremely limited as to how much information it can effectively
carry. It is a low-involvement medium and it can convey only a
limited amount of information.
The more information it attempts to convey, the less real infor-
mation that is really conveyed, the less real education that goes on.
As the information load increases, consumers are inclined to
tune it out or to form wrong impressions. Also, if the message is
the same for too long, there is a "wear-out" with repetition, and
people become bored and no longer pay attention.
These are truthful statements, facts about advertising. It is gen-
erally agreed by experts in mass communications that broadcasting
particularly is an ineffective medium for conveying detailed health
information that is directed at a limited segment of the population.
Because consumer attentiveness to advertising is low, health mes-
PAGENO="0526"
520
sages about specific products may engender confusion and misinfor-
mation.
Importantly, I think you should know that in a major proceeding
before the Federal Trade Commission, which was decided just 8
months ago after consideration of an extensive evidentiary record,
the Commission rejected a proposal to require advertisements for
OTC antacids, to disclose warning information that FDA has re-
quired in antacid labeling.
The Commission's decision was unanimous, and it terminated the
rulemaking based on a full record demonstrating that the inclusion
of label warnings in medicine advertising is unnecessary to protect
consumers, will be ineffective in communicating medical informa-
tion to the at-risk groups, and will discourage beneficial self-medi-
cation with OTC products.
Of particular importance this morning, Mr. Chairman, there is
ample evidence in that record documenting the point that warn-
ings in advertising are not effective in communicating medical in-
formation to at-risk groups.
The presiding officer who sat through all of those hearings con-
cluded that the witnesses have persuasively argued the limitations
of the commercial media to make the kind of disclosures under con-
sideration, which were warnings in antacid advertising.
I would also note one last point, and that is, as a practical
matter, it takes about 15 to 20 seconds to say the 48-word warning.
Imagine trying to get that 20-second warning in a 20 or 30 or even
a 60-second radio advertisement.
In our judgment, a far more effective way to communicate this
health concern is the way that it is happening-through doctors,
pharmacists, nurses, labeling, public service announcements, PTAs,
school districts, the press, and other ways.
The last point: We question whether there is a need for legislated
retail notices. The bill would require every retail establishment
selling aspirin to display a notice containing this 48-word warning,
and failure to do so would constitute a criminal act.
There are literally tens of thousands of retail establishments,
bars, restaurants, service stations, motels, hotels which, as a con-
venience to the traveling public and others, sell small cartons of as-
pirin-containing products.
We wonder if it is appropriate to put thousands of small retailers
in jeopardy of a criminal violation of the law for failure to display
this notice?
In conclusion, while we defer to the Aspirin Foundation and Gov-
ernment on the science and industry's voluntary programs, we be-
lieve that consideration of the need for and details concerning
warning requirements, particularly warnings in advertising, is best
left in the first instance to the two agencies, FDA and FTC, which
have responsibilities and expertise.
We ask that the Congress not enact this bill at this time, give it
a chance to play out a little more so we can all find out more about
Thank you, Mr. Chairman.
[Testimony resumes on page 540.]
[The prepared statement of Mr. Cope follows:]
PAGENO="0527"
521
STATEMENT
OF
THE PROPRIETARY ASSOCIATION
ON H.R. 1381
REQUIRING SPECIAL WARNINGS IN LABELING
AND ADVERTISING OF SALICYLATE-CONTAINING PRODUCTS
BEFORE THE
SUBCOMMiTTEE ON HEALTH AND THE ENVIRONMENT
COMMITTEE ON ENERGY AND COMMERCE
UNITED STATES HOUSE OF REPRESENTATiVES
MARCH 15, 1985
WASHINGTON, D.C.
I. INTRODUCTION AND SUMMARY
Good morning, Mr. Chairman and Members of the Subcommittee. I am James
D. Cope, President of The Proprietary Association. With me this morning is
Daniel F. O'Keefe, Jr., Senior Vice President, General Counsel and Secretary of
the Association.
I will summarize the main points of my written statement, but I ask that it be
included in its entirety in the official record.
The Proprietary Association, whid~ we call the "PA," is the century-old trade
association representing manufacturers and distributors of over-the-counter
("OTC") medicines such as aspirin, cold tablets, cough syrups, and many others,
some of which you probably have in your medicine cabinet at home. Some of
these products are among the most commonly used consumer products in the
United States, such as Bayer Aspirin, Vicks Formula 44e, Anacir~, Bufferint,
Contac, Thmse, and Tylenole. PA members, large -and small, account for about
95 percent of the sales of OTC medicines in the United States.
PAGENO="0528"
522
Let me emphasize at the outset that we share the concern for children that has
been raised with respect to this rare and elusive, but very serious disease called
Reye's Syndrome. We do not propose to discuss the scientific issues or the
voluntary efforts by the aspirin industry in response to the available information.
The Aspirin Foundation, rather than The Proprietary Association, has been
involved in both the science and the voluntary program to address the Reye's
Syndrome matter. We defer to them on both matters.
Our purpose today is to address the broader issues raised by H.R. 1381,
specifically, the enactment of legislation which would apply to all salicylate-
containing products and would:
* Require all labeling of such products to carry a bracketed or boxed
48-word specific warning, flanked by color-coded symt)oIs;
* Require all advertisements (print, broadcast, outdoor, transit, and
point of purchase) to also contain the 48-word warning;
* Require all retail establishments at which such products are sold to
display a notice containing the warning;
* Require FDA to Issue regulations; ~and
PAGENO="0529"
523
Make non-compliance with the bill's requirements a misbranding
violation under the Federal Food, Drug, and Cosmetic Act.
The Proprietary Association is deeply troubled by the overall thrust of the
proposed legislation and the basis upon which it is being considered at this time.
We believe that, if adopted, H.R. 1381 would establish an unwise precedent for
future regulation of the labeling, advertising, and retail sale of over-the-counter
medicines.
IL GENERAL BACKGROUND
A. The Role of Self-Medication in the Nation's Health Care System
OTC drugs are an integral part of the health care system of the United States.
These products are composed of ingredients whose pharmacological act ons are
well understood and there is a wide margin of safety In their use. Their safety,
labeling and effectiveness, including quality control and manufacturing process,
is extensively regulated by the U.S. Food and Drug Administration. OTC
medicines provide safe and effective treatment for a multitude of ailments,
enabling the pthlic to forego time-consuming and expensive doctor visits and the
attendant discomfort of delayed treatment. They are Inexpensive and con-
veniently available In many thousands of retail outlets - Including food stores,
pharmacies, and discount and department stores - everywhere. Self-medication
today constitutes an early and ftmdamental level of health care; without self-
medication, physicians would be overwhelmed by patients seeking relief for
symptoms and ailments that can and should be treated by self-care. Thus. use
PAGENO="0530"
524
of OTC drug products for the treatment of conditions capable of lay diagnosis
provides an economical and convenient alternative to understandably more costly
physician visits.
The U.S. Department of Commerce has underscored the significance of OTC
medicines in the nation's health care system. A statement, made in 1978 by the
Commerce Department, has even more validity today.
Self-medication with proprietary drugs is a signif-
icant factor in the U.S. health care scheme.
Escalating costs of health care create a greater
need for low cost self-medication than ever
before. Seventy-five percent of all illness and
injuries are initially treated through self-care and
OTC medication. If only a small percentage of
self-treatment was shifted to medical practition-
ers, the patient load would disrupt the US. health
care system. (U.S. Department of Commerce,
U.S. Industrial Outlook 1978, at 131 (January,
1978)]
B. Regulation of OTC Medicines
Under the Federal Food, Drug, and Cosmetic Act ("FDC Act" or "the Act"),
Congress has placed the responsibility of assuring the safety, effectiveness, and
truthful labeling of over-the-counter medicines under the primary Jurisdiction of
the Food and Drug Administration. Thus,Congress has delegated primarily to
FDA the responsibility to make the scientific and policy Judgments necessary to
assure the safety, effectiveness, and truthful labeling of over-the-counter
medicines and to protect and Inform the putlic with respect to them.
Regulation of advertising of OTC medicines I*s been delegated by Congress
primarily to the Federal Trade Commission ("FTC") tmder the Federal Trade
PAGENO="0531"
525
Commission Act ("FTC Act"). That Act forbids OTC medicine manufacturers
from disseminating any false advertisement, defined to mean an advertisement
which is misleading in a material respect.
This sound division of jurisdiction between the two agencies, with FDA expertise
directed primarily to questions of science and FTC expertise directed primarily
to questions of consumer understanding of advertising, has been in effect since
1938 and has served the public well.
III. CONGRESSIONAL ACTION WOULD BE PREMATURE
As we understand the facts, the concern underlying the proposed legislation is
that there is evidence that there may be an association between the use of
aspirin and the development of Reye's Syndrome. We also understand that there
is genuine disagreement among scientists and medical experts regarding the
alleged association between the use of aspirin and the development of Reye's
Syndrome. Indeed, we understand that the very purpose of a Public Health
Service study now under way is to bring the best possible scientific knowledge
to bear on the question, and that that task has not yet been completed. It is
also our understanding that the Department of Health and Human Services has
concluded that the public education programs being sponsored by the Department
and the Aspirin Foundation are adequate to meet the public health need while
FDA considers the matter.
A petition was filed with the FTC on January 16, 1985, by the Public Citizen
Health Research Group requesting that agency to require manufacturers of OTC
PAGENO="0532"
526
aspirin-containing products to place a warning concerning Reye's Syndrome in all
advertisements for such products. To the best of our knowledge, that petition
is pending before the agency and no determination has been made that the
warning requested by the petition would be justified.
We believe that, as a matter of sound decision-making regarding warnings in
OTC drug labeling and advertising, government action must be based upon
generally accepted scientific data. The proposed legislation would decide the
scientific issues now by legislation and prescribe specific warnings that neither
agency has thus far seen fit to impose. We believe that it would be premature
for Congress to substitute its own judgment, particularly in an area of honest
scientific dispute, for that of the agencies with the expertise and the express
statutory responsibility for OTC product labeling and advertising and to mandate
specific warning language based solely on its own assessment of the health risks
presented by a particular product class. If Congress acts now and it is later
concluded that there is no association between salicylates and Reye's Syndrome,
the legislative requirements would remain in effect though unjustified - a
cumbersome and unfair situation.
lv. THERE IS NO NEED FOR LEGISLATED LABELING WARNINGS
There is adequate legal authority in the present Federal Food, Drug, and
Cosmetic Act to require scientifically justified warnings on OTC medicines.
However, FDA has not deemed such warnings to be required on the basis of
available scientific data.
PAGENO="0533"
527
Moreover, as the Subcommittee members are aware, FDA for years has imposed
warning requirements on OTCs along with other important information including:
(1) the product name;
(2) a statement of identity;
(3) the conditions which the medicine is designed to treat;
(4) directions and dosage instructions;
(5) drug interaction precautions, if any;
(6) a list of active ingredients and quantities of such ingredients;
(7) an expiration date, when needed;
(8) the net quantity of contents; and
(9) the name and address of the manufacturer, packer or distributor.
Thus, the label tells the consumer - in understandable terms - what the product
is for, how to use it properly, and cautions which should be exercised in its use.
Medicinal products are frequently sold in relatively small packages, thus
increasing the need for judicious use of label space to assure that the critical
information on labels is seen by the consumer.
Consistent with this reality, over the years the FDA has generally taken the
position that requirements for OTC label warnings should be limited, to use on
specific products when the need for a particular warning has been scientifically
demonstrated. Not only would scientifically unsupported warnings divert the
attention of the consumer from important label information necessary for proper
use by all consumers of the product, such warnings would dilute the significance
of other warnings which are scientifically supported and which the consumer
therefore needs to know to use the product safely. In addition to causing
confusion, unnecessary warnings can needlessly frighten consumers.
PAGENO="0534"
528 I
H.R. 1381 would require a bracketed or boxed 48-word warning on aspirin and
other salicylates, with color-coded signs and symbols and no permitted
flexibility. Would the prominence and space required for this warning obfuscate
other necessary label information and warnings? And would the use of symbols
- required for no other label information - lead consumers to believe that the
proposed label warning is the 2~ one they should read? The only information
that is really important?
We submit that all of these questions and indeed the issue of imposing a special
warning on drug labeling in this instance should be considered first and foremost
by the FDA, as it Is presently doing. Special legislation is not needed.
V. ADVERTISING CANNOT EFFECTWELY CONVEY WARNINGS
H.R. 1381 would also require all advertising for salicylate-containing products to
carry a 48-word warning. The bill thus fails to recognize the function and limits
of product advertising. Its function generally is to Inform potential consumers
of the availability of the advertised product in the treatment of a particular
ailment, to attempt to implant a positive image in the minds of the consumer
about the product and about one of its attributes, and to do so in a way that
the consumer will remember the prokict's name when that consumer is In the
market to purchase that type of product. Believe me, that Is most difficult to
do. There is one other important thing to know about advertising: It is
extremely limited in how much information It can effectively contain.
PAGENO="0535"
529
Advertising is a low involvement medium which can convey only a limited
amount of information. The more information advertising attempts to
communicate, the less effective the communication will be. As the information
load increases, consumers are more likely to "tune out" or form wrong
impressions. Furthermore, advertising "wears out" with repetition and people
become bored and no longer pay attention.
It is generally agreed by experts in mass communications that broadcast
advertising is an ineffective medium for conveying detailed health information
that is directed at a limited segment of the population. Because consumer
attentiveness to advertising is low, health messages about specific products may
engender confusion and misinformation. In addition, consumers who are not at
risk may develop a generalized impression that the advertised product is unsafe
and should be avoided. As a result, consumers may be discouraged from using
OTC medicines - like aspirin - that are safe and effective for most members
of the population.
The Proprietary Association devoted considerable energy and resources in
challenging the imposition of ill-advised warnings on OTC drug advertising in a
major proceeding before the Federal Trade Commission. In that proceeding -
the "Warnings" TRR after consideration of an extensive evidentiary record,
the Federal Trade Commission rejected a proposal to require advertisements for
OTC antacids to disclose warning information that FDA has required in antacid
labeling.1 The Commission's unanimous decision to terminate this rulemaking
was based on a full record demonstrating that the inclusion of label warnings in
1 49 Fed. Reg. 46,156 (November 23, 1984).
PAGENO="0536"
530
OTC medicine advertising is unnecessary to protect consumers, will be
ineffective in communicating medical information to at-risk groups, and will
discourage beneficial self-medication with OTC products. Of particular
importance to this Subcommittee's deliberations, there is ample evidence in that
record documenting the point that warnings in advertising are not effective in
communicating medical information to at-risk groups.2 The Presiding Officer in
that proceeding concluded that the witnesses "have persuasively argued the
limitations of the commercial media to make the kind of disclosures under
consideration [warnings in antacid advertising]."3
These same considerations, we believe, apply to the Reye's Syndrome warning
that would be required in salicylate-product advertising under H.R. 1381. It is
doubtful whether such a warning will be effective in conveying accurate and
meaningful information about Reye's Syndrome to parents of children who may
be at risk. At the same time, by singling out salicylate products for a warning
in advertising, the proposed legislation could needlessly alarm consumers and
discourage use of OTC products that are safe and beneficial.
There is extensive evidence that consumers prefer to obtain medical information
in a manner that permits a full understanding of its implications and personal
relevance rather than receiving such information in product advertising.4 One
trusted communication medium is the doctor-patient relationship. Another is
public service announcements that more fully describe the medical information
2 Prepared Statement of Michael F. von Gonten and accompanying study,
Proposed Trade Regulation Rule Concerning the Advertising for
Over-the-Counter Antacids ("Warnings TRR Proceeding").
3 Report of the Presiding Officer, "Warnings TRR Proceeding," Novem-
ber, 1979, at 167.
4 Food and Drug Administration. Consumers and Medication, May 17,
1974, at 60; Prepared Statement of Dr. Louis Lasagna, "Warnings
TRR Proceeding".
PAGENO="0537"
531
involved and place it in proper perspective. Labeling is another preferred means
of obtaining medical information on OTC medicines.
By amending the Federal Food, Drug, and Cosmetic Act, H.R. 1381 would make
failure to observe the bill's advertising provisions (and regulations issued under
it) a violation of that Act. This provision would seriously disrupt the historically
recognized jurisdictional distinction between OTC drug advertising and OTC drug
labeling. The FDA, as the agency empowered to regulate OTC drug labeling,
should be the agency which handles the labeling concerns addressed by this bill.
To the extent product advertising issues are involved, the FTC is the proper
forum. Thus, insofar as the bill would modify the Federal Food, Drug, and
Cosmetic Act to impose a warning requirement for OTC cjrug advertising of
specific products, it would encroach on the FTC's authority to consider the need
for Information disclosures in OTC medicine advertising.
I might note, as a practical point, that it takes 15-20 seconds to read the 48-
word warning required by the bill. Im~ine trying to incorporate that into a 20
or 30- - or even a 60- - second radio spot.
VI. THERE IS NO NEED FOR LEGISLATED RETAIL NOTICES
H.R. 1381 would also require every retail establishment selling aspirin to display
a notice containing the warning. Failure to do so would make a retailer guilty
of misbranding under the Federal Food, Drug, and Cosmetic Act. A misbranding
PAGENO="0538"
532
violation constitutes a criminal offense for which persons can be both fined and
imprisoned.
Aspirin is one of the most widely available products in America. It is sold in
tens of thousands of drugstores, department and variety stores, grocery stores,
and discount houses, as well as in small "mom and pop" retail establishments
such as gas stations, motels, restaurants and bars.
It ~is inappropriate to place thousands of small retailers in jeopardy of a criminal
violation of the Federal Food, Drug, and Cosmetic Act for failure to display the
notice required by the bill.
Thus, we believe that legislation requiring display of retail notices is unneces-
sary, unduly burdensome, and unwise.
VII. SUMMARY AND CONCLUSION
In sum, we believe that consideration of the need for and details concerning
warning requirements for particular OTC products is a task best left in the first
instance to the two agencies - FDA and FTC - with respective responsibilities
for regulating OTC product labeling and advertising. The scientific basis for
such requirements is currently under study. The current efforts by the agencies
empowered by Congress to protect the public health should be allowed to work
their course before legislative action preempts their work. The FDA has the
scientific expertise to address these problems and should be able to bring their
scientific judgment to bear on the issue in fashioning any further response that
may be indicated.
The implication and precedent of legislative requirements for warnings in
advertising, special warnings in labeling and special notices for retail estab-
lishments are such that The Proprietary Association believes that H.R. 1381 is
unwise as a matter of policy and urges that it not be enacted.
In closing, let me thank the Subcommittee for its time and willingness to receive
the views of The Proprietary Association.
PAGENO="0539"
533
SUPPLEMENTAL STATEMENT
OF
THE PROPRIETARY ASSOCIATION
ON H.R. 1381
REQUIRING SPECIAL WARNINGS IN LABELING
AND ADVERTISING OF SALICYLATE-CONTAINING PRODUCTS
BEFORE THE
SUBCOMMITTEE ON HEALTH AND THE ENVIRONMENT
COMMITTEE ON ENERGY AND COMMERCE
UNITED STATES HOUSE OF REPRESENTATIVES
APRIL 5, 1985
WASHINGTON, D.C.
I. INTRODUCTION
The Proprietary Association (EPA' or ~the Associa-
tion~) is filing this Supplemental Statement to bring to the
Subcommittee's attention certain problems members of our
industry have encountered in attempting to examine pertinent
data from the Reye Syndrome pilot study. While summary results
from that pilot study have been made public, important raw data
have not been released in sufficient detail to allow an
independent and meaningful scientific evaluation of the pilot
findings. We strongly urge that such data be made available
promptly for independent review by the scientific community and
interested parties.
In The Proprietary Association's March 15, 1985
Statement, the Association emphasized that it shared the
Subcommittee's concern over the rare, but very serious disease
called Reye Syndrome. The PA also pointed out, however, that
it is opposed to requiring warnings on over-the-counter (ROTC")
medicine labels unless the need for such warnings is justified
by generally-accepted scientific data. Because the pertinent
PAGENO="0540"
534
scientific data underlying the Reyé Syndrome pilot study has
not been made publicly available for independent review, there
is no way for the scientific community to determine whether the
pilot study offers any support for the suggestion that there
exists an association between aspirin usage and the development
of Reye Syndrome. Release of these data is particularly impor-
tant under these circumstances because the pilot study is the
stated basis for the current concern regarding Reye Syndrome.
The PA strongly opposes prejudging scientific issues
and denying interested parties a meaningful opportunity to
examine pertinent data. The OTC industry is vitally interested
in determining whether there are indeed reliable and valid data
demonstrating an association between aspirin and Reye Syndrome.
Without access to such data, however, no such determination can
be made--by industry, the scientific community, or by
Government.
II. BACKGROUND
The PA's concern about access to this data from the
pilot studies must be viewed against a historical context.
While the Association itself has not been involved in past
attempts to obtain data from Reye Syndrome studies, we under-*
stand from some of our members who have been involved, however,
that there is a long history of difficulties in exposing under-
lying data on this issue.
PAGENO="0541"
535
Following the receipt of allegations that there was
an association between aspirin usage and the development of
Reye Syndrome, the FDA in February of 1982 established a Working
Group to review four state Reye Syndrome studies performed by
the Departments of Health of Ohio, Michigan (two studies), and
Arizona. Each of the state surveys had been sponsored by the
Centers for Disease Control ("CDC~) either with funds dr
personnel. However--and distressingly--neither FDA nor CDC
were able to obtain copies of the raw data from these studies.
Nevertheless, based on summarized results of these data, the
Department of Health and Human Services (RHHSW) directed the
FDA to promulgate a regulation requiring label warnings for
aspirin-containing products.
From the time that the Reye Syndrome issue first
arose, interested persons had sought unsuccessfully to obtain
scientific review of the state surveys, including a thorough
and independent examination of underlying data. Although it
had the express legal authority to demand underlying data under
its contract with Ohio, CDC failed to request the material, and
instead determined to rely upon summaries of the studies
prepared by the state investigators. CDC also refused to
assist in efforts to obtain the release of the underlying data
and referred interested persons to the states' Departments of
Health. The states, in turn, repeatedly denied or simply
ignored requests for access to the underlying data.
PAGENO="0542"
536
Given these circumstances, on June 4 and 11, 1982,
Plough, Inc. filed lawsuits in Ohio and Michigan, respectively,
seeking court orders directing the production of data from the
Reye Syndrome studies. Pursuant to these suits, and other
independent discovery, the data were ultimately obtained by
Plough. Significantly, it was Plough, not the states, which
gave the information to CDC and FDA.
After review of these data, HHS, on November 18, 1982,
reversed its earlier decision and acknowledged that the scien-
tific record concerning an alleged association between the use
of aspirin and the onset of Reye Syndrome was substantially in
dispute, and that new government-supported studies were needed
to resolve the controversy. See 47 Fed. Reg. 57,886 (1982) at
Docket Ref. 105. It was against the backdrop of these events
that HHS created a task force of scientists to design and con-
duct a nationwide study of Reye Syndrome and its possible link
with medications. The pilot study that began in November 1983
was intended to be the preliminary field work to assist in the
development of methodology for a nationwide Reye Syndrome study.
III. DATA FROM THE REYE SYNDROME PILOT STUDY SHOULD BE
RELEASED TO INTERESTED PARTIES AND THE SCIENTIFIC
COMMUNITY SO THAT THEY CAN BE SUBJECTED TO PEER REVIEW.
Prior experience regarding Reye Syndrome demonstrates
that scientific issues shotild not be prejudged and that data
from Reye Syndrome studies should be subjected to public scru-
PAGENO="0543"
537
tiny before drawingconclusions. It is therefore of critical
importance that data from the Reye Syndrome pilot study be
released so that an independent scientific inquiry can be made.
In particular, relevant information and key data,
including medical records of cases during diagnosis and treat-
ment, medical records concerning the underlying illness of cases
and controls, and more complete versions of questionnaires used
during the actual interviews of cases and controls have not been
released to interested parties. Other information from the
pilot study has been made available, but only in a Rwhited_outw
format with critical information deleted, thereby making
meaningful analysis impossible. It is necessary, for example,
to have access to the medical records so that, by comparing the
preliminary and final diagnosis, it can be determined whether
cases actually had Reye Syndrome and when and if they were
given aspirin.
The principal reason given for withholding this data
is that it is necessary to protect the privacy rights of
individuals. The PA is always mindful of such rights. But we
understand that privacy is not really at issue, since parties
interested in examining these data have undertaken to honor the
privacy of the individuals involved, and only want an oppor-
tunity to analyze these data themselves. Thus, members of the
industry have indicated that they are not interested in names,
addresses, and telephone numbers of cases, controls, and their
physicians. Rather, for example, they seek release of such
PAGENO="0544"
538
information as the age and sex of cases and controls in order
to determine that cases and controls were adequately matched.
The PA, therefore, strongly urges that further data
from the Reye Syndrome pilot study be made available to public
scrutiny.
IV. WITHOUT SUBJECTING THE DATA FROM THE REYE SYNDROME PILOT
STUDY TO INDEPENDENT SCIENTIFIC ANALYSIS, IT IS NOT
POSSIBLE TO DETERMINE ITS VALIDITY.
Under current law, the determination whether a Reye
Syndrome warning is required is governed by two provisions of
the Federal Food, Drug, and Cosmetic Act (FDC Actw)__section
502(f)(2), which requires adequate warnings against unsafe
uses, and s~ection 201(n), which provides that labeling. may be
misleading if it fails to reveal material facts about the
consequence of using a drug. 21 U.S.C. SS 352(f)(2) & 321(n).
Neither of these provisions can be read consistently with the
concept underlying H.R. 1381.
The legislative history of section 502(f)(2) of the
FDC Act makes clear that Congress did not intend to require
warnings about speculative or hypothetical risks. During the
legislative debate on the bill that eventually became the Act,
the sponsor (Senator Copeland) stated that the. provision was
directed to wpossible misuse' of drugs, that is, use under
conditions or in dosages known to be unsafe. See 81 Cong. Rec.
2,019 (1937). This interpretation of section 502(f)(2) was
confirmed in 1951 in testimony on the Durham-Humphrey Amendments
PAGENO="0545"
539
enacted that year. See Hearings on H.R. 3298 before the House
Interstate and Foreign Commerce Comm., 82d Cong., 1st Sess. 20
(1951) (testimony of Oscar R. Ewing, Administrator of the
Federal Security Agency).
Similarly, section 201(n) of the Act was not intended
to require warnings about every conceivable risk that might
arise from use of a drug. This provision applies only to risks
for which there is sufficient medical evidence of a significant
hazard to meet the statutory test of materiality. Thus, in the
preamble to its regulations governing prescription drug label-
*ing, the FDA declared that warnings are to be included only
wwhen evidence exists on the basis of which experts qualified
by scientific training and experience can reasonably conclude
that the hazard is associated with the use of the drug.~ 44
Fed. Reg. 37,447 (1979). With the Reye Syndrome pilot study,
scientific experts have not yet had the opportunity to make an
independent determination as to whether these data are sound.
Without release of these data to interested parties, no such
scientific determination can be made.
V. CONCLUSION
Members of the PA are strongly committed to ensuring
that all OTC products are safe and that no personal privacy is
invaded. Data from the Reye Syndrome pilot study must be
released for public scrutiny in order to allow an independent,
scientific determination as to whether these data are valid.
52-266 O-85--18
PAGENO="0546"
540
Mr. WAXMAN. Thank you, Mr. Cope.
Mr. Chayet?
STATEMENT OF NEIL L. CHAYET
Mr. CHAYET. Thank you, Mr. Chairman.
My name is Neil Chayet, here on behalf of the Committee on the
Care of Children. Dr. David Lang was to be with me this morning.
He was to take, from your State of California, the Red Eye. He
had, unfortunately, a medical emergency within his own family.
His wife just gave birth to a child that has recently been in the
intensive care unit, and he felt at the last minute he really should
not be here. He did send a telegram to you fully supporting this
statement, and offering to meet with you as soon as possible.
I am particularly sorry he is not here, because he has been in-
volved in this from the very beginning. I am very sorry to have to
take a position that is contrary to your legislation today, because I
believe that you are in very good faith, and that all the people here
today, particutarly the parer~~s, have had as much impact on me as
anyone else.
There is only one problem. The science does not support the
warning, period. And it is really a shame, and it is a very difficult
position to take. I feel kind of like a voice in the wilderness, but
that is the way it is, and nobody can change it.
No matter how much is said, no matter how many words are
spoken, nothing can change that.
Now, there have been two phases to this situation. You have
heard them referred to as the "early studies." The "early studies"
were disastrous, Mr. Chairman.. Of those studies, three were
thrown out by the agencies themselves.
Only one survived, and just barely, and when that study was
looked at, it wasn't known who took what when. It is as simple as
that. It wasn't known what kind of medication was taken.
It wasn't known whether the kids in the cases had actually even
had Reyes syndrome, cases were excluded. It was a tragedy. But
something happened, Mr. Chairman.
I want to be sure you understand.
Mr. WAXMAN. Please go on.
Mr. CHAYET. I understand that, but what I am trying to say is
important, and I just would like you to hear me just briefly.
Mr. WAXMAN. I am listening to you, and you are recognized for 5
minutes to speak. You can use your 5 minutes any way you wish.
Mr. CHAYET. OK. All I am trying to say is that the reason that
the Government reversed itself on the initial labeling was not be-
cause of industry pressure. It was because the science simply
wasn't there, and a mistake was made, that was why the Academy
of Pediatrics recommended no relabeling of aspirin at that time,
because the science wasn't there.
By the way, if there is any doubt about that, I refer you to the
document you have in front of you, which I filed. There is a state-
ment by the FDA itself, which is a very interesting statement
about those early studies. It reads:
PAGENO="0547"
541
There is currently uncertainty about whether the reported statistical association
between Reyes syndrome and aspirin has any, any reasonable clinical significance.
That was the problem, Mr. Chairman.
If you read that statement of the Government itself, it just tears
to shreds all those early studies. Now, we are in another phase. Of
course, in the meantime, an error was made.
What may have been the biggest publicity campaign in the histo-
ry of this Nation about a drug was launched. How do you call it
back when an error has been made? It is a very difficult question,
believe me, for everyone.
And, what happened in the interim? I hope that what I am about
to mention to you didn't happen, but it might very well have.
Today is a story of "what-if." Well, what if the following hap-
pened? We reviewed the early PSA's released by the Government.
We asked the Becker Research Group and First Market Research
Group to interview people as impartially as possible. They chose
100 people from a shopping mall.
They showed to those people the Government PSA's and then
interviewed them, and 40 percent of them believed that aspirin was
the sole cause of Reye's syndrome. And 45 percent believed if you
didn't give aspirin to your child, you would prevent Reyes syn-
drome.
The one thing Dr. Wolfe and I, and we all agree on, is that de-
layed diagnosis of Reye's syndrome is fatal.
Mr. CHAYET. What if somebody saw the Government PSA's and
said my child couldn't have Reye's because we. didn't give him aspi-
rin, and delayed the diagnosis. What if that led to death? That is
why the doctors produced their PSA, because the Government PSA
was shown to be misleading.
Now, we have the pilot study and I wish I could say to you that
there is now credible scientific evidence for the warning, because I
would like to at this point say if it were only true, because every-
body else is saying it. But it isn't true.
Now, we have asked for the raw data of that study-and I have
to say the Government has been trying as hard as it can within the
constraints of the law to give us the raw data-but we have a prob-
lem, because the raw data that we have been given thus far simply
doesn't make it. It doesn't measure up, it isn't there, and I refer
you to the last tab of my testimony which was received yesterday,
which indicates the beginning of what I really hope isn't true, mas-
sive, incredible problems with that material. But we don't know
yet, and I wonder if I could ask you for some help? We need some
help in getting the raw data because what has been passed by the
Congress in good faith is apparently making it impossible for us to
get it.
We asked the Government for it, they said they don't have it. I
think they are answering accurately.
We asked the private contractor for it. They say we can't give it
to you because of the Privacy Act, and the Freedom of Information
Act is written into our contract and we can't violate those laws.
So, we can't get what we need to review this clinical record. We
don't want to identify these poor children or these families, we just
want to see if there is credible evidence of hazard. At least thus
PAGENO="0548"
542
far, there isn't. This warning is misleading. The science isn't there,
and I spent the last 20 years trying to find and work with impar-
tial, excellent physicians and scientists, because let's face it, what
the real issue is today is credibility. That is the question.
When do you warn, and who can you believe, and American
people may well be getting fed up with one warning after another
that turns out not to be right. That is why I would appeal to you
today to help us get the raw data and help us find exactly what the
evidence is.
I don't think the Institute of Medicine has seen that raw data
yet, I don't think the FDA has seen it. I don't know who has seen
it. I would like to appeal to you to help us find out so we can all
have unanimity here.
[Testimony resumes on p. 639.] -
[Mr. Chayet's prepared statement follows:]
PAGENO="0549"
543
TESTIMONY ON BEHALF OF
THE COMMITTEE ON THE CARE OF CHILDREN
PRESENTED BY:
DAVID J. LANG, M.D.
CHAIRMAN, DIVISION OF PEDIATRICS
CITY OF HOPE NATIONAL MEDICAL CENTER
DUARTE, CALIFORNIA
COORDINATING COMMITTEE, CCC
AND
NEIL L. CHAYET, ESQUIRE
GASTON SNOW & ELY BARTLETT
BOSTON, MASSACHUSETTS
LEGAL COUNSEL, CCC
BEFORE THE SUBCOMMITTEE ON HEALTH AND THE ENVIRONMENT
OF THE COMMITTEE ON ENERGY AND COMMERCE
OF THE HOUSE OF REPRESENTATIVES
HONORABLE HENRY A. WA)C'~AN, CHAIRMAN
ON H .R. 1381 "THE EMERGENCY REYE * S SVNDROME
PREVENTION ACT OF 1985"
MARCH 15, 1985
PAGENO="0550"
544
TABLE OF CONTENTS
TAB
Testimony Statement
Correspondence/Article from 1983 re: previous studies
on Reye Syndrome
- letter to Dockets Management Branch from Alvan R.
Feinstein, M.D.
- letter to Walter R. Dowdle, Ph.D., Chairman of
Reye Syndrome Task Force from Heinz F. Eichenwald,
M.D., Chairman of the Committee on the Care of
Children Coordinating Committee
- letter to Queta Bond, Ph.D. of the Institute of
Medicine from Heinz F. Eichenwald, M.D.
- article: "NIH, Japanese Studies Fail, to Back
Aspirin-Reye's Tie"
Scripts from the 1982 public service announcements
developed by the Public Health Service and summaries
of marketing researching studies of reactions to
these announcements by the public developed by
Becker Research Corporation at the request of the
Committee on the Care of Children 3
Citizen Petition: August 10, 1983 4
Interrogatory 1(a) and responses in reference to the
lawsuit of the Public Citizen Health Research Group
(Plaintiffs) V Dr. Frank Young, Commissioner of the
Food and Drug Administration (Defendants) .5
Statements and correspondence re: the current PHS
Study on Reye `Syndrome
- summary of statements by Alvan R. Feinstein,M.D.
presented at the hearing of the Institute of
Medicine on August 6, 1984
- letter to .M. Harry Jennison, M.D., Executive.
Director of the American Academyof Pediatrics from
Heinz F. Eichenwald, M.D., Chairman of the Committee
on the Care of Children Coordinating Committee
- Correspondence from Neil L. Chayet, on behalf of
the Committee on the Care of Children, to Eugene
S.' Hurwitz, M.D. of the CDC and to Mark Novitch, M.D.,
Thomas Scarlett, Esq., .and to Richard 3. Riseberg,
Esq., of the F.D.A 6
Article: "Potentiation of the Toxic Effects of Aceta-
minophen in Mice by Concurrent Infection with
Influenza B Virus: a Possible.Mechanism for Human
Reye's Syndrome?" from Pediatric Research (Vol. 18),
No. 2, 1984)
Articles:
- Boston Globe editorial, November 12, 1984
- articles - February 27, 1985 8
Text of mailgram sent to all television stations on
January 17, 1985 on behalf of the Committee on the
Care of Children 9
Preliminary analysis of the raw data from the Public
Health Services pilot study on Reye Syndrome 10
PAGENO="0551"
545
Mr. Chairman and Subcommittee Members:
The Committee on the Care of Children (CCC) is an organiza-
tion of approximately 1200 pediatricians from throughout the
country. It was formed in the fall of 1982 to address areas of
concern to pediatricians and their patients and has spent a
great deal of time since its inception reviewing matters re-
lated to Reye's Syndrome. The CCC is heade4 by a Coordinating
Committee of leading pediatricians from throughout the coun-
try. None of the members of the Coordinating Committee, nor
any of the members of the full Committee, are paid for any of
their efforts with regard to the CCC. From its inception, the
CCC indicated that its work in areas which relate to industry
would be funded primarily by industry, because of the belief
that industry has an obligation to fund arms length efforts to
seek the truth with regard to matters of controversy. The CCC
believes that there is in fact harmony between the interests of
industry in providing products which benefit the health of the
public, of the physician who prescribes such products and of
the patient who is the ultimate recipient of such products and
whose best interests bring all of us here today. On behalf of
the CCC, we are pleased to respond to the invitation of
Chairman Waxman to testify with regard to HR. 1381, which
deals with a matter of great importance to physicians and
patients throughout the nation.
The position of the CCC with regard to this matter has
remained constant and consistent: the public should be warned
PAGENO="0552"
546
immediately with regard to any product if such warning is
preceded by credible scientific evidence of hazard. (The CCC
filed a Citizen Petition, a copy of which is included as
Attachment 4, with the Food and Drug Administration in August
of 1983 on the generic issue of "When to Warn." The CCC is
still awaiting a substantive response to said Petition).
As the Subcommittee is no doubt aware, in 1982, the then
Secretary of Health and Human Services announced his intention
to change the labeling of aspirin containing products and
launched a nationwide publicity campaign warning patients of an
alleged association between aspirin and "Reye-s Syndrome". The
impact on the physicians and patients of this nation was enor-
mous, with patients expressing great concern One member of
the CCC reported receiving several hundred calls per month from
patients inquiring as to how to treat children with high
fever. In addition, a physician treating children with rheuma-
toid arthritis, of which there are approximately 150,000
throughout the nation, reported that parents and children were
refusing aspirin, which is the drug of choice for such cases,
(acetaminophen is not effective in treating inflammatory condi-
tions) and insisting that other drugs (including experimental
drugs) be prescribed.
Furthermore, the CCC attempted to ascertain the impact of
the government's extensive publicity with regard to this matter
and an impartial survey of response to Government television
PSAs indicated that 40% of those who viewed such material con-
PAGENO="0553"
547
cluded that aspirin was the sole cause of Reyes Syndrome, and
45% actually believed that not giving aspirin to a child could
prevent Reye's Syndrome, something which the doctors believe
could be extremely dangerous since it could lead a parent to
believe that his or her child could not have Reye's Syndrome
because he or she had not been given aspirin, leading to the
one thing which all agree is extremely dangerous - - delayed
diagnosis and treatment of Reye's Syndrome. (Please see
Attachment 3.)
The problem was that as physicians tried to calm their
patients, they also became increasingly concerned that the gov-
ernment action was not supported by credible scientific stud-
ies. The CCC asked that an impartial review be conducted of
the early studies, and it was concluded that they were fatally
and fundamentally flawed. (Please see Attachment 2.) In fact,
virtually every independent organization or individual scien-
tist reviewing the studies that initially gave rise to this
controversy has arrived at the same conclusion; the CCC is
therefore not an exception, but represents the widely held
opinion of these studies.
The CCC was not alone in its concern over this matter. In
November of 1982, the Executive Board of the American Academy
of Pediatrics issued a statement which urged that relabeling be
delayed pending further study, and that in the meantime, cau-
tion be used with respect to all anti-pyretic medication.
Subsequently, the FDA itself in an answer to interrogatories
PAGENO="0554"
548
propounded in an action brought by the Health Research Group,
stated as follows: "... there is currently uncertainty about
whether the report of statistical association between Reye's
Syndrome and aspirin has any reasonable clinical signifi-
cance. (Please see Attachment 5.)
In March of 1983, newly appointed Secretary of Health and
Human Services, Margaret Heckler, called for more study of this
issue and convened a Public Health Task Force composed of rep-
resentatives of the Public Health Service, the FDA and the
CDC. The Task Force contracted with the Institute of Medicine
of the National Academy of Sciences, which assisted in monitor-
ing the development of a protocol and which held a number of
public meetings with regard to this matter. At each of these
meetings, representatives of the CCC, along with many other
organizations, presented comments, noting a number of problems
with the intended protocol. Some of the suggestions made by
those parties were accepted by those responsible for the study,
but others, including a number of suggestions of the Institute
of Medicine, were not accepted. The purpose of the pilot
study, the results of which were released earlier this year and
which may have precipitated the legislation pending before the
Subcomttee at this time, was to validate the methodology of
the larger intended study, and was not intended to be utilized
to provide further evidence of association. In fact, there was
concern that premature release of the pilot study might preju-
dice attempts to complete an impartial larger study because of
PAGENO="0555"
549
the phenomenon of `recall" and "referral" bias based on public-
ity. There is no question, however, that serious ethical
questions are raised when any study, regardless of its initial
purpose, indicates a public health hazard. The question
remains, however, whether the pilot study was itself conducted
in a manner which gives rise to reliable and credible evidence
of a meaningful association between aspirin and Reye's
Syndrome. There is increasing concern that there may be ex-
tremely serious problems with regard to the data; we were ex-
tremely concerned to note recently reported comments by Dr.
Floyd Denny, Chairman of the Institute of Medicine Committee
named to review and monitor the study. Dr. Denny is quoted as
describing the study as "a flawed study, of course" and is fur-
ther reported to have stated that the study focused on very
small numbers of patients, had very poor geographical distribu-
tion and reflected "three or four" changes in the way the
interviews were carried out. (Please see Attachment 8.)
It is indeed regrettable that we come before you today with
no answer to this fundamental question because the raw data
with which to answer this question have not been made available
to us, or as far as we know, to anyone else. This is not to
say that the various government agencies involved have not
attempted in recent weeks to make large amounts of data avail-
able; the problem is that the data released thus far have
raised some extremely serious questions, some of which can only
be answered by a review of the clinical records involved. A
PAGENO="0556"
550
number of requests for this information have been made, but the
response thus far has been that the records are not available
under the Freedom of Information Act because the government
agencies are not in possession of same (therefore they alleged-
ly do not constitute an agency record) and yet, when inquiry is
made of the private contractor which carried out the study, the
response is that the contract with the government specifically
provides that this matter shall be governed by the FOl and
Privacy Acts, which are then interpreted as preventing the
release of such data -- a kind of `Catch 22' with unfortunate
consequences for all. We request in this forum, as we have in
virtually every forum open to us, that the doctors be provided
with the data they need to review the pilot study; they are
ethically and legally bound not to release patient-specific
information which could lead to the identification of individ-
ual patients. The doctors in no way wish to identify the
patients or contact the patients or their families in any way,
and it would indeed be paradoxical if the material released
thus far were able to be utilized in some way to identify the
patients, while doctors who were only interested in validating
important research were denied that opportunity. All of the
members of the Coordinating Committee of the CCC have acted as
trusted consultants to various agencies of the Federal
Government and other organizations, including NIH, FDA, the
Military, and the National Academy of Sciences. It is com-
pletely inappropriate to suggest that these individuals cannot
PAGENO="0557"
551
be trusted to protect patients privacy when they do so as a
matter of course every day.
We are enclosing with this statement the results of a pre-
liminary review of the pilot study data, and as can be clearly
seen from this material there are many unanswered questions
which mandate the availability of further information. (Please
see Attachment 10.)
It is most important to state that the CCC is not
interested in "nit-picking the data, but rather in
ascertaining if the present warnings and proposed regulatory
action are warranted. (Please see correspondence at
Attachment 6.) It is significant and unfortunate that no one
from the CDC is present here today (according to the previously
announced witness list) to respond to the questions concerning
the scientific base for all of the present activity.
Furthermore, we have great concern over the manner in which the
pilot study results were disclosed; the Institute of Medicine
report, based on its December 13, 1984 meeting at which a sum-
mary of the data was presented (and for which no meeting trans-
cript or tape is available), indicates the importance of peer
review of the data. If indeed the study results are fully
supportable by the study, and the study is one of which its
supporters are proud, why has there been such difficulty in
being able to review the statistical and clinical data on which
the study is based? It is the usual practice for such studies
to be reveiwed by peers prior to publication, and certainly
PAGENO="0558"
552
prior to the implementation of any conclusions. This is a
normal process that insures scientific accuracy and lack of
bias, and without it, no study is recognized as acceptable.
Lastly, it is necessary to address one very important
guestion of policy. Many have asked, why not warn now, because
"what if" the purported association turns out to be true. This
is a difficult question, and one to which we have given a great
deal of thought. We believe that in the short and long term,
the "what if' argument is a dangerous one; "what if" a drug to
which millions of people are turned, turns out to be as bad or
worse than the original suspect. (Please see Attachment 7
which includes an article referring to acetaminophen and Reye's
Syndrome.) "What if" parents believe, based on the strength of
the warnings, that the drug is indeed the sole cause of Reye's
Syndrome and delay diagnosis and treatment? `What if" the par-
ents of children for whom aspirin is the drug of choice (i.e.,
those with rheumatoid arthritis) refuse to allow aspirin to be
used? And what about parents who believe that they have caused
harm or death to their child by giving a drug that is in fact
not connected with the disease? And lest we forget, this is
not the first time the government might be mistaken; the trage-
dy surrounding the swine flu vaccine was directly related to a
precipitous warning program, which left in its wake no swine
flu, but hundreds paralyzed by Guillain-Barre Syndrome. The
program was no doubt well-intentioned by those who conceived
and implemented it, but the resulting consequences indicate
PAGENO="0559"
553
that the "what if" approach to public policy can be fraught
with hazard.
As for the future, we can only hope that credible evidence
can be found to settle this controversy. We therefore believe
that it is essential that further studies be carried out. The
Yale University School of Medicine has been working in prepar-
ing a study that would involve thousands of pediatricians
throughout the country. Again, we believe that industry has an
obligation to fund arms-length efforts to find the truth and we
are confident that such a study will be able to be announced in
the near future. Many precautions are being taken to insure
the credibility of such a study; in addition to the excellence
of Yale University, with its procedures to safequard integrity,
the American Academy of Pediatrics has appointed Dr. Sanford
Cohen of Wayne State University as a Liaison to the study. Dr.
Cohen, in turn, has been asked to chair an Advisory Panel which
will include some of the finest epidemiologists and clinicians
from throughout the country.
In conclusion, for all the reasons noted above, we cannot,
at this time, support mandatory labeling of aspirin-containing
products. In fact, we believe that the label proposed in H.R.
1381 could well be viewed at this point as resulting in
misbranding of said products, based on the scientific evidence
available to date. We simply must have credible scientific
evidence before proceeding with such a step, and we hope very
much that the Subcommittee will assist in securing this evi-
dence.
Again, we appreciate the invitation providing us the oppor-
tunity to be present here today and look forward to working
with all parties who have a vital concern for the children of
this nation.
PAGENO="0560"
554
COMMITTEE ON THE CARE OF CHILDREN
COORDINATING COMMITTEE MEMBERS:
Chairman, CCC Coordinating Committee:
Heinz F. Eichenwald, M.D., a William Buchanan Professor of
Pediatrics with the Department of Pediatrics for the
University of Texas Southwestern Medical School in Dallas,
Texas
Members, CCC Coordinating Commitee:
John Baum, M.D., the Director of Arthritis and Immunology-MCH
Strong Memorial Hospital in Rochester, New York
Harvey L. Chernoff, M.D, an Associate Professor of Pediatrics
with Tufts University School of Medicine and a Senior
Pediatric Cardiologist with the New England Medical Center
Hospital in Boston, Massachusetts
Joseph F. Fitzgerald, M.D., the Director of the Gastrointestinal
Disease Section for The James Whitcomb Riley Hospital for
Children in Indiannapolis, Indiana
Burton H. Harris, M.D., the Director of the Division of
Pediatric Trauma for the New England Medical Center
Hospital in Boston, Massachusetts
Robert A. Hoekelman, M.D., Professor and Associate Chairman of
the Department of Pediatrics for the University of
Rochester School of Medicine in Rochester, New York
David J. Lang, M.D., the Chairman of the Division of Pediatrics
for the City of Hope National Medical Center in Duarte,
California
James P. Orlowski, M.D., the Assistant Director of the Pediatric
and Surgical Intensive Care Unit for the Cleveland Clinic
Foundation in Cleveland, Ohio
Consultant, CCC Coordinating Committee:
Sidney S. Gellis, M.D., the Acting Chief of the Center for
Genetic Counseling and Birth Defects Evaluations for the
New England Medical Center Hospital in Boston, Massachusetts
PAGENO="0561"
555
Yale University
I SCHOOL OF 4~rC~E
CE'~,l~ L'at
333 Cd..r Sere~
P.O. L'~ LW
February 23, 1983
203 4364757
Dcckecs !`.ar.a;amenc Sranch
RFA-305
Food and Drug Administration
Roan 462
5600 Fishers Lane
Rockville, Maryland 20857
Ladies and Gentlemen:
The Co=.ittee on the Care of Children has asked me, as a consultant
previously un~mvolved in this problem, to review and coent on the
epidemiologic studies that purport to show an association between ~eye's
Syndrome and Aspirin. These studies are being used as fundamental backgrn~.~zd
d.ata for your decision regarding the proposed labelling of aspiria-ccncainiz;
products. The three epidemiologic reports are quite well `enown by their sites of
ortg~n as the Arizona, Michigan, and Ohio studies. They appeared, respect4veiy in
PEDIATRICS 66:859 (Dec.), 1980; in JA~'A 247:3089 (June 11), 1982; and in JAMA 248:
687 (Aug. 13), 1982.
After reviewing the published reports of these studies, I conclude that all
three of these case-control studies are serIously biased, particularly by the
failure to select an appropriate control group. The choice of an appropriate
control group is a coon problem in case-control studies, but the trio under
review here all share the same major flaw, which renders all three unacceptable as
unbiased scientifIc evidence. My reasons for drawing this comclusicn are as fo1~.s
In determining the positive or negatIve effects of a pharmaceucIcalagent,
the "gold standard" of scientific evidence is a randomized controlled clinical
trial. The FDA has played an important and admirable role in helping set thin
scientific standard of evaluation and in demanding that the standard be fulfilled
when claims are made about the action of pharmaceutical agents.
In its usual application, a randomized controlled trial contains at least
three operating principles that enhance its scientific quality and that give
credibiliry cc, the results: -
1. All patIents entered into the trial must fulfill approprIate criterIa
for eligibility. These criteria demand that patients must have suitable therapeutIc
indications for the main pharmaceutical agent(s) under study, and must not have
contraindications to any of then.
2. The compared agents are assigned with randomization. The purpose of
randomization is to ensure that "susceptibility bias" is mac created because
certain agents are preferentially aaaigne~ to certain subgroup. of patient~ who are
~re (or less) severely ill than the others, a~d who thereby have worse (or better)
prognoses for the outcome event.
PAGENO="0562"
556
Dockets MarLagesent Branch February 23, 1983
3. The outco~ event is deternined with "double blind' sethods, The
purpose of these nethods is to prevent the outcoce event fron being detected
or identified in a nanner that is bfased by the exanloer's knowledge of which
treatnent the recipIent received.
If we were able to perforn a randosi:ed clinical trial testing whethir
aspirIn causes Reye's Syndrnse, we would cosply with all three of these denands:
(1) The patients would be children eligible for the trial because they are sick
enough to receive aspirin therapy. (2) To ensure that the treatnents are
equitably assigned to the nost and least severely ill of these children, they
would be randonized tc' receive either aspirin or the cooparative agent (which
sight be placebo or acetonincphen). (3) The subsequent diagnosis of Rays's syndroce
would be node under double-blind conditions.
Since randonized trials cannot feasibly be conducted to deternine the
relationship between aspirin and Raye's syndrona, we have been forced to rely on
case-control studies. As I pointed out in a recent paper on epideniologic research
published in the SEW ENGLAND JOURNAL OF MEDICINE (307:1611 (Dec. 23). 1982),
scientific standards need not be abandoned in a case-control study nerely because
randoni:ation was not possible. With suitable scientific attention, all three of
the cIted principles can be attained or reasonably well approxirated in a case-
control study. Nevertheless, all three of the cited princIples seen to have been
ositted in all three of the Arizona, Michigan, and OhIo studIes.
The consequences of violating the third principle (about double blindIng) are
inporrant, but difficult to estinate quantitatively, since the published reports
do not describe exactly what happened. It seens clear that the interviewers
soliciting data about antecedent aspirin usage were quite aware of which patIents
were cases and which ones were controls. It also seens clear that the interviewers
were aware that the investigators were testing the hypothesis that aspirin nay
cause Reye's Syndrone. In this circun.stance, the opportunity for "ascertainnent
bias' is substantial. Without having seen or reviewed the individual fornats that
were used by the interviewers, however, and without having checked with the
investigators to detersine exactly how the interviews were conducted (and by whon),
I cannot detern.ine exactly how nuch bias nay have occurred. Nevertheless, when
investigators have deliberately taken adequate scientific precautions to guard
against ascertainrent bias (by keeping interviewers unaware of the research
hypothesis, etc.), the precautions are usually described when the research is
reported. No such precautions are nentioned in these three reporrs.
Regardless of the inpact of ascertainment bias, susceptibility bias surely
occurred in these studies because the investigators did not establish suitable
criteria for eligibility (to satisfy Principle 1) and did not perform suitable
satching of clinical severity (to satisfy Principle 2). The investigators clam
to have notched the cases and controls on the basis of type of illness (e.g.
influenza, varicella) and on the basis of height of fever. Neither ofthase
criteria La satisfactory to account for severity of illness. to a ooo_ra0d00~ed
stuoy, unless a specific index is used to classify severity of illness (rather
than fever alone, anorexia alone, headache alone, etc. or nultivariate C00bLnatiocs
of these features), the best way to determine severity of Illness is to ~ik the
parent ~ she or he decided to give the child aspirin, acetoninophen, ~ other
osdication, or no medication. These reasons for giving or not giving trestnaot
constitute the "therapeutic indication" that would be used to deters-ice ~ patients
eligibility for s randomized trial of a pharo.sceu:idil agent. The therapeutic
existing case-control evidence about the alleged danger of aspirin for Reye'a
Syndrome. I believe you would act wisely if you follcwed the prsvious precedent
set by the FDA in the reserpine/breast cancer controversy. By delaying any
action nov on the labellIng of aspirin-containing products, you can help the FDA
maintain its stature, its dedication to high scientific principles, and its useful
guidance services to the parents of sick children.
Sincerely yours,
~lvsn R. Feinstein
Professor of Medicine and Epide~ology
Director, Clinical Epidemiology Unit
PAGENO="0563"
55?
______________Committee on the Care of Children______________
50 MIlk Skeet, F'tfteenth Floor, Boston, Ma.ssachu,stts 0~109 * Tdephonr: (617) 4510803 Telex: 95113 Telecopler: (617) 451.~'~)
FEDERAL EXPRESS
May 6, 1983
Walter R. Dowdle, Ph.D., Chairman
Reye Syndrome Task Force
Centers for Disease Control
1600 Clifton Road
(1-6007)
Atlanta, GA 30333
Dear Dr. Dowdle:
In response to the April 8, 1983 Notice at Federal Register
48(69) :15331 requesting information regarding the development of
a new epidemiologic study to evaluate the possible relationship
between the use of medications and Reye Syndrome, the Committee
on the Care of Children (`CCC") respectfully requests that you
consider our recommendations set forth below. Also, the CCC
requests close coordination of the proposed new epidemiologic
study with the experts of the CCC. The CCC has an effective,
efficient relationship with pediatric departments of
university-affiliated medical centers and practicing
pediatricians across the country, and can facilitate the
development, implementation and completion of a multi-center
study on Reye Syndrome and medication usage.
By far, the preferred approach would be for HES to ask the
Institute of Medicine of the National Academy of Sciences to
plan, implement, and analyze such a study since such an approach
would assure the highest quality and impartiality. In addition,
and in recognition of the level of difficulty involved in this
proposed study, the CCC recommends the formation of a working,
consultative group with membership consisting Of representatives
from academia, clinical medicine, epidemiology, the CCC, consumer
advocate organizations, the Food & Drug Administration, industry,
Department of Health and Human Services, National Institutes of
Health, and the Centers for Disease Control. The function of
this group wguld be to supervise and review aspects of the study
and insure careful and complete compliance with the protocol.
This degree of careful attention, to detail should facilitate
agreement between all concerned parties, to the end that a
carefully constructed, well-designed study will be performed, in
COORDLNATThIC COMMTI'TEE Joseph F. Fiszgrald. M.D. Dacid). Lang M.D.
Heinz F Eich,nsoald. M D . Cha:rman IsdO??OpOlC lnd:ano Bolt:::or,. Maryland
Della,. T,zas Bsar,or H. Harris. M.D. James P. Orloscsk:. M.D.
John Bases. M.D. Bose',. Massachawtts Clcelond. 0/co
Roch,sstr. New York Robert A. Hoeke/man. M.D. CONSUI,TANT
Haroey L. Chernoif. M.D. Rochester. New York Sorry Delis. M.D
Bosinn. Maaaarhsa,r:s Sos:o:. Massachasaits
PAGENO="0564"
558
May 6, 1983
Page 2
a manner sufficient to satisfy the questior.s of careful
scientists. It must be recognized that a number of individuals
and organizations in and out of government have taken a strong
stand pro and con with regard to the aspirin issue; a committee
consisting primarily of representatives of groups that have
expressed such views would not be judged impartial nor could it
be expected to- be. However, the input from this working group
may be useful to a full, careful analysis of the problem.
The CCC maintains that the development of careful protocols,
well-trained investigatory teams, and the selection of physicians
experienced in the recognition and accurate diagnosis of Reye
Syndrome are essential components to a careful study. The CCC
respectfully requests the opportunity to work closely with the
Public Health Service in the design and implementation of a
multi-center, case-control, retrospective epidemiologic study on
Reye Syndrome and medication usage.
Dr. Joseph F. Fitzgerald at Indiana University Medical
Center, James Whitcomb Riley Hospital is a member of. the Coordi-
mating Committee of the CCC, and serves as; Mid-West (Central)
Regional Director of a multi-center study entitled the "Reye
Syndrome Study Group.' This study group -consists of at least 16
medical centers wl~o have agreed to osmotherapy vs. pentobarbital-
augmented osmotherapy in a randomized fashion on identical
clinical protocols. Application has been made to the National
Institute of Health for funding, with a site visit conducted on
February 28, 1983. The principal investigator of the study is
Dr. Wallace Berman at the Medical College of Virginia. This
group has received word of a favorable site visit and that
approval for funding is under consideration. As you know, the
coordination of 16 or more medical centers in a collaborative
study is an awesome undertaking, yet such undertaking has the
considerable advantages, of large numbers of potential entrants
into the study. These collaborating medical centers could serve
as the framework to evaluate the role. that salicylates and other
medications play in the -development of Reye Syndrome. The CCC
would be willing to work with the Reyc Syndrome Task Force in the
development of a protocol that effectively identifies and
minimizes the problems inherent in case-control epidemiologic
studies. Unless these studies are performed by investigators
with experience in both the disease entity and the appropriate
techniques employed in studying the disease, the results may
again be seriously flawed and inconsistent with the dictates of
scientific excellence.
PAGENO="0565"
559
May 6, 1983
Page3
The CCC further recommends that a protocol development group
be formed as quickly as possible, with representation from the
aforementioned groups. The protocol produced by this group
should be reviewed by appropriate experts, and should allow
sufficient tine for careful deliberation; at~ the same time,
however, we stress the urgency of this matter, and offer our full
cooperation in having the study in place by the next flu season.
Specific attention should be given to criteria for the
diagnosis of Reye Syndrome, the selection of appropriate con-
trols, mechanisms *for the control of various forms of bias,
establishment of site visits, training investigators among the
various collaborating medical centers and the development of a
highly detailed standard to quantitate the severity of illness.
The principles enunciated in Dr. Alvan R. Feinstein's comment to
the Advanced Notice of Proposed Rulemaking (Federal Register
47:57886, December 28, 1982) sets forth the specific factors that
constitute a `gold standard" that must be followed rigorously and
adhered to for the study to~ hold scientific validity.
Furthermore, Dr. Feinstein's December 23, 1982 article in the
New England Journal of Medicine reinforces the requirements of a
well-controlled study. These principles must become an integral
part of any case-control study.
Furthermore, the CCC recommends the adoption by the Reye
Syndrome Task Force of the following criteria for the diagnosis
of Reye Syndrome cases to be included in the proposed study:
1. A clinical history compatible with Reye Syndrome.
A. Usually a variable course of respiratory illness,
chicken pox, or acute gastrointeritis.
B. Sudden onset of unexplained vomiting, protracted or
relentless vomiting may be present.
C. An alteration of consciousness and/or progressive
neurological deterioration.
D. The cerebral spinal fluid examined within 24 hours of
admission must contain less than 10 white blood cells
per cc and be sterile.
E. Association of seizures, hypoglycemia, abnormal breath-
ing pattern in infants.
2. Alteration of liver function without evidence of hepatitis.
PAGENO="0566"
560
May 6, 1983
Page4
A. SGOT (AST) greater than two times the upper limit of
normal and an SGPT (ALT) greater than two times the
upper limit of normal.
B. A free flowing venous or an arterial ammonia level
greater than two times the upper limitof normal.
C. Prothrombin time greater than two standard deviations
above the mean.
D. A serum bilirubin less than three milligrams per
deciliter.
3. A closed liver biopsy consistent on light microscopy with
Reye Syndrome obtained within 24 hours of admission.
One of the most difficult parts of this study is to cor-
rectly diagnose the disease. The CCC believes that the use of
liver biopsy,* interpreted by experienced pathologists familiar
with the staining technique and characteristic features of the
disease, is an essential ingredient for this `study, and is a
prerequisite for selecting medical centers to participate in the
collaborative study.
Another essential factor in this study should be the extra-
ordinarily difficult task of matching cases with controls. Care
must be taken to insure accurate knowledge of variables, such as
aspirin or other medication. If controls are allowed some degree
of leeway in the predisposing viral illness, then a biased study
result will occur. The only independent variable must be aspi-
rin. Furthermore, it is another essential prerequisite that the
cases and controls be comparably ill with the identical specific'
illness. For example, cases with influenza B cannot be matched
to "controls' with other respiratory illness that do not predis-
pose to Reye Syndrome. Specific etiologic identification of the
illness of controls as well as cases is necessary. The Reye
Syndrome studies in the past includ~d cases that were clearly
more ill, with higher fevers, more dehydrated and required more
fluid than the controls. Varying degrees of illness of chicken
pox, influenza A and B were present. These factors suggest that
children with Reye Syndrome may have some predisposition, genetic
or otherwise, to have a more severe prodromal illness that may
result in the subsequent development of Reye Syndrome.
The protocol development group may want to consider quanti-
tating the severity of illness via a non-specific toxicity
score" (i.e. develop a standard measure of severity as assessed
PAGENO="0567"
561
May 6, 1983
Page 5
by a physician with years. of experience in the diagnosis of Reye
Syndrome). In addition, we believe that to achieve a good result
from this study, it is essential to involve skillful, experienced
clinicians all along the way. The use of inexperienced investi-
gators, armed only with questionnaires, will bias the study such
that it will be rendered meaningless.
Also, careful case-control matching for race, sex, similar
geographical location , socio-economic and other factors must be
employed.
There are some experts that believe that requirements for a
case-control study, as set. forth in Dr. Feinstein's article,
cannot be met. We vigorously maintain that if these criteria are
not met, the study is not worth doing because like earlier ones,
it will generate results that are misleading and incorrect. Had
the studies of the past been carried out using the principles we
have listed, no dispute would exist at the present time about the
role of aspirin.
It is thus our recommendation and request that the Reye
Syndrome Task Force, in cooperation with the CCC and Dr. Joseph
F. Fitzgerald, a member of Coordinating Committee cooperate to
develop a protoco~, train investigators, and implement a well-
designed and carefully controlled multi-center tri~tl that
attempts to answer questions relating to the possible relation of
aspirin and other medications to Reye Syndrome.
Furthermore, this is to confirm that the representatives of
the CCC have been in contact with you relative to a meeting with
the Task Force dealing with protocol design and implementation.
Furthermore, we understand that this meeting will take place as
soon as can be scheduled and we look forward to discussing these
matters in depth with you at that time.
Very truly yours,
C
Heinz F. Eichenwald, M.D.
Chairman, Committee on the
Care of Children
/kmp
End.
cc: Arnold J. Friedhoff, M.D.
John Baum, M.D.
Harvey L. Chernoff, M.D.
Joseph F. Fitzgerald, M.D.
Burton H. Harris, M.D.
Robert A. Hoekelmann, M.D.
David J. Lang, M.D.
James P. Orlowski, M.D.
Sidney Gellis,. M.D.
Neil L. Chayet, Esq.
PAGENO="0568"
562
August 3, 1983
FEDERAL EXPRESS
Queta Bond, Ph.D., Director
Divisions of Health Promotion
and Disease Prevention
and Health Sciences Policy
Institute of Medicine
National Academy of Sciences
2101 Constitution Avenue
Washington, D.C. 20418
Dear Dr. Bond:
We have received the United States Public Health Service
Proposal for a Study on Salicylates and Reye's Syndrome. Pursuant
to your request, we have analyzed the proposed study methods and
design. Our comments are set forth below. Also, as we discussed,
several committee members will make an oral presentation to the
Institute of Medicine's Committee on Reye's Syndrome and Medication
on August 8, 1983. I will contact your office on August 5, 1983
to make final arrangements.
I. Background
The Committee on the. Care of Children is a group of parents
and approximately 1200 physicians which was formed as a result of
the belief of a number of academic and clinical pediatricians
that the debate over the safety of aspirin as it related to
Reye's Syndrome was not being carried on in an unbiased, scientific
manner.
Aspirin is the most widely used over-the-counter drug in the
United States, and any claims that it may n~t be safe in certain
situations cannot be lightly disregarded. On the other hand,
aspirin has been viewed as a safe drug for over 80 years and any
claims that it may not be safe must be examined with great care.
Unfortunately, the recent debate over the safety of aspirin seems
to have focused more on the motivations of the participants than
on a dispassionate analysis of the studies which questioned the
safety of aspirin.
PAGENO="0569"
563
It. Introduction
Dr. Walter Dowdle and the members of the Reye's Syndrome
Task Force are to be commended for the protocol they have developed.
It is carefully construct~d and represents a major effort by the
members of the Task Force.
We are convinced that this protocol represents a first step
towards answering the questions raised in the Ohio, Michigan and
Arizona Departments of Public Health studies. These studies were
poorly designed, replete with methodologic flaws that invalidate
their results. As summarized by Dr. Alvan R. Feinstein in his
comment to the ANPR of December 28, 1982 (47 Fed.Reg. 57886),
"...1 would*be reluctant to consider the evidence
from these three studies as being scientifically
satisfactory. The only conclusion I would draw
from the studies is that more and better research,
of higher scientific quality, is needed to answer
the question." (Comment, p.3)
The "better research, of higher scientific quality" is the
objective of the IOM's Committee, the CDC, and the Committee on
the Care of Children. We believe that the Task Force Protocol
may be adequate, with certain adjustments mentioned below, to
meet this objective. However, there are potential problems in
the protocol that must be addressed before the protocol will
withstand careful scientific scrutiny. These potential problems,
with our recommendations, are discussed below.
I II. Recommendations
- ~iver biopsies must be utilized to confirm the
diagnosis of Reye's Syndrome (see t~ichtensten PK,
et al; Grade I Reye's Syndrome, NEJM 1983; 309:133-
9). Should the study include cases that are not
Reye's Syndrome, an unacceptable degree of inaccuracy
will occur. Also, the histologic material be
collected in a standardized manner, and that this
material be reviewed by a panal of "expert" patholo-
gists prior to statistical analysis.
- Serologic diagnosis must confirm that identical
antecedent illnesses are present in cases and
their matched controls.
PAGENO="0570"
564
Experienced clinicians and scientists at tertiary
care medical centers should perform this study, to
insure the diagnosis of Reye's Syndrome and the
careful nanagement of the study. Using medical
centers would enhance the quality of the study and
the validity of the results. CDC control could be
readily maintained through on-site visits, spot-
checking of interviewing techniques, etc. Also, a
multicenter study in progress has been funded by
the NIH, which will examine two treatment protocols
on outcome of children suffering from Reye's
Syndrome. These same participating medical centers
could perform this salicylates and RS study in a
less expensive, more thorough fashion than other
centers that do not have a study on Reyes Syndrome
study. in place.
Local departments of public health should not
oversee this study. We respectfully submit that
local public health participants are very likely
infected with observer bias in ligh of their
participation in the prior CDC studies in Ohio,
Michigan and Arizona. The criticisms these officials
were subjected to during critical analysis of
these studies makes them unacceptable directors of
this study.
The interviewers must be blind to the research
hypothesis. Otherwise, unacceptable bias will
result.
The attending physician, rather than a public
official, should contact the "case' requesting
enrollment in the study. The protocol does not
call for the physician to be notified that his
patient is to be enrolled. Such an oversight
could create a situation where parents are asked
to enroll their child in a study when they are not
emotionally. equipped to answer the questions asked
by the interviewer. Prior physician approval must
be sought.
The primary care physician for the "control"
should also be notified before any serum samples
are taken. The physician should draw blood samples
from very young patients.
PAGENO="0571"
565
- The "controls" and physicians caring for the cases
devote an appreciable amount of time to this
study. It should be considered whether to pay
these individuals for their efforts.
IV. Conclusion
We recommend that the strictest possible criteria be generated
for the selection of cases and controls for entry into this
study. Cases must be evaluated by skillful clinicians, experienced
in the recognizing of Reye's Syndrome. In addition to a compatible
clinical course and the meeting of necessary laboratory criteria,
histologic analysis of tissue obtained by percutaneous liver
biopsy must be performed.
All cases and matched controls must have the same predisposing,
antecedent illnesses as determined by serology.
In addition, we recommend that this study be conducted in a
medical center setting, where experienced physicians will actively
participate to see the study through to completion.
Please call me or other members of the Committee on the Care
of Children if we may answer any questions.
Very truly yours,
Heinz F. Eichenwald, M.D.
HEE/ral
Enclosures
PAGENO="0572"
566
NIH, Japanese Studies Fail
To Back Aspirin~Reye's Tie
Mr,!, :1 Tr,hun, Rrp~~r~
Sr. Louis - Scientific presentations at
the recent National Reye's Syndrome
Foundation (NRSF) annual meeting here
gave little attention to and no support for
the connection proposed by case control
studies last year between salic~ ate use in
children and development of Reyc's syn-
drome (RS).
An "education campaign" had bei!n
launched in 1982 by the Surgeon General
warning the public not to use aspirin for
children with varicella or influenza-like
illnesses. A warning label on salicylate-
containing products had been proposed but
was not put into effect when questions
about the validity of the data in the studies
arose and the Committee on the Care of
Children, a group of leading pediatricians.
sought a federal court injunction against
issuance of the label (MT. Jan. 26).
The Centers for Disease Control (CDC)
has not yet issued a morbidity and mortal-
ity report on RS cases for 1982-1983.
Ilowever. a chart of cases and mortality
reported to the NRSF front December 1.
1982 to June 15. 1983, available at the
meeting, listed ~4 eases and 27 deaths.
Ohio topped the listwith 26 cases. two fa-
tal. while Michigan and Texas followed
with nine and seven, respectively. One tzL-
tality occured among the former and four
among the alter.
I Itiwever, ni" inedtcatton use data were
supplied, and difficulties in positive diag-
nosis make interpretation of the statistics
difficult. Dr. George Ni. Johnson. of Far-
go. NI).. discoverer of the syndrome in
the United States, commented that ``a ma-
jor vuricella outbreak in North Da~ota has
produced no KS cases" in the state. Ile
noted th.ii this agreed with other investiga-
tors' earlier suceestitins that RS was con-
nected in sonic w a> with tnlltieni;i- U.
whi~h did not prisitrec a major outbreak in
the United .States this winter.
Two preliminary reports at the meet-
ini.!--sille on a n;ttittitwidc su~ cy of f 3 )j~f
pediatric clinics in Japan (where KS l)ic-
~ioiisl~ has been reported) and the otherin
a National Institutes of I Icalth study coot-
pat tug l<.S sur~ us ors and heir un.tf fcet.d
I iintl~ tttcmber~ in their ability to ``handle
suhtcvlates'' - tutfered no cvid..'nec It) stp-
port a salicylateiRS connection.
Dr. Fumio Yamashita, a rnembef of the
Japanese Ministry of Health's RS study
committee, explained that the survey gath-
ered information on both RS and "acute
encephalopathy of obscure origin" to
compare aspirin intake between the
groups. Using CDC criteria for RS and de-
fining the other group as having similar
symptoms without SGOT and SGPT ele-
vations, the investigators found the peak
incidence of both to coincide with the
height of a six-month influenza-B epidem-
ic over 1981-1982.
According to the Kurume University
pediatrician, 54 RS and 75 acute encepha-
lopathy cases have been reported, with
confirnied aspirin intake in just 9.3% and
89~ of cases, respectively. Investigators
are now following up on the 1 1% of both
types of patients w hose drug intake is `un-
known" and the 26% and 32c~, respec-
tively. of patients on whom drug usage in-
formation is "uncertain." Nearly half the
reported KS cases had received nonste-
roidal aitti-inflanintatory agents and anti-
consulsants, as well as antibiotics. No
drugs were given in 20.4% (if the RS
cases, and in 29.3% of the acute encepha-
lopathy cases.
Dr. Yamashita concluded, "If this rep-
resents the accurate incidence of salicylate
usage. these drugs may not be a major nsk
factor itt the paihi genesis of KS in Japan."
L)r. Anita 1). (itu, NIH, reported on the
first five KS surs i'~ors she tested for their
response to.ispirin. compared to their non-
RS fantily nietitbers. 11cr conclusion: "RS
patient survivors did not have any difficul-
ty handling safie> lates after their illness."
Administration of' aspirin at 10, 20, and
30 nsg'kc a day, built up over a six-day
hopitaf sta> . pri~lu~~d no clinical. hio-
henncal . or hctii;itofog i~il ahuii'uiialittes,
anti neither seruiti nor urine salicylate fey-
cia differed significziiitly between the for-
liter KS patients and fantily members.
Neuropsychotogical tests revealed no sig-
nificatut difference between R~ patients
and their siblings. l'attents diii have higher
intihod\ tiicr~ iii sariLelfi. incastCs, intlu-
en.~,i- \. .iitd l~' k in Ran virus, and
``there 5' as no dicasi.' .issi ciatton with
Ill .:\ i> )C. * [lie stud~. u eiiotiuiuing.
PAGENO="0573"
567
~p,c~czbIJ 4~JERAL Iaign, stare fran an underlying deficiency
in the IDA's standards and procedures. Id., at 1-2.
~i the basis of this, and other opposition to the PDA's proposed
warnings, the FDA's campaign to warn the public of the purported
association betwaen aspi.rin and Reyes Syndrcxre is being reviewad and
undoubtedly will be revised, pending the outcane of further scientific
studies initiated by the Goverrrnent.
It is always easier to state, in hindsight, that a particular
publicity campaign was improper or excessive. Witness the 1959
contaminated cranberry publicity cairpa.ign and the 1979 nitrite publicity
campaign. Howaver, had these proposed regulations, including the
standard on reliability, been in effect prior to the aspirin/Hayes
controversy, unwarranted publicity concerning a highly tenuous danger to
public health might have been mitigated or avoided. Prior `to the
publicity campaign, the FDA would have been required to determine
whether the studies net generally accepted scientific standards for
rrethodological and statistical significance. Upon that determination, a
contrary decision with respect to the need for publicity may have been
reached, and much needless public anxiety prevented.
Standards for the Content of Publicity
These proposed regulations establish standards for h~ the Agency
crafts its publicity which must be net before the agency' issues
publicity. Operating under the asstrrption that preventing
PAGENO="0601"
595
misinterpretations and exaggerations of public announcetents is better
than trying to ccrçensate parties after the fact, this standard helps
the FDA tailor its publicity so that it achieves its intended
cennunication.
Agency rules regarding the content of press announcet~nts
should vary depending on the ccxrplexity of the agency
action, the sophistication of the likely aedience of
beth the lreediate reporters as well as the ultinate
readers and viewers - and the possibility of
harm... .Agency rules should also indicate the proper
tencr and format of publicity anno~mce~nts. Gellhorn,
at 1430.
There are nmny instances where, even though the content of a
cont~rplated announcenent is literally accurate, the phraseology, timing
of the release, or ncde of dissenination is likely to exaggerate or
minimize in the mind of the public the significance of the iressage
intended. These standards wettld require the FDA to take steps to
minimize this possibility, and in sate instances, to refrain altogether
fran issuing such a provocative announcErent.
The recent aspirin/Reyes controversy illustrates the need for these
standards. At best, the stndies relied upon by the FDA indicated a
possible "association" between aspirin use and Reyes ~Syndrare. As part
of the publicity carrpaign waged by the governirent, the Surgeon General
in 1982 nade public service radio announcerent recordings explaining
that there may be an association between Reyes Syndrane and aspirin, and
sent approximately 8,000 copies of these radio anriouncenents to radio
stations. (47 F.R. 57886 at 57897). However, the public's reaction to
these am nanrents deronstrated its general inattentiveness to the
scientific distinction between "association" and "causal relationship."
The fact that the public (infers) .. .the causal nature of
an association, has been det~n.strated by the effects of
the FDA's "educational" progran regarding ~SA and RS. A
PAGENO="0602"
596
pilot personal intercept interview study, c~thucted by
Becker Research Corporation and carrnissioned by ~C,
ocnfimt~ these fears.. .In the Becker study, one hundred
three respondents ~re asked to listen to a taped massage
fran the Surgeon General. Dr. Koop addressed the
possible association bet~e.n PS and the use of ASA in
children under 16. ~ respondents consisted of parents
with children under 16.. .The objective of the research
project s~~s to dete~nine parents' under-tanding of the
Surgeon General's massage. After hearing the msage,
40% of the respondents stated that they believed that ASA
causes PS. In addition, 43% of parents believed that if
they did not give ASA to their children, they oculd
prevent the developr~nt of PS. fl~se effects are
oonsiste.nt with the experience of the ~ Coordinating
Carinittee n~i±,ers, ~ have faced ntsrerous parents
frightened by the publicity of the Goverrn~nt. The
parents have responded to the Goverrsrents publicity
canpaign in an irrational fashion rather than
understanding the subtleties of the statistical
"association".
A survey of press coverage of the ~ "educational"
caspaign confinns this unintended result.. .For exairple,
in an article a~earing in the New York Timas on Nov~iiber
17, 1982, Jane Brudy, an e~~rienced health reporter,
makes the stat9zEnt that "the only kna~'n possible
preventive (of PS] is to avoid giving aspirin
(salicylate) and rredications containing aspirin to
children with viral illnesses... "Thousands of newspaper
articles have been written which misinterpret the maaning
of "association", encouraging parents to prevent PS by
avoiding ASA, which, according to the newspaper accounts,
has been sha~n by studies to "cause" PS. CtC Carmant, at
22-23.
The public reaction to the Surgeon General's massage was
predictable. It ~u1d not have been difficult for the governrrent to
pretest its publicity massage prior to the news releases. The FDA, UJ~e
any goverrre.nt agency, has an obligation to carrrn.micate in a manner that
conveys accuracy in the public' s cat~rehension of FDA massages.
These proposed regulations require the FDA to consider alternatives
to publicity in achieving its goals. The Adeinistrative Conference
reccznrethed in 1973 that "where public hann can be avoided by irrirediate
discontinuance of an offending practice, a respondent should be all~ed
PAGENO="0603"
597
an opportunity, where feasible, to cease the practice (pending a legal
test) in lieu of adverse agency publicity." (38 P.R. 16839). ?dverse
publicity often constitutes a deprivation not subject to effective
judicial review, and therefore, should ho exercised only as a last
resort if necessary to achieve a ccspelling public interest. I*~/PDA
policy is "to avoid publicity that might adversely affect persons or
organizations where a reasonable and equally effective alternative is
available, (such as] . . .the discontinuance of a violative practice,
ccxrbined with an effective recall of violative products fran the
marketplace." (42 P.R. 12436 at 12439).
`ft~se proposed regulations require the FDA to choose the least
obtrusive rrethod of dissemination of its public massage, geared toward
the narr~st audience possible for the carounication to be effective.
¶ihose regulations require the FDA to determine, first, the narr~sest
audience it oust reach (e.g., physicians, pharmacists, hospitals,
specific groups of the public, general public, etc.), and second, which
nethod of dissemination will effectively reach that particular audience,
but no further. Since a physician ~vuld be less likely than the general
public to exaggerate the neaning of a specific warning, such as the
"association" between aspirin and Peyes Syndrare, targeting specific
massages toward specific audiences will be ouch trore effective in
actually protecting the public. In the aspirin/Reyes controversy, for
exasple, it quickly becare apparent that:
The FDA.. .has no standards to determine whether a warning
should be directed to the consuner of the nedication when
he may be unable to determine whether he is at risk fran
the hazard which pratpted the warning and unable to
assess the significance and magnitude of that risk.
Z'breover, where, as here, the subject of the proposed
warning is a drug which has been widely utilized and
studied for many years, the FDA oust consider the
PAGENO="0604"
598
possibility that any warning will cause consi.sre~rs to
shift to less ss~ll-kr~jn or less wall-studied
drugs,. ~. [and result] in fear and confusion in the mind
of the public. CCC CclTlrent, ~ at 2-3.
N~ that the whole issue of whether there even is a statistically
significant association betwaen aspi.rin and Reyes Syndrare is being
restudied by the Governrrent, it is evident that;the publicity issued in
connection with aspirin/Reyes was excessive. If nothing else, the
ITanufacturers of salicylate-containing products have been ecor~nically
damaged, patients question their physicians' advice to use such
products, and the FDA's stature has diminished in the eyes of the public
for "j~n~ing the guns. These proposed regulations are intended to avoid
similar situations.
Pi~vance Notice
In accordance with the rec~rrr~ndations of the ~ninistrative
Conference these proposed regulations provide for advance notice of
proposed publicity to interested persons. ~ purpose of advance notice
is t~fold: 1) to provide interested persons an opportunity in advance
to prepare a response to such publicity; and 2) to provide interested
persons an opportunity to catrrent on such publicity prior to its
issuance in order to insure its accuracy and fairness.
The class of persons entitled to advance notice under these
regulations is broader than the car~a.rable class entitled to notice in
}~S regulations (45 C.F.R. 17.1 et. ~.) governing adverse publicity,
in that it includes any person who is likely to be, or in fact,
adversely affected by the issuance of publicity by the FDA. This could
include for exanple, rt8nufacturers of identified products, as wall as
physicians who prescribe such products. These regulations are also
broader than those governing publicity fcor~rly considered by the FDA
PAGENO="0605"
599
(42 F.R. 12436) in that they require that advance notice be provided in
circunstances where publicity, as defined herein, is contarplated in
ounjunction with proposed rulanaking.
Notice of contariplated publicity shall be by publication in the
Federal Register, and/or such trade publications, joum~als and
newsletters, as deened necessary for effective notice. The requirer~nt
of providing advance notice of publicity serves as a procedural elerr~nt
of due process protection for these liicely to be adversely affected by
the ountariplated publicity. These regulations irrp~se on the FD?~ the
further requirar~nt that the notice itself be carefully s~vrded so as not
to precipitate a pranature public reaction. Therefore, the actual text
of proposed publicity should not be included in notices.
As previously indicated, one of the major reasons cited by the
Mninistrative Conference for requiring advance notice of contemplated
publicity is to afford those likely to be adversely affected "a
reasonable opportunity to prepare in advance a response to such
publicity." (38 P.R. 16839). The value of a response to publicity
should not be underestinated.
When a fire believes that ~ will be issuing publicity
about its products or activities, immediate contact with
the agency's Press Office by a professional public
relations person on behalf of the fire is vital.
Defensive releases, the s~rding of the PDA release, the
nedia likely to be used, facts which undereine the
agency's case, etc., are aLl. elements to be considered in
defensive publicity. Since pi~licity bearing the official
PDA stamp of approval often makes headlines, the finn
should be prepared to irrirediately respond with its side of
the disputed story, lest a next-day correction be buried
on an inside page or anitted entirely fran the news.
O'Reilly, James T., Food & Drug ~deinistration:
Regulatory Manual, S22, at 47-48. (Sheppards 1979).
PAGENO="0606"
600
These proposed regulations insure as ~ll that the FDA, as a result of
the participation by interested parties, will be able to provide the
public with full and ~ll balanced information.
Retractions and Corrections
m'ese proposed regulations establish procedures for the retraction
and correction of FDA publicity that is shown to be erronecus or
misleading. Similar statutory provisions require the Cons~.rtEr Product
Safety Camdssion to take reasonable steps to publish a retraction of
any inaccurate or misleading thfo~tion it had publically disclosed.
15 U.S.C. 2055(b) (7). The Aáninistrative Conference re~rrrended
specifically that agencies issue retractions or corrections "in the sane
manner (or as~close thereto as feasible) as that by which the original
publicity ~as disseninated." (38 F.R. 16839). The proposed regulations
require that a retraction or correction "be issued in a manner likely to
reach those persons who received the original inforn~tion to the extent.
this is reasonably feasible." The goal of reaching the sane audience
with the new information, rather than siirply issuing a new statetent in
the sane manner as the damaging staterents, is n~re likely to have the
desired effect, and is consistent with the original FDA proposal for
regulations governing agency publicity. (42 F.R. 12436 at 12441). Upon
petition of a party adversely affected by FDA publicity, the FDA shall
expedite the request for retraction or correction of erroneous or
misleading publicity, so as not to vitiate its effectiveness through
delay.
In addition to correcting ioproper FDA publicity, these regulations
provide for the Carrnissioner to seek corrective publicity in cases t~there
PAGENO="0607"
601
the fault of misinterpretation or exaggeration lies with third parties.
This discretionary approach was specifically proposed by the FDA:
In cases where infontation by FDA has been misinterpreted
by other persons or presented by the rredia In such a way
as to be misleading to the public, the agency will
~sider the issuance of clarifying infonration.
Although the agency is net responsible for publicity
generated by an outside source that is adverse to a finn
or product, the Ccxanissioner nay seek corrective
publicity at his ~~in discretion, or at the request of the
adversely affected party, if the agency has infonration
available that ~.ould indicate that such publicity was
grossly misleading to the public and that it ~uld be in
the public interest. (42 F.R. 12440)
In light of the Inçortant role that FDA publicity plays in generating
public interest and Jc~.ilodge in matters of public health, it follovs
that issuance of responsive publicity - to correct unwarranted public
reactions injurious to particular persons, firms, professional groups or
products - ~uld be equally inçortant in furthering FDA objectives.
Conclusion
In the absence of legislative or julicially iirposef guidelines
governing the FDA's issuance of publicity, these regulations respond to
the persistent cry for such control: "Unless the public `need' for an
irrrrediate anno(mcmrEnt is substantial, the ideal procedure ~u1d be to
postpone agency publicity which is likely to have a significant and
adverse ispact until the naned respondent has had an opportunity for a
hearing." Gelihorn, at 1429. Likewise, a manufacturer of a product
maligned by improper publicity nay 1~e "cond~rned by publicity without a
hearing or any other s~rblance of due process." Z~brey, at 177. These
proposed regulations parallel the statutory provisions governing the
release of information controlled by the Consuner Product Safety Act.
15 U.S.C. 2051 et. ~. Under the Act, the Consuaer Product Safety
Connission may publicly disclose info~tion adverse to a manufacturer
PAGENO="0608"
602
only after providing notice of the proposed disclosure and an
opçortunity to subeit canr~nts, and after assuring itself of the
accuracy of its infontation and the fairness to the rranufacturer of the
publicity. 15 U.S.C. 2055(b) (1).
Upon satisfying the proposed requirarEnts, the FDA ~u1d issue the
proposed publicity. The detennination of the issuance of publicity
sha.U co~rstitute final agency action for the purpose of appeal. An
aggrieved party may challenge the FDA detennination in a court of
ca~etent jurisdiction. Effective reviecq will be rrade possible by the
existence of these regulatory standards and of a record of the FDA's
fir~ings that ~re required prior to the issuance of the publicity in
question.
C. ~VII~r~]AL IMP~C~
Petitioner relies on the FDA's Proposed Policies and Procedures for
canpliance with the National flivirorsrantal Policy Pct (NEPA), published
Tuesday, Dec~nber 11, 1979, 44 Federal Register 71,742, providing for an
exaiption to the requirarent for an envirorritEntal ispact analysis
report. specifica-1.ly, petitioner relies on proposed 21 C.F.R.
§25.23, Actions That Are ~c1uded Fran the Requiretent For the
Preparation of An ~ivirorutental Asses~e~:
(c) An applicant or petitioner requesting action of a
type subject to categorical exclusion under §25.24 is not
required to suheit an envirorsrental asses~rent if the
applicant or petitioner specifies the provision of this
part that exeopts the action fran the requirarent for an
envirorrrentaJ. asses~rent and provides infonration that
establishes to the agency's satisfaction that the action
requested is incleded within an excluded category and
rree~ts the criteria for the applicable categorical
exclusion.
§25.24 Catecorical ~cclusions provides:
PAGENO="0609"
603
(a) General actions belonging to any of the classes
designated in paragraph (b) of this section as
categorical exclusions nornally do not require the
preparation of an envirorrr~ntal asses~nt, because, as a
class, they will not result in the production or
distribution of any substance and, therefore, will not
result in the introduction of any substance into the
erlvirorlnEnt.
(b) ~ctions of any of the follc~ing classes are
categorically excluded:
(1) ... (C]onduct of public affairs activities...
(4) Liasai functions with.. .the public, and
iedustrial finns or organizations.
(9) Publication of notices in the Federal Pegister.
(12) Issuance of procedural or adeinistrative
regulations.
This patition for the adoption of procedural or adoinistrative
regulations governing the issuance of publicity fran the FDA falls
squarely within the categorical exclusions entzrerated in §25.24(b).
Petitioner relies as ~U upon the FDA' s prior deternination that
an envirorsrental ixr~act stat~rent is not required in conjunction with a
proposal for regulations governing FDA publicity. In the FDA's
stat~nt of Publicity Policy in connection with proposed publicity
regulations published Friday, March 4, 1977, 42 Federal Pecister 12,436,
12,440, the FDA stated:
~ Carrnissioner has carefully considered the
environxrental effects of the proposed regulation and,
because the proposed action will not significantly affect
the quality of the h~zren envirorn~nt, has concluded that
an environrrental iopact stat~rEnt is not required.
As the regulations proposed herein are identical in nature to those
originally proposed by the FDA, this exclusion likewise a~lies here.
D. ~c~a~iic i~cr
`Not applicable as of filing date of this petition.
52-266 O-85--20
PAGENO="0610"
604
E. ~~ICP~TI~
fl~ ur~ersign~ certifies, that to the best ]c~*tl~ge and belief of
the uthersigned, this petition includes all irtfont~tion and views on
which the petition relies, az~ that it includes reprsentative data and
info~tion Ja~n to tha petitioner which are unfavorable to the
petition.
(Naire of Petitioner) C~4ffIT~ (~ ~ CARE CF Q~DREN
50 Milk Str~t
(Mailing Address) Boston, Massachusetts 02109
(Telephone Ntrnber) (617) 451-0803
By Its Attorneys:
Michael X. fr~rrell
Neil L. O~ayet
Henry T. Golc±r~an
Peter A. Weasel
~ & STA~CP(LE
2121 K Street, N.W.
Suite 750
Washington, D.C. 20037
(202) 861-6200
PAGENO="0611"
605
UNITED STATES DISTRICT COURT
- FOR THE DISTRICT OF COLUMBIA CIRCUIT
PUBLIC CITIZEN HEALTH RESEARCH GROUP,
Plaintiffs,
V. ) Penn., 3.
DR. FRANX YOUNG, Commissioner, ) Civil Action No.
Food and Drug Administration, ) 82-1346
Defendants.
Defendants' Answers To
Plaintiffs'lnterroga-tories And -
Document Production Req~uest
Interrogatory 1(a): Set forth in detail all reasons why the
Food and Drug Adiainistration.(~FDA") has not issued a final
decision concerning whether or not salicylate-containing
drugs should be labeled to warn about the association between
salicylates and Reye's Syndrome.
Answer: The major reason FDA did not issue a final decision
concerning whether or not salicylate-containing drugs should
be labeled to warn about the possible association between
salicylates and Reye Syndrome is that there is currently
uncertainty about whether the reported statistical associa-
*tion between Reye Syndrome and aspirin has any reasonable
clinical significance. A statistical association does not
necessarily imply causation. It can be a result of an
PAGENO="0612"
606
artifact of the study methods used or the reported
association could be a result of other unidentified factors
which are independent of a causal relationship. These
possibilities raise uncertainties about the propez interpre-
tation of the scientific studies and there is a reasonable
likelihood that the study now underway and described in more
detail below will resolve that uncertainty.
The current uncertainty about the possible association
between Reye Syndr~one and aspirin is reflected in the
November 8, 1982 statement of the Executive Board of the
American Academy of Pediatrics ("AAP"). The AAP stated that
while "there should be cautious use of any antipyretic medi-
cation in the treatment of influenza or chickenpox[,]...
[the Board didj not feel that labeling aspirin-containing
preparations as being contraindicated in these illnesses is
in the best interest of children or the practice of pedi-
atrics.~~ This statement, represents the first expression of
doubt by an independent scientific body concerning the need
for a label warning on salicylaté-containing drug products.
While the agency is not bound by the P~AP statement, the
statement could not simply be ignored. The, AAP is the domi-
nant voice representing the nation's pediatricians. The AAP
statement caused the agency to rethink its position regarding
the label warning and is primarily responsible for the
PAGENO="0613"
607
agency's decision to seek additional studies before making a
final decision on label warnings.
It should be emphasized that the FDA is now and was in
November of 1982 well aware of the disagreement bçtween the
Committee on Infectious Diseases of the American Academyof
Pediatrics and the Executive Board concerning the November 8,
1982 statement. However, the Executive Board speaks for the
AAP and the agency considers the November 8 statement to
represent the views of the AAP. In view of the lack of con-
clusive data on the possible causal relationship between Reye
Syndrome and aspirin, the agency is not surprised that there
is some difference of opinion between scientists within the
AAP as to the approach adoptad by the Executive Board.
Indeed, the agency was in November of 1982 arid is now
aware of considerable disagreement in the scientific com-
munity as a whole concerning whether the evidence suffici-
ently establishes a clinically significant association
between Reye Syndrome and aspirin. The agency believes that
these disagreements between reputable experts emphasize the
uncertainty of the current data. It is therefore prudent to
await the results of the additional study that is now
.underway before issuing a final decision on whether to
require label warnings.
The uncertainty about the adequacy of the four epidemi-
ological studies on Reye Syndrome is reflected not only in
PAGENO="0614"
608
the disagreement among prominent and qualified experts, but
also in the scientific studies themselves. While the agency
emphasizes that it does not consider all of the studies to be
scientifically invalid, there are deficiencies inthe design
and implementation of the studies that lessen the confidence
that can be placed in the results of the studies. These
prominent deficiencies include the following:
(1) lack of formal protocols defining the study rules;
(2) lack of comparability between cases and controls as
to time between illness onset and interview;
(3) lack of consistent and comparable verification of
medication brand names and recording information
from labels;
(4) lack of data collection and analysis in such a way
as to be confident that the medications were being
used for the treatment of the antecedent illness
rather than Reye Syndrome;
(5) lack of sufficient characterization of the ante-
cedent illnesses to demonstrate that the controls
had illnesses of severity comparable to that of the
antecedent illnesses in the cases;
(6) reliance on school absentee lists to generate
matched controls with the consequent uriderrepresent-
ation of pre-school children and chic)cenpox associ-
PAGENO="0615"
609
ated cases (which has peak incidence in late spring
and summer); and
(7) lack of adequate precision in disease diagnosis to
be confident that all cases truly had Reyes
Syndrome. -`
The agency is also aware that the reported association
between Reye Syndrome and salicylates might be explained by
the use of salicylates for treatment of the symptoms of
Reye Syndrome. Although this hypothesis has not been proven,
neither has iTt beer~ ruled out.
The deficiencies enumerated above were known to the
agency at the time it initially decided to propose a label
warning for salicylate-containing drug products. The agency
was nevertheless willing to rely on these studies because of
the then perceived broad support of the scientific coimnunity.
When the AAP issued its November 8 statement, however, the
scientists and policyi~iakers within FDA gave credence to the
statement and re-examined the issues. The agency's concerns
about the deficiencies in the studies were thus amplified.
Considering the deficiencies in the studies, the disagreement
inong experts, and the position of the AAP, the agency
concluded that the conduct of an additional study was
necessary before a final decision on the need for label
warnings could be made.
PAGENO="0616"
610
The agency emphasizes that it has not totally rejected
t~e scientific studies completed to date. Indeed, these
studies form the basis for the agency's decision to go for-
ward with a public education campaign. The agency believes
that at the present time the public education campaign is
adequate to inform parents that they should consult a physi-
cian before administering aspirin or any other medication to
their children to treat flu or chickenpox.
The decision that the current scientific data are ade-
quate to support an educational campaign, but not suffici- -
ently certain for a final decision as to whether a label
warning is necessary is obviously one that involves a large
degree of judgment. The agency is aware that in certain cir-
cuxustances suggestive but not conclusive data may be suffi-
cientto support a regulatory action such as the one sought
here. In exercising its judgment in this instance, the
agency has considered carefully the sufficiency of the
current data and the likelihood of possible harm from a delay
in making a final decision. The agency has concluded that
the likelihood of harm from a delay -- in light of the ade-
quacy of the public education campaign as an interim measure
-- is minimal and that the need for additional reliable data
to resolve the current controver~y is significant. Because
the agency believes that such data can be generated in a
reasonable period of time, the agency has concluded that it
is in the public interest not to make a premature final
decision as to the need for a label warning and to instead
wait until an additional study is completed before making
such a decision. (The precise timetable for the ongoing
study on Reye Syndrome is set forth below in Answer to
Interrogatory 1(b).)
PAGENO="0617"
611
The above is a portion of a document filed under the penalties of
perjury by:
Joseph P. Mile
associate Commissioner for Regulatory Affairs
Food and Drug Administration
Margaret A. Cotter
Assistant Director
Office of Consumer Litigation
Gerald C. Kell
Attorney:
Office of Consumer Litigation -
Civil Divi~iom -
U.S. Department of Justice
It reflects the question of interrogatory 1 (a) and the answer
thereto.
PAGENO="0618"
612
1.
SCIENTIFIC STANDARDS AND REQUIR~ENTS IN AN
EXPERL~NTAL TRIAL OF A THF.RAPEUIIC (OR OTHER) MANEUVER
Baseline Criteria:
*Zero-time: date at which an appropriately
eligible person is randomized for start
of treatment.
*Eligibi]it~: persons treated at zero time
must have suitable clinical condition,
warranting treatment.
.Temporal precedence: treated persons must
have no baseline evidence of an "adverse
event" whose later diagnosis might be
ascribed to the treatment.
2.
SCIENTIFiC STANDARDS AND REQUIRENENTS (cont'd)
Baseline Similarity:
Treatment assigned by randomization, so
that compared groups will be similar in
clinical severity and prognostic
susceptibility to outcome event.
Identification of Treatments:
Determined by ongoing inquiry, as
treatment is received, before occurrence
of outcome events.
Identification of Outcome Events:
Objective (or "double blind") methods to
avoid bias caused by knowledge of
preceding treatment.
3.
SCIENTIFIC STANDARDS AND REQUIRL'ENTS (cont'd)
Avoidance of "Transfer Bias":
Follow-up obtained for all eligible
people who are treated, so that
outcome events represent full spectrimi
of occurrences. Results are reported
and analyzed for everyone, with no
arbitrary exclusions.
Quality of Data:
Check for observer variability and
errors in getting data, and in converting
raw observations to coded classifications.
Institute improvements when problems are
noted.
PAGENO="0619"
613
4.
SU~O~ARY OF SCIENTIFIC STANDARDS AND PROBLEMS
STANDARD CURRENT PBS PROTOCOL
Zero-tine `Not specifically identified in both
"cases" and `controls'.
Eligibility `Status cannot be determined in
absence of zero time.
Temporal `Case group may include "monophasic"
Precedence cases whose treatment was given for
early manifestations of Reye's
Syndrome.
5.
SUMMARY OF SCIENTIFIC STANDARDS AND PROBLEMS (cont'd)
STANDAB CURRENT PBS PROTOCOL
Baseline `In absence of a zero-time to denote
Similarity baseline, baseline states cannot be
clearly identified or compared.
sIn choosing treatment, parents or
pediatricians may use different
criteria that are not considered
or accounted for.
`Baseline "severity" cannot be well
demarcated from check lists of
unstandardized daily ratings for
diverse clinical attributes, or from
"matchings" based on fever and
etiol~gic diagnosis of baseline
state.
6.
SUMMARY OF SCIENTIFIC STANDARDS AND PROBLEMS (cont'd)
STANDARD CURRENT PBS PROTOCOL
Identification `No specific strategy (e.g. separate
of Treatments control group) used to avoid (or
detect) "recall bias".
`In absence of a demarcated zero-time,
when did "treatment" begin?
`What dosages, cc~binations of agents,
or sequential changes in pattern will
constitute "treatment" with a
particular agent?
PAGENO="0620"
SUMMARY OF SCIENTIFIC STANDARDS AND PROBLDtS (cont'd)
- STANDARD CURRENT PHS PROTOCOL
Identification of
Outcome Events
`Although false positive diagnoses
will be checked, what will be done
about false negative diagnoses in
borderline cases deemed negative
because they did not receive a
suspected drug?
`Cases reported to State Health
Departments may not represent true
clinical spectrt~ of the disease.
`Bias is created by excluding
"controls", but not "cases", with
chronic illnesses requiring
salicylate treatment or frequent
visits to physician.
Quality of `Despite careful attention to many
Data issues in quality, problems in
observer variability or errors are
difficult to monitor, detect, and
correct in pre-coded data forms.
614
7.
Avoidance of
Transfer Bias
PAGENO="0621"
615
?rHEUNWERSfrV~,TEXAS
H~EDKLLAS
s+Nv1.E'3TERJe M4D~NOO.
A TM N .A/~... f ~4i~
Si t'~'~ti DALLAS. TEXAS 75235
August 10, 1984 TELEP7IONE(214)61$.3112
Dr. M. Harry Jennison
Executive Director
American Academy of Pediatrics
1801 Hinman Avenue
Evanston, IL 60204
Dear Harry:
Thank you for taking time from your busy schedule to meet with the group from the
Committee for the Care of Children.
In accordance with your request, I am listing some of the major objections raised
by panel members of the Institute of Medicine Committee , CCC consultants and myself,
to the protocol developed by the PHS for its planned study of Reye Syndrome and its
relationship to aspirin administration. None of these suggestions appear to have
been accepted. It should be pointed out that the voluminous document containing the
protocol was received only seven days prior to the meeting of August 7 and thus
detailed analysis was not possible, especially not of the various ques.tionnaires
that had been prepared.
The ~ objections are the following:
1. Definition of cases. The so-called CDC criteria have been demonstrated to
overdiagnose a substantial number of cases (20 to 25%); the proportion of under-
diagnoses remains unknown. The PHS proposes to continue to use the present
criteria. I presented some of our own data that clearly show their lack of
speci ficity.
2. Whether a case i Reye Syndrome will be judged by a committee (membership
unspecified) reviewing unspecified documents (hospital records?). It is my under-
standing that they will be asked to classify cases as "yes" or no"; obviously
there will be a sizeable group of "maybe's" but apparently no provision is made
for this. Similarily, cases verified by liver biopsy will not be separately
analyzed.
3. The concept of "zero time' is absolutely crucial to the performance of a study
of this type (as explained in written material prepared by Dr. Alvin Feinstein).
No provision is made for this in the PHS protocol.
PAGENO="0622"
616
* Page. No. 2
Dr. N. Harry Jennison
August 10, 1984
4. It is impossible to estimate when Reye Syndrome begins in monophasic cases and
thus the relationship of the illness to medication cannot be determined. The PHS
will include monophasic cases and will not analyze this group separately. In addi-
tion this group of patients seems to include a substantial proportion of cases that
are not Reye Syndrome. It is our belief that patients showing a biphasic clinical
course represent the only group suitable for analysis.
5. In order to match cases and controls, it is necessary to match them for severity
of the prodromal Illness. The PHS plans to develop `a severity index after the
study has been completed, using the data generated, which is, of course, entirely
improper from a statistical standpoint.
6. One of the three state health departments chosen for this study is Ohio. As
you know, this organization has been severely critized for its activities during
the so-called `Ohio Studies," because arbitrary exclusion of cases occurred as well
as other serious data errors which have never been satisfactorily explained. The IOM
Committee had specifically recommended that Ohio should be excluded from any parti-
cipation.
7. Recommendations for changes in the protocol made by the American Academy of
Pediatrics and by the IOM have, in general, been disregarded.
8. The results of the preliminary study which was designed to identify various
problems will not be fully analyzed or be available in detail until October 1 or
later, yet the PHS will submit the `final" protocol to the 0MB on September 1, a
date which, for all practical purposes, means that no action can be taken at this
time to incorporate any suggestions for significant changes. The ION Committee
indeed was told that no extensive changes can be made, so the whole meeting of
August 6 was an exercise in futility.
9. The preliminary study performed by the PHS generated some strange numbers: the
mean age of the patients with Reye Syndrome was over 10 years, the mortality rate
was 25% (compared to the less than 5% found in the second Ohio study). No attempts
were made to explain these findings or to determine why the proportion of severe
cases in the preliminary study was considerably greater than that recorded in other
investigations.
It is our belief that the proposed PHS study will not be the definitive one that has
been promised but once again data will be collected that can be manipulated to pro-
vide any desired answer. It is particularly worrisome that few, if any, suggestions
from the IOM, the AAP, or the CCC have been incOrporated into the protocol and that
the door is now closed to any further discussion or changes. All of this has
created the impression that the PHS is not interested in discovering the truth but
only wants to justify previous recommendations and activities.
PAGENO="0623"
617
Page No. 3
Dr. M. Harry Jennison
August 10, 1984
I would, of course, be pleased to furnish any additional information that you
might require.
With warm regards.
Sincerely,
L.. ~
Heinz F(Ei~chenwald, M.D.
William ~t~chanan Professor
of Pediatrics
HFE/ag
cc: Mr. Neil Chayet
PAGENO="0624"
618
GASTON SNOW &ELY BARTLETT
COUNSELLORS AT LAW
ONE FEDER~~L STREET
BOSTON, MASSACH CS ITT S 0~ 10
617/420-4t,00
FEDERAL EXPRESS
December 6, 1984
Eugene S. Fturwitz, M.D.
Medical Epicemiologist
Center for Disease Control
1600 Clifton Road
Atlanta, Georgia 30333
Dear Dr. Hurwitz:
I am very pleased that we had the opportunity to talk last
Friday and discuss in some detail matters related to the Reye
Syndrome Controversy.
I would like to note that our telephone conversation was
precipitated by a call from you last Friday morning which I returned
a few hours later.
You began our discussion by inquiring as to the starting
date of our study and requesting a copy of the study protocol,
which is enclosed with this letter. I will be meeting with Drs.
Feinstein and Horwitz in New Haven next Tuesday, December 11,
to discuss additional details and updating of the protocol; we
further anticipate that the Coordinating Committee of the Committee
on the Care of Children (`CCC") will be approving the final documents
in the very near future.
You also inquired as to the starting period. At the present
time it is our intention to mail to all pediatricians inthe country
as soon after the first of the year as practical. we are at the
present time working on the final stages of securing funding for
the study, as well as establishing an independent scientific advisory
committee and a special International Science Exchange oversight
committee. The basic policy for the study will be governed by
the CCC Coordinating Committee, the scientific advisory committee
and the Yale University Group, all of which will remain fully
autonomous on all policy matters. We will notify you as to the
PAGENO="0625"
619
GASTON SNOW & ELY BARTLET
actual starting date as soon as it is set. I would note parenthet-
ically that even with the full resources of the federal government
and the assistance of the Institute of Medicine, it took longer
than expected to get the government study underway. Suffice it
to say that the CCC Coordinating Committee, the International
Science Exchange and all interested parties are desirous of commencing
this study as soon as possible.
We also discussed the manner in which the study would be
performed and specifically we discussed ways in which the govern-
ment study and the clinician-based study could work cooperatively,
particularly in areas where the same cases are encountered. We
also discussed the possibility of a meeting to discuss this and
other issues and I would like to confirm by this letter that we
are very much looking forward to such a meeting as soon as possible;
I will be telephoning your office from Yale on Tuesday to further
discuss this.
You also inquired as to whether or not the study would contem-
plate the prospective use of aspirin by clinicians as a part of
the study. Although we both agree that this would be ideal from
the point of view of the study, we also both concurred that there
could be serious resulting implications. If one believes that
the early studies are inconclusive, it would be completely appro-
priate for a prospective study to be done; but I believe there
would be serious legal and ethical problems given the unfortunate
and premature publicity surrounding this matter. I'm also concerned
that in view of the low incidence of Reye Syndrome, that any kind
of prospective study involving any medication would not be feasible
and that we are thus forced by legal, ethical and scientific con-
straints to utilize only a retrospective case control study model.
I should add however that at the recent ccc meeting held at
the Annual Meeting of the American Academy of Pediatrics in Chicago
and attended by approximately 200 pediatricians, one doctor sugges-
ted that he would be willing to follow, on a prospective basis,
his patients with influenza and chicken pox; when the entire group
was asked if they thought that busy pediatricians would be willing
to engage in such prospective activity, nearly all those present
responded affirmatively.
We also discussed the pilot study. As I informed you, the
CCC Coordinating Committee has not sought the release of those
data because of very serious concerns that it is inappropriate
to release the pilot data. As we discussed, the goal of all involved
in this àontroversy should be the seeking of scientific trust;
as you are aware, our complaint has been that the regulatory
activity and publicity has been premature and exaggerated and we
believe that releasing the pilot study results would simply com-
pound and confuse that situation.
PAGENO="0626"
620
GASTON SNow & ELY BARTLE
You also inquired as to the status of the CCC/Public Service
Announcement (PSA). Although you made it clear that this matter
is within the jurisdiction of the Secretary and the FDA, you
expressed interest in its present status. As I informed you,
we are dismayed at the events of November 5, 1984 and subsequent
action by the FDA, the result of which has been great confusion
amongst the public. Because of that confusion, we will during
the next week be making an attempt to meet with the FDA and work
cooperatively to prepare and release a single clear message to
the public. As we discussed, the CCC/PSA was released to counter
the government PSA of last season, the impact of which was to
convince 40% of the people who viewed it that aspirin was the
sole cause of Reye Syndrome and 45% that not giving aspirin could
prevent Reye Syndrome. It is indeed unfortunate that the FDA,
acting on information from the Health Research Group (HRG),
believed that our PSA had just been released when in fact it was
released nearly one year ago. I would hope that you would agree
with the recommendation that a single message be released at this
time to ameliorate the confusion and if so, that you would make
your views known to the appropriate parties.
I am extremely pleased that we were able to coinmeuce a dialogue
with regard to these matters and look forward to talking with you
next week and hopefully establishing a meeting date in the very
near future.
Sincerely,
/ ~-~- c ~- ~ ~` /
Neil L. Chayet
NLC:nfp
Enclosure
cc: Heinz F. Eichenwald, M,D.
Arnold Friedhoff, M.D.
Ralph Horwitz, M.D.
Alvan Feinstein, M.D.
Thomas Reardon, J.D.
(dictated, but not read)
PAGENO="0627"
621
GASTON SNOW &ELY BARTLETT
COUNSCLLORS AT LAW
ONE FEDERAL STREET
BOSTON, MASSACHTJSETTS 02110
617/426-4600 "5/ese-a~co
FEDERAL EXPRESS
January 16, 1985 O~~D*33~3~
Mark Novitch, M.D.
Deputy Commissioner
Food and Drug Administration
5600 Fishers Lane
Rockville, Maryland 20857
Dear Dr. Novitch:
I am writing to confirm our telephone conversation of this
afternoon. On behalf of the Committee on the Care of Children,
we are extremely pleased that you have granted our request that
physicians and scientists working with the Committee have the
opportunity to review the raw data upon which the Reye Syndrome
pilot study is based. Our conversation of this morning follows
that of last Friday in which I requested this opportunity and
we appreciate very much your prompt response to that request.
You requested the names of the individuals who would be
reviewing these data and they are as follows: Heinz Eichenwald,
M.D., David Lang, M.D., Alvan Feinstein, M.D. and Ralph Horwitz,
M.D. All of these individuals are doctors and, of course, will
fully respect any part of the data which is confidential in the
event that any identifiable hospital or medical information is
part of the review process.
This is also to confirm the nature of the raw data that we
have requested. It includes the computer or other tapes which
have been prepared in the course of analysis of the data, the
original questionnaires and case report forms as filled out by
the interviewers, the hospital records of the patients, and the
physician reco:ds if available. You indicated that you saw no
problem with the scope of this request and would be asking Dr.
Henry Meyer to contact me today or tomorrow to arrange the logistics
of the review of this material. As we discussed, Dr. Lang is
planning to come to the East Coast in conjunction with the review
of this material and it is, therefore, imperative that we work
out the logistics of the review as quickly as possible.
PAGENO="0628"
622
GAsToN SNOW & ELY BAHTLET1
Mark Novitch, M.D.
January 16, 1985
Page 2
We also discussed the nature of the review. You asked if
we were intending to `nit-pick" these data; this is to confirm
that we have no intention of engaging in such a practice, we are
only interested in ascertaining whether there are or are not
serious flaws in this study or its methodology or conclusions,
and if there are not, we have no intention of attacking the study.
We are still, at this time, very hopeful that we will be
able to proceed with a proposed clinician-based study of this
matter and we have already requested a meeting with Dr. Hurwitz
in this regard. I am enclosing a letter which Isent to Dr.
Hurwitz following a telephone conversation. I also spoke with
him again last Friday and appreciate his statement that he would
recommend that we would be permitted to see the data, although
he did state that he is not in possession of it as it had already
been turned over to the FDA. I also reiterated my request for
a meeting as soon as possible to discuss ways of cooperating with
regard to the clinician-based study and the government study,
and he restated his beliefs that such a meeting would be appropriate
and indicated.
I am also enclosing a copy of a mailgram we have sent to
television stations indicating that we are about to review the
raw data of the pilot study and requesting that the Public Service
Announcement which we sent to stations nearly one year ago not
be aired pending review of the pilot study data.
We also discussed present efforts relating to labeling and
our concern that labeling being worked out between industry and
the government also include careful attention to the impact of
such labeling on the physician and patients. I appreciate your
recognizing that doctors and patients have a real interest in
these discussions and also appreciate your willingness to include
us at an appropriate time prior to final agreement between the
Agency and industry in this regard. Such involvement is extremely
important to all of us who have been concerned with this matter.
Thank you for your attention to these matters.
With kindest regards.
S. 1,
i . ~ayet
NLC:md
Enclosures
PAGENO="0629"
623
GASTON SNOW &ELY BARTLETT
COUNS~LL0RS AT LAW
ONE FEDERAL STREET
BOSTON, M&SSACHIYSETTS 02110
617/426-4600
January 31, 1985
Mark Novitch, M.D.
Deputy Commissioner 0055, SEW 0055 0005
Food and Drug Administration
5600 Fishers Lane
Rockville, MD 20857
Dear Dr. Novitch:
This is to confirm my telephone conversation with your
office of January 29th. I am most pleased that we will be
meeting at your office next Tuesday, February 5, 1985 at 11:00
A.M. I thought that I would drop you a note to confirm this
meeting and to indicate to you that I will be accompanied by
Dr. David Lang who is coming from Los Angeles especially for
this meeting and Dr. Ralph Horwitz who will be coming from
Yale.
The purpose of this meeting will be to informally discuss
ways in which we can work with your office in reviewing the
raw data of the pilot study. I should note that I have just
received from the FOl Branch the materials provided by Mr.
Elengold and we expect to be reviewing this material prior
to our meeting.
It is my further understanding that Dr. Meyer will be
joining us and we very much look forward to seeing you both
at that time.
With kindest regards.
Sinc
Neil L. ayet
NLC:md
cc: Henry Meyers,.M.D.
David J. Lang, M.D.
Ralph Horwitz, M.D.
PAGENO="0630"
624
GASTON SNOW&ELY BARTLETT
COUNSCLLORS AT LAW
ONE FEDERAL STREET
BOSTON, MASSACHTJSETTS 02110
617/426-4600
January 28, 1985
Mark Novitch, M.D. N~~55 0005
Deputy Commissioner
Food and Drug Administration
5600 Fishers Lane
Rockville, MD 20857
Dear Dr. Novitch:
I am writing by way of follow up to my letter and to
our telephone conversation of January 16, 1985. As you may
recall, you indicated Dr. Meyer would be calling me on January
17, 1985. When I did not hear from him, I telephoned him
and he informed me that nothing could be done with regard
to our request for data until after Inauguration Day, January
21, 1985. However, on Friday, January 18, 1985, he telephoned
to inform me that a meeting would be held in his office on
Tuesday, January 22, 1985, and we were invited to attend.
We arrived at the appointed time and were informed that
Dr. Meyer could not be present; however, representatives
of the FDA and CDC were present and a full discussion of
the various requests for data regarding the Pilot Study
ensued. Dr. Faich, who chaired the meeting, informed us
that a public meeting was going to be convened by the Institute
of Medicine on February 13, 1985. He further informed us
that efforts were underway to provide all interested parties
with a data tape and copies of the case report forms and
questionnaires. However, he stated that it was unclear as
to exactly when these materials could be made available,
because all potentially identifiable data had to be purged
from both the tape and the case report forms. In fact, he
stated that there could be no guarantee that the material
would be ready in time to conduct an independent analysis
prior to the intended public meeting.
At this point, Dr. Ralph Horwitz and I reiterated the
request I made to you during our telephone conver5atiOr~s
and in my letter that it is essential that the doctors be
permitted to examine the medical records of the cases. As
PAGENO="0631"
625
GASTON SNOW & ELY BARTLETT
Mark Novitch, M.D.
January 28,. 1985
Page 2
we have discussed, it is essential that we be able to ascertain
the date of onset of the disease, and the clinical course
of both the prodromal illness and the Reye Syndrome. Further,
it is essential to ascertain whether or not the cases were
monophasic or bi-phasic, and also to observe the nature of
the pathological findings. Dr. Faich and Mr. Elengold
responded that it would not be possible for US to obtain
this information. The reasons given were that the records
contain identifiable patient data and even if names, hospitals,
and states were stricken, it would still be possible to trace
back the records to the individual because of the various
dates. We have no desire to trace back any of this information
and would in no way be contacting the family or making any
use of the data other than to examine the records. The
doctors would be ethically bound not to breach the confidentiality
of the records, and furthermore would be willing to agree
to any special arrangement to safeguard any conceivably
confidential data. In addition, however, Mr. Elengold
stated that all parties including the physicians interested
in this matter would have to be treated as if they were the
"Washington Post." We would hope that the doctors who have
been involved with this matter, and who have been invited
to assist the Institute of Medicine and other parties for
two consecutive years, would be able to be treated in a
manner which differed from the Washington Post, and we
respectfully request that further consideration be given
to this matter and that the doctors be able to secure the
needed data, which includes the patients medical records,
screening logs, if any, as well as the data tape and
questionnaires.
We were also dismayed to learn that despite the
recommendation of the Institute of Medicine to release the
Pilot Study results, no one from the IOM has yet seen any
of the underlying data. We were informed that a committee
of physicians did see the patient records, but there was
much uncertainty on this point. We would appreciate it if
you could ascertain whether any group or individuals other
than the contractor, Public Health Service Representatives,
and representatives of the CDC have seen these data. I
believe that you informed me that no one at the FDA had seen
the raw data either, and we would appreciate it if it could
be ascertained exactly who has reviewed the underlying data.
Lastly, we were informed that even if the FDA, PHS Task
Force, or the CDC wanted to allow us to see the medical
records, this would not be possible because they are not
in the possession of the government. Further, those present
at the meeting were uncertain as to whether or not the records
PAGENO="0632"
626
GASTON SNOW & ELY BARTLETT
Mark NovitCh, M.D.
January 28, 1985
Page3
were in the possession of Westat, the study contractor. We
hope that we will not be in the position of being told that
the records are not available because they are not in the
possession of the government, and also not available because
Westat is bound, as an agent of the government, not to nake
the records available because of federal agency confidentiality
restrictions.
We urgently request that you assist us in securing these
data as quickly as possible. It is extremely difficult to
accept the fact that the study results were publicly released
three weeks ago, although the data was gathered many months
previouslY~ and yet, more than three weeks after the release,
with further public meetings planned, we are still unable
to obtain any of the underlying data.
I will be telephoning you shortly to discuss whether
there is any way the physicians who have been involved in
this matter can obtain the material they need to evaluate
the pilot study and its conclusions.
With kindest regards.
Sincerely,
Neil L. Chayet
NLC : md
PAGENO="0633"
627
GASTON SNOW &ELY BARTLETT
COUNSELLORS AT LAW ~OstPG *AR?~(TT
ONE FEDERAL STREET
BOSTON, MASSACHUSETTS 02110 ~ALO*LTO,C*U~Op~*gA3O5
617/426-4600
TCLEX:94 OSSO GASTON SSN CGUFORN!ASTq~iG~,
February 21, 1985
Richard J. Riseberg, Esquire
Assistant General Counsel
Public Health Services
5600 Fishers Lane ~z/e~S-7SOO
Rockville, MD 20857
Thomas Scarlett, Esquire
Chief Counsel
Food and Drug Administration
5600 Fishers Lane
Rockville, MD 20857
Gentleman:
I am writing to confirm our meeting of Tuesday, February
19th. I very much appreciate the opportunity to discuss with
both of you, in depth, the situation concerning further efforts
to secure the raw data of the Reyes Syndrome Pilot Study. As
we discussed, it would indeed be paradoxical if the material
which is presently being released in accordance with the
Freedom of Information (FOl) A~t procedures was to result in
identification of patients being made possible, while Doctors
vitally interested in this matter were unable to review the
clinical and hospital records which they are seeking.
On behalf of the Committee on the Care of Children, we are
requesting that the Food and Drug Administration and/or the
Public Health Service request of its contractor, Westat, the
production of the hospital records of the 29 cases referenced
in the Pilot Study. By production, I would like to emphasize
that we would leave full discretion to you as to the precise
manner in which these records would be made available. It may
well be possible that they could be kept in a central deposi-
tory for viewing without copies being made and taken and, in
any case, we feel quite certain that the appropriate direct
identifiers can be struck from the records in a manner which
will make individual patients unable to be identified. Fur-
thermore, we would be willing to adhere to any reasonable pro-
cedure which would bind the Doctors who will review these
PAGENO="0634"
628
GASTON SNow& ELY BARTLETT
Richard J. Riseberg, Esquire
Thomas Scarlett, Esquire
February 2!, 1985
Page 2
records not to attempt to to identify or contact any of the
patients involved.
We believe that the Freedom of Information Act permits, and
in fact mandates, that this material be made available. Case
law clearly indicates that the Act favors disclosure over very
narrowly construed exemptions. Furthermore, the balancing test
applied to the medical records exemption clearly tips in favor
of disclosure where there is a public interest, particularly
when personal identifiers are eliminated. You indicated that
the medical or hospital records were not a "deliverable" under
the contract and are therefore not in the possession of the
Agency. We believe that a government request that this mater-
ial be made available as a modified deliverable under the con-
tract, would remedy this situation and free the contractor from
any contractual problems relative to the Freedom of Informa-
tion or Privacy Acts.
Finally, as we discussed, we believe that it would be most
unfortunate if the posture of the government were to be that it
is not in possession of the records, while, when we turn to
Westat, we are informed that we are unable to obtain the
records from Westat because of Freedom of Information and Pri-
vacy Act requirements provided for by contract. I would hope
very much that we would not be faced with this kind of "Catch
22" situation. On the other hand, we do recognize that there
are serious questions involved as to the privacy of indi-
viduals, which privacy we fully respect and would not want to
see breached. The above is a suggested means of securing the
raw data which is essential for review of the study and if you
have any suggestions as to other ways in which the material can
be obtained, we would most appreciate hearing them.
In any case, time continues to be of the essence with re-
gard to this matter, and we urgently request that the materials
requested be made available as soon as possible.
With kindest regards,
Sincerely,
Neil L. Chayet
NLC : md
cc: Thomas Reardon, Esq.
Heinz Eichenwald, M.D.
PAGENO="0635"
Potentiation of the Toxic Effects of
Acetaminophen in Mice by Concurrent Infection
with Influenza B Virus: a Possible Mechanism for
Human Reye's Syndrome?
hi. G. MACDONALD.3?) P. P. MC(~RATH. D. N. MCMARTIy4, 0. C. WASHINGTON, AND 0. Ht'DAK
Dc'parirnent "I Child IIi'uhh and Den'/iipinvni. (ieo'irt' itiI)hji7~)i)fl L'niii'eniti'. tiathinv'hn. 1) C and Dhi'iiiun
ui Buikh('?fl)Or) wud (ii Iuiuiiutv O//ti('uu/ 1tiuuluuu,'ui.i. I'ixuiand i)uuuit iulu,uu,uuuiraiju,,. 8liiu.uda. t!a,uiand t.S
Summary
Using weanling mice of two different genetic strains we dam-
onstr,zled a potentiation of the lossc affects of acctaminophen by
prior infection with influenoa B uiruwlheC57Bf,/6N(B6)str,ijn
of mice is genetically predisposed to increased tn5icit) from
acetaminophen when the hepatic c~tochrome P450 mixed func-
tion otidase s~stem is preinduerd. When 36 animals are pre-
treated with iniluenea B nirus and an mixed function oxidase
s~stem inducing agent before admiflistering aectaminophen, ne
obscrsed a significant incidence if at~ pical"fattp" user p'jihotogy
on light microscopy similar to llte microsesicular steatosis seen
in human Re~e's syndrome. F3ectron microscopic changes in the
user of these animals resemble Ihose published to dale in human
Reye's sndrume.
Abbresiations
El1)~., egg infectious dose 50%
EM. electron microscopy
ER, endoptasmic reticulum
l.M. light microscopy
3-MC, 3-meth~lehulanthrene
\ll'O, mixed function oxidase
P hS. periodic acid Shifrs reagent
RS. Re~e's syndrome
SER. smooth endnplasmic reticulum
TCID., tissue culture infectious dose, 50%
~hllD., mouse infectious dose
This study was designed to test the hypothesis, now supported
by several investigators, that RS in humans may be caused by
the interaction of viruses. environmental factors, and host genetic
factors. There is a body of animal data demonstrating the poten.
ttatton of effects of viral infection on the host by chemical agents,
especially insecticides (6. 8, 16). Acetaminophen toxicity has
been shown to be potentiated by alcohol, and in too patients
with mononucleosis (9, 13. 23). Theophyltine tosicity is in-
creased by concomitant infection with either inlluen~a A or
tnlluenza B virus ((2. 211). Viral potentiation xtfcersain chemical
tosuns. e.g.. .t-pentenotc acid and allatosin. results in an esperi.
mental syndrome very simitar to human RS (4, 24. 321. Possible
explanations for these ellects include the adverse elli,'cts of xc'
nobtotics on the integrity and function of the immune s~stem,
and effects related to the huotranstbrmation 01 foreign agents,
which may he metabolized to pharmacologically active inter-
mediates by components ot'ihe cstochrome P45(1 bIK) s~stem.
RS. or very similar clinical disorders, are found in many
different geographic regions of the world. A review of the item.
tore would suggest that RS can be precipitated by many chemi.
cally unrelated compounds, each 01 which has the capacity to
cause subclinical, biochemical, and functional abnormalities of
the liver and immune system.
We elected to study the e(Tects of influenza B virus infection
(which us commonly implicated in the prodromal illness before
tinsel ol RS( on two inbred strains 0)' mice which are known vi
diller signulicanily in the way that their hepatie MFO system
responds to chemical agents. We chose to study .tcenaminviplien
l'or two reasons. First, because it isa commonly used antipvrenic
in children which is Icing promoted in the LISA. and can he
obtained without prescription. Second, because the metabolic
pathwa~s (or the drug have been well worked out and linked
with the aromatic hydrocarbon responsiveness of the MFO sys-
tem in mice.
In general, all high(y tipophihic senobiotics are rendered more
water soluble and hence. more readily excreted, by the micro-
suuinal %IF() eniy me s~stem located in the SER 01 he liver and
tither tusues. Molecular oxygen and reduced NADPH are re~
quired (or the reaction. tnductiiun of this enzyme system is
associated with an increase in microscopicatly visible SF.R. and
it is interesting that prvuhfrranuon it SER has been presiousiv
reported in cases il RS (2. ~(ul. vlust NIFO reactions are nnedi.ted
thruuugh the hemeprotein cytochromz P.450.
Mitchell, slid. (141 showed that acetaminophen.induced he.
paste necrosis is caused by a toxic metabvuhite 01 the drug, which
hinds cuvatently to tissue macromolecules, including nucleic
acidu and proteins. The toxic metaholite represents a small part
ol'the original dose of acetuminophen (approximately 4i'i) whets
the drug is taken in therapeutic doses. The maJvtnt~ of the drug
is conjugated directly with sulfate of glucuronide and then ex-
creted. The toxic metahohite shown in Figure I is thought to be
produced by metabolism via the cytochrome P.450 enzyme
system. This metabolute us detositied by preferential conjugation
wuth a nucleothitue sutphsdrst trupeptide. glutathione. In anuuttal
studies, when glutathione in the liver is either depleted (e.g.. due
to malnutrition) or overwhelmed by a very arge dose of acet.
aminophen, the activated metabuu(ite remains unconjugaued and
free to combine citsalently xiuth vital nucleophilic macromole-
cules in the hepatocyte, leading to eventual hepatic cell death in
a typtcat centrolohular distribution Fig. 21.
Tttvurgeirseen, en al. 31(1 linked metabolism of acetam(nophen
by the cyiochrom P.4511 system to the inducihility of a~l hydro-
carbon hydrimxsIa~e in inbred mice. I'he degree of aryl hydrocar-
lion hsdrovyla~ responsiveness has. in turn, been linked lvi tIme
presence or absence of the gene locus known as the Ah locus,
which is inherited as an autowuntat dominant in mice(3t), There
629
ACETAMINOpIIgyI, VIRUS, AND REYE'S SYNDROME
OflSt.jAsijOA/mguiiaiu$)suum,n
PFt)ty URiC Ri SF situti
Copinghi Oil lnlu.niaiutn*t Peduui'ic Resmicii Foui,dation. inc.
Vol IX. No. 2. `154
I":.Iud,ni.% I.
PAGENO="0636"
630
ANIMALS WTTRI AR LOCUS
RECEIViNG 3MC. ACETAMINOPPIEN
ANIMALS WITH Al. LOCUS RECEIVING
ANIMALS WITH AC LOCUS RECEIVING
ACETAMINOPREN AND INFLUENZA BVIRUS
`I).
~
i-I
A B C
I
D OOMIOEARSO~.RSr~
ANIMALS WITH AN LOCUS RECEIVING
INFLUENZA B VIRUS' 3MC ACETAMINOPHEN
E
Fig. 3A
Fig. 38
Fig. 3C
FIg. 3D
F~g. 3E
Fig. 3F
ANIMALS WITHOUT Ah LOCUS RECEIVING
INFLUENZA B VIRUS' 3MC' ACETAMINOPHEN
F
ACETAMINOPHEN. VIRUS. AND REYE'S SYNDROME
Liver samples were taken immediately into glutaraldehyde for macroscopic lesIonS WerE recognizable in the liver, representative
EM. Other ttver samples from the same animals were prepared sectIonS were taken from these areas and, when possible, also
appropriately for trozen Section. and subsequently stained with from apparently normal areas of the same livers.
Oil.red.O for lipid. Further samples were ftsed in Bouins for Microsomal preparations were made from the livers from (5
Giemsa and PAS staining, or homogenized for microsomal pre~ animals tn each study group (including controls) (33). The ani-
aratlon. Sections for LM were prepared by Baker Histology roals "crc kIlled hy cervical dislocation. TIte livers were imme~
Great Falls, VA( and were examined by two of us. M.G.M. and diate(y removed and. aller raptd collection of specimens for LM.
D.N.. a vetennary pathologist. D.N. was unaware of which weighed and siashed with ice cold 0.02 M Tris-HC1/0.l 5 M
treatment schedule the animals had receised. Necrotic and non- KCL huller. pIt 7.4. They were then homogenized in 1.5 vol.
necrotiC lesions were quantified and graded by the method of umes olthe same huller, using a glass homogenizer with a Te(lon
Chalkley 13). pestle. The homogenate was centrifuged at 2.0(03 g for 15 mis.
Seventy number coded electron microscopic samples. `epre. and the supernatant was decanted through a double layer of line
sentative of study groups and controls. were examined by P.M. meshed gauce. The supernatant was then centrifuged at (115.0(0)
and G.W.. also without knowledge of treatment schedule. When g for 45 mis at 4C. The resulting pellet was washed by resus..
PAGENO="0637"
631
MACDONALD AT 4L
pension in 0.1 M sodium pyrophosphate buffer. pH 7.4, to
remove remaining hemoglobin and recentnfugcd at 05.000 g
For 45 mm. The pellet w~s resuspended in 2 ml of 0.02 M Tris-
HCI/0. 5 M KCL buffer.
!sn:txnt' ussar. The protein concentration of the microsomal
suspension was determined by the method of Schacterle and
Pollack (25) and the cyrochrome P.45(1 concentration by the
method of Omura and Sam (17) from the CO dil%rence spectra
of reduced microsomes. using as extinction coell'icienl of 91
mM-I em-I br .~ 490-451) nm.
RESULTS
LI! findip,ç's (34).
1) When acetaminophen was given alone. significant cen.
trolubular necrotic lesions(35) typical of acetaminophen
toxicity were first recognized on l.M at a dose of 300
mg/kg in both B6 and D2 mice (Fig. .3a.
2) When acelaminophen was gtscn to 116 and D2 animals
pretnfected wiih tnlluenza B virus. significant ccntrohib.
ular necrosis 11mm appeared am a dose of 2)0) mg/kg
suggesting some potentiation of acetaminophen tosietly
by the sirus (Fig. 3b1.
3) When the chtochrome P.450 enzyme system was in-
duced with 3.MC. as would be expected, the toxic el%'cts
of acetaminophen were markedl~ potenmiamed in the 86
mice, and stgnilicant centrolohular lesions were first
recognized in these animals at a dose of ISO mg/kg (Fig.
3d. A minor potentiation of acemaminophen cth,ct was
seen in D2 animals (Fig. 3d).
4) Significant potentiation of the toxic effects of acetamino~
phen was recognized in both 86 and D2 animals when
pretreated with tnlluenza virus belbre receistng acel~
aminophen and 3'MC(Fig. 3e and I). In a small number
of animals, treated with all three agents. we recognized
the appearance of a distinct histologic patliolisgy in the
liver a ditTuse microxexicular steatosis. Srsiv percent of
those with microvesicular smeatosis did not base coexist-
ing centrolohular necrosis. The incidence ol this linding
was significantly greater in the 86 animals, and appeared
to be dose related over the range 150-251) mg/kilo.
5) Mortalily(wimhin 40 h of acetainintipheis adminisiration)
was markedlb increased in 116 animals. by prior induc.
lion of the MFO s~stcm with 3.MC when aceiaminophi.'n
was given at a dose of 25(1 ntg/kilo. in otin.tntluced
animals, there was no excess mortality oser control
animals (approximately 0.5%). With prior induction of
the MFO system the rate rose to6%. When Ihese animals
were also pretreated with influenza B virus the mortality
rate increased to 19%. (A smaller increase in mortalily
(-12%) was seen in infected D2 micej.
Inflammatory lesions were seen in less than 2% of the liver
samples. Glycogen depletion, recognized tin PAS'siained liver
sections, was most often associated with severe centrolohular
necrosis, but was not specific to any treatment regimen.
1.1! Iindinr5-s. A total of 70 mouse livers were examined by
EM. including livers from 86 and D2 mice, receiving 1511 or 200
mg of acetaminophen plus influenza B virus and 3.MC. Also
examined were livers from untreated animals, and aitimal re-
ceiving: I) sterile saline alone or in combination with virus,
acetaminophen. and/tsr 3-MC: 2) sterile altantoic ttuid alone, or
in combination with one of the two tither active agents and/or
3-MC.
No remarkable changes were seen in the controls, except in
the case of some 02 aitimals receiving undiluted inituenea B
virus examined 0 d alter infrction. Ihese aiiinials showed an
increase in number a) miertihiiijies in some cells antI some
disruptions of lie mimochondrial ulirastruciure (Fig. 4).
the 1)2 animals receiving 1511 mg acetaminiip(icn plus 3.MC
and virus showed some loss of gl~cisgen and slight distention of
the endoplasntic reticulum. 1hz 02 anintals recetsing 2(01 nig
- . -~`-~`- . v~. ``~"~~-~r.'
~ ~
a -- ."~v,~*1I .,~5_.
- , ~ `-.` ~ *-,: -"~
~` *` t, ~ i_,
:,~`. - --- ~~~`f*rzt, ~
4 -~
- ,,~
1'
--
S ,,,d.4,~w
-i~~ :,,
4 ~
Fig. 4. D2 mouse. lIcensing inituenna B virus only. showing increase
in micmolsudiesiairio, 1 and some miiochondnal changes (it).
ofacetaminophen plus 3-MC and virus showed almost complex.-
ltisv,iiglyctsgcn. gitiiig the liver parench~ nsal cells a momh.catcn
appearance. Except (or a slight spor.tdie distention 01 the I R.
the tither cstoplasmic organdIes were spared (Fig. 51.
The Oh mice receiving acetaminophen. 3.NIC. and sirus
showed profound cltanges. The 86 animals receiving 15(1 mg ti)
acemaminophen plus 3-~stC and virus showed what appeared lii
be numerous vacuoles in the cell cytoplasm. Closer examination
of these sacuoles revealed the fact that these structures were
dismentions of ihe endoplasmic reticulum. Other organdIes ap-
peared relatively normal (Fig. 61.
The B6 mice receiving 2(0) mg of acemaminophen plus 3-MC
and virus showed progressive distention of the ER. with almost
complete disruption of the normal cymop(asmic architecture in
many of the liver parenchyma) cells (Fig. 71. In some animals
the organdIes appeared so prtsfoundlv disrupted that mans txf
tIme cells were dead, and the nuclear ultrastruclure showed loss
of normal organization. Fatty accumulation, corresponding to
the microvesicular steatosis seen on Lbt. appeared to be within
the distended ER lFig. 6(.
Tlti.'~e changes seen in the B6 mice were mostly confined to
the liver parench~ ma) cells, hut in occasional Kupferce(I showed
similar changes. The other cells of the liver, such as the cuhoidal
epitliclial cells tif the bile ductules and endothelial cells, appeared
un;il)icted.
Lit:ciiti' a.s.vais. Arithmetic means of she espet-imental data
were compared using Student's (test, with P < 0.05 Ibm the two.
laded test as the limit of significance. The expected increase in
cbittchrome P.450 on induction with 3.MC was conllrmed. But
PAGENO="0638"
~qi~
~
U
U
-n
z~
~
`U
>
-4
2
0
X
m
2
C
0
2
0
0
PAGENO="0639"
MACDONALD AT4L
addition to acetaminophen and 3-MC. Similar changes in the
ER have been reported on EM examination of the liver of an
adult male .vullbring rim aeetaminiiphen overdiise, and Isv
ihaler ci a!. (29) Svobisi* ci a!. (28) tn human R.S (18). Fat
deposits, corresponding Its thosi.~ seen on l.M, vvere within dis-
tended areas of he ER.
Svoboda eta!. (2)1) studied the livers of sin patients with RS
by LM and EM. and attempted to correlate he changes seen
with the clinical course of the disease. They found that on l.M.
intlammation and necrosis were especially prominent in fatal
cases and that "Aside from loss of mains dense granules, alter-
Swiss in mitocheindrial structure were minimal or absent. No
ultrastructural batures served to distinguish-patients who died
from those who survived." They concluded that Althiiugh de-
rangement of mitochondrial unction may be inttxirtanl in the
pathogenesisof RS. such derangement iv nut necessarily reflected
in the ultrtvtructure olthe mitoehondria."
Thaler ci a!. (29) noted the presence of numerous microbodies
in liver cells on EM. They were not impressed by any significant
mitoi:hondrtal change. Several incontptete reports have been
published, such as the one by Morales ciii!. (15) which merely
relbrsto "rniti~hondnal changes and dilatiiin of the endiiptasmie
Structural changes in the hepatic cell milochondria in RS have
been emphasized by Pants ci a!. (26). These authors believe that
there is a parallel between recovery of mitochondriat ultrastruc-
ture and clinical improvement of the patient, and vurgest that
mttoehondnal damage is important in the evolution of RS.
Although mitochondrial changes did become apparent with
progression of the toxic process in our study mice, they were
invanably preceded by swelling of the ER. Our findings resemble
those descnbed by Ssoboda elI!. (28) and to a lesser extent by
Thaler cI a!. (291. Direct companson of our mouse samples with
liver samples frism humans was handicapped by the lack iii
availability ot human biopsy specimens, because liver hiipsv is
nil lunger regarded as a routine procedure in diagnosing Rh (221.
Our review ol publushed [Ms led us to cviitclude that dilatation
ol the ER proceeds significant hepatic mitisihuindrial damage in
the progression of huntan RS, hut that the ER changes are ol(en
overloiiked by the authors when describing EM findings.
Studies to date on tlte ellects of drug-virus interaciiiin tin lie
immune system have indicated that stimulation of interibron
production by the virus will depress the MFO system 17, 2. 201.
Our histologic data suggest that activation of certain components
at the cylochrome p.450 MFO system might he a mechanism
br potential acetaminophen lonicity in our study mice. In light
of this, the results of cytochrome P45(1 enzyme assays ire
contrary to expectations: however. interpretalion is handicapped
by methuidologic problems. It was our intention to attempt iii
correlate cytischreime P.450 values, not only with individual
treatment regimens. hut also with histologic findings in hut
individual muiuse livers. This was the reason for attempting
enzyme estimatiuins on the sante livers from which samples vvere
obtained fitr LM and. in slime cases. EM. In fact. enutynie-
histology correlation vs-as not possible, because animal livers hid
to be pooled tn order lit separate sufficient microsomal material
for subsequent enzyme assay. \lthouglt our results do not indi-
cate that microsomal P.45(1 induction us a mechanism by which
the tunic ellects ul acetaminophen are puitentiated by inhluenea
B virus in these animals, it is certainly possible hal studies ui)
larger numbers of animals and use of more sensitive meihuds for
eney nne assay: along with methodology to separate out mdiv toil
types of P.450. might produce dillering results.
The pitfalls of direct estrapolation from animal data to he
human are well recognized. But, the finding that the typical liver
toxicity iifacetaininophen is signilicantly enhanced in mice Isv
eonciimitant viral iiilectiuin is of nta~or potential signilicance ii
the human. Animal studies by McLain ei a!. (13) and Gilmhiin'eer
cliii. ti), on lie ciinshined ellects of alcoltiil and aectaminophen
have been confirmed in humans. Aletihilie subjects may sutfor
serious tosie ellects Irons usually inituscuuius quantities of dcci-
aminuphen. paitcularlr if they are abusing 16cr chemical sub-
stances. Acetaittinuihen tiivi~iy alvii aiilicars iui be pmicii:r.icd
by cunconpitant miiitonuclciisis 123).
.hcetaittintiphen isa coiiiniuils used antipvretic in children aid
is being promoted in tie United States. This promotion is hose
lacilitated by the apparent indictnicitt if s.ulieyLutes us a causal
agent in RSI2I(. The evidence (tat tither commonly used drugs
are nut ettuitogicalt~ associated vs ith RS us estremels weak.
Taking into consideration the numerous agents which have
been causally related to an RS.like syttdru.ume in man, we In.
pothesize that virul-seniihiuptie interaction may be an underlying
ntechanism by which many foreign chemtcals might produce Rh
in a susceptible individual (27). Those all'ected may have reit-
dercd susceptible by prtor conlact with some noxious environ-
mental substance. and/tsr by genetic factors, perhaps manifested
through the immune system.
REFERENCES AND NOTES
i. .Siias.S VnxsdlE5andNpep'p.DWGeneijceonpsoofint..uiiujuivai
Psi idiuoisimis ui aivi tpsdvcarpsn h~druu*pLuu in uuliuc.i
huni,cnissph,s-viey(.uccpR.yims-avi.uiiuu7,~
2. Rivu. R. L md SLmuipe. St 5- 11 vaiheiugs ui R cue's mdi,,, I,
in: 1) 1 Pii.mek. Rise's sumPdron~n. p. 77 Gun,, and tiravu.
\u~\,urk.i'i'ai
1. Chaikirs ii. W.; Stcihuul fun' iSo quaniiiative morpPinio~ic aiscimsis if
i. Nai (aocu,'rRes.4 dlii'idSi.
a ci,.. v R .1 edema. F.. Purdm. V., and S~ndPn'g. D H.: Viral Vuiu,Pu,ti.u,
ui uheinuc.mi iuuuns us iSo exunnienidi nndpuunpe nihipogivcu..i,ia. unmet's.
633
Fig. 7. )lepatueyte from Rh mouse receiving 3-Mt. virus, and 211)
mgulacctaminuiphen. with distended rnvltipicsmie retieuluniil)t.Rtuiid
ulirastructural alteration of mitisihondriamNil.
PAGENO="0640"
aloputby and fatty sheets) dernenasion. Am. 3. De~ Die.. /9:1091(1974).
5. Cracker. 3. F. S.. Rozee. K. R., Onene. R. L. Osgoso. E. S.. and Hulaings?. 0.:
Insecticide and ctnal election as a cause of fauy oiscm'sJ chaegm and
rncrphatttpsthytn the mouse. Lzm'tn2 22)1974).
6. Crocken. 3. F. S.. Bent. H. R. H.. MacDonald. 8. C.. 0mm. 8. L and
Fxtdsschon. 0. 3.: Reyn's syndrnmen A diwate of chrnsuott anti strut inter-
In: Di. Poilat,k., Ree'ssysdrnme.pp.33t...54t(Crs.oseandStnatton
N~m York. 974).
7. 0mIiioa. L B. and Manncnng. C. 3.: Srttueniiai admsnozsation ttfpihoi-
nosinic acid and polftnhncyttdylic acid indace interferon and depress he
hepouc cytocht'ome P-t50dependens mononygenaae system. Biixhem. S,o-
phis. Ret. Commun. IlK 9471(982).
8. Fnend, M. and Teainer. D. 0.: Polnch)oeinated Biplsnny). intenaction 04th
du~k hcpatttisntnus. Silence, 1O. 13(4(1970).
9. Coldtingcr. R.. Ahmed. K. S.. Pitchumoni,C. S.. and Wtyc)ey. S. A.: Concom-
tan) alcohtd and drug atrstse enhancing acetamineplsets tonicity. Am. 3.
Gauteuentenn).. .0: 3051(978).
(0. Cunesoto. M.. Tomhattgh. C. C.. and Sohoanno. K. B: Reyn'snnndnrnte mode)
tns)nnttnphospboer,u(P.l,f,..Jiutr. Ret. (atnstrat.'t(. Itt. 194)19421.
It. Ke(knnnan. C.. Sham. C. 8.. and Lynen.Keflernnun. M.: Any) hytlritcarhon
hydrosotase isducibilisy and bennchogesic cunninonta. N. Erg). 3. Med..
2,96 934(1973).
2. Kramer. M. 3.. Funtkanta. C. 1.. Karp. 3. R.. Shapiro. C. C.. rtenr,tn. W. E..
and Brenman. C. W. Altered iheoplsylline cteaamnce dunngan influenza
,tutlts'eak. Pediatnirs. 69 4761(9)21.
Ii. McLatn.C.J..Krenshons.J.p..pnnennees.F.j..andHeitnsun.j.t..:poteociac.tn
olacetatninophen hepatosoutcity by alcnttn(. 3. Am. Med. Mane.. 244. 251
((0)0),
14. btisohefl. 3. R.. itdtom. 0. 3.. Fount. W. Z.. Ci(tcne. 3. R.. and Bit/tn B. B.:
Acenaminophen-induced hepauc necroste. WV. 3 Pttarnnacol. foR Then..
(.87 185(1173).
IS. Morales. A. 8.. Bourtettis. C. H.. Jr.. Ts,tpu(.dt. S.. and ChuLachantu-. E.:
Encephatopashy and laity dogonenatutn otthe uisceea. An electron Micro-
st.ttpscnudy. Am. 3. ((in. PattsoL5. 755(l'ihft).
(6. Mullen. P. W.: Immunopharmacologtcal considerations tn Rein's syndromes
a possible senobinsic initiated disorder? Bittcttem. Phaennac,tL 27: laS
1(r)).
17. Omura. T. and Sato. 8.: The emboss mononide lending pigments of (june
mionosontmn. 3. Blot. (hens. 230: 237)1) t tOut.
10. Petenstin. P. and Vdstnup. H.: Relation hesonen liner function and hepatitcote
ultmustructume in a case ot paeacesansot intonicatton. Digessioss. 19. 4)5
11979).
19. Po(lack. 3. 0.: Models of chemical and uteus ntenacsiois and best relation to
a multipleetiokspr otReyessondnome. In:J. F. S. (nicker Reye'ssyntieunsz.
II. pp. 34t-Jh094jrure and Stnuo.an, Nest York, 197')).
20. Renton. K. W.: E(TectsotInfecstne and ImmuneStimulaston oas Thenpby)tine
Miitabtoltsm. Semtn. Pinnnn.ttel..5. 17)110)11.
21. Report on the scsenttltc morkslsop on Reyn's syndrome and its ptmutb(e aunit-
ct.attos roth salteylate use. Department of Health and Human Serutcns.
187
Public ))ralth Sernice. Food and DrugAdminisseas,oe Held May 24th (982.
at National Inssttutesofltealth.
22. Reyes Syndromec National Institute of Health Consensus Denn(opnsens Con.
lcscni.e. Man.h 11)8).
23. Rosenberg. I). M.. Meyer. A. A.. Manning. I. I).. and Nuiclito. F. A.: Aunt-
aminoplton and hoyaiic dyuluncsiun in niActious monitnucleosis. South.
Mcd. J.. ii 161) ((977).
24. Ruben. F. I .: Rct:rnt :kiili.pnuonis and ,:i:ntn:hui,,.ns lire enponnnrntal
mln(rlsi')Roucssni%(si.mc.(n:.trs(ro9koroeyessnndrome(tpp
395-397 (intro and Stnoit,,n re.. ~ Yoik. 9799
25. &hautrn(o. (1 9. and PolLick. 8. I..: .7 nimphlied nncuh,uI Ion hr quanu:iat.e
asian 01 ..mal( aniouot.sof protein in hiiAo~ic nuatunal. Anal. Oau:hem.. 51
6 `4 I 117 Ii
26. Schubert. W. K.. Ptntn. I C.. and Panin I S.: fnorph::li:pathc and 14117 liter
(Royi s nun,(riitnn). In: It. P::ppon and F. S.haltiicc )`nogics.s in Liuor
t)ttoasu-s. Viii. 4 pp 490-493. (Grune and Siuoiuitn Noun York. 972).
27. Sult:tan.t).tlnat. 3. Z and Corey. L: Epidomialiigy of keyes syndrome. Eps-
(em. Ruin I (21(1941).
26. Studsisia. I) I md Ruiuidn. /. K.: Pathology of the liter in Reins S1ndrome.
Lab. trtucst. .f 57) ((975).
29. Thulee. M Rruhn. F. W.. .Npprlluaum. 94. 74.. and Goodman. I.: Reyes
nnndn'.tmeinto,ns.J.Prijiatr.. 7' 639(11)70).
30. Thiurgitirnoon. S. S. Fclton. 3. S.. and Nolrens. D. W.; Gerniicdiflrnrrcen in ihe
aromatic hndriorurbon.induu:(n(r n.hydniisulation if 2.uurtylain,no (linurene
and ai.cuaminophe,s produi.ed hepatotuso.ity in mice. Mid. Pharmaco(.. II:
St. Th:ynoursscn. S. S. and Notniuns. D. W.: The .hh Incas and the uncuainolisos of
chennuca)tarctnogens and other ioicugo compounds. Ado. Cancer Ret.. 25:
32. Wotsb. S. K.. Gel). P.C.. Brysuin. M. S.. Llounrllyn. C. C.. and Madgn. C. E.:
Rrtr's snndriumr.like disean in mice led z(latouin and mitt-ted uilh
Conua.kio tines. Presented at the Reyes syndrome III Symposium: Detroit.
Nontimber. (`190.
33. In order to ,uhsain a miononuimal pullet ofnu(Ttrirns size (icr enzyme assay, it
(itund nru.rouann 10 `ut-il the liters friima minimum uf ihten animals.
34. Using Stopuinr Prugerusite logistic Ruigeession. all compansoss quoted lob-
nine uigni/uant to (`<0:911.
.55. Censiui)otrular nrcru'tis uau considered nipniflcant uhen is oat u(eaety mrog.
cited in (i)°i in mitre tithe hopalic (obulesenamiord.
Sb. The authors thank Dms. 0. W. Nrlens and C. MeLuren for their inualuable
.idu ice and support kin the pninprul.
37. Ru'quonts for roimnno uhould liii addressed to: Dr. Vlhain C. `McDonald.
(hi(drro's ltintpitat National Medical Center. Ill Michigan A nenue. NW.
A.tnhirgiiin. I)C. 21)1(11.
JO. Ihiu soccarch oat sizrtoned by he Dtuinion of Denn(opmenual Phannaoology.
ant) the Si,reau of 9uligu's. FDA.
31). Rc'coisod Sir nulsiu:amii,o lelsnuary 0, liftS.
40. Accepted (lie putslicaiion Augusa 17. 1983.
634
ACETAMINOPHEN, VIRUS. AND REYES SYNDROME
ANNOUNCEMENT
The annual meeting of the American Society of Pediatric Nephrology will be
held at the Hilton Hotel in San Francisco on Tuesday. May 1. 1984, from 9:00
a.m. to 5:30 p.m. The morning session of the symposium will focus on reflux
nephropathy-anatomical, bacteriological, genetic and radiological implications-
and the afternoon session will cover prostaglandins in newborn physiology and
renal function. For further information, please contact Dr. Russell Chcsney,
Secretary-Treasurer. American Society of Pediatric Nephrology. University of
Wisconsin Clinical Science Center (Rm H4/452), 600 Highland Avenue, Madison,
Wisconsin 53792.
PAGENO="0641"
635
Mailgram sent to all television stations on January 17, 1985
MAILGRAM TEXT
I am writingto you on behalf of the Coordinating Committee
of the Committee on the Care of Children. We have received inquiries
as to the status of the Public Service Announcement on Reye Syndrome
which was sent to your station by this Committee nearly one year
ago, (February, 1984.) Last week, the Department of Health and
Human Services released the results of a pilot study which showed
a strong association between aspirin and Reye Syndrome. We are
making every effort to secure the data on which that study is
based and to review that data as quickly as possible. In the
meantime, we request that the Committee's Public Service Announcement
not be aired. We will notify you as to the results of our review
as soon as they become available.
Thank you for your attention to this matter.
Thomas M. Reardon, Esquire
Gaston Snow & Ely Bartlett
One Federal Street
Boston, Massachusetts 02110
(617) 426-4600
52-266 0-85-21
PAGENO="0642"
636
PREPARED IN CONNECTION WITH THE TESTIMONY ON
BEHALF OF THE COMMITTEE ON THE CARE OF CHILDREN
BY:
DAVID J. LANG, M.D.
CHAIRMAN, DIVISION OF PEDIATRICS
CITY OF HOPE NATIONAL MEDICAL CENTER,
DUARTE, CALIFORNIA
COORDINATING COMMITTEE
BEFORE THE COMMITTEE ON HEALTH AND THE ENVIRONMENT
OF THE COMMITTEE ON ENERGY AND COMMERCE
OF THE HOUSE OF REPRESENTATIVES
HONORABLE HENRY A. WAXNAN, CHAIRMAN
ON H. R. 1381 "THE EMERGENCY REYE' S SYNDROME PREVENTION
ACT OF 1985"
The following is to provide you with some comment
on the CCC's preliminary review of the data from the
pilot case-control study conducted by the CDC of the
possible association between aspirin use and the risk
of Reye's Syndrome. CCC has initiated an impartial
review of the data tape and other material made available by
the FDA. Unfortunately, the tape contains only a portion
of the data that were available to the investigators, and
we have not yet seen any of the original questionnaires
or medical records for patients included in the study.
Consequently, our comments pertain only to the data
contained on the tapes and cannot be considered as a
criticism of the overall study or the preliminary results
reported by the investigators. We shall first present
our specific comments on the data reviewed on case
subjects with Reye's Syndrome, and conclude with a brief
summary statement.
PAGENO="0643"
637
Specific Comments
1. The preliminary report made public by the CDC
investigators was based on 29 cases of Reye's Syndrome.
(There were three additional cases with a prodrome of
chicken pox who were not included in the preliminary report
or in the data made available to us. No explanation is
provided for this exclusion.) However, the data we were
provided contained 27 cases, including three subjects who
were excluded because they failed to meet the diagnostic
criteria for Reye's Syndrome (subject numbers 90015,
90017, 90030).
2. For eight cases (including the three who were excluded
by the investigators) we are unable to confirm the presence
of central nervous system symptoms necessary for the diagnosis
of Stage II Reye's Syndrome. Although some of these cases
were reported to have had lethargy and/or excitability,
none were reported as confused, combative, delirious, or
disoriented (subject numbers 90015, 90017, 90022, 90024,
90029, 90030, 90031, and 90032). From the data included
on the tapes, we are unable to discern the reasons for
excluding three of these cases and including the other five
cases.
3. Each of the three excluded cases were classified as
not using aspirin during the patient's illness.
4. For some subjects the documentation of symptoms
appears to be incomplete. For example, subject 90001 was
coded as having severe confusion on day 1 of illness and
day 5 of illness, but no evidence for confusion on days 2-4.
Without the medical record, we are unable to determine whether
this unusual clinical course accurately reflects the patient's
illness or may be an artefact of the strategy used for
collecting data. In the pilot study the investigators asked
patients to focus on a particular symptom (e.g., cough or
vomiting) and to recall whether the symptom was present on
each illness day (e.g., day 1, day 2, day 3, and so on).
This strategy is quite different from the customary method
for taking a clinical history in which the patient is
asked to describe all of the features of their illness on
each day. Using this method, the patient would report
fever and cough on day 1, the addition of nausea and
vomiting on day 2, and so on. We cannot be sure that the
two methods would yield similar data, but the distinctions
are obviously crucial (e.g. for case 90001, we are
unclear whether Reye's Syndrome began on day 1 or day 5 of
illness).
PAGENO="0644"
638
5. In at least two cases we have serious concerns about
the possible occurrence of errors resulting from temporal
precedence -- i.e., did the case subject receive aspirin
before or after the earliest symptoms of the onset of
Reyets Syndrome. For case 90001 and 90027 the first dose
of aspirin was taken on the same day that the subject had
evidence for Reye's Syndrome onset. Without examining the
medical records and reviewing the questionnaires we are
unable to exclude errors due to temporal precedence.
6. Only six of the 24 cases had a clear cut biphasic
illness, and the mean duration of the prodromal symptoms
before the onset of Reye's Syndrome was just 4.6 days.
7. Our review of the data tapes emphasized the
importance of specified criteria for defining a patient
exposed to aspirin. Some patients in this study who were
classified as aspirin users took a single tablet early in
the prodrome and became ill with Reye's Syndrome many days
later. Other patients took no aspirin until the day the
symptoms of Reye's Syndrome began. Both of these types
of patients were combined with subjects who used aspirin
regularly from the beginning of the prodronal illness to
the onset of the Reye's Syndrome. We have previously
proposed that patients be classified according to their
pattern of aspirin use and separately analyzed. No atten-
tion to this issue is evident in the preliminary analysis
of this data.
Summary
We wish to emphasize that our comments are based on
a small portion of the data already coded by the investigators
and made available to us as part of a special data tape.
We did not have access to any of the questionnaires or
medical records of the subjects included in the pilot
case-control study. Perhaps the most important conclusion
of our review is the need for more data. Without the medical
records, we cannot perform a careful and thorough assessment
of the work completed by the investigators, Consequently,
we are not able currently to conclude that the pilot study
provides convincing evidence for a valid association between
aspirin use and the risk of Reye's Syndrome.
PAGENO="0645"
639
Mr. WAXMAN. The Centers for Disease Control, American Acade-
my of Pediatrics, Secretary of Health and Human Services, the Food
and Drug Administration, all believe there is credible evidence of the
connection of aspirin to Reye's Syndrome. The Aspirin Foundation,
which I assume is made up of aspirin manufacturers, has been
willing to undertake a voluntary labeling. Is that right, Dr. White?
Dr. WHITE. Yes, but not accepting that there is any connection.
Mr. WAXMAN. I see. Now, the central issue to parents is whether
or not they should give their children aspirin to treat the discom-
fort of chicken pox or flu. And, if you believe that there is a suffi-
cient scientific evidence to justify a precautionary warning, what
possible purpose is served if that message is not clear and unambig-
uous?
Dr. White, don't you think that message ought to be clear
enough to warn parents not to use aspirin for those symptoms?
Dr. WHITE. I think if you look at our total package it is clear. We
have great concern about labeling properly because of all the
things that should be on the label and perhaps they all have equal
weight, and on the other hand, when we deal with Reye's Syn-
drome, which we do in the case of public service announcements,
and also the posters, we not only describe there is the potential for
this relationship, we also describe the symptoms of the onset of
Reye's Syndrome and what the action of the parents should be at
the time.
Mr. WAXMAN. Are you willing to say that your position is that
there is a potential connection between aspirin and Reye's Syn-
drome and therefore a parent should be aware of that if they are
going to give their children aspirin to treat chicken pox or influen-
za?
Dr. WHITE. I am saying that there is--
Mr. WAXMAN. Would you subscribe to what I just said? I will
repeat it. Is the statement you would subscribe to, there is a poten-
tial enough connection between aspirin and Reye's Syndrome that
parents may not want to give their children aspirin to treat dis-
comfort of chicken pox or flu?
Dr. WHITE. As I said before, just a few minutes ago, we do not
subscribe to the link that has been proposed. We do believe that
there are some people who are willing to accept it and being con-
fronted with the request, voluntarily-keep in mind that that
means-to label, we decided that it was reasonable to cooperate
and that is what we are doing.
Mr. WAXMAN. OK. I appreciate the testimony each of you has
given. I think the clear statement you have made is that whatever
is being done is being done voluntarily, and to the extent that any-
body voluntarily is willing to make some kind of statement that
shows the connection depends on each individual company.
There is only one company that has made a clear, unequivocal
statement close to that label, that is Schering-Plough. Isn't that a
fair characterization? I might just point out Schering-Plough's
product is St. Joseph's aspirin for children~ It is aspirin for chil-
dren. Therefore, one might wonder if their warning label is more
explicit because of their fear of liability because their aspirin is
geared for children.
PAGENO="0646"
640
Dr. WHITE. I can't speak to that, but I do know they are market-
ing a nonaspirin for children. Almost every other physician who
has been up here today has asked what about his children and his
grandchildren, and I have said on public television I have made no
effort whatsoever to communicate any concern on my part to my
son about his son and my grandson in regards to Reye's Syndrome.
Mr. WAXMAN. Do you figure that he is one of the 80 percent that
has heard about it already from the public service announcements?
Dr. WHITE. That may be the case, but I haven't tried to reinforce
it or tried to lead his knowledge of that by calling him up ahead of
time.
Mr. WAXMAN. Have you asked whether he has knowledge of it?
Dr. WHITE. No, I haven't even done that.
Mr. WAXMAN. Thank you very much.
Mr. Wyden. -
Mr. WYDEN. Thank you, and this has been an important panel,
and helpful panel to me.
Dr. White, I came to this hearing not having any misgivings
about the safety and effectiveness of aspirin. I think it is a tremen-
dous medical program in and of itself, but I really hope the indus-
try will now take steps to answer some of the serious questions
that have been raised. I want to get into just a couple of the areas
very briefly. You heard the testimony of the American Academy of
Pediatrics, their advice to parents and physicians is extremely
clear-in the case of chicken pox and flu, be safe, don't go with as-
pirin.
It seems to me that by not mentioning a Reye's Syndrome in the
precautionary label and instead asking parents to consult their
physicians, we are essentially diluting the effectiveness of any
warning. Do you agree with that appraisal?
Dr. WHITE. We have some concern about what impact this pro-
posed warning would have on the other warnings that are on the
label. One of the most important ones is concern this product ought
to be out of the reach of children. There is much more of a problem
in the United States with that than there is with Reye's Syndrome.
Mr. WYDEN. Proceeding, if I might, to get your reaction to this
very impressive testimony of the American Academy of Pediatrics,
the approval and scientific body for pediatricians, I would like to
know whether you suspect individual pediatricians might exercise
different risk assessments than those used by the academy in eval-
uating the danger of aspirin in young children?
Dr. WHITE. I believe that Mr. Chayet has very good evidence
there are a lot of pediatricians who don't hold to that position.
These groups that are groups of physicians very seldom represent
the rank-and-file position.
Mr. WYDEN. I think that is certainly making light of approval of
an association with enormous prestige in this field. The APA is rec-
ognized as the premier representative of pediatric medicine, and
you seem to think that they are just not very important. What do
you advise a worried parent, then? Go with the advice of the Amer-
ican Academy of Pediatrics, or go with the critics? You are telling
me-
PAGENO="0647"
641
Dr. WHITE. I am telling the individual, first of all, they ought to
seek some kind of professional help; that it is an individual deci-
sion and their doctor ought to make the decision.
Mr. WYDEN. But the professional association made up of those
doctors, clearly singled out by those doctors as prestigious and phil-
osophical, a professional association with great stature, has given
us counsel and yet you seem to think that worried parents should
look at something other than what the pediatricians are saying. I
am just wondering what parents should look at in that case.
Dr. WHITE. What we are doing right now, I believe, is cautioning
people not to use aspirin for children and teenagers who have
chicken pox or flu without first consulting their doctor. We are not
convinced of the cause-and-effect relationship here. We have agreed
that there is enough concern and there is enough confusion that
there ought to be a single message and here it is, and we are very
serious, spending day and night trying to get that message out.
Mr. WAXMAN. Would you yield?
Mr. WYDEN. Yes.
Mr. WAXMAN. The Secretary of Health and Human Services is
allowing you to decide voluntarily whether to warn people about
something you don't believe, that is there a clear connection be-
tween taking aspirin and Reye's Syndrome. The Department claims
they believe it but they are saying the best way to get the message
across is to let you, who do not believe it, communicate that mes-
sage. I think what we have is a clear communication of the fact
you don't believe it and therefore nobody is going to get that opin-
ion from you.
It seems to me that is quite an amazing position for the Food and
Drug Administration and the Department to take to let somebody
who doesn't believe in a position be the one to communicate that
position.
Mr. DICKSON. May I address that, because it does address the dis-
cussions we have had with the Food and Drug Administration.
Mr. WAXMAN. I said it more rhetorically. It is Mr. Wyden's time.
Mr. WYDEN. Thank you, fine.
Mr. DICKSON. The fact is the Food and Drug Administration is
not saying that there is a definite link between aspirin use and
Reye's Syndrome. In fact, the Food and Drug Administration has
told you today that they did not have enough evidence to regulate.
Under that circumstance, a voluntary program makes a lot of
sense.
Mr. WYDEN. The Food and Drug Administration said there was a
probable connection, No. 1, and we brought out an incredible array
of prestigious scientists-the chairman just read them off-all of
them agreed there is a link.
What kind of evidence would convince you? How much more evi-
dence do we have to have? Only an industry-done study-is that
basically it?
Mr. DICKSON. No; that is not basically it. But a good study, sir,
and the data that have been discussed today, the pilot study that
has been talked about, was a preliminary study, just to look at
methodology.
PAGENO="0648"
642
FDA has said the study they are running must be completed. We
have not yet seen the protocol for FDA's study, so we don't know
what it is going to look like.
Mr. WYDEN. Let me read you from the Department's pilot study:
Recently completed for the Department of Health and Human Services substan-
tially strengthens earlier evidence of association between the use of aspirin contain-
ing drugs and the development of Reye's Syndrome.
So all the evidence is cascading upon us. I wrap this up by put-
ting it in a personal context: I am a parent of a 1-year-old who we
hope we will see as a backcourt star for the Portland Trail Blazers
in a few years and I come away from this hearing having signifi-
cant doubts about whether or not what we are doing in this critical
area is going to promote public health and safety. You have taken
somebody who had no doubts 3 or 4 hours ago when we started and
I have been convinced that there are many unanswered questions.
I am very fearful that we are going to let this problem slide
through the next flu season and more and more parents and more
and more children will suffer and it is all unnecessary.
Thank you, Mr. Chairman.
Mr. WAXMAN. Just for the record, Mr. Chayet, you say in your
testimony "It is essential the committee indicated," refers to the
committee you represent,
That it works in areas which relate to industry and would be funded primarily by
industry because of the belief that industry has an obligation to fund arms length
efforts to seek the truth with regards to matters of controversy.
I want to point that out.
Mr. CHAYET. We believe that strongly, Mr. Waxman. There has
got to be a search for truth. Industry has to-I asked Dr. Wolfe's
organization for money, I don't know whether the check is in the
mail or not-but really, I am serious. Where will the funding come
from?
Mr. WAXMAN. Are you a scientist?
Mr. CHAYET. I am an attorney, sir.
Mr. WAXMAN. OK.
Mr. CHAYET. I have spent my life with scientists and I look for
the ones that I can trust and believe in, and all the people you
have heard from today, they are fine people, they are under tre-
mendous pressures because of the early errors that were made by
the--
Mr. WAXMAN. You are an attorney and represent an organiza-
tion that has funds from the aspirin industry; is that a correct
statement?
Mr. CHAYET. You can say that real quickly, but that is the way it
really is, because this is a matter of life and death and I believe
that my profession has an obligation not to just say things, because
we are attorneys, that we don't believe in. It is about time we
change that. I have to tell you I have gone everywhere and I will
bring you with me to the scientists to seek the truth. I can tell you
if we ever found out, and not after 10 years of study, and without
nitpicking, if we ever found out that there was a relationship be-
tween Reye's Syndrome and aspirin, we would be the first to be
before you to say so, sir.
Mr. WAXMAN. That is what they say in law school.
PAGENO="0649"
643
Mr. CHAYET. I resent that comment; I am sorry.
Mr. WAxM~i~. You have to make the best case you can.
That concludes our hearing for today. We thank all the witnesses
for participating.
Our meeting stands adjourned.
[Whereupon, at 1:05 p.m., the hearing was adjourned.]
[The following letters and statements were submitted for the
record:]
PAGENO="0650"
644
GASTON SNOW & ELY BARTLETT
COUNSELLORS AT LAW JO6~0W80~TLETT (1901-1960)
ONE FEDERAL STREET
BOSTON, MASSACHUSETTS 02110 PALO ALTO CALIFORNIA 94306
617/426-4600 TELECOPY4I5/65 6-9299
March 28, 1985 CO~A~GABL~5,FLORI
The Honorable CABLP:REEKOM
Henry A. Waxman
Subcommittee on Health & Environment 006006 6600
U.S. House of Representatives
Room 512, House Annex I PCOENIO,ARIZONA8SOI6
Washington, DC 20515
Dear Congressman Waxman:
Once again, on behalf of the Committee on the Care of
Children(CCC), I would like to express our appreciation at
having been invited to present testimony to you and other mem-
bers of the Subcommittee. As I indicated to you at the opening
of my testimony, Dr. David Lang, who was to appear as a member
of the Coordinating Committee of the CCC and present its testi-
mony, was unable to be present because of a medical emergency
in his own family; I expect that you received his telegram
expressing his regret, the reason for his absence, and his
endorsement of the testimony presented to the Subcommittee on
Friday, March 15, 1985.
I am enclosing for the record a final copy of the statement
and attachments presented and would appreciate it if you would
see that the final copy of the statement and this letter are
entered into the record. I would also appreciate it if you
would provide me with a transcript of my oral remarks for
review at your earliest convenience, in the event any
corrections are necessary prior to insertion into the record.
There are several points that I would like to clarify fol-
lowing the hearing, and also several requests that I would like
to make on behalf of the Doctors. First of all, I would like
to reiterate that legislation calling for mandatory labeling is
well-motivated, based on the information that you and your
staff have apparently received. Your repeated statements that
the "science is not in question" indicates that you have not
been made aware of the fact that not only is the science in
question, but a great deal of the previous science on which the
PAGENO="0651"
645
GASTON SNOW & ELY BARTLETT
The Honorable
Henry A. Waxman
Subcommittee on Health & Environment
March 28, 1985
Page 2
bill is based has been discredited. The action of former
Secretary Schweiker in reversing the call for the labeling of
aspirin was not merely a fluke, nor was it because of industry
pressure; it was, we believe, because of the stark realization
that the scientific basis simply was not present to support
such action. Similarly, the statement of the Executive Board
of the Academy of Pediatrics, supporting that reversal and
calling for new studies, was also not based on industry pres-
sure, but again, on the realization that the scientific basis
for the action was fatally flawed. I would be very pleased to
provide you with additional materials which indicate just how
poor the early studies were and also to arrange for you to meet
with those who have reviewed this material in depth.
I would like to. reiterate that it is the CCC's opinion that
the massive publicity campaign in the face of the discrediting
of the early data is inappropriate and dangerous. We believe
that children may have died because they were the victims of
delayed diagnosis of Reye's Syndrome, with their parents
believing they could not possibly have Reye's Syndrome, because
they did not take any aspirin. In addition, we believe that,
as was made very clear at the hearing, there is no question but
that the publicity is leading parents and children to take
other drugs which could possibly be implicated in Reye's
Syndrome. I call your attention to a copy of an article,
enclosed with our statement, which appeared in the respected
journal, Pediatric Research, indicating that acetaminophen
could be implicated in Reye's Syndrome. Thus, your no doubt
well-intentioned remarks concerning Tylenol could turn out to
be tragically wrong. Most physicians and scientists with whom
we have spoken doubt that either aspirin or acetaminophen are
implicated in Reye's Syndrome, but the fact is that the
question has not been well-studied, and the article raises the
spectre that millions of people may be sent down the wrong road
with no justification whatsoever.
Prior to the hearing held on March 15, we believed that the
present course of events was merely misleading and dangerous;
following the testimony presented by the parents who appeared
befQre you, we now believe that it is not only misleading and
dangerous, but that it is extraordinarily cruel to parents who
have lost their children to Reye's Syndrome. If there was ever
any question that the actions of the government and other
groups have convinced people that their children would not have
PAGENO="0652"
646
GASTON SNOW & ELY BARTLETT
The Honorable
Henry A. Waxman
Subcommittee on Health & Environment
March 28, 1985
Page 3
died but for their having given them aspirin, the hearing has
erased any such doubt. To fasten this burden upon these
parents--that they contributed to their childrens' death--on
the basis of the scientific evidence available to date, is
unconscionable. The fact that publicity and inappropriate
labeling could cause death or disability by delaying diagnosis,
together with the burden placed on parents who had given their
children aspirin in an attempt to help them, vastly overshadows
all other aspects of this matter. It must be noted, however,
that this entire matter has had a devastating impact on the
physician-patient relationship, as well.
It is true that the results of the pilot study have been
recently released and that this study has been endorsed by the
Institute of Medicine.
The pilot study indicates an association between aspirin
and Reye' s Syndrome. We would very much like to be supportive
of this study, and as I indicated to the Subcommittee at the
hearing, we will not hesitate to endorse it if such endorsement
is indicated following a review of the raw data on which the
study is based. Since the announcement of this pilot study,
however, we have made an attempt to secure the raw data on
which it is based'and thus far have been unsuccessful in secur-
ing what is needed to analyze the reported results. What we
have found has led a noted researcher and clinician to conclude
that a valid association cannot be confirmed at this time. In
addition, Dr. Floyd Denny, who has been involved in observing
this study, has recently been quoted as stating that the study
is flawed. Representatives of the government have been consid-
ering our requests for additional data and thus far have indi-
cated that they cannot be made available because of Freedom of
Information and Privacy Act considerations. We earnestly
request your help and that of the Subcommittee in helping to
secure the release of this data, without which we will not be
able to fully review the study. The Doctors have no desire to
identify any of the patients or families involved and, in fact,
are ethically and legally bound not to violate any
confidentiality, and would be willing to enter into any further
agreements to reassure all parties that such violation would
not occur.
The question now remains ~is to the future. Because of the
past difficulties that have surrounded and continue to surround
PAGENO="0653"
647
GASTON SNOW & ELY BARTLETT
The Honorable
Henry A. Waxman
Subcommittee on Health & Environment
March 28, 1985
Page 4
the government studies in this area, we believe that it is
essential for another study to be launched as quickly as pos-
sible. P preliminary protocol has been prepared by a group of
excellent researchers and clinicians at a leading University.
This protocol, if implemented, would involve thousands of
clinicians throughout the country in a study of Reye's
Syndrome. This study would not be carried out in a manner that
would be adversarial or hostile to any further government stud-
ies, and, in fact, extensive efforts are underway to assure
that such a study will be carried out cooperatively. The pre-
liminary protocol which has been prepared is excellent and
innovative. In addition, steps have been taken to insure that
the protocol, its implementationS and the study results are
credible. The American Academy of Pediatrics has appointed a
liaison to the study; this distinguished physician has, in
turn, been asked to chair an Advisory Panel which will consist
of some of the best clinicians and epidemiologists from
throughout the country. In addition, there is being consid-
ered ways to involve all those who have had an interest in this
matter, including patient and consumer groups, as well as rep-
resentatives of the press and the government. We would also
hope that a member of your staff could participate in this pro-
cess. The goal is to insure that the study is carried out with
complete integrity.
There is another matter to which I would like to call your
attention. I expect that the reason I was called to the table
with the Aspirin Foundation and the Proprietary Association was
because of the need for economy of time. As I indicated to you
and to the other members of the Subcommittee, the CCC does not
represent and is not a part of industry; it never has been and
it never will be. We believe, however, that industry has an
obligation to find out whether its products are causing harm to
the public, and if industry claims that a government study is
faulty, it has an absolute duty not only to criticize that
study, but to see to it that such studies are impartially
reviewed, and that additional studies are carried out at arms-
length.
Lastly, I would like to clarify one further point. You
asked me if, in fact, I was an attorney representing this group
of physicians and I replied in the affirmative; I also added
that in matters such as this which involve life and death, I
believe that an attorney has an obligation to represent both
PAGENO="0654"
648
GASTON SNOW & ELY I~ARTLETT
The Honorable
Henry A. Waxman
Subcommittee on Health & Environment
March 28, 1985
Page 5
the interests and positions of his clients, and also to be cer-
tain that the position of his clients is fully supportable.
~From the very beginning, it was the clear wish of our clients
that we secure the best and most impartial clinicians and
scientists to advise all of us with regard to this matter, and
we have done so.
I would respectfully request the following of the
Subcommittee:
1. That action on H.R.l38l be delayed pending further
analysis of the conclusions of the pilot study;
2. That, in order to hasten this process, which will take
a relatively short time once the data is made available, that
the Subcommittee assist in securing the data as quickly as pos-
sible;
3. That the Subcommittee assist in the monitoring of the
review of the data of the pilot study, the proposed government
study, and the clinician-based study referred to above;
4. That a member of the Subcommittee staff be commissioned
to review the raw data of all studies to date, a process which
we would be pleased to assist in any manner deemed appropriate;
and
5. That the Subcommittee assist in expediting the
Citizens' Petition enclosed with the attached statement, which
would establish ground rules and criteria for public warnings.
Again, we appreciate the opportunity to be of assitance to
the Subcommittee in this most difficult situation.
Sincer y,
Ne~'~C~
Enclosures
PAGENO="0655"
649
Natonal Assodatkn of Tn~ck Stop Operators
1199 N. Fairfax Street Suite 801
P.O. Box 1285
Alexandria. Wginia 22313
(703) 549-2100
March 28, 1985
The Honorable Henry A. Waxman
Chairman
Subcommittee on Health & Environment
House Committee on Energy & Commerce
2415 Rayburn House Office Building
Washington, D.C. 20515
RE: H.R. 1381, Emergency Reye's Syndrom
Prevention Act of 1985.
Dear Chairman Waxman:
The National Association of Truck Stop Operators wishes to go on record
as opposing certain provisions contained in Section 2 of H.R. 1381, requir-
ing retail establishments which sell aspirin and salicylate-containg pro-
ducts to display the notice prescribed elsewhere in the Section. Although
the association understands the objectives sought to be achieved in the
bill, subjecting truck stop operators who sell these products to criminal
misbranding penalties under the Food, Drug and Cosmetic Act is unwar-
ranted, unjustified and beyond the proper scope of that statute.
The National Association of Truck Stop Operators ("NATSO") is a non-profit
trade association located in Alexandria, Virginia. Among its membership
are approximately 800 individual truck stop operators who collectively
provide a full range of services to the trucking industry and the travel-
ling public. These businesses represent a significant portion of the
fuel marketing, motel, restaurant, convenience store operations, and repair
services available along with the nations Interstate and federal highway
system.
In addition, NATSO members are predominantly small businesses. As
independent marketers of petroleum products, truck stop operators have
fought to minimize government intrusion into various areas of energy
regulation. Similarly, the truck stop industry has contended with efforts
to force these businesses to shoulder unfair burdens under the environ-
mental laws, as well as heavy tax burdens. The effect of H.R. 1381
is to impose yet another unreasonable burden on truck stops in the form
of the proposed posting provision. It is to this almost-hidden aspect
of the bill that NATSO takes strong exception.
PAGENO="0656"
650
The Honorable Henry A. Waxman
March 28, 1985
Page Two
Truck stop operators are not well suited to comment on the parent major
elements of H.R. 1381. NATSO truck stop members do not manufacture
or principally distribute the over-the-counter (OTC) medicines to which
the bill is directed. Neither do NATSO members undertake, ir~ any organ-
ized effort, to advertise such products, the sales of which represent inf in-
itesimal percentage of the business conducted by this industry. Appro-
priate responses on the labeling and media advertising requirements which
would be imposed by the bill are best left to those groups who are direct-
ly affected.
However, NATSO members stock and sell OTC medicines, including aspirin,
because they are commonly requested by customers. Consequently, truck
stop operators would be subject to the warning display provision and
the related criminal penalty for "misbranding" proposed by the bill.
NATSO submits that this proposed posting provision and penalty for retail
establishments exceeds the jurisdiction Congress has fundamentally placed
in the Food & Drug Administration. The Food, Drug and Cosmetic Act
as it presently reads does not empower the FDA to promulgate regulations
applying to retail establishemnts and H.R. 1381 should not mandate that
such authority now be created. Any amendment which would have the
significant and pervasive effect of rewriting FDA's basic jurisdiction
should not be adopted as "throw" to a bill addressing a specific health
question. Such a change should only be adopted after Congress has
conducted a detailed study and evaluation of the effects it would have.
NATSO is aware that the FDA has previously issued a posting requirement
effecting retail establishments in its saccharin regulations. This lone
action, however, does not establish that the agency in fact possesses
the authority to regulate retail businesses in the sale of otherwise regu-
lated products. Moreover, Congress should be aware that this singular
example of a retail posting requirement has been ineffective at best.
The FDA has no capacity to enforce such a regulation and it therefore
has not attempted to do so. Indeed, the posting provision proposed in
H.R. 1381 would require an army of investigators trooping throughout
the countryside invading grocery stores, drug stores, convenience stores,
bars, airports, truck stops and nearly every conceivable type of retail
establishment whose customers may expect to purchase a bottle of aspirin.
Since the improbability and impracticality of this situation is apparent
on its face, this subcommittee should refuse to consider imposing any
posting requirements.
The lack of legal basis to regulate retail businesses and the impossibility
of enforcing such a provision should convince this subcommittee to reject
the proposal. If not, NATSO contends that many retail establishments
would be forced to elect not to sell aspirin and other salicylate-containing
products rather than risk exposure to criminal penalties. The vagaries
of happenstance enforcement, along with the inconvenience and expense
of trying to comply with the provision, would make unacceptable the
need to retail these products which do not constitute a meaningful amount
of business for truck stops and other similar establishments. Although
we doubt this subcommittee is seeking to remove these products from the
shelves of these stores, that result would be the prudent course for many
businesses, Instead, the subcommittee should focus its attention on ways
to inform and educate the public, such as those described in the testimony
of the Propietary Association and others who have suggested ways to
achieve this goal.
In conclusion, the National Association of Truck Stop Operators opposes
the posting provisions of H.R. 1381 and recommends to the subcommittee
that it seek other alternatives that would not impose an unnecessary
and erroneous burden on retailers such as truck stops. We ask that
this letter be included in the official record of the subcommittee's hearing
on this bill.
Sincerely
RONALD L. Z GL FV
President
PAGENO="0657"
651
AMERICAN REYE'S SYNDROME ASSOCIATION
STATEMENT ON H.R. 1381, THE "EMERGENCY
REYE'S SYNDROME PREVENTION ACT OF 1985"
The American Reye's Syndrome Association submits the
following statement on H.R. 1381, the "Emergency Reye's Syndrome
Prevention Act of 1985." H.R. 1381 would require a warning in
the labeling and advertising of salicylate containing products
and a notice in retail establishments where such products are
sold to the effect that such products should not be administered
to persons under 21 years of age who have chicken pox, influenza,
or flu symptoms because the products are "strongly associated"
with the development of Reye's Syndrome.
Introduction
The American Reye's Syndrome Association is a not-for-
prof it, tax exempt organization composed of health professionals
and laymen who seek to find the cause(s), cure(s), and
treatment(s) of Reye's Syndrome. The Association is dedicated to
informing the American public about all facets of Reye's
Syndrome, with particular attention to the need for timely
recognition of its symptoms. While there exists no cure for
Reye's Syndrome, several treatment modalities are often effective
in containing physiologic damage and minimizing residual effects
such as neurologic injury. Early recognition of the symptoms is
critical to the effective utilization of these treatment modali-
ties.
PAGENO="0658"
652
The Association has made its intellectual resources
available to the federal government to render any assistance it
can in efforts properly directed toward educating the public
about Reye's Syndrome and toward the design and implementation of
research programs directed at determining its causes and iden-
tifying appropriate treatments and a cure. The Association will
continue its efforts in this regard.
The Association has been keenly interested in the debate
concerning the alleged association between the use of salicylates
and Reye's Syndrome. It has participated in numerous government
and privately sponsored symposia regarding this alleged asso-
ciation and, by virtue of its medical advisory panel and
experience, is considered expert in the matter. In September,
1982 the Association's executive director testified as an expert
witness before the Subcommittee on Natural Resources,
Agricultural Research and Environment, Committee on Science and
Technology, which investigated that alleged association.
Reye's Syndrome
Reye's Syndrome is a condition of unknown etiology which
strikes between 600 and 1,200 children and adolescents in the
U.S. per year. Some cases have also been reported in adults. It
was first identified in 1963 by an Australian physician, Douglas
PAGENO="0659"
653
Reye, and was later described in the U.S. by Dr. George .Johnson.
Its symptoms classically appear following viral infections such
as varicella and influenza. Those symptoms include unexpected
vomiting, lethargy, personality change and, frequently, coma.
Reye's Syndrome affects many body organs, particularly the brain
and liver. Its mortality rate is believed to range from a low of
20 percent to a high of 40 percent. Surviving patients may incur
neurologic damage. Others recover with no detectable residual
effects.
While there is no known cure for Reye's Syndrome, it can be
treated by monitoring body fluids, relieving cranial pressure,
aiding respiration, administering drugs, and implementing anti-
convulsive measures. Such treatment significantly reduces the
mobidity rate of the disease. Proper early diagnosis is criti-
cal, however, to the administration of such treatment.
Unfortunately, Reye's Syndrome is extremely difficult to
detect and isolate because its symptoms are common to several
well-known diseases. This difficulty is compounded by the fact
that the lay community and even the medical community have only a
limited familiarity with the disease. Thus, absent a confir-
matory analysis of the liver tissue, misdiagnosis of Reye's
Syndrome is believed to occur in 25% of cases.
PAGENO="0660"
654
Position of the American Reye's Syndrome Association on H.R.
1381, The "Emergency Reye's Syndrome Prevention Act of 1985"
The American Reye's Syndrome Association opposes H.R. 1381,
the "Emergency Reye's Syndrome Prevention Act of 1985," because
it would require manufacturers to misinform consumers that an
association has been established between the use of salicylates
and Reye's Syndrome. Such an association has in fact not been
established. As the Subcommittee is aware, many cases involving
Reye's Syndrome show no history of salicylate use or show the use
of medications other than salicylates. Some studies suggest an
association between certain environmental toxins and the disease.
As the Subcommittee is also aware, the Department of Health and
Human Services has concluded that present evidence is insuf-
ficient to establish that such an association exists.
The Association believes that since a relationship between
salicylate use and Reye's Syndrome has not been established,
warnings such as those required by H.R. 1381 could mislead con-
sumers into thinking that by avoiding salicylates they would eli-
minate the risk of Reye's Syndrome. In so doing the bill could
actually hinder proper efforts such as those of the Association
which are directed toward educating consumers about Reye's
Syndrome in order to facilitate early recognition, diagnosis and
treatment.
PAGENO="0661"
/ 655
Discussion
Studies conducted in Ohio, Michigan, and Arizona in 1981
prompted early interest in the question whether salicylate use
was associated with Reye's Syndrome. The Association expressed
its views on those studies in comments to the Food and Drug
Administration dated February 25, 1983. Essentially, those views
were that the studies were scientifically insufficient to warrant
a Reye's Syndrome warning on salicylate-containing products, that
additional studies should be undertaken, and that the resources
of the federal government were better directed in the interim
toward encouraging the early recognition, diagnosis, and treat-
ment of Reye's Syndrome.
Since then the results of the pilot phase of the U.S. Public
Health Service study on the use of medications and Reye's
Syndrome have been released. Those results showed a higher
correlation between the use of aspirin and the incidence of
Reye's Syndrome than between the absence of aspirin use and the
incidence of the disease. As noted, the Department of Health and
Human Services does not regard the results of that pilot study as
sufficient to require a Reye's Syndrome warning on salicylate
containing products. Rather the Department believes that the
public should be informed of the results of the study, as it has
been doing, and that the full study should continue.
PAGENO="0662"
656
In addition, the Department and the aspirin industry have
agreed that until the PHS study is completed, certain measures
should be undertaken in the interests of protecting the public
health. Those measures include removing label indications for
flu from children's aspirin; labeling aspirin products with war-
nings directing the consumer to his physician before admi-
nistering aspirin containing products to children (including
teenagers) with chicken pox or flu; and accompanying those
efforts with an appropriate public education campaign.
The Association supports these efforts as consistent with
its goal of informing the public about all facets of Reye's
Syndrome. The Association also urges that studies such as the
PHS study be continued in order to determine with credible scien-
tific evidence whether an association exists between the use of
certain medications and Reye's Syndrome. The Association con-
tinues to believe, however, that unless or until such an asso-
ciation is demonstrated efforts such as those required by H.R.
1381 are misdirected because they would lull consumers into
thinking that by avoiding the use of aspirin they will avoid the
incidence of Reye's Syndrome. In so doing those efforts would
hinder legitimate efforts such as those of the Association which
are properly directed toward facilitating early recognition of
the symptoms of the disease.
PAGENO="0663"
657
The American Reye's Syndrome Association has concentrated
its efforts on educating parents and physicians about Reye's
Syndrome and its early warning signs. While empiric evidence is
lacking as to the success of such programs, experience suggests
that they are in fact extremely effective in increasing early
awareness of the. symptoms of the disease and thereby help ensure
adequate treatment. The Association will continue these public
awareness campaigns via public service announcements, brochures,
lectures and otherwise. Undoubtedly, the mission of the
Association in this regard is an enormous one and merits the full
cooperation and support of the federal government.
The Association believes that undue preoccupation with the
question whether an association exists between salicylate use and
Reye's Syndrome has already done significant damage to early
recognition programs. The Association is concerned that if war-
nings of the type contemplated by H.R. 1381 are put into effect,
efforts directed toward increasing early recognition of Reye's
Syndrome will continue to be inappropriately undermined.
Conclusion
The American Reye's Syndrome Association supports the
efforts of the Department of Health and Human Services and the
aspirin industry as announced on January 23, 1985 by 11115
PAGENO="0664"
658
Secretary Margaret M. Heckler to remove label indications for flu
from children's aspirin; to label aspirin products with warnings
directing the consumer to his physician before administering an
aspirin containing product to children, including teenagers, with
chicken pox or flu; and to accompany these efforts with an
appropriate public education campaign. Such efforts will have
the effect of educating parents about Reye's Syndrome.
The Association also believes that the proper and construc-
tive role for the federal government is to fund further research
on factors which may be associated with Reye's Syndrome, possibly
including certain medications; to continue basic research on the
disease; and to educate the public and the medical community
about the disease g~ disease, especially early recognition of
its symptoms and proper treatment thereof. The American Reye's
Syndrome Association continues to pledge its full intellectual
resources to aid in such efforts.
The Association opposes, however, measures such as those
contained in H.R. 1381, the "Emergency Reye's Syndrome Prevention
Act of 1985," which would require warnings to the effect that an
association has been established between use of such products and
Reye's Syndrome. The present body of credible scientific
knowledge on Reye's Syndrome does not establish such an asso-
ciation. Warnings which state that it does would only serve to
undermine efforts aimed at properly educating the public and the
medical community about Reye's Syndrome.
Respectfully,
AMERICAN REYE'S SYNDROME ASSOCIATION
PAGENO="0665"
659
Statement
of the
American
Pharmaceutical
Association
The National Professional Society of Pharmacists
THE AMERICAN PHARMACEUTICAL ASSOCIATION, THE
NATIONAL PROFESSIONAL SOCIETY OF PHARMACISTS, IS PLEASED
TO HAVE THIS OPPORTUNITY TO PRESENT ITS VIEWS ON FLR.
1381, THE "EMERGENCY REYE'S SYNDROME PREVENTION ACT OF
1985".
WE WELCOME THE OPPORTUNITY TO PRESENT THIS STATEMENT
FOR THE RECORD OF THE HEARING HELD BY THE HEALTH
SUBCOMMITTEE ON H.R. 1381, THE "EMERGENCY REYE'S SYNDROME
PREVENTION ACT OF 1985". As YOU KNOW, THE AMERICAN
PHARMACEUTICAL ASSOCIATION (APHA), AND ITS THOUSANDS OF
PHARMACIST MEMBERS HAVE HAD A CONTINUING DEEP INTEREST IN
COMBATTING THE REYE'S SYNDROME PROBLEM, AND IN PROVIDING
TO THE PUBLIC ACCURATE AND RESPONSIBLE INFORMATION TO
ASSIST IN AVOIDING THE OFTEN TRAGIC CONSEQUENCES OF THIS
DISEASE.
APHA HAS COOPERATED FULLY IN EFFORTS TO IDENTIFY AND
IMPLEMENT AN EFFECTIVE PUBLIC EDUCATION PROGRAM SINCE 1982
WHEN THE REYE'S SYNDROME ISSUE WAS FIRST BROUGHT TO ITS
ATTENTION. BEFORE PROCEEDING TO SPECIFIC POINTS REGARDING
THE BILL CURRENTLY UNDER CONSIDERATION BY YOUR
SUBCOMMITTEE, WE WISH TO REVIEW THE ACTIONS TAKEN BY APHA
TOWARD THIS END.
PAGENO="0666"
660
IN THE FALL OF 1982. THE HEALTH RESEARCH GROUP (HRG)
PROVIDED APHA WITH INFORMATION REGARDING FINDINGS OF AN
ASSOCIATION BETWEEN THE USE OF SALICYCLATE CONTAINING DRUG
PRODUCTS. PRIMARILY ASPIRIN. AND THE EXISTENCE OF THE
DISEASE IN THAT POPULATION DEEMED AT RISK OF REYE'S
SYNDROME. THE ASSOCIATION WAS REQUESTED TO SUPPORT A
VOLUNTARY LABELING PROGRAM INITIATED BY HRG THAT WOULD
HAVE PLACED A WARNING LABEL ON THE CONTAINER OF AFFECTED
DRUG PRODUCTS SIMILAR TO THAT NOW SPECIFIED IN H.R. 1381.
APHA, ALONG WITH THE AMERICANPUBLIC HEALTH ASSOCIATION,
DID OFFER ITS SUPPORT FOR THE PROPOSED LABELING PROGRAM.
HOWEVER. THE HRG PROGRAM PROVED TO BE SHORT-LIVED AT THAT
TIME.
THE HRG VOLUNTARY LABELING PROGRAM BECAME ENMESHED
IN A STORM OF CONTROVERSY AS TO WHETHER SCIENTIFIC
EVIDENCE ACTUALLY SUPPORTED THE ACTION PROPOSED.
NONETHELESS. THE DEPARTMENT OF HHS PUBLISHED IN THE
FEDERAL REGISTER ON DECEMBER 28. 1982 AN ADVANCE NOTICE OF
PROPOSED RULEMAKING THAT WOULD HAVE REQUIRED BY REGULATION
THE LABELING OF AFFECTED DRUG PRODUCTS WITH A REYE'S
SYNDROME WARNING. IN RESPONSE TO THIS NOTICE. APHA FILED
COMMENTS SUPPORTING THE HHS PROPOSAL AND SUPPORTING
FURTHER STUDIES. APHA ARGUED THAT IN THE ABSENCE OF A
CLEAR CONCLUSION BASED ON DATA THAT ANY ERRORS RESULTING
THEREFROM SHOULD BE ON THE SIDE OF OPTIMUM SAFETY.
PAGENO="0667"
661
SUBSEQUENTLY, THE HHS PROPOSAL WAS WITHDRAWN WITH AN
INDICATION THAT ADDITIONAL SCIENTIFIC STUDIES SHOULD BE
UNDERTAKEN TO RESOLVE THE SCIENTIFIC CONTROVERSY THAT HAD
RAGED SINCE THE REYE'S SYNDROME ISSUE HAD BEEN PUBLICIZED.
ALTHOUGH APHA THUS JOINED ALL INTERESTS IN AWAITING
THE OUTCOME OF FURTHER SCIENTIFIC STUDIES, THE ASSOCIATION
NEVER LESSENED ITS INTEREST IN, OR CONCERN ABOUT THE
ISSUE, AND IT HAS CONTINUED TO KEEP ITS MEMBERS INFORMED
ABOUT DEVELOPMENTS REGARDING THE PROBLEM.
THE NEXT SIGNIFICANT EVENT, FROM APHA'S STANDPOINT,
WAS THE RELEASE IN JANUARY 1985 OF THE REPORT OF THE
NATIONAL ACADEMY OF SCIENCES INSTITUTE OF MEDICINE: "THE
PHS STUDY OF THE REYE SYNDROME: RECOMMENDATIONS BASED ON A
REVIEW OF THE PILOT STUDY DATA". IT IS NOT NECESSARY TO
RECOUNT THE DETAILS OF THE IOM REPORT. FOR APHA, IT WAS
SUFFICIENT THAT THE STUDY REPORT WAS DEEMED TO SHOW "A
STRONG ASSOCIATION BETWEEN THE REYE SYNDROME AND THE USE
OF ASPIRIN." THIS INFORMATION, COUPLED WITH THE IOM
OBSERVATION AND RECOMMENDATION THAT "CONSIDERING THAT DATA
FROM PREVIOUS STUDIES ALSO SHOW AN ASSOCIATION OF USE OF
ASPIRIN AND REYE SYNDROME.. .STEPS SHOULD BE TAKEN TO
PROTECT THE PUBLIC HEALTH BEFORE THE FULL STUDY IS
COMPLETED", CAUSED APHA TO REACT AS PROMPTLY AS IT COULD.
THE FEBRUARY 1, 1985 ISSUE OF AEJIARMACY WEEKLY, THE APHA
NEWSLETTER. SENT TO APPROXIMATELY 50,000 APHA MEMBERS.
PAGENO="0668"
662
CARRIED AN INSERT POSTER WARNING THE PUBLIC ABOUT REYE'S
SYNDROME AND THE ASSOCIATION BETWEEN THE DISEASE AND THE
USE OF ASPIRIN IN THE POPULATION AT RISK. APHA MEMBERS
WERE URGED TO USE THE WARNING POSTER AND PERMISSION WAS
GRANTED FOR ITS REPRODUCTION. A COPY OF THE POSTER IS
ATTACHED FOR THE INFORMATION OF THE SUBCOMMITTEE AND FOR
THE HEARING RECORD. THE APHA ACTION WAS CONSISTENT WITH,
AND RESPONSIVE TO, THE URGING OF HHS SECRETARY HECKLER
THAT THE PUBLIC BE GIVEN SUCH WARNING. IN ADDITION, APHA
CONTINUED TO REPORT TO ITS MEMBERS ON THE ACTIONS OF THE
U.S. ASPIRIN MANUFACTURERS IN VOLUNTARY LABELING CHANGES
IN THEIR PRODUCTS AS PART OF A NATIONAL EDUCATION PROGRAM.
APHA WILL CONTINUE TO KEEP ITS MEMBERS INFORMED OF
REYE'S SYNDROME DEVELOPMENTS. THE MARCH 1985 ISSUE OF THE
ASSOCIATION'S JOURNAL, AMERIcAJi PHARMACY, CARRIES A
COMPREHENSIVE ARTICLE REGARDING THE CURRENT STATUS OF THE
SITUATION. A COPY OF THIS ARTICLE ALSO IS ATTACHED FOR
THE INFORMATION OF THE SUBCOMMITTEE AND FOR THE HEARING
RECORD.
WHATEVER THE OUTCOME OF FURTHER STUDIES CONDUCTED
WITH REGARD TO AN ASSOCIATION BETWEEN THE USE OF
SALICYLATE CONTAINING DRUG PRODUCTS AND REYE'S SYNDROME.
APHA IS SATISFIED THAT TAKING STEPS TO ALERT AND EDUCATE
THE PUBLIC REGARDING THIS SITUATION IS PRUDENT. WE ARE
SATISFIED THAT THE ASSOCIATION HAS ACTED BOTH RESPONSIBLY
AND JUDICIOUSLY IN RESPONDING TO THIS PROBLEM.
PAGENO="0669"
663
TURNING TO H.R. 1381, APHA IS CONCERNED THAT THIS
VEHICLE FOR ACTION MAY. HAVE AN INHIBITIVE EFFECT ON
VOLUNTARY EFFORTS IN THIS AND FUTURE SIMILAR SITUATIONS.
THIS STATEMENT HAS NOTED THE EFFORTS MADE BY APHA TO
ALERT ITS MEMBERS AND THE PUBLIC TO THE REYE'S SYNDROME
PROBLEM AND MANY IMPORTANT FACTS ABOUT IT. THESE STEPS
WERE TAKEN BY THE ASSOCIATION IN ITS SENSE OF PROFESSIONAL
RESPONSIBILITY. Now, THE ASSOCIATION FINDS THAT THE
INFORMATION AND MATERIALS IT HAS PROVIDED ITS MEMBERS
WOULD BE OUT OF COMPLIANCE WITH THE SPECIFIC REQUIREMENTS
OF H.R. 1381.
WE WOULD ALSO CALL TO YOUR ATTENTION THAT PROVISIONS
OF THE BILL REQUIRING INCLUSION OF THE WARNING "IN ALL
ADVERTISEMENTS" PLACED BY PHARMACIES WOULD BE IMPOSSIBLE
TO SATISFY IN MANY INSTANCES. IN CASES WHERE THE
TECHNICAL REQUIREMENTS CAN BE MET, THE PRACTICAL RESULTS
STILL LIKELY WILL BE ELIMINATION OF PHARMACY
ADVERTISEMENTS FOR AFFECTED DRUG PRODUCTS. THE PROBLEM
EXISTS BECAUSE OF THE REQUIREMENT THAT THE WARNING IN SUCH
ADVERTISEMENTS BE PRINTED, AT LEAST IN PART. IN YELLOW AND
RED INK.
MANY PUBLICATIONS CARRYING PHARMACY ADVERTISEMENTS
DO NOT HAVE THE CAPACITY FOR MULTICOLOR PRINTING OR THE
CAPACITY TO PRINT IN THE COLORS SPECIFIED. MOREOVER. THE
PAGENO="0670"
664
COST OF REQUIRED MULTICOLOR ADVERTISEMENTS, EVEN IF
TECHNICALLY POSSIBLE, IS SO MUCH GREATER THAN A "BLACK AND
WHITE" AD, THAT PHARMACIES CAN ONLY BE EXPECTED TO FOREGO
THE ADVERTISING OF AFFECTED DRUG PRODUCTS.
APHA BELIEVES THAT H.R. 1381 ALSO IS TOO BROAD IN
ITS APPLICATION TO SALICYLATE CONTAINING DRUG PRODUCTS.
THE SUBCOMMITTEE SHOULD BE AWARE THAT MANY TOPICAL DRUG
PRODUCTS (LIMITED TO EXTERNAL USE) CONTAIN SALICYLATES.
To APHA's KNOWLEDGE, THERE IS NO EVIDENCE WHATSOEVER, NOR
HAS THERE EVER BEEN ANY SUGGESTION. THAT SUCH DRUG
PRODUCTS ARE IMPLICATED IN THE CAUSATION OF REYE'S
SYNDROME. To THE ASSOCIATION'S KNOWLEDGE, ONLY DRUG
PRODUCTS THAT ARE INGESTED HAVE BEEN ASSOCIATED WITH THE
DISEASE IN THE POPULATION AT RISK.
MR. CHAIRMAN, APHA PLEDGES ITS CONTINUED SUPPORT OF
EFFORTS TO ERADICATE THE THREAT OF REYE'S SYNDROME AND TO
EDUCATE THE PUBLIC REGARDING THIS DREAD DISEASE. THE
ASSOCIATION STANDS READY TO ASSIST IN VIRTUALLY ANY WAY
THAT IS PRACTICAL AND REASONABLE TO ACHIEVE THESE
OBJECTIVES. WE WELL RECOGNIZE THAT YOUR MOTIVATION IN THE
INTRODUCTION OF H.R. 1381 HAS THE SAME AIMS.
PAGENO="0671"
665
WE MUST NOTE. HOWEVER. THAT ALTHOUGH APHA BELIEVES
THAT CURRENT STEPS TO ALERT AND EDUCATE THE PUBLIC ABOUT
THE ASSOCIATION BETWEEN SALICYLATE CONTAINING DRUG
PRODUCTS AND REYE'S SYNDROME ARE FULLY JUSTIFIED. THE
FINAL SCIENTIFIC JUDGMENT IS YET TO BE MADE WITH REGARD TO
THIS ISSUE. FURTHER PLANNED STUDIES SHOULD PRODUCE
SUFFICIENT DATA TO ASSIST IN THE RESOLUTION OF THIS
SCIENTIFIC CONTROVERSY.
APHA PLANS TO WORK WITH OTHER ORGANIZATIONS TO
CONTRIBUTE TO AN ANALYSIS OF THE DATA. THE APHA AND THE
AMERICAN ACADEMY OF PEDIATRICS (AAP) WILL JOINTLY REVIEW
THE DATA SOON TO BE RELEASED ON THE ASSOCIATION BETWEEN
SALICYLATE CONTAINING DRUG PRODUCTS AND REYE'S SYNDROME.
THE SCIENTIFIC EXPERTISE OF APHA's ACADEMY OF
PHARMACEUTICAL SCIENCES AND THE CLINICAL EXPERTISE OF AAP
WILL FORM THE BASIS OF APHA POLICY ON THIS MATTER IN THE
FUTURE. AND FOLLOWING OUR REVIEW WE WILL BE PLEASED TO
DISCUSS THIS WITH YOU IN GREATER DEPTH.
0269P
PAGENO="0672"
666
t~u~
A study by the Federal government's Centers
for Disease Control has found a strong
association between the use of aspirin in
children with flu or chicken pox and the
development of the potentially fatal illness
Reye's Syndrome.
Symptoms of Reye's Syndrome include
vomiting, fever, lethargy, and convulsions.
The symptoms generally appear as the child
seems to be getting better.
* Do not use aspirin for children or
teenagers with the flu or chicken pox without
first consulting a physician.
* If symptoms of Reye's Syndrome appear,
immediate medical attention is required.
For additional information, consult your pharmacist.
The American Pharmaceutical Association
` The national professional society of pharmacists
PAGENO="0673"
667
HHS Gets Voluntary Label Warning
On Aspirin-Reye's Syndrome Link
Plough, Inc., which makes the St. paign to ensure that parents [are] be a consequence of the "decline in
Joseph line of aspirin products, made aware of the possible link." use of salicylates among younger
agreed on January 10, 1985, to co- One specific measure taken by children in recent years." Unaware
operate with the request from Health Heckler was to ask that "makers of of the possibility of Reye's in their
and Human Services Secretary Mar- aspirin products take two steps vol- older children, parents may be con-
garet M. Heckler to add warnings to untarily. tinuing to give aspirin to them for
aspirin labels about a possible link * First, to immediately remove any chickenpox or flu.
between aspirin and the sometimes labels which recommend that aspi- In CDC's pilot study, nearly 50%
fatal children's disease, Reye's syn- on products be used to treat flu or of ail cases investigated occurred in
drome. chickenpox in children or teenagers; children over age 10, and 15% were
By the next day, other major man- I Second, to label all aspirin prod- in those aged 15 and older.
ufacturers, acting through the As- ucts to indicate that there is a pos-
pirin Foundation, had also decided sible association between the use of Industry Response
to go along with the HHS recom- aspirin and Reye's syndrome in chil- In responding to Heckler's re-
mendations. dren and teenagers, and that aspirin quest about new labeling, Plough
In early January, the National should not be used in those cases Inc., stated that the company would
Academy of Sciences' Institute of unless a physician is first con- go along with the suggested changes,
Medicine (IOM) released its critique sulted." although it still has its doubts about
of the Centers for Disease Control's Heckler asked that the new label- the reality of any health risk to chil-
pilot study of the alleged connection ing be retained until the full-scale dren from using aspirin.
between the use of aspirin in chil- CDC study has been completed and In a statement on its action, a
dren who contract chickenpox or flu its data thoroughly analyzed. Plough spokesperson said, "We in-
and the later onset of Reye's. Be- The Aspirin Foundation agreed to tend to cooperate with the secre-
cause of the strength of the findings, delete from children's aspirin label- tary's request for label changes
lOM, which had previously been ing any suggestions for use in flu, pending further studies. Within
adamantly opposed to releasing the and to add: "Consult a physician be- minutes of the secretary's state-
preliminary results of the pilot phase fore giving this medicine to chil- ment, Plough started examining all
of the investigation, reversed itself dren, including teenagers, with reasonable steps to develop a pro-
and strongly recommended that: chicken pox or flu." Labels will ap- gram in response to the secretary's
1. The Public Health Service release pear on products by the next flu sea- request."
the results of the pilot study to the son. On January 16, Ralph Nader's
public and to scientists for review Heckler also stated that she was Public Citizen Health Research
and analysis. planning to communicate with me- Group, long an advocate of warning
2. Because analysis of the pilot study dia leaders, including the presidents labels about the Reye's-aspirin con-
data reveal a strong association be- of the major networks and the nection, petitioned the Federal Trade
tween Reye's syndrome and the use American Newspaper Publishers Commission to require that all ad-
of aspirin, in concert with previous Association. She asked that they run vertisements for aspirin include cau-
investigations of the epidemiology public service announcements al- tionary statements on the potential
of the illness, "steps should be taken ready supplied to them, and also give link. Public Citizen asserts that even
to protect the public health before the new data special news coverage, if aspirin labels are changed, the in-
the study is fully completed." dustry's print, television, and radio
3. The publicity generated by the New Trends commercials "currently mislead par-
release of the results is not likely to One important point, she said, ents into believing that there is no
prejudice the results of the full-scale deserved particular emphasis. Sur- danger in giving aspirin-containing
study any more than "the current veillance data reported to CDC dur- medications to their children who
climate of public opinion." ing 1984 revealed that only 190 new have chickenpox, flu, or flu-like
cases of Reye's syndrome occurred symptoms."
Labeling changes (compared with 379 in 1974 and 198 Although it has not y~t taken any
Based on these recommenda- in 1983); however, the number of of the request, FTC spokesperson
tions, Secretary Heckler issued a for- cases among children over 10 years Susan Ticknor commented that "we
mal statement on January 9, which of age has actually increased. do have measures we can take to act
reiterated her earlier request for a CDC suspects that the downward quickly" if the situation is judged to
"vigorous public education cam- trend among children under 10 may be an emergency.
12 American Pharmacy Vol NS25, No.3, March 1985/140
52-266 0-85-22
PAGENO="0674"
seemstobegettingbetter.
* Donotuseaspirinforchildcenor
teenagerswith thefluorchickenpoxwithout
flontconsultinga physician.
* UsymptomsofReye'sSyndromeappesc.
Inunediatemedlcalattention isrequired.
CDC Study Data
Occasionally getting lost in the
subsequent call to battle were the
actual data from the CDC study.
The investigation was conducted
between February and May 1984, and
included 29 Reye's syndrome cases
and 143 controls. The control cases
were children with similar anteced-
ent diseases to those who developed
Reye's syndrome, but hadn't con-
tracted Reye's, who had been ad-
mitted to the same hospital or
emergency room, attended the same
school, or were identified by ran-
dom-digit dialing.
Ninety-seven percent of the case
children were reported to have re-
ceived salicylates during the prodro-
mal illness, compared with 28%
(emergency room controls), 23%
(same hospital), 29% (school), and
55% (random digit dialing).
Conduded CDC: `The risk de-
fined in the pilot study was com-
parable or greater than that
determined in previous studies."
One interesting observation, which
shows something about the way the
media work in this country, is that
the original report on the pilot study
had stated that the statistically com-
puted risk for development of Reye's
after aspirin was 12-26 times more
than without aspirin. However, in
its first letter to be picked up by the
media, Health Research Group re-
ferred solely to a risk factor of 25;
the fact that a range of possible risk
(depending on which statistical
model is used) was actually reported
has somehow been lost in the strug-
gle to simplify, for quicker and eas-
ier reading.
Study Limits
In its comments on the pilot study,
the IOM cautioned that "in spite of
this association [between aspirin and
Reye's], questions remain because
of the small sample size and the lim-
ited sources of cases."
Elsewhere, tOM noted: "The pilot
study data suffer from changes in
methods during its conduct and the
limitation of a small and geograph-
ically limited sample."
lOM therefore concluded; "Data
from the full study are needed to
determine if the pilot study findings
are reliable," and added, "Because
of uncertainties characteristic of ob-
servational studies, ideally a num-
ber of studies should be available to
corroborate scientific findings."
More information on Reye's syn-
drome and use of medication is
needed, commented IOM, "to guide
both clinical practice and public
health measures."
Pharmacist Role
Obviously, pharmacists can play
a vital role in disseminating the new
results about a stronger link be-
tween aspirin and Reye's syndrome.
William Grigg of FDA's Press Of-
fice said that pharmacists no longer
need to hedge in counseling pa-
tients about giving aspirin to chil-
dren with chickenpox or flu: "Our
advice is not to use aspirin in chil-
dren with these illnesses unless
there's some overriding reason-an
uncontrollable fever, for instance.
And in that case, parents ought to
consult a physician before giving as-
pirin; we are currently sending out
letters to all family physicians and
pediatricians informing them about
the new data."
Also available is a poster designed
by FDA about the dangers of giving
aspirin to children with flu or chick-
enpox. Copies are available from:
Publications Office, Room 15B18,
HFW-40, Food and Drug Adminis-
tration, 5600 Fishers Lane, Rock-
vile, MD 20857.
668
~u~o
AstudyhytheFederalgovernnsent'sCenters
forOlseaseContoolhas founda strong
asaocialionbetweentheuseofanpirinmn
children with flu orchicken pon and the
development of the potentially fatal illness
Reye', Syndrome.
Symptoms of Reye's Syndrome include
vomiting, fever,lethargy.andconvulsioos.
Thesymptomsgenerallyaooearasthechild
For additional information, consult your pharmacist.
® TheM ,aoPhaemamsficalAssodatioo
Th.oatlcoalpeofss.losulsactetyafphsemad.ts
APhA distributed a poster warning of the link between aspirin use and Re~ge's syndrome as
part of the February 1, 1985, issue of apharmacy weekly. Pharmacists were urged to display
the poster as a public health service to their patients.
Amedean Pha,macy Vol NS25, No.3, March 1985/141
PAGENO="0675"
669
Statement
of the.
National
Association.
of Chain Drug
Stores, Inc.
INTRODUCTION
The National Association of Chain Drug Stores (NACDS) respectfully submits
the following statement for inclusion in the record with respect to legis-
lation (H. 11. 1381) the "Emergency Reye's Syndrome Prevention Act of 1985."
NACDS is a trade organization founded in 1933 which represents the manage-
Isent of 171 corporate drug chains. As an industry, our members are operat-
ing in excess of 17,000 retail drug stores throughout the United States
with annual sales of more than $22 billion In 1984. In the Over-The-Counter
analgesic category, NACDS estimates that chain drug stores registered $320
million in sales during 1983.
GENERAL COMMENTS
Concerning the overall focus of the legislation currently before the House
Energy and Commerce Health Subcommittee, NACDS commends Chairman Waxisan for
his efforts in stimulating further dialogue and discussion with respect to
this important health care issue. NACDS also applauds all voluntary efforts
by the Federal Government, the Pharmaceutical Industry and the Medical Com-
munity in developing programs and materials to advise consumers, parents
and individuals under 21 years of age about the potential link between the
use of aspirin and aspirin-containing products and Reye's Syndrome. We
believe that these efforts have greatly helped to elevate an awareness among
the general public of the possible dangers of aspirin use and Reye's Syndrome
which will help to ensure that parents will consult with a physician before
PAGENO="0676"
670
giving aspirin-type products to children who have flu of chicken pox. In our
view, the voluntary approach is very effective and it must be an on-going pro-
cess with commitments from all health related organizations, especially those
associations which represent pediatricians and general practitioners that come
in direct contact with parents and their children.
SPECIFIC INDUSTRY CONCERNS
NACDS noted with interest the testimony which was presented before the Health
Subcommittee on March 15, 1985. Statements by the public witnesses were
very compelling, and it is apparent that more information needs to be com-
municated to the American public so that future incidences and the personal
tradegy of this dreaded illness can be avoided.
As to the specifics of H. R. 1381, the bill in its present form would pose
several major problems to Chain Drug Stores in terms of compliance with the
effective date of the Act. Based on an informal survey of a number of our
corporate IFembers, it is our concern that Chain Drug Stores would not be
able to logistically meet the 30-day deadline for compliance with labeling,
advertising and the display of warning notices in retail stores. In that
NACDS represents a number of large corporate drug chains that have in excess
1,000 retail outlets in a dozen or more states, compliance with the various
requirements of the 30-day deadline would be impossible. From the date of
enactment, the turn-around time to disseminate the necessary information to
our members who must then advise all of their stores is insufficient under
H. R. 1381. NACDS, therefore, recon~mends the following timetable with regard
PAGENO="0677"
671
to compliance by retail drug stores: We believe that our corporate members
could have in p1-ace at the retail level the warning notice in 60 days. Con-
cerning retail advertising, the Chain Drug Industry would need at least 90
days in which to modify print and media advertising that has already been
purchased. The labeling deadline poses the most significant challenge to
our industry which stocks and offers for sale a wide range of private label
and brand-name aspirin containing products. In order to convert aspirin
labeling, our industry would need at least 270 days to comply. This time-frame
would start from the point at which revised labeling is received from manufac-
turing companies. It is our concern that a delay by manufacturing companies
in supplying adequate labeling for goods shipped before the effective date and
for those goods already in the distribution pipeline not be imputed to retailers.
When complete revised warning labeling for all aspirin related products is in
place, NACDS strongly recommends that the requirement for displaying retail
warning notices be eliminated. In our view, once the new labeling is available,
it is unnecessary to mandate warning notices at the retail level.
VIOLATIONS - CRIMINAL PENALTIES
Additionally, NACDS is extremely concerned about the criminal penalties that
are contained in H. R. 1381 for misbranding violations. If the legislation
is enacted into law, the Chain Drug Industry will make every effort to fully
comply. However, much of our ability to respond to the requirements of the
Act will depend solely on how quickly manufacturing companies provide corpor-
ate drug chains with revised labeling. We, therefore, strongly recommend that
the penalty provisions not be applied to retail drug stores until a minimum
of 360 days following enactment of the legislation.
To conclude, unless the legislation is amended to reflect the concerns that
NACDS has expressed relative to the compliance aspects impacting upon retail
drug stores, we are opposed to H. R. 1381. NACDS appreciates the opportunity
to provide testimony on the "Emergency Reye's Syndrome Prevention Act" and it
is our hope that this statement will be given full consideration.
PAGENO="0678"
672
~)~ESS (P ThE UNIT~ STATES
HOWE (P REPRESENTATIVES
before the
StBCXt4NITTEE ON HEALTE P1~D TEE EE~II~J~1ENT
C(}IMERflS CF TEE AMERICN~I ADVERTISING FEDERATION
ON H.R. 1381, The E~tergency Reye `s
Syndrai~ Prevention Act of 1985
This stat~nt is respectfully sthnitted by the Aserican Advertisir~
Federation, a national trade association which includes within its nembership
all of the varicus elaients of the advartisim industry. The itentbership of
the AAF includes canpanies which mam.ifacture and sell consuter products,
advertising agencies, newspaper and magazine p.t)lishers, radio and television
broadcasters and neb,orks. J~pproximately 22 other trade associations with
nemberships canposed of cx~panies engaged in varicus advertising pursuits also
hold riembership in the AAF. The Federation also represents the "grass roots"
of the advertising industry because it is the parent body of sore than 200
local advertising clubs and federations located thrcughout the United States
and having a canbined nembership of approximately 36,000 advertising
practitioners. These local organizations, like the parent body, include
advertisers, advertising agencies and advertising nedia Within their
nembership.
PAGENO="0679"
673
We share with the sponsors of this bill a great concern with respect to
the illness knovn as Reye `s Syndrans. Because of its potentially deafly
nature this disease is a prc~er subject of attention by the health authorities
of the United States governnent. A crash program is already underway to
determine the cause of thin malady and great strides have already been taken
in alerting the ptlic to the possible connection beteeen the disease and drug
products which contain salicylate thra.igh a major voluntary public service
ad~rtising campaign. As ~e will point cut in sore detail later, PAF pled~s
to do all it can to assist in furthering and accelerating these important
efforts to alert the public. We are not persuaded, h~ver, that this matter
is a prcper subject for legislation at this time and thus submit these
canrrents in cpposition to the enactment of the a1~rtising provisions of H.R.
1381.
While sate of air views may have broad application to the entire bill,
our expertise concerns ad~rtising and therefore ~ direct cur cassents to the
prcposed requirenent to include in "all ad~rtisenents" a 48 s~rd disclosure
with respect to the suspected connection beteeen Reye `s Syndrane and the use
of products which contain a salicylate. We ladc the expertise to
independently camient substantively on the connection betMeen the disease and
the product tot instead rely upon the ~inions of experts, and in partirular,
the Food and Drug Administration. As ~u kncw, Catunissioner Fraak E. Young
has unequivocally stated that this legislation is "unnecessary" because
"definitive scientific data are still not available" and because the public
is being inforned by an "extensive public education program".
PAGENO="0680"
674
In partioilar, ~e direct ~ur attention to the position of the FI~ on
four epix3eniological sttz3ies (state surveys) and a pilot stody which began in
November, 1983 and determined the protocol for the national stody which
is nn~ underway. This record evidence sakes it crystal clear that the
country's sost qualified experts and expert bodies are ~rking at tc~ speed to
readi a determination as to whether salicylates are involved in the occiirance
of Reye `s Syndrare. In sbort, a law reguiring irendatory edvertising
disclosures is premature for it vRuld have as its premise only preliminary
stodies whose findings are in dispute. Surely, national legislation sheuld
have a better basis.
In view of the voluntary progran it cannot be said that information as to
the suspected lir~ is not reaching the Airerican poblic. In fact, the
voluntary approach nay be sore effective than the system which ~uld be
imposed by the bill. Pt~lic service television and redio anna.incarents (PSAs)
are a sore effective naans of disseminating the necessary information than
product edvertiserents which contain the reguired disclosure together with the
usual selling nessage. Viewing and listening take place in an atsosphere
characterized by conflicting demands for attention created by the prograinning
and the large iuther of eds seen or heard during arry viewing period. An
advertisacant which tries to convey canplex, technical information with
mulitple nasseges will not achieve its camminications objectives. (~ the
other hand, a pLt)lic service anricEncarent, which has a single terse nessage,
can penetrate the viewer/listener's consciousness and be understood. This has
been daannstrated by an experinent conducted by the Stanford Heart Disease
Prevention progran in the mid-nineteen seventies. A report on that stody,
PAGENO="0681"
* 675
which involved the airing of 50 television and 100 radio spets together with
other nedia efforts, sh~ied that information as to heart disease can be
caninunicated via electronic madia if that is the central itessage. Lancet,
June 4, 1977.
In the typical broadcast viawing or listening situation, the audience
is stbjected to a multiplicity of massages each clamoring for attention.
Advertisers are well aware of this and tailor their ads to get across as
simple and clear a massage as pessible. Additional canpiex information
quickly falls victim to the perception phenunenon knce~'n as "information
overload'. Simply stated, the information processing ability of hunans is
finite with the result that as information input is increased, its
assimilation decreases, understanding falls off and confusion increases.
Thus, a warning massage in electronic advertising accanpanied by the usual
selling massage will catniu~nicate neither stateitent effectively. The warning
may be ccmpletely misunderstood or, sore likely, mantally "tuned ait".
One does not have to be a madia expert to recognize that a massage of 48
words, i.e., the massage which would be mandated by the bill will almost
caupletely preenpt the typical 30 second television or radio spDt. Because
the advertising massage cannot run fran the very beginning to the very end of
a 30 second ad, two to three seconds are lost. This prc~osed massage would
take up to 18 seconds of the 27-28 seconds which are available. Can anyone
question that it would be econanically unrealistic to pay the rates for 30
second broadcast spets and receive only 9-10 seconds of selling time?
PAGENO="0682"
676
And it is not the answer to state that the advertiser could buy longer,
60 second ccissarcials. A 60 second spot will cost s~.t)stantially sore without
necessarily providing the corresponding increase in effectiveness.
In fact, it is our vie~i that the impDsition of a warning reguiresent upon
advertising would severely limit broadcast advertising in this area. The
added cost of longer cansarcials would be stagering. In the FTC's antaãid
rulenaking proceeding, its Bureau of Econanica estimated that the cost of
inserting only a 6 second sodiun warning in a 30 second television spot would
cost the three largest antacid manufacturers $5.3 million. This bill's effect
would be to increase enornously the cost of readilag the audience via
television and radio advertising. Cbviaisly this advertising requirenent
would sake advertising for salicylate-containing products practically
ilnpDssible in c*.itdoor advertising and severely burden and clutter all other
forms of advertising. Thus, the likely result of this bill would be to reduce
the anount of surh consusar product advertising in these categories and
have the exact cpp)site effect of the one desired, at least in terms of
providing incentives for increased constrer information.
Imposing a burden of this type on product advertising is bad p~blic
policy due to the broad, unwarranted precedent it establishes. Clearly, surh
a precedent is likely to be extended to to other products, especially
where contra-indications are involved. It is difficult to see where Congress
would drag the line once it assunes the FTC's and FW~'s authority in this
field.
PAGENO="0683"
677
Finally, this bill directs the Secretary of Health and Human Services to
pranulgate the regulations reguired to enforce its labeling and advertising
provisions. Thus it would place the Departhent in the field of regulating
consuter advertising, a field where it has no expertise. Without question the
hardest fought and irost debated issue faced by the 73rd, 74th and 75th
Congresses while enacting the Federal Food, Drug and Cosmetic Act ~es
jurisdiction over false advertising. Early bills gave the Department of
Agriculture or the smbryo Food and Drug Administration jurisdiction over both.
The FTC and a large number of members of Congress objected. Judge Davis, then
the Chairman of the Federal Trade Ccinmission, testified:
The Canmission has generally been against the pDlicj of legislators
to create overlapping jurisdictions and different procedures; and it
is suggested that that is exactly what is done here; and s~ think that
it would be sore expensive, and think that it would create sore
confusion, not only frcm the standpoint of the Covernment, but
fran the standpoint of the p~blic.
Hearings on S. 2800, Senate Cceimittee, 73rd Congress, Mardi 1934.
p. 231.
In air view, Chairman Davis' canrrents make as much sense today as they did
fifty years ago. H.R. 1381 would recpen this ancient schism and blur the
bright line of division between the jurisdiction of these two agencies. The
Congress sheuld leave advertising regulation of consuter products including
over-the-counter drugs to the FTC, the agency qualified to deal with it.
Conclusion
As noted, the Canmissioner of the Food and Drug Administration has
testified that this legislation is "unnecessary". He has stated that
PAGENO="0684"
678
"the evidence needed to suprort mandatory labeling is not, in our view,
available at this time." Clearly, if there is not enough evidence for
mandatory labeling, there certainly is not encugh evidence to mandate
unprecedented advertising warnings for over-the-counter drug products.
In a true and accurate sense, this bill constitutes a sentence on a case
in which the evidence is still being gathered and, in which a verdict of
associaton has not been rendered. It is reminiscent of the farous demand
of the Qieen of Hearts in Lewis Carroll's Adventures In Wonderland:
"Sentence first - verdict afterward.' Such a procedure was deemed odd in
the nineteenth century and it is not less so today.
We ask the Subccumittee to place this matter in abeyance pending a
definitive decision by the Ccxnmissioner of the Food and Drug Administration.
In the meantime, the public education progran will be wrking and will be
attempting to reach that n~ ever snaller percentage of the population which
may be unaware of this possible medical problem.
For our part, we pledge to alert cur general membership including air
local advertising clubs throughout the United States and strongly urge then to
assist in every way pessible to educate the public about the Reye `s Syndrcrre
issue through public service advertising. As members of the board of directors
and the executive canmittee of the Advertising Council, we will contirue to.
suppurt their efforts to disseminate information on this subject. We also will
~rk with all elements of the advertising canmunity including the media in
cooperating with these ilnprtant efforts.
Again, we share the concern over this serious public health issue bit we
cannot agree that lawful product advertising is an apprcpriate or effective
vehicle for the dissemination of warnings of this kind. If this legislation
were to be accepted it s~uld create extremely broad precedents for the whole
over-the-counter drug area and place a dark shada~i over marty other product
categories as well.
Respectfully submitted,
Ha~ard H. Bell, President
American Advertising Federation
1400 K Street, N.W.' Suite 1000
Washington, D.C. 20036
PAGENO="0685"
679
U.S. HOUSE OF REPRESENTATIVES
Before the
Subcommittee on Health and the Environment
of the
Committee on Energy and Commerce
COMMENTS OF THE
AMERICAN ASSOCiATION OF ADVERTISING
AGENCIES, INC. on H.R. 1381 -
These comments are respectfully submitted by the American
Association of Advertising Agencies, Inc. (the `A.A.A.A.") in
opposition to H.R. 1381. That bill would, among other requirements,
mandate that all advertisements of products containing aspirin or
other salicylates -- including broadcast advertising, print advertising,
oui000r anc even transit aOverUsIng -- contain a specific, 1,6-word
warning surounded by a black border and bracketed by color-coded
signs and symbols.*
* That warning must expressly state:
`WARNING: This product should not be given to individuals
under the age of 21 years who have chicken pox, influenza or
flu symptoms. This product contains aspirin or another salicylate
which has been strongly associated with the development of Reye's
Syndrome, a serious and often fatal childhood disease."
The warning must be blocked within a box and surrounded by yellow
and red warning signs.
PAGENO="0686"
680
The A.A.A.A., the national association of the advertising agency
business,* respectfully submits that the requirement in H.R. 1381
that all advertising of aspirin products include a warning regarding
aspirin usage by those younger thafl 21 years is not in the best
interest of either current and potential aspirin product users or
aspirin manufacturers and marketers. Specifically, the requirement
of a warning: (1) fails to pay heed to the legitimate but limited
functions of product advertising, and (2) fails to recognize that
numerous alternative means already exist for transmittal of full and
fair health information to purchasers of aspirin products.
Advertisements are, in essence, attempts to communicate the
most helpful and relevant selling information to the largest available
audience at the.least cost, with the goal of persuading potential
consumers to select a particular product from a given class. Concise
communication of truthful information perceived useful by the consumer
is the only effective means of attaining that goal.
The task of creating an effective advertising communication is
difficult under any circumstances, requiring an advertising agency
that isexpert in communicating with the public at large.** In the
broadcast media in particular, given the limits of a 15- or 30- or 60-
second radio or television advertisement, an advertiser and its agency
must `zero in" on the crucial message in as little time as possible,
and must avoid cluttering the advertisement with data not directly
relevant to the commercial's principal purpose. Limited available time
and space must be used to best advantage, and inclusion of information
not easily understood by the viewing audience must be avoided.
* The A.A.A.A. includesin its membership approximately 700
advertising agencies with offices throughout the United States
and the world. In addition to creating and placing most national
advertising, A.A.A.A. member agencies handle a substantial
amount of local and retail advertising for goods and services.
** What is the most helpful and relevant consumer information
regarding any particular product depends, among other things
on the product's characteristics and the desires of the purchasing
public. An advertising agency's job is to understand such
considerations and to devise a message that memorably and
effectively presents salient information about the offered goods
or services.
PAGENO="0687"
681
By its very nature, then, advertising can convey only a limited
quantity of information. Most product advertising is intended to alert
consumers to the availability of either a product or a brand; not to
overwhelm the consumer with an avalanche of product data or information
not generally applicable. When too much information is forced into
a confined space or time, the result is simply a less effective
communication as a whole. When too much `message' is placed in an
inappropriate medium, the risk of consumer confusion and erroneous
perceptions increases dramatically, as does the chance that some
consumers seeing or hearing the advertisement will simply ignore it
entirely. It would be particularly unfortunate in this.context if
consumers who are not at risk of any adverse consequences from
aspirin use -- a group which we understand constitutes nearly all
aspirin consumers -- were to develop an erroneous impression that
they should avoid aspirin usage altogether as a result of brief contact
with the bill's required warning.
The A.A.A.A. does not represent itself to be an expert in the
complex fields of pharmacology and medication, so it is not in a
position to comment on the general advisability of the language of
the warning proposed in H.R. 1381. * However, if the policy objective
~ th~ hi1~ tc ~`~`-e~e ~o~'su"~e'- awa'eness of pote'~tial conse.~uences
of aspirin intake by particular sub-groups of our society, surely there
are more approopriate means than advertising to disseminate such
detailed information. For example, package labels and inserts,
physician pamphlets and verbal instructions, pharmacist suggestions,
and other industry and medical education efforts -- all of these would
appear to provide more appropriate mechanisms for dissemination of
the substantive information with which H.R. 1381 is concerned. While
some of the alternative methods of communication surely offer more
promise than others, all of them appear to be potential ways to
disseminate the intended message without requiring a misguided
effort to make advertising perform a duty for which it is ill-
equipped, and for which it has never been intended.
* We note that Dr. Frank Young, Commissioner of the Food and
Drug Administration, explained to this subcommittee on March
15, 1985 that "the definitive scientific data are still not available,"
so that "the evidence needed to support mandatory labeling is
not, in our view, available at this time." Statement by Frank
E. Young, March 15, 1985, page 3.
PAGENO="0688"
682
In sum, the A.A.A.A. believes that whatever policy goals are
to be served by H.R. 1381, they should be sought by the numerous
available means of information dissemination other than advertising.
Advertising, as a unique and specialized form of communication,
should be left unhindered to perform its immediate, concise, and
practical function.
Respectfully submitted,
THE AMERICAN ASSOCIATION OF
ADVERTISING AGENCIES, INC.
Executive Vice~Rt~dent
Washington, D.C. 20036
(202) 331-7345
Of Counsel:
David Versfelt
Donovan Leisure Newton & Irvine
30 Rockfeller Plaza
New York, N.Y. 10112
(212)307-4100
PAGENO="0689"
683
/
of the
AMERICAN NEWSPAPER PUBLISHERS ASSOCIATION
and the
MaGAZINE PUBLISHERS ASSOCIATION
The American Newspaper Publishers Association (ANPA) is a national trade
association, representing about 1,400 newspapers responsible for publishing
more than 90 percent of U.S. daily circulation. The Association includes a
number of non-daily newspapers as well. The Magazine Publishers Association
(MPA) is a national trade association, representing approximately 750 consumer
magazines within the United States. We appreciate this opportunity to comeent
on H. R. 1381, The Emergency Reye's Syndrome Prevention Act of 1985, legisla-
tion which we believe raises certain First Amendment issues which Congress
should carefully consider.
Our concern centers on Section 2 of the bill. Section 2(v) mandates that
all advertising of drugs containing aspirin or another salicylate contain a
specifically-worded statement regarding the hazards associated with the use of
aspirin by children. Because the bill would amend already existing legisla-
tion, failure to carry the warnings in advertising would invoke criminal pen-
alties. The section directs the Secretary of Health and Human Services to
prouvlgate regulations to implement the required warning statement. The sec-
tion also requires that the warning statement be centered in a rectangular box
between two yellow arrows each containing the word "warning" and two red
circles.
Although ANPA and MPA understand the public health concerns which have
motivated this legislation, we believe the Congress should proceed with cx-
t~eme sensitivity and great caution when it considers regulating speech as a
method of regulating the sale and use of an entirely legal product.
By seeking to extend the warning label requirement to advertising, to
specify the precise words to be used in such advertising, and to direct the
promulgation of regulations by which the government would judge the contents
PAGENO="0690"
684
of advertising and impose criminal sanctions for the failure to carry the ad-
vertising, H.R. 1381 proposes a substantial expansion of governmental control
over the commercial speech of advertisers and, indirectly, over the newspapers
printing that speech. ANPA and MPA strongly suggest that the expansive reg-
ulatory scheme embodied in H.R. 1381 goes well beyond anything the record
might support.
FIRST AMENDMENT CONCERNS
In a series of decisions including Virginia State Board of Pharmacy v.
Virginia Citizens Consumer Council, Inc., 425 U.S. 748 (1976), Central Hudson
Gas & Electric Corporation v. Public Service Commission of New York, 447 U.S.
557 (1980), and In Re R.M.J., 455 U.S. 191 (1982), the U.S. Supreme Court has
recognized that advertising enjoys significant First Amendment protections.
While the Court has indicated that some of the full protection of political
speech may not be accorded purely commercial speech, the burden is on the
government to show a compelling need for regulation and also to show that the
regulation is no more extensive than necessary. See, In Re R.M.J., !!.~*
Enactment of H.R. 1381 would be a significant escalation of regulation of
speech in this area. It is one thing to mandate a warning label on aspirin
containers and quite another to specify statutorily the precise language which
must be contained in advertisements as well as in packaging, and to provide
for a system under which the government would judge the content of advertising
to determine if criminal penalties should be imposed.
PAGENO="0691"
685
ANPA and NPA reiterate that the First Amendment protections offered com-
mercial speech are not absolute, and that some forms of regulation are permis-
sible.For example, place and manner restrictions are applicable, as is regula-
tion of commercial speech that is false or deceptive. Similarly, there may be
restrictions on advertisements for transactions or products which are illegal.
See ~g., Pittsburgh Press Company v. Human Relations Comm'n., 413 U.S. 376
(1973). None of those justifications for regulation of conanercial speech ap-
plies to aspirin advertising. Aspirin is not illegal, nor is aspirin adver-
tising inherently misleading or deceptive. Likewise, the approach of H.R.
1381 is not a time, place or manner restriction. Instead it mandates publica-
tion of required content.
In Central Hudson Gas & Electric Corp. v. Public Service Cotanissiom of
New York, 447 U.S. 557 (1980), the Supreme Court struck down a New York reg-
ulatory ban on promotional advertising by electric utilities. In his concur-
ring opinion in that case, Justice Blackmun expressed concern about regulating
speech that is not deceptive or misleading "... in order to manipulate a pri-
vate economic decision that the state cannot or has not regulated or àutlawed
directly".
The Court recognizes that we have never held that commercial speech may be
suppressed in order to further the State's interest in discouraging pur-
chases of the underlying product that is advertised. Permissible
restraints on commercial speech have been limited to measures designed to
protect consumers from fraudulent, misleading or coercive sales techniques.
447 U.S. at 574.
It may be argued that the warning message required by H.R. 1381 is simply
an example of the kinds of warnings and disclaimers that the Supreme Court, in
several of the recent commercial speech cases such as Virginia Pharma~y and In
Re R.M.J., has indicated may be permissible forms of regulation. Uniformly,
however, references to the possibility of requiring such disclaimers occur in
PAGENO="0692"
686
the context of a discussion of commercial speech that is deceptive or mislead-
ing. For example, in Virginia Pharmacy, Justice Blackmun notes that
The [attributes of commercial speech such as its greater objectivity and
hardiness] nay also make it appropriate to require that a commercial mes-
sage appear in such a form, or include such additional information, warn-
ings, and disclaimers, as are necessary to prevent its being deceptive.
425 U.S. at 771, n. 24 (Emphasis added).
There is no suggestion that aspirin advertising is so inherently decep-
tive or misleading as to require the mandatory inclusion of a specifically-
worded warning message. This is not t~ say that aspirin advertising which is
deceptive or misleading is immune from challenge. Under Section 5 of the
Federal Trade Commission Act, (15 U.S.C. Sec. 45), the FTC clearly has the
pm~er to deal with such advertising. Absent such a specific finding, it
should not be assumed that aspirin advertising per se is deceptive without a
health warning, any more than automobile advertising would be deceptive with-
out a warning about the dangers of driving.
In the Central Hudson case decided in 1980, the Supreme Court outlined a
four-step analytical framework for examining restrictions on commercial
speech:
In commercial speech cases, then, a four-part analysis has developed. At
the outset, we mast determine whether the expression is protected by the
First Amendment. For commercial speech to come within that provision, it
at least must concern lawful activity and not be misleading. Next, we ask
whether the asserted governmental interest is substantial. If both in-
quiries yield positive answers, we must determine whether the regulation
directly advances the governmental interest asserted, and whether it is not
more extensive than is necessary to serve that interest.
447 U.S. at 566.
When this four-part test is applied to H.R. 1381, the first two inquiries
can be answered positively: aspirin advertising, in general, is not mislead-
ing and is therefore protected by the First Amendment, and the asserted
PAGENO="0693"
687
governmental interest -- public health -- is substantial. It is in connection
with the last two questions that LANPA and NPA believe the commercial speech
provisions of H.R. 1381 do not satisfy this constitutional test: whether man-
datory warning messages in aspirin advertising "directly advance[s] the
governmental interest asserted," and mmre importantly, whether the govern-
ment's intrusion into commercial speech "is not nore extensive than is
necessary."
Whether a government specified warning message carried in aspirin adver-
tising "directly advances" the governmental interest in public health is open
to serious question and should at least be the sub~ject of careful debate and
specific factual showings. Aspirin advertising and packaging already contains
certain health information. The new more prominent warnings would divert the
consumer's attention from this important information and dilute the effective-
ness of that information.
A more critical inquiry is whether the kind of approach represented by
H.R. 1381 unnecessarily involves the government in a pervasive system of reg-
ulating non-deceptive commercial speech. No matter how seemingly laudable the
goal, any legislation which proposes to delegate to government the power to
decide what will be published and to impose criminal penalties for the failure
to publish a specific statement is constitutionally most troublesome. ANPA
and MPA believe this would impinge on the constitutionally-protected rights of
advertisers, the press, and ultimately the public.
PRACTICAL CONSIDERATIONS
Dictating the use of specific colors in advertising raises many practical
concerns. First, not all media are able to offer color advertising; although
many newspapers offer color capabilities to advertisers, often the location of
PAGENO="0694"
688
color advertising is limited to preprinted materials and special sections.
Second, using two colors (red and yellow) on a black and white page may bring
additional attention to the warning, but this effect would be minimized if the
advertiser was able to run the entire advertisement in full color, as any
legislation would certainly have to permit. Finally, requiring the use of
color at all means additional expense to advertisers, an expense which has not
been documented nor supported in the course of considering this legislation.
CONCLUSION
Commercial speech restrictions must be a "last resort" action of govern-
ment. Only where there is a concrete showing that an identifiable problem
cannot be solved by means other than restricting speech can the government
turn to measures such as those embodied in this legislation. The process of
reaching this decision must include a ~ assessment of all the informa-
tion now available to the public concerning aspirin and the health issues sur-
rounding them. Having taken that and all other factors into account, then,
and only then, can restrictions on commercial speech be considered. It is not
at all clear that this rigorous process has been followed in advancing these
legislative measures.
The principal concern of ANPA and MPA about this legislation is the pro-
posed resort to government regulation of speech as a means of regulating a
product which for whatever reason, the government chooses not to regulate
directly.
We believe a very troubling precedent is set whenever the federal govern-
ment determines the content of the speech of private entities. H.R. 1381 pro-
poses to do that. Absent compelling circumstances and clear evidence that
other, less intrusive, alternatives are ineffective, this kind of governmental
action is inimical to the preservation of free speech and a free press in out
free society thus the case has not been articulated which would support as
harsh a statutory restriction on commercial speech as that embodied in H.R.
1381.
PAGENO="0695"
689
` FOR THE RECORD
"I~J A ASSOCIATION OF NATIONAL ADVERTISERS, INC.
155 EAST 44TH STREET, NEW YORK, NY 10017 (212) 697-5950
STATEMENT OF
THE ASSOCIATION OF NATIONAL ADVERTISERS, INC.
ON H.R. 1381
REQUIRING SPECIAL WARNINGS IN LABELING AND
ADVERTISING OF SALICYLATE-CONTAINING PRODUCTS
BEFORE THE
SUBCOMMITTEE ON HEALTH AND THE ENVIRONMENT
COMMITTEE ON ENERGY AND COMMERCE
UNITED STATES HOUSE OF REPRESENTATIVES
The Association of National Advertisers, Inc. (~A.N.A.") is a
not-for-profit corporate trade association, organized and exist-
ing under the laws of the State of New York, with offices' at
155 East 44th Street, New York, New York 10017. It is composed
of approximately 400 companies, with over 2,000 subsidiaries and
divisions (many of which are relatively independent advertiser
entities), located throughout the United States. They sell a
wide range of products and services and employ advertising as
an important element of their marketing and public relations
programs. Although A.N.A.'s membership includes many of the
nation's largest advertisers, it also comprises a large number
of smaller ones. Approximately one-third of A.N.A. members
spend under $5 million annually for advertising. A.N.A. members
collectively' account for over two-thirds of all national and
regional advertising expenditures in the United States.
It has always been a fundamental policy of A.N.A. to defend
against abridgment or erosion of advertisers' right to advertise
truthfully any product or service that can lawfully be sold.
Inevitably subsumed under this cardinal principle is the propo-
sition that truthful advertising should not be collaterally
abridged by imposing upon it an emasculating requirement to warn
against grave dangers from use of a product where such dangers
have not, been established to exist.
We believe that to be the situation with regard to the alleged
association between salicylate-containing pharmaceuticals, child-
ren's flu-like diseases, and Reye's Syndrome. However, we leave
the arguing of that highly technical, scientific matter to others
more expert than ourselves in that area. If the danger has truly
been proven to be real that is one situation; but unless and until
it has been, we respectfully submit that H.R. 1381 should not be
enacted.
Officers: Directors:
SPENCER C. BOISE, MaOH, thc.-CRaiccac B. OHSDRLUN. WEISPRA CR(pONHcT DOUGLUST. MACLURE, FoR ROAR Coopacy
HERBERT N. BAUM, Caopbell Soop Co-VIO'COlLFRaO VIM ARMSTRONG. AT&TComounoaSocs WILLIAM S. MCGRANAAAN. RANaotsoc-VAEo HA.
E~WITT F. HELM, JR., PNSIURII SHARON E. BAUM. CBeckcaI Back JOHN J. MEAGER, JR.. Conbe Icoopooted
RICHARD K. JEWETT, Pitney Boses-Tnasotet JAMES B. BLOCEI. Colt. Inc. MILESA. NELSON, 3M Coep.cy
SAMUELTHURM, SecicitAne PcesiRnt JOHN H. CHILDS. Hooc AR. DON A. OSELL,The Rtsbcy Cotnpany
WILLIAMS. KISTLER. Ho Pceoidect JOSEPHJ DOHERTY, Dacco-Coccaig Rbeglas Cooccason BARBARA PESIN. Hoot Pcnd~ts, Inc.
BERBEETA AHLGREN, Ho Fctsidrct JOHN H. DOBBS, HoBby Foods Cc!pclabioc JOHN J. POWERS, Easteac BodakCoepacy
HARRY L DAVLWG. Ho Pcesident ROBERTA. GOLDSTEIN.TAB Pmot,: B Gaoble Coccpacy ROBERTA. RECHHOLTZ, AdolpH Coos CoRpacy
CLERE ROLT. Hoe Pcesidtcl and Assistant to the Pnroideto DONALD U. GO1.DSTROM. Actottoog WaRd Icdiistces, Inc. SANFORD E. REISENBACH, Waco: Bcotttecs, Ito.
ANTHON C. LUNT. Ho Pteodect DAVID L EOODMAN,10, CAms Coopaey THOMAST. RYAN,THe GBHtte Coop.cy
JAMES B. COSSROVE, AosistattTreasscet .odDetcetaty MICHAEL ES. EIRHC Bass Cotpoo.tiso CHARLES L. SHEMELY, CaeRe Coopacy
GILBERT H. WElL. Stneol Colosel RORERTF. LAUTEROORN. IctecnaSooal P~o Cotnpacy DELHDYO THOMAS, Lack D'LakeN. Inc.
PBTERW. ALIPORT. PooReR Eccenftss
PAGENO="0696"
690
For virtually a decade A.N.A's policy has enjoyed constitutional
recognition and backing, subject only to a narrowly confined
exception (Central Hudson Gas & Electric Corporation v. Public
Service Commission of New York, 447 U.S. 557, at page 564), which
we shall now discuss with respect to its application to truthful
advertising of salicylate-contaifling products.
The three tests which all must be passed before abridging legis-
lation can be constitutional, are concisely stated by the Central
Hudson court:
If the communication [the advertising) is neither
misleading nor related to unlawful activity, the
government's power [to restrict] is more circum-
scribed. The State must assert a substantial
interest tobe achieved by restrictions on commer-
cial speech. Moreover,. the regulatory technique
must be in proportion to that interest. The limi-
tation of expression must be designed carefully
to achieve the State's goal. Compliance with this
requirement may be measured by two criteria. First,
the restriction must directly advance the state in-
Eirist involved; the regulation may not be sustained
if it provides only ineffective or remote support
for the govern nt's purpose. Second, if the gov
ernmental interest could be served as well by a more
limited restriction on commercial speech, the exces
sive restrictions cannot survive. (Ibid.)
The burden of proof is firmly on the proponents of abridging or
hobbling laws. "The party seeking to uphold a restriction on
commercial speech carries the burden of proving it." Bolger v.
Youngs Drug products Corp., 103 S. Ct. 2875 at 2882 n.20 (1983)
~ (citing Central Hudson, 557 U.S. at 570). One need only read the
Supreme Court's fine-toothed combing, and consequent rejection,
of the government's assertions of substantial state interests and
of their direct advancement by General Bolger's restrictions upon
Youngs' advertising, to appreciate how heavy that burden of proof
is.
Thus, unless arid until the burden has been fulfilled of proving a
causal relationship between children's ingestion of salicylates
in the presence of flu-like diseases and the occurrence of Reye's
Syndrome there must be a failure by the government to satisfy the
first prerequisite for exemption from the First Amendment: es-
tablishment of "a substantial interest to be achieved by [the)
restrictions on commercial speech."
PAGENO="0697"
691
Interestingly, if that causal relationship were proven, passage
of H.R~l~l would be unnecessary. Section l5(a)(l) of the
Federal Trade Commission Act, 15 U.S.C. S 55(a)(l), provides in
pertinent part, "[I]n determining whether any advertisment is
misleading there shall be taken into account . . . the extent to
which the advertisement fails to reveal facts material * .. with
respect to consequences which may result from the use of the
commodity to which the advertisement relates under the conditions
prescribed in said advertisement, or under such conditions as are
customary or usual."
Even if the first constitutional hurdle were cleared, moreover,
the next two would be too high for the proponents to leap, at
least so far as advertising is concerned. H.R. 1381 would be
ineffective, or at best remote, for directly advancing the govern-
ment's "warning" goal, and would excessively restrict commercial
speech via advertising because labeling would be the appropriate,
adequate and far less restrictive means of whatever communication
might be called for. (Let us repeat that it is not advertisers'
burden to prove ineffectiveness or remoteness of the proposed
restrictions, but the government's to establish the converse.)
There are many warnings and contraindications that are necessary
to make the great and increasing variety of otc medicines safe
and effective for use without medical supervision. There would
be no less reason to impose restrictions upon the advertising of
all of them than for those proposed in H.R. 1381. Much, if not
most, otc pharmaceutical advertising would collapse under such
burdens, to the frustration of the public policy manifested in
the Food, Drug and Cosmetic and the Federal Trade Commission Acts
of promoting lay use of such products.
Self-medication with proprietary drugs is a sig-
nificant factor in the U.S. health care scheme.
Escalating costs of health care create a greater
need for low cost self-medication than ever before.
Seventy-f ive percent of all illness and injuries
are initially treated through self-care and OTC
medication. If only a small percentage of self-
treatment was shifted to medical practitioners,
the patient load would disrupt the U.S. health
care system. [U.S. Department of Commerce, U.S.
Industrial Outlook 19.78, at 131 (January, 1978)].
It is not surprising that the Federal Trade Commission, after
studying, deeply and extensively, the voluminous data produced in
a trade regulation rulemaking proceeding, concluded that generi-
cally advertisements were an inappropriate medium for conveying
drug warnings. While the specific product line involved was ant-
acids, there was no question in anyone's mind but that the basic
principle of a blanket requirement (such as H.R. 1381 proposes)
PAGENO="0698"
692
was what was at test. And, there is also no question but that
the proponents for the principle had a full opportunity to make
their case for it. The result is understandable, and was correct.
The March 15, 1985 statement of The Proprietary Association, at
pages 5-6 describes it, and the relevant inadequacies of adver-
tising, quite well; we need not repeat its contents here.
In short, the necessity to prove that the restrictions upon com-
niercial speech, especially upon advertising, proposed in H.R. 1381
are exempt from the forbiddance of the First Amendment has not
been met by its proponents as to any one of the specified condi-
tions. All of them must be satisfied for its restrictions upon
advertising to be valid.
Respectfully submitted,
Dated: March 28, 1985 ASSOCIATION OF NATIONAL
ADVERTISERS, INC.
By: ~2~1~LLL
DeWitt F. Helm, Jr
president
Gi4bert H. Weil ~
General Counsel
PAGENO="0699"
693
STATEMENT OF THE
NATIONAL ASSOCIATION OF BROADCASTERS
ON
H.R. 1381
"The Finergency Reye's Syndrcine Prevention
Act of 1985"
Mr. Chairman and members of the subcommittee.
The National Association of Broadcasters ("NAB")JJ
submits these comments to be included in the record of the
subcommittee's hearings on H.R. 1381, a bill that proposes
mandatory warnings about Reye's Syndrome for all labeling
and advertising of aspirin-containing products. Because NAB
represents the broadcast media, its comments address only
the advertising proposals of H.R. 1381 -- and specifically
speak to the unique and restrictive context of radio and
television advertising.
This bill has been proposed as an emergency measure
to ensure that teenagers and mothers of children know about
the potential risk of Reye's Syndrome associated with certain
aspirin use so that those at risk can act, in an informed
way, to avoid potential harm. Getting the word out about the
potential risks of such a serious and often-fatal disease as
Reye's Syndrome is the goal of this legislation. It is,
jj NAB is a nonprofit incorporated association of radio and
television broadcast stations and networks. NAB membership
includes more than 4000 radio stations, 700 television
stations and the major commercial broadcast networks.
PAGENO="0700"
694
unquestionably, an important goal. It is a goal that surely
all inVolved parties are working to achieve.
And it is a goal that the National Association of
Broadcasters and its member radio and television stations
want to help effectuate -- just as NAB and radio and televi-
sion stations across the country have worked to alert the
public to other immediate potential health hazards, from toxic
shock syndrome to the rash of adulterated Tylenol products.
Getting the word out about an immediate danger is something
broadcasters can facilitate.-- through broadcast news programs
and news updates and through public service announcements,
messages from aspirin manuafacturers and references by radio
announcers. Broadcasters have gotten the word out many times
before. And they intend to do so now with regard to the
potentially dangerous association of aspirin with Reye's Syn-
drome when taken by children and teens with flu or chicken
pox. Broadcasters stand ready to help shore up the current
voluntary warning program in this emergency situation.
But NAB does not, and cannot, stand ready to sup-
port government-imposed warnings on broadcast aspirin adver-
tising. For NAB believes that such a government mandate
would be unnecessary, unworkable, ineffective and possibly
counterproductive to other important public goals.
A. Broadcast &lvertising Is Neither Appropriate Nor
Effective for the Task of Educating the Public on the
Contraindications of Over-the-Counter Medicines.
Product advertising on radio and television does
convey some health-related information to the public. But
PAGENO="0701"
695
the nature of broadcast advertising is not suited to the task
of educating the public on the detailed contraindications of
over-the-counter ("OTC") medicines. This is so because typi-
cal radio and television ads are limited to 30-second spots.
Such a brief exposure is hardly sufficient time to deliver
usable and non-alarming information on the contraindications
of OTC products -- along with the selling message for the
product. And the warning suggested by H.R. 1381 would con-
sume 20 seconds -- two thirds of the typical ad. While dis-
closures generally, and particularly those involving warnings,
may be informative and useful in labels, disclosures in broad-
casting are far less effective and may in fact be unduly
alarming or confusing to the consumer.
Television and radio ads, typically 30 seconds
long, can accommodate only a limited number of concepts.
Too many ideas contained in a message would only serve to
confuse the consumer and frustrate the public policy goal of
consumer awareness of effective OTC self-medication.~a' Bur-
dening brief broadcast ads with required disclosures increases
the number of concepts presented and thus may preclude full
information processing of those disclosures by the typically
2/ The Supreme Court has recognized the public policy bene-
fits of informing consumers as to the availability of con-
sumer-aiding products. See Virginia Citizens. Consumer Coun
cil, Inc. v. State Board of Pharmacy, 373 F. Supp. 683 (E.D.
Va. 1974), aff'd, 425 U.S. 748 (1976); Terry v. California
State Board of Pharmacy, 395 F. Supp. 94 (N.D. Cal. 1975),
aff'd ~L curiam, 426 U.S. 913 (1976). .
PAGENO="0702"
696
passive viewer or listener of broadcast advertising.-~1 It
is the contention of Professor Roger Blackwell that consumers
might only grasp a general knowledge of product availability
from broadcast advertising. In fact, because of selective
perception, consumers will perceive only some of the stimuli
they receive and may misinterpret that material to which they
do not devote some attention.
Consumers who watch or listen to advertising over
the broadcast media are passive participants to the communi-
cation of commercial messages. And many elements impact upon
the advertiser's ability to reach consumers. For example,
adjacent commercials, the nature of the advertised products
and even outside stimuli may affect the manner and accuracy
of consumers' perceptions. FTC Associate Director Wallace
Snyder agreed with the experts in the FTC antacids warnings
rulemaking that the broadcast media are inappropriate for
conveying information on contraindications because it is a
"low-imvolvement" med ium.-~i'
It is not likely that mandated warnings about
Reye's within aspirin and aspirin-containing product adver-
tising will be as effective as a voluntary effort undertaken
3/ See testimony of Michael Ray, Professor of Marketing,
Stanford University; Scott Ward, Professor of Marketing,
Harvard Business School; and Roger Blackwell, Professor of
Consumer Behavior, Ohio State University in FTC antacids
warnings rulemaking, TR 1484.
j/ FTC Bureau of Consumer Protection, Staff Report and
Recommendatibns Advertising for Over-the-Counter Antacids,
No. 215-56, at 195 (August, 1983) ("Antacids Staff Report").
PAGENO="0703"
697
by manufacturers, distributors, advertising associations,
broadcasters, NAB and other organizations. Nor are mandated
warnings necessary, given a voluntary multi-industry warning
program. But it is likely, very likely, that passage of the
proposal pending before the subcommittee would produce un-
necessary and undesirable side effects.
One, Congress will have taken a step seen as not
sure enough by the agency expert about advertising and con-
sumer perception, the FTC. That is, Congress would be legis-
lating that every ad, here aspfrmn ads, must, by government
order, warn consumers about a rare but possibly fatal occur-
rence -- which information can be conveyed to and understood
by the public in a voluntary and effective campaign -- a cam-
paign to get the word out, not one to cause public questioning
of reasonable self medication with aspirin products.
Two, Congress would, by passage of H.R. 1381, be
second-guessing the scientific judgment of the FDA processes
on the medical underpinnings of contraindications. That too
is unnecessary. A stepped-up voluntary program can and will
get the necessary word of caution out and will do so immedi-
ately. Meanwhile the expert agency, the FDA, will come to
some solid conclusions about the association of aspirin and
Reye's and about contraindications required in labeling.
Three, passage of advertising provisions like
those in H.R. 1381, by itself or by its prpgeny, may reduce
consumer reliance on labeling and may scare of f consumers
PAGENO="0704"
698
who overgeneralize advertising warnings from appropriate
aspirin self-medication.
B. Once a Voluntary Warning Program Has Alerted the Public
About Reye's Syndrome, Labeling Becomes the Appropriate
and Effective Method of Conveying Consumer Information
on the ContraindicationS of Aspirin and Reye's.
The FDA has found OTC aspirin products "generally
safe and effective." Mandatory inclusion in advertising of
aspirin label cautions may reduce the effectiveness of label
warnings and, at the same time, may discourage OTC aspirin
use by consumers who overgeneralize the warnings in adver-
tising, Those consumers would lose the benefits of effective
aspirin self-medication.
The proposed legislation would extend label warnings
(not yet required by the FDA) to aspirin advertising. But
automatic application of label warnings to advertising is not
justified simply by the fact of labeling restrictions. Pro-
duct labeling serves a wholly different role from that of
advertising. Advertising functions to awaken a general con-
sumer awareness of the product and of the product's intended
use. Some advertising also manages to distinguish a product
brand from other similarly-used products. For the ad to be
the most effective, the consumer must be both attracted to
and interested in the simple information presented.
By contrast, product labels function to explain in
greater detail the particular characteristics of a product
and thus go fa~ beyond piquing consumer awareness. Labeling
PAGENO="0705"
699
is an effective medium for providing important health infor-
matior~ because labels may be reread for clarity and because
they are reviewed at the point of the purchase where the con-
sumer may make the best decision based on thoughtful consid-
eration of the information on hand. The role played by pro-
duct labeling is complementary to, but distinct from, the
role of advertising.
Requiring warnings in advertising, particularly
broadcast advertising, may in fact serve to reduce consumer
reliance on effective labeling information -- to the consumers'
detriment. FTC associate Director Snyder, in the antacids
warnings rulemaking, cites two FDA studies, done in the early
l970s, which found that substantial numbers of consumers read
labels for safety information.-~1 Labeling is an effective
method through which consumers properly and adequately receive
FDA cautionary information. The mandated inclusion of any
warnings in aspirin advertising itself likely would reduce con-
sumer reliance on label information and encourage consumers to
depend on advertised warnings as the last word in information.
C. Aspirin Warnings in Broadcast Mvertising May Mislead
and Unnecessarily Alarm Consumers.
Even the most attentive of listeners and viewers
may be both confused and alarmed by the warnings proposed for
aspirin advertising. Broadcast commercials simply cannot
5/ Antacids Staff Report, supra, Snyder Memorandum at 40-41.
52-266 0-85-23
PAGENO="0706"
700
accommodate additional clarifying information and still pre-
sent a selling message in a 30-second spot. And a barrage
of information would cause either inattention or confusion.
The potential for consumer confusion from brief
warnings should not be understated. Nor should the potential
impact on advertising decisions be overlooked. Confusion
created by warnings may in fact discourage broadcast adver-
tisements for OTC medications. Reduced advertising may re-
sult where broadcast messages cannot accommodate lengthy dis-
closures and effective selling messages -- or where selling
messages are rendered ineffective by required disclosures.-~!
Reduced broadcast aspirin advertising would unquestionably
lessen consumer awareness of effective OTC products.
Aspirin use is generally safe and effective for
the vast majority of consumers in the vast majority of uses.
But those same consumers, passively involved with broadcast
advertising, likely may overgeneralize the warnings in
aspirin. Required disclosures may serve to mislead and alarm
consumers about the potential risks of OTC aspirin. Required
advertising warnings simply would mislead consumers about the
risks of OTC aspirin use.
D. Conclusion
NAB believes that the immediate need to alert
mothers and teenagers to the potential risks of youngsters'
6/ See Thanscrip~ of the antacids rulemaking, TR 1484, Dr.
Larry Light's testimony.
PAGENO="0707"
701
taking aspirin for flu and chicken pox can be met and will
be met through a stepped-up voluntary warning program. NAB
and the nation's broadcasters stand ready to help get that
word out. But NAB believes that reaching beyond a voluntary
warning program and beyond labeling to mandated warnings in
aspirin advertising, particularly for radio and television
advertising, goes well past effective and needed measures
and would disserve the public interest.
PAGENO="0708"
702
OUTDOOR ADVERTISING ASSOCIATION OF AMERICA, INC.
March 28, 1985
Honorable Henry A. Waxman
Chairman
Subcommittee on Health and the Environment
Committee on Energy and Commerce
2415 Rayburn House Office Building
Washington, D.C. 20515
Dear Mr. Chairman:
The following statement is submitted by the Outdoor
Advertising Association of America, Inc. for inclusion in
the official hearing record of the March 15, 1985 hearing
on H.R. 1381 -- the "Emergency Reye's Syndrome Prevention
Act of 1985."
The Outdoor Advertising Association of America, Inc.
(OAAA) is the trade association of the standardized outdoor
advertising industry. The Association is comprised of one
hundred and seventy member companies that serve 7,900 dis-
tinct local advertising markets throughout the United States.
The OAAA understands the concerns evident in H.R. 1381
to make the public aware of the potential association between
the use of aspirin and the development of Reye's Syndrome.
Nevertheless, the advertising disclosures proposed in Section 2
of this bill are very poorly conceived. A 48-word boilerplate
warning is not going to be effective when inserted into adver-
tising. The proposed warning is so ponderous and unsuitable
that it cannot be adapted to most advertising for salicytate
products. The simple fact is that this bill would destroy
all incentive to advertise these products. The advertising
provisions of H.R. 1381 are, therefore, counterproductive
since there will be few if any advertisements to carry the
warnings if the bill is enacted.
There is a superficial appeal in the proposed statutory
scheme. Nevertheless, it is based upon the flawed premise
that a lengthy and technical label warning will be communicated
effectively through advertising. The bill reflects a wholesale
misunderstanding of how information is conveyed in advertising
and ignores the basic fact that a message must be tailored
National Headquarters
SUITE 403, 1899 L STREET, N.W., WASHINGTON, D. C. 20036-3881 (202) 223-5566
PAGENO="0709"
703
Honorable Henry A. Waxman
March 28, 1985
Page Two
for the precise medium in which it is disseminated. The manner
in which this bill would impact on aspirin advertisements in
the outdoor medium provides a good case study of how H.R. 1381
fails in this regard.
It is generally understood that complex and comprehensive
disclosures are not an effective method for conveying information
in advertising. The most basic problem is that every medium
imposes unique constraints on the manner in which information
is communicated. For example, a standard outdoor advertising
poster is 12 feet by 24 feet in size. This may seem like
a large area. Certainly a 48-word warning could be accommodated
physically within that space. But the size of the lettering
would have to be relatively small for the warning to fit and,
even then, the warning would occupy so much space that there
would be little useable area remaining for the advertiser's
message. Moreoever, there is no likelihood that such a warning
could be read by a motorist. This problem is not confined
to the outdoor medium alone. Theoretically, a 48~word warning
could be recited within the confines of a 30 second radio or TV
spot. Nevertheless, the warning message would have to be
read very quickly to allow any time at all for the principal
message.
Beyond these practical limitations, the mere fact that
the warning is incorporated in an advertisement does not mean
that it will be understood. The proposed warning is too long
and too complicated to convey the desired information. Adver-
tising for consumer products, such as aspirin, generally relies
on simple, evocative messages specifically designed for the
particular medium through which they are disseminated. Even
a single, well conceived warning would notbe effective in
all media because each medium is different.
This fundamental principal has been recognized in other
regulatory contexts where affirmative disclosure requirements
have been adapted to the specific media involved. For example,
in 1978 the Federal Trade Commission issued guidelines for the
inclusion of fuel economy disclosures in automobile advertising.
The Commission recognized the different constraints imposed by
each medium and incorporated separate disclosures for broadcast,
print and outdoor media. Likewise, during the last Congress,
this Subcommittee enacted the Comprehensive Smoking Education
Act of 1984 which establishes separate cigarette health warning
systems for package labeling, print advertising and outdoor
advertising.
The simple fact is that the advertising provisions of
H.R. 1381 cannot achieve their ostensible purpose. In the
OAAA's view, this warning scheme, however well intentioned,
will not work. The development of an affirmative disclosure
system should be left to the FDA and FTC which have the
requisite expertise in this area. In a real sense, this bill
would have the perverse effect of preventing those agencies
from implementing a truly effective disclosure system to deal
with the Reye's Syndrome problem. For these reasons the OAAA
urges the Subcommittee to reject the advertising provisions
of this bill.
S in~74Z~
Vernon A. Clark, President
PAGENO="0710"
704
L~JtLL. ~ L~\/ S1~it~ ThI~T r( ~,
~Xfl&Ev~iLY ~IFHC~L.1~LT i'b ~r~z-r Th \~ ThQ.
f~Vf~)1S i~4~j~L'f ~~cshu~, ~iy cii~
~L1\TR, JDj~i~y ~ ~
~ i'ri2~ p~t~ ~3~t&LL ~
~ ~ `~f~J~ o~ P~,
~ik.i~/ bt~ o~ IV17'ft~-44 P.2'-~ t~3
AFr~c&. ~ ~T~)o !~/~y BATTLE t'OtTH
~gyEs, S\~j~0~, ~ ~To SA)' ,
f~t'~t~)T ~LC..(-4 ~c,oLZ~~ ~ ~ t~k~~S ~g~mk1~Ly
~ ~ Su 1~t~'i v, N c~
S~1~ 7 LL~J ~
N~ ~Ri~I,~i .~f»=~31~s,
~ ~ `~-~ ~- ~ ~
~ P~ Vfl~y CP~tI~J(~'
S~i ~A4~C J\ (4,4 LL1~ LOH c
Li~ lo (~S U~T, Si-iQ~ L~-e~~
`f~'~ `j'o i~P~~f~L ~J1~ Ls~vft~
¶_~1 ~
~I~? ~Ay~c~1~ ~-~-) ~ Th~F~~JF~ ~
1\ £)4~tL~. ~ (P~ 1~ ~ H~4~
`-~-~ ~ M~ f~2S*~g~~
~ 1~.
~C~4~c~L ..SM~ ~
1~.) ~T~&c~j~y ~tc~-i~' 1~c~ ~ ~ ~
PAGENO="0711"
705
J~'t~ tLA)~C~~ )~Co~L) o3 U~3eSI~Ay. ~
~Y~t~IL~I ~I- -rk~i~,t~y WI H~4~ SH~ ~
Ia ~ c~-rttL~& `~1M~k LQ )JO 1~~I~*1~ c?*~c
cD~) t~Rsb$~y ~ i~ Ot4R Pi~c&.
C1PL4~&f~j~. o1~S J~: ~4v~44 ~&~Q~O,~-)
MO~ilt~)Cz7 S'it. V'~w1i1Q~ Ot~)C-t!~ c~1~
-rw,c~~ V~', S~-~~iDLY ~ ~
c~ ~
Mv. ~ -rl4~) t~&~1Q ~
cr~,y~ .J~O ~1~~i1
~t :TPLP~~~~ ~
~ ~ iF ~ -~t~
W~ .~1~(kf~ c)I~i .~ H~ R. u~ .S~Mi~x~j~y
~ .~ic1-~ ~ :~t~t~.~0-
-1~ 5L~~ ~ it~p~-~~ S~1 i~~(ji~ ç~j
~ t~ 1~ MoRiJ I ~7, ~L~1k2~i ~)ot~
~ ~tMJ~T ~ _~ ~ o~ ci1~ f)~.
L$~$ -r~, ~ ~ t~,
Ia.. 3~1~ ~ t~) F~ ~crt') tS
II
* *~1~r~v ?~1c$~) 1~ cJ~~i1 A~Jr~ ~
* SIX ~1,
* o~v1o~5L~/. *~L$[»=~ic~~ WL ~L<~&)f$'
k~. *t4J 1\ B LI4~1&~1 * A~t~ ~
k~1L 1~. OL~1»=~ L~CJ~L Ho~i~ L
PAGENO="0712"
706
iou~ L4'~ m~M1 -rt~v ~
~ i~L ~I~'~Th ~) ~L1'~1~ ~ -fl~T ~
~ ~ ~-VI~&. i~-~
~ ~1~b~L\-r~ t~rt~ ~i~r~i Lk?\)IT.
G~c~ iV ~ ~ ~ zMy QTfrIe~
`~\S 1~k1~ I?~~ ~ iTo
Th~ i ~sc»=jt H ~
~1' ~ >~j~c~b~ ~,T~ii7AL. A ~$~tt~)ALTA~
l~ ~ I\j~t~ T~. O~1OLT~
kS ~fl~i I~Y1~ `~ ~*,.. `~ i~ f~I~iY~
~ i~T v~ l-1i4~ ~
~ ~3 ~t~fW~~J Si?~ o~k ~ ~4~Q1M
~ ~.R ~
~ ~ ~ ~ ~ I
~k) ~ ~o(~-iJt'~C~ JY1Af~M ~2~5 ~
~ ~bL~ ~
~ tx~ ç~ u4
&~f ~ i~S ~PN~$iYiS ~ R~ Y4S)~)
Th t~
* > * ~44~ ~ *
.1~g ,
V~Vt~&. ~`IVtbJ 1k~%~t'~)
* C~4tL,t~ tA*11~ W1M~~' ~ CpiJ ~Ri
* ~ t~kV~'
-fl~j *u~) ~ ci~t~
PAGENO="0713"
707
i~v1 V~~H1' c~-r ~ 13i~ 1~~!:L~1~ ~
`~ i~i1 P6'I'~ ?_I ~)& i~t~ ~ -Th'~P ~A3~
~ c~k~i( LOj~ t~$ AL~Y«=.. ~i
R~L ~tt~ )S 1~T d~t~)
~41 ~-i
cMk~ ~1A1L4~ I~ ~i'
~ ~ W~H~ ~
w1~ ~
~3~I9~5
~ cj,~c,c i~
PAGENO="0714"
PAGENO="0715"
ORPHAN DRUG ACT REAUTHORIZATION
WEDNESDAY, MARCH 20, 1985
HOUSE OF REPRESENTATIVES,
COMMITTEE ON ENERGY AND COMMERCE,
SUBCOMMITTEE ON HEALTH AND THE ENVIRONMENT,
Washington, DC.
The subcommittee met, pursuant to notice, at 10:30 a.m., in room
2322, Rayburn House Office Building, Hon. Henry A. Waxman
(chairman) presiding.
Mr. WAXMAN. The meeting of the subcommittee will please come
to order.
One year ago, the subcommittee conducted the first oversight
hearing on the Orphan Drug Act. We found that we had made an
excellent beginning and created high expectations. Our goal for
this past year was to sustain our early success. Today we are
pleased to be able to say that we are living up to those high hopes.
The pharmaceutical companies, both large research-intensive
firms, and small biotechnology and~ generic firms, are stepping for-
ward to sponsor drugs for rare disorders. The Food and Drug Ad-
ministration, particularly its Office of Orphan Products Develop-
ment, has shown the American public that we are going to keep
our promise to make orphan drugs available. Independent scien-
tists have taken the challenge to be more attentive to orphan drug
research, and the voluntary organizations like the National Orga-
nization for Rare Disorders, continue to remind us of the need for
ever greater success. They are our standard bearers and our inspi-
rational leaders.
For too many years, the story of orphan drugs has been one of
hopelessness. After only 2 years of the Orphan Drug Act, we have
proven that the story can be rewritten. The orphan drug problem
can be solved, and for an increasing number of drugs, is being
solved.
Congratulations for a good year are in order today. We must re-
member that it will never be profitable to conduct research on an
orphan drug or to market one. No matter how much we have done,
each new orphan drug is a challenge. Every year we must ask our-
selves how we can improve our effort and whether additional re-
sources are warranted.
At our current pace, pharmaceutical companies will soon have
adopted all those orphan drugs which do not require a lot of new
research. Will we be able to get pharmaceutical companies to spon-
sor orphan drugs at an earlier stage when original research is nec-
(709)
PAGENO="0716"
710
essary? Will we need additional Government funds to support
human and animal research because companies are not willing to
conduct it?
Many people tell us the problem with orphan medical devices is
as great as with orphan drugs. Should the act be expanded to in-
clude medical devices?
These are some of the questions we want to explore today. We
have an impressive list of witnesses, all of whom are actively ad-
dressing the problem of orphan drugs and medical devices. We look
forward to hearing from them.
Our first witnesses are the Commissioner of the Food and Drug
Administration, Dr. Frank Young, and the Director of the Office of
Orphan Products Development, FDA, Dr. Marion Finkel.
We would like to ask them to come forward. And as they come
forward, I would like to call on any of my colleagues who wish to
make an opening statement.
If not, we want to welcome Dr. Young and Dr. Finkel to this
hearing today. We are pleased to have you with us. Your prepared
statements will be made part of the record in full. We would like to
ask you to summarize those statements so we will have a full op-
portunity for questions and answers.
STATEMENT OF FRANK E. YOUNG, M.D., PH.D., COMMISSIONER,
FOOD AND DRUG ADMINISTRATION, PUBLIC HEALTH SERVICE,
DEPARTMENT OF HEALTH AND HUMAN SERVICES, ACCOMPA-
NIED BY MARION FINKEL, M.D., DIRECTOR, OFFICE OF
ORPHAN PRODUCTS DEVELOPMENT, FOOD AND DRUG ADMIN-
ISTRATION; TOM SCARLETT, GENERAL COUNSEL
Dr. YOUNG. Thank you very much. It is, indeed, a pleasure and
an honor to be here today to discuss this program with you. I be-
lieve that the accomplishments have been great over the past 2
years, but as you pointedly reminded us, we cannot rest at this
point. There are substantial issues that must be faced and new dis-
eases that must be dealt with.
I am also very proud to have Dr. Finkel on the staff who has
done an exceptionally fine job not only in administering this pro-
gram, but in working with members of the academic and industrial
communities, as well as consumer and patient representatives, to
bring this program to fruition.
Perhaps I can best summarize in a short period of time by calling
our attention together to the chart that is over there. Basically, we
have attempted to outline for you the program, the dates that it
occurred, and the orphan designations; the sponsor commitments;
the drug device marketing applications; the exclusivity applications
approved; and the number of grant applications. The baseline is
the period from May 1982 to December 1982 where we are begin-
ning to get activities in place but do not yet have the act there. As
you can see, there is a progressive increase in the number of
orphan designations as time progresses.
Particularly important was the passage of the amendment, and
you can see, as in the prepared comments, that there was a
marked increase in the number of designations following the
amendment. That removed the sole responsibility to deal with fi-
PAGENO="0717"
711
nancial issues and enabled us to use a 200,000 patient population
as a criterion. The sponsor commitments have also continued to
grow over this period of time.
Looking at the next column, the drug and device marketing ap-
plications, you can see that we received a total of 13 and corrected
for 4 as shown in the footnote, as a function of time of submission.
And then we had a progressive increase in the number that had
been submitted.
Probably the most important figure for our attention is the
number of approved devices and drugs.
Moving from what was one to three approvals per year prior to
the enactment of the act, there has been a substantial increase
reaching a peak of seven in the last full year. And you can see the
one at the bottom refers only to the year to date.
Important in our total program is the ability to have grant appli-
cations. I should say, Mr. Chairman, that these grant applications
are somewhat different than the grant applications at the National
Institutes of Health. These are designed to take the identified
projects, as you pointed out in your opening statement, to do the
appropriate research, examinations and to then convert these into
orphan products.
During this period of time, we have been able to fund 19 grants.
This will be augmented substantially by an additional million dol-
lars that we received this year from one of the National Institutes
of Health, enabling us to go further with the research grant ap-
proach.
It is estimated that at least 50 percent of these grants will yield
products that can be brought to the marketplace under the Orphan
Drug Act. That's an extremely important conversion factor, and I
must emphasize that unlike the very important basic research pro-
grams that are sponsored by the National Institutes of Health,
these research programs are product-specific and designed to bring
products to the market. And as you will see from the material that
we submitted for the record, the vast majority of these are to uni-
versity faculty members who are doing fundamental and applied
investigations that are designed to bring these products further,
and eventually to bring them to the marketplace.
We feel that great diligence must be taken to be sure that the
act is not violated or misused. It is important to remember, in our
opinion, the very goal of this; to bring products that would not
heretofore be brought to the American public. And it is not de-
signed primarily to be profitable.
We have some concerns for which we would be delighted to
answer questions in regard to some of the patent provisions of the
act. There has been a much greater experience with patent exten-
sion over a period of time, and my testimony focuses on that.
If I could read my conclusion, Mr. Chairman, it might be helpful
for those that are listening to our testimony today.
It is evident, Mr. Chairman, that the Orphan Drug Act is serving
the purposes that you intended. We are gratified by the response of
the pharmaceutical industry, clinical investigators and the volun-
tary and professional organizations to the needs of patients with
rare diseases. Through such cooperation, we can predict continued
PAGENO="0718"
712
success in this field and thereby aid members of the American
public who have rare but significant disorders.
Particularly important is our research program that has stimu-
lated interest in this important class of drugs and devices. An ex-
ample of that comes to mind involving the drug mesna to prevent
severe inflammation and bleeding of the urinary bladder in pa-
tients receiving high doses of the anticancer drug, cyclophospha-
mide.
Although preclinical studies were performed by another drug
company, Adria Laboratories is now sponsoring clinical trials with
support from FDA under its grants program. Recently, the Nation-
al Cancer Institute has expressed interest in participating in the
development of the drug in order to facilitate its availability.
The bottom line is, of course, the number of orphan drugs that
have been marketed and are likely to be marketed in the next few
years. Prior to the act and our program, in most years about one to
three of the orphan drugs were approved for marketing annually.
In 1982, four drugs were so approved, and you can see the in-
crease that we have seen in that particular program.
In addition, in 1983, there were five drugs an4 one medical
device, and in 1984, seven drugs were approved including pentami-
dine for P. Carinii pneumonia, the most common cause of death in
patients with AIDS, and naltrexone for treatment of drug addic-
tion. We anticipate that the total yearly number will continue at
least at that level or rise as applications are received and approved
for the products that have already been adopted.
In addition, an increased focus on orphan drugs can be anticipat-
ed in view of the needs in the areas of cancer chemotherapy and
biotechnology. Thank you very much.
[The prepared statement of Dr. Young follows:]
PAGENO="0719"
713
STATEMENT
BY
FRANK E. YOUNG, M.D., Ph.D.
COMMISSIONER OF FOOD AND DRUGS
FOOD AND DRUG ADMINISTRATION
Mr. Chairman:
I am pleased to have been given an opportunity to appear before the
Subcommittee to describe the results of FDA' s Orphan Products
Development Program and the activities of the Department of Health and
Human Services' Orphan Products Board. With me today is Dr. Marion
Finkel, Director of Orphan Products Development at the Food and Drug
~drninistration.
When the former Assistant Secretary for Health, Dr. Edward Brandt,
appeared before the Subcommittee a year ago, he stated that the Orphan
Drug Act and the climate it created had stimulated the development and
marketing of orphan drugs by the pharmaceutical industry. At that
time, he indicated that the industry had cooperated fully by `adopting"
all the orphan products that were available for adoption, so to speak,
by virtue of conplete or nearly corrplete investigations. I am
delighted to say that this cooperation continues and that the interest
of drug and device manufacturers has out waned.
I will outline first what has been accortplished under each new section
of the law that was added by the Orphan Drug Act.
Section 525: Protocol Assistance
N~i section 525 of the Federal Food, Drug, and Cosmetic (FD&C) Act
states that a sponsor of an orphan drug may request written
recommendatior.~ for the ounclinical and clinical investigations that
PAGENO="0720"
714
stist be conducted with the arug before it can be approved for
marketing. We have received nine requests for protocol assistance.
This is a small n~nber in coitparison with the large n~ber of requests
received for orphan designation under section 526 but it is r~t
surprising in view of the effort that goes into preparing a request for
protocol assistance. In order to provide cur reviewing divisions with
the information they need to make a written recorrrnendation, a sponsor
nust suirrnarize all available pertinent information, provide the
clinical protocols it plans to use, state what it believes are
appropriate studies to be performed for market approval and formulate
specific questions it s~uld like FDA to address. Most sponsors prefer,
instead, to meet with FDA periodicalJ~y cm an informal basis to discuss
the corapleted researdi and their proposed plans for further study.
Nevertheless, this ssction of the Act is useful for those who prefer to
obtain a written recormut~ndation on the appropriateness of their
research plans.
Section 526: Orphan Drug Designation
New section 526 of the FD&C Act provides for the designation of drugs
as ormhans in order to render the~i eligible for the financial
incentives of the Act. FDA has granted 53 requests for orphan drug
PAGENO="0721"
715
designation since November 1983 when our designation guidelines were
made available to sponsors. Six requests have been disa~roved, either
because of an inadequate pharmacologic rationale or because the drug
was not considered to be an orphan.
The October 1984 amendment to the definition of an orphan drug had a
significant ii~act on receipt of requests and designations. The new
definition permits sponsors to aPply for designation without submitting
projected costs of development and distribution and projected return
from sales for drugs intended for patient populations in the U.S. of
feaer than 200,000 patients. In the 12 month period prior to the
aer~irent, 22 designation requests were granted. In the 4 1/2 month
period since the amendrr~nt 31 requests were granted. The vast majority
of designated drugs are intended for diseases with fewer than 50,000
patients in the TJ.S. I have supplied for the record a list of
designated orphan drugs.
Section 527: Exclusive Approval
N~q section 527 provides a seven year period of marketing exclusivity
for the first sponsor of an unpatentable orphan drug who receives
marketing approval from FDA. This section provides important
PAGENO="0722"
716
advantages over the exclusivity provisions of the Drug Price
Coispetition and Patent Term Restoration Act in that an additional t'~
years of marketing exclusivity is offered and protection is granted
against toth full and abbreviated new drug applications.
In the 5 1/2 months that we have been providing information to sponsors
on h~'i to submit a request for marketing exclusivity, we have received
17 requests and have granted 11 so far. These approvals are contingent
upon the sponsor's obtaining marketing approval and being the first to
do so. New drug applications have been approved for ts~v of these
products and their sponsors are cperating under the exclusivity
provisions of the Act.
Section 528: Open Protocols for Investigational Drugs
New section 528 encourageS sponsors of designated investigational
orphan drugs to make those drugs available f or treatment purposes while
the controlled trials needed for marketing approval are being
conducted. FDA's policy with respect to these `treatment
investigational new drug applications" (treatment IND's) is to permit
distribution of the orphan drug for treatment purposes after
preliminary evidence of safety and effectiveness for the intended use
has been accumulated; distribution can then be made to patients with
serious illness for whom other therapy is rot available or
appropriate.
PAGENO="0723"
717
Distribution of an orphan drug under section 528 is generally preceded
by a request from FDA to the drug's sponsor to establish a treatment
IND. ~en a corrpany agrees to distribute an orphan drug under
section 528, we publish a notice in the Federal Register and an article
in the FDA Drug Bulletin informing physicians about the availability of
the drug and h~z it nsy be cbtained. Additional avenues for informing
physicians are also being considered.
I'~ cospanies are distributing orphan drugs under our formal treatment
IND policy and another will do so later this year. ~any other
con~anies, h~ever, are already making their drugs available without a
request from us. In these cases, treatment INDs may be held by
independent investigators as well as by the drug sponsor. Of 28
additional drugs and medical devices on the sponsor coimnitment list,
which I shall describe in a norrent, 13 are or were being distributed by
drug corrpanies or by the Centers for Disease Control.
Section 227: Orphan Products Hoard
The Orphan Drug Act also added section 227 to the Public Health Service
Act which provides for the establishment of an Orphan Products Board
within the Department of Health and Human Services. The Board meets
approximately everj ts~o months. It has, in addition, held three public
meetings. The Board concerns itself with broad issues, such as
PAGENO="0724"
718
factors that might serve as disincentives to orphan drug development,
the extent to which orphans exist in the medical device area, and
methods for dissemination of available information on orphan diseases
and orphan drugs. The first annual report of the activities of the
Board, required under the Orphan Drug Act, was transmitted to the
Congress in October 1984 and the second report is in preparation.
~kfter holding a public hearing and considering written corstents, the
Board authorized the establishment of a new entity to provide
information to patients and their families, physicians, clinical
researchers, and the general public on rare diseases and the
availability of orphan drugs to diagnose or treat these diseases. The
National Information Center on Orphan Drugs and Rare Diseases was thus
established in September 1984 through a contract funded by FDA.
The existence of the Center was publicized by a press release and a
brochure distributed to voluntary rare disease associations. The
Center currently receives oore than 150 inquiries per rronth, primarily
from patients o~ the general public. An article intended for health
professionals that describes the Center will soon be published in the
FDA Drug riulletin. This should increase physician and clinical
investigator participation. The Center, in cuoperatiori with voluntary
rare disease associations, will prepare approximately 30-50 fact sheets
this year on specific diseases.
PAGENO="0725"
719
It also is preparing a directory of educational materials on orphan
drugs and rare diseases that are available from the voluntary rare
disease organizations.
Sponsor C~nitrnents
I ~uld like to describe briefly other activities FDA conducts under
its Orohan Products Develomiient Program.
Under cur program, we identify drugs, medical devices and medical foods
that appear to be useful for an uncormm~n or comim~n disease but that
have no coimnitted sponsor to -complete development and submit a
marketing application. Depending upon the circumatances, we seek
sponsors by several mechanisms: for examele, we publish notices in the
Federal Register and make presentations to the Corrninissicn on Drugs for
Rare Diseases of the Pharmaceutical Manufacturers Association or the
Institute of Orphan Drugs of the Generic Pharmaceutical Industry
Association.
Since May 1982, 31 orphan products have been adopted as a result of our
efforts to seek sponsors through these procedures. Three of these are
medical devices. Three adopted products have been approved for
PAGENO="0726"
720
marketing and marketing applications for 12 others are under review.
All products for which we have sought sponsors have teen adopted. I
have provided a list of the sponsor cormnitments for the record. Some
of the sponsors of these products have requested orphan designation.
During the past three years 66 distinct orphan products have been
adopted formally by the pharmaceutical and rredical device industries,
as manifested by beth the sponsor comaitrrents to marketing that we have
obtained and by the requests for orphan designation that have been
received. In addition, over 30 orphan drugs are being studied by drug
cortpanies independent of the Orphan Drug Act provisions.
Grant Awards
Under its appropriations, PDA received increases for orphan product
developrrent that resulted in distribution of $500,000 in F~ 83 and
$1 million in FY 84 for support of research on orphan drugs and madical
devices. These funds enabled us to support 19 grant aoolications. I
have provided a list of these applications for the record. FDA will
use $1.4 million of its appropriations for fiscal year 1985 to fund
orphan drug qrants; in addition, the National Institute of Child Health
and Human Development has transferred $1 million to us for this year
only to support research related to its mission. In addition, the
Pr's Budget for fiscal year 1986 includes $1 .5 million to
continue FDA' s reseach grants and contracts for orphan drugs.
PAGENO="0727"
721
Conclusion
In ~nclusion, Mr. Chairman, it is evident that the Orphan Drug Act is
serving the purpose that you intended. We are gratified by the
res~nse of the pharmaceutical industry, clinical investigators and the
voluntary and professional disease organizations to the needs of
patients with rare diseases. Through such rooperation we can predict
continued and sustained success in this field arid thereby aid meirhers
of the Amerian tublic who have rare bet significant disorders.
Particularly iirmortant is our research program that has stimulated
interest in this irrportant class of dtugs and devices. An exarple that
comes to mind involves a drug, Mesna, to prevent severe inflartri'ation
and bleeding of the urinary bladder in patients receiving high doses of
the anticancer drug, cyclophosphamide. Although preclinical studies
were performed by another drug corrpany, Adria Laboratories is ri~w
spDnsoring clinical trials with sup~rt from FDA under its grants
program. Recently, the National Cancer Institute has expressed
interest in participating in development of the drug in order to
facilitate its availability.
The bottom line is, of course, the number of orphan drugs that have
ceen marketed arid are likely to be marketed in the next few years.
Prior to the Act and our program, in most years about one to three
orphan drugs were approved for marketing annually. In 1982 four drugs
were approved; in 1983 there were five drugs and one medical device;
and in 1984 seven drugs were aoproved, including pentamidine for
P. Carinii pneumonia, the most ooirrron cause of death in patients with
AIDS, and Naltrexone for treatment of drug addiction. We anticipate
that the yearly total will continue at least at that level or rise as
applications are received and approved for the products that have
already been "adopted." In addition, an increased focus on orphan
drugs can be anticipated in view of needs in the areas of cancer
dierrotherapy and biotechnology.
PAGENO="0728"
722
Mr. WAXMAN. Thank you very much, Dr. Young, for your testi-
mony. Let me address a question to Dr. Finkel, if I might.
Did you have grant applications last year, and do you have grant
applications this year which are worthy of funding but cannot be
funded because you don't have enough funds?
Dr. FINKEL. Yes, Congressman Waxman. Each year we have a
few additional applications that are worthy of funding, and we hold
them over and use the funds from the next year. And we expect to
do the same this year.
Mr. WAXMAN. Would it be helpful if your grant awards could
cover the cost of preclinical animal studies? Under current law,
grants may only be made for human testing.
Dr. FINKEL. Well, under the FDA appropriations, there is no stip-
ulation that the testing must be only for clinical studies. We have
elected, because of the sum, to devote the money to clinical testing.
Mr. WAXMAN. So you don't feel that you need a change in order
to be involved in the preclinical part of the activities for the devel-
opment of orphan drugs?
Dr. FINKEL. No.
Mr. WAXMAN. Should the Orphan Drug Act be expanded to in-
clude medical devices?
Dr. YOUNG. We feel that the act already enables us to begin to
focus on a few medical devices. We feel that with increasing fre-
quency, particularly in the area of diagnostic kits, there will be a
need for devices. We would support such an action.
Mr. WAXMAN. Should they be eligible for grants for human test-
ing, and should they be eligible for the provision which grants 7
years of exclusive marketing rights for nonpatentable orphan
drugs?
Dr. YOUNG. We would prefer at this time to be as flexible as pos-
sible with regards to the designation. As Dr. Finkel said, we al-
ready have the ability to do both preclinical and human studies.
That flexibility is extremely helpful for us.
I believe the extension of patent exclusivity would also stimulate
support in this important area.
Mr. WAXMAN. Have there been any problems with the 7-year ex-
clusive marketing provisions for nonpatentable orphan drugs?
Dr. YOUNG. I would like Dr. Finkel to answer that, as she can
speak most clearly to this. And we do have some problems, as I
mentioned. Marion, would you comment, please?
Dr. FINKEL. The most common problem is the situation where
either an unmarketed product or a marketed product with a new
use has some type of patent. It might be a product patent or a proc-
ess patent. And at the time that the drug would be approved for
the new use, there might be 1 or 2 years remaining of that patent.
At that point, we could not grant 7 years' exclusivity since the
patent was in existence. And the firms have told us that without
those 7 years they would not go ahead.
On the other hand, it would be a detriment to the public if firms
waited until the patent expired before marketing the drug so they
could get the 7 years.
Another problem relates to the language of the act. It says that
exclusivity can be granted if a U.S. Letter of Patent cannot be
issued, but it doesn't say what kind of patent cannot be issued.
PAGENO="0729"
723
If the language said, "if a use patent cannot be issued," which is
the case in most of these situations, regardless of the fact that they
might have other patents, then most of our problem would be obvi-
ated.
Dr. YOUNG. Mr. Waxman, I do have Tom Scarlett, our general
counsel here. We have been looking into the question of that very
important point that Dr. Finkel raised in regards to the last few
years of a patent, and we would be interested in exploring this fur-
ther.
But perhaps Mr. Scarlett could provide some additional informa-
tion on that.
Mr. WAxMAN. Or perhaps we could suggest that Mr. Scarlett
work with our staff to see if we could come up with language to
resolve those difficulties. If you want to make any comments, we
welcome them.
Mr. ScA.iu~rr. We are looking into the question of whether the
language can be interpreted, if it cannot be, we will work with the
staff.
Mr. WAx~,tA.r~. Mr. Whittaker.
Mr. WHITTAKER. I have no questions.
Mr. WAxi~.N. Mr. Leland.
Mr. LELAND. Thank you, Mr. Chairman.
Dr. Young, I understand that the regulations that establish an
orphan drug tax credit still have not been issued by the Treasury
Department. At a press conference to announce the approval of the
drug, primozide, for Tourette's Syndrome on August 7, 1984, Secre-
tary Heckler said she would be in touch with Secretary Regan
about the tax credit regulations.
be? you know why they haven't been issued and when they will
Dr. YOUNG. The information that we have is that the Depart-
ment will be issuing them soon. We have our guidelines out that
complement those, and we hope within the not too distant future,
measured in days and weeks, not months and years, the tax credit
regulations will be forthcoming.
Mr. LELAND. It's also my understanding that the orphan drugs
which pharmaceutical companies have agreed to sponsor usually*
have complete or nearly complete human testing. Are companies as
willing to sponsor orphan drugs when very little testing has been
done, so that the company will be responsible for conducting the
necessary tests? if not, why not? And what should we do to get
greater cooperation?
Dr. YOUNG. We have, as shown over there, 54 designations. Ap-
proximately half of the designations come from major companies
that would be able to support such studies. To date, we have found
that there has been good cooperation through Dr. Finkel's office in
stimulating these events.
In each of the oversights, if. there is any flagging of this atten-
tion, I believe that further stimulation might be developed. But it
seems to be working quite well at this time.
Dr. Finkel, did you wish to add to that?
Dr. FINKEL. Of the 54 designations, about half of that research is
in the early stages, and there are both large companies and small
companies that are developing new orphans
PAGENO="0730"
724
Mr. LELAND. Do you think, Dr. Finkel or Dr. Young, that we will
soon find that the Government must fund the initial research
before pharmaceutical companies will get involved and sponsor a
drug?
Dr. YOUNG. It is a very important question of the total funding.
In the aggregate, in biomedical funding, approximately 85 percent
of the total research efforts throughout the Nation are supported
by the Federal Government. This primarily is related to basic re-
search, and the Congress has been very helpful in providing the
sustained support.
There are also, based on what we know from the National Insti-
tutes of Health, substantial support in various activities of orphan
drugs. The key issue will be what will happen in the future.
It appears at the moment that industry is putting substantially
increased dollars into research, particularly in the field of biotech-
nology and some of the device areas. If this trend continues and if
it can be stimulated through the good efforts of Dr. Finkel's office
calling attention to this, we may be able to get an ever-increasing
amount of funds developed for these projects.
We cannot let, though, research support flag; otherwise, we
would not bring these important medicines to the American people.
We intend to watch that very carefully.
Mr. LELAND. The National Information Center on Orphan Drugs
and Rare Diseases was set up to provide information to patients,
doctors, researchers, and the public about the availability of
orphan drugs and rare diseases. Dr. Finkel, it's my understanding
that the contract for the center was not done by competitive bids
and was awarded to a company which has not computerized the in-
formation.
Why did you select such a company, and does it duplicate what
the National Organization for Rare Disorders was already doing?
Dr. FINKEL. Well, this organization has already had a contract
with the Department of Health and Human Services to provide in-
formation on diseases, most of which have been common diseases.
And we thought they were very well set up to add the orphan dis-
eases to the program.
They are working very closely with the National Organization
for Rare Disorders to gather information from the organizations,
and also, to transmit queries back to the organizations.
Mr. LELAND. Well, what about the information being computer-
ized? The state-of-the-art should be in place, shouldn't it?
Dr. FINKEL. Eventually, yes. They are just really starting up, and
when they get everything together they will computerize it.
Mr. LELAND. Thank you, Mr. Chairman.
Mr. WAXMAN. Thank you, Mr. Leland. Mr. Nielson.
Mr. NIELSON. The only comment I would have is to congratulate
the chairman for his farsightedness in this particular area, and
also the FDA for doing as well as you have so far. I'm supportive of
the act and the efforts that the chairman has made in this respect.
Mr. WAXMAN. Thank you very much, Mr. Nielson. Mr. Sikorski,
any questions?
Mr. SIK0R5KI. No, sir.
Mr. WAXMAN. Well, Dr. Young, Dr. Finkel and Mr. Scarlett, we
thank you very much for your participation in this hearing. We are
PAGENO="0731"
725
going to work with you on these few issues that are outstanding
and stand shoulder to shoulder and continue our efforts.
Dr. YOUNG. Thank you very much, Mr. Chairman, we look for-
ward to that.
[Testimony resumes on p. 745.]
[The following letter was submitted for the record:]
PAGENO="0732"
726
DEPARTMENT OF HEALTH & HUMAN SERVICES Public Health Service
Food and Drug Administration
Rockville MD 20857
MAR 2 1 ~85
The Honorable Henry A. Waxman
Chairman, Subccxttstittee on Health
and the Environment
Committee on Energy and Commerce
House of Representatives
Washington, D.C. 20515
Dear Mr. Waxman:
The enclosed material is being submitted for the record of the hearing
conducted by the Subcommittee on Health and the Environment on
March 20, 1985 on the Orphan Drug Act:
(1) A list of orphan drug and biological product designations
through 1984;
(2) A list of sponsor commitments;
(3) A list of orphan drugs and devices approved from June 1982
through Decertber 1984;
(4) Ts~ lists of grant awards:
(a) September and November 1983, and
(b) September 1984;
(5) The Executive Summary of the Annual Report to Congress for
1983 of the Orphan Products Board;
(6) A chart shoaing the number of designations, sponsor
cctstiitments, marketing applications, marketing exclusivity
applications and funded grant applications in six nonth
increments from 1982 to the present.
In addition, s~ are submitting to the Subcommittee a list of
designations that also contains estimated patient po~a.ilations
considered to be confidential and not releasable to the ~itblic under
FDA's Freedom of Information regulations. We therefore request that
the Subccastitittee not release or otherwise make this document piblic
without first notifying the Agency.
Sincerely yours,
Henry H. Dausch
Director, Legislative Affairs Staff
Enclosures
PAGENO="0733"
Name of
Drug/Biological
Product
Generic-alpha-i-anti-
trypsin (recombinant
DNA origin)
Trade-not estabi ished
Generic-alpha-l-proteinase
T~Tbitor (Alpha-i PD)
Trade-not established
Generic-antimelanoma
i~T~ooy XllDIE-OO1-DTPA-
III IN
Trade-Same as generic
Generic-antimelanoma
9~fl8oy X1iiltiE-OOI-RTA
Trade-Same as generic
Generic-antithrombin III
ThrT!T)
Trade-ilot established
Sponsors Uarne
and Address
Cooper Biomedical, Inc.
3145 Porter Drive
Palo Alto, CA 94304
Cutter Laboratories
P.O. Box 1986
Berkelby, CA 94701
Xoma Corporation
3516 Sacramento Street
San Francisco, CA 94118
Xoma Corporaticn
3516 Sacramento Street
San Francisco, CA 94118
Cutter Laboratories
P.O. Box 1986
Berkeley, CA 94701
727
SUBMISSION FOR THE RECORD/ORPHAN DRUG HEARING 3/20/85
ORPHAN DRUG AND BIOLOGICAL PRODUCT DESIGNATIONS
THRU 1984
(Approved for ilarketing*)
(Exclusive Approval **)
BIOLOGICAL PRODUCT DESIGNATIONS
Proposed Use
Supplementation therapy for
alpha-i antitrypsin deficiency
in the ZZ phenotype population
Replacement therapy in the
Alpha 1 P1 congenital
deficiency state
Diagnostic use in
imaging systemic and nodal
melanoma metastasis
Treatmemt of Stage III mela-
noma not amenable to surgical.
resection.
For use as replacement therapy
in congenital deficiency cf
AT-Ill for prevention and
treatment of thrombosia and
pulmonary emboli
PAGENO="0734"
Name of
Drug/Biological
Product
Generic-amSaCrifle
`~~~msidyl
Generic-bacitracin, U.S.P.
T~not established
ORPHAN DRUG AND BIOLOGICAL PRODUCT DESIGNATIONS
THRU 1984
(Approved for ?lerketing*)
(Exclusive Approval **)
ORPHAN DRUG DESIGNATIONS
Proposed Use
Treatment of patients with
acute adult leukemia
Antibiotic-associated
pseudomembranous entero-
colitis caused by toxins
A and B elaborated by
Clostridium difficile
Sponsors Name
and Address
Warner-Lambert Co.
201 Tabor Road
Morris Plains, NJ 07950
A.L. Laboratories, Inc.
452 Hudson Terrace
P.O. Box 1021
Englewood Cliffs, 13 07632
Generic-chenodiol
~8~henix*/~
For patients with radiolucent
stones in well opacifying
gallbladders, in whom elective
surgery would be undertaken
except for the presence of
increased surgical risk due to
systemic disease or age.
Rowell Laboratories, Inc.
210 lain Street West
Baudette, linnesota 56623
Generic-clofaZimine
i~8-tamprene
Treatment of leprosy resistant
to Dapsone and the ENL and
lepra reaction
Pharmaceuticals Division
Ciba-Geigy Corporation
556 Morris Avenue
Summit, New Jersey 07901
~enerjc-cromolyn sodium
Tã~-~romoral
ilastocytosiS
Fisons Corporation
2 Preston Court
Bedford, lA 01730
Generic_Cyproterofle
acetate
Trade-Cyproteron
Gener ic-diaziquofle
Trade-not established
Treatment of severe hirsutism
Treatment of primary brain
malignancies (Grade III-IV
astrocytomas)
Berlex Laboratories, Inc.
110 East Hanover Avenue
Cedar Knolls, NJ 07927
Warner-Lambert Co.
201 Tabor Road
Morris Plains, NJ 07950
728
PAGENO="0735"
BIOLOGICAL PRODUCT DESIGUATIONS (Continued)
Proposed Use
Treatment of selected cases of
strabismus and blepharospasm
strabismus - 14,700 patients
blepharospasni - 1,500
Treatment of potentially life-
threatening digitalis intoxi-
cation in patients who are
refractory to management by
conventional therapy.
Amelioration of recurrent
attacks of acute intermittent
porphyria temporally related to
the menstrual cycle in
susceptible women and similar
symptoms which occur in other
patients with acute inter-
mittent porphyria, porphyria
variegata and hereditary
coproporphyria.
Sponsors Name
and Address
Alan B. Scott, 1.D.
2232 llebster Street
San Francisco, CA 94115
Burroughs-Wellcome Co.
3030 Cornwallis Road
Research Triangle Park
North Carolina 27709
Abbott Laboratories
Pharmaceutical Products
Division
North Chicago, IL 60054
729
Name of
Drug/Biological
Product
Generic-botulinum A toxin
1F9~9~culinun
Generic-digoxin-specific
9~Th~Iy fragments
Trade-Dig ib md
Generic-hemin
19~9~anhematin*
PAGENO="0736"
730
ORPHAH DRUG DESIGHATIOUS (Continued)
lame of
Drug/Biological
Product
Generic-epoproStenOl
~~6~cyclin, PGI2, PGX
Trade-Flol an
Generic-epoprostenol
Trade-Cycl o-Prostin
Gener ic-ethanolaroine
Trade-not established
Replacement of heparin in
certain patients requiring
hemodialysis
Replacement of heparin in
certain patients requiring
hemodialysis
Bleeding esophageal varices
Treatment of advanced adenocar-
cinoma of the ovary
Acceleration of corneal
epithelial regeneration and
healing of stromal incisions
from corneal transplant
surgery
Genetic carnitine deficiancy
Sponsors lane
and Address
Burroughs Weilcome Co.
3030 Cornwallis Road
Research Triangle Pork
lorth Carolina 27709
The Upjohn Co.
301 Henrietta Street
Kalamazoo, ill 49001
Glaxo, Inc.
P.O. Box 13960
Five bore Drive
Research Triangle Port
North Carolina 27709
Ivas Laboratories
685 Third Avenue
New York, bY 10017
Chiron Corporation
4560 Horton Street
Emeryville, CA 94603
American bcGaw
Division of Americsn -bos:~:a1
Supply Corporstion
2525 ilcGaw Avenue
Irvine, CA 92714
Sigma Tau, Inc.
723 North Beers Street
Holodel, Hew Jeroey 07733
Dolor Pharnscestical Cc,
130 Lincoln Street
Copiague, bY 11720
Proposed Use
Generic-hexamethYl-
~T5~ine
Trade-HexaStat
Generic-human epidermal
growth factor (urogastrone)
Trade-not established
Generic-L-carflitine
Trade-not established
Generic-L-Carnitine
TPD~8Hot establiuhed
Generic-L-5 Hydroxytryp-
Ri~(L-5HTP)
Trade-Not established
Primary and secondary
carnitine deficiency
of genetic origin
Treatment of postanoxic
intention nyoclonus
PAGENO="0737"
731
ORPHAN DRUG DESIGNATIONS (Continued)
Name of
Drug/Biological
Product
Generic-roonooctanoin
`a~TIoctan
Gener ic-PEG-adenosine
~iã~T~ise (PEG-ADA)
Trade-Imudon
Dissolution of cholesterol
gallstones rotained in the
cocoon bile duct
For use as enzyme replacement
therapy for ADA deficiency
in patients with severe
combined iromssodeficiency
(SCID)
Pneuviocystis carinii pneumonia
Pneumocystis carinii pneumonia
Prevention of calcium renal
stones in patients ~iith hypo-
citraturia and for the avoidance
of the complication of
calcium stone formation in
patients with urate lithissis.
For use in the prevention of
recurrence of pneumothorax in
patients at high risk of
recurrence, e.g., patients
with cystic fibrosis
Adjuvant to levodopa or lays-
dopa and carbidopa treatment
of selected cases of idiopathic
Parkinsons disease
(paralysis agituns),
postencephalitic parkinsonism,
and symptomatic parkinuonism.
Lypholled, Inc.
2020 Ruby Street
Melrose Park, IL 60150
Rhone-Poulenc, Inc.
52 Vanderbilt Ave.
New fork, NY 10017
Charles Y. C. Pak, 1.0.
The Univ. of Texas Health
Science Center at Dallas
5323 Harry Hines Blvd.
Dallas, Texas 75235
Lypholled, Inc.
2020 Ruby Street
llelrose Park, IL 50150
Farmacon, Inc.
P.O. Box 586
Westport, CT 06881
Proposed Use
Sponsors Name
and Addrenn
Ascot Pharmaceuticals Inc.
7701 11. Austin Avenue
Skokie, Illinois 60077
Enzon, Inc.
300C Corporate Court
South Plainfield, NJ 07080
Generic-pentamidine
TE~6Tonate**/*
Trade-Pentam 300
Generic-pentamidine
T88ElFTonate
rrade-not established
Generic-potassium citrate
T~DtTrocit
Generic-quinacrine HCI
`rFi~iNot established
Generic-selegiline HCI
ãRfleprenyl
52-266 0-85-24
PAGENO="0738"
732
ORPHAN DRUG DESIGNATIONS (Continued)
Name of
Drug/B iolog ical
Product
Generic-sodium rsonooercap-
toundecahydro-~i2.~-dOdeca-
borate
Trade-Borol ife
Treatment of glioblastoma
muitiforme as an alternative to
conventional photon therapy
Sponsors lame
and Address
Nuclear Medicine, Inc.
900 Atlantic Drive, IN.
Atlanta, GA 30332
Generic-spiramycin
Trade-Rovanyci ne
For use in the uymptsnatic
relief and parasitic cure of
chronic cryptosporidiouis in
patients with immunodeficiency
Rhone-Poulenc, Inc.
52 Vanderbilt Ave.
New York, flew York 10017
Generic-tenipouide (VM-26)
TFD8DiTot established
Treatment of refractory
childhood acute lympho-
cytic leukemia (ALL)
Bristol-Myers Co.
Pharmaceutical Research &
Developcient Division
P.O. Box 4755
Syracuse, MY 13221-4755
Generic-triethylene
~Th~aFochloride
Trade-Cuprid
Treatment of patients with
Wilson's disease who are
intolerant, or inadequately
responaive to, penicillamine
Merck Sharp and Dchoe
Research Laboratories
Division of Merck and Co.,
West Point, Pa 19486
Generic-viloxazine
hydrochloride
Trade-Viva lan
Treatment of narcolepsy and
cataplexy
Stuart Pharmaceuticals
Division of DCI Americas ~
Wilmington, Delaware 19097
Gener ic-13 1lmeta-
T~ooenzy1guanidine
Trade-Not establ ished
Generic-131 I-SB-iodornethyl-
T~i~Eholesterol
Trade-Not established
Diagnostic adjunct in
patients with
pheochrsrnocytcma
Adrenal cortical imaging
lillian 11. Beierwaltes, 1.7.
Physician-in-charge,
Nuclear Medicine,
University of Michigan
Medical Center
1405 E. Ann Street
Ann Arbor, Michigan ~6109
William H. Deierwaltes, M.D
Physician- in-charge
Nuclear Medicine
University of Michigan
Medical Center
1405 E. Ann Street
Ann Arbor, Michigan 48109
Generic-2 ,3-dimercaptosuc-
~ThT~7~cid (DMSA)
Trade-not established
Treatment of lead poisoning
in children
Johnson and Johnson
Baby Products Co.
Grandview Road
Skillman, law Jersey 08868
Proposed Use
PAGENO="0739"
Same of
Biological Product
Generic-Antithrombifl III
~~ç~n)
Trade-Anti thrombin
Generic-Erwinia
t~ã~ag i nasa
Trade-Sot established
Generic-Factor XIII
TFDX8Fibrogammin
Acute lymphoblastic
leukemia
Congenital Factor XIII
deficiency
Sponsors lame
and Address
Kabi Vitrum Inc.
600 Steamboat Road
Greenwich, CT 06830
Lypho fled, Inc.
2020 Ruby Street
lelrose Park, IL 60160
Hoechst-Roussel
Pharoaceuticals, Inc.
Route 202-206 lorth
Somerville, I.J. 08876
Generic-sheep antidigoxim
Trade-Digidota
Life-treatening acute cardiac
glycoside intoxication canifested
by conduction disorders, ectopic
ventricular activity and (in uomè
cases) hyperkalemia
Boehringer iannheim Corporation
1301 Piccard Drive
Rockville, Ilaryland 20850
733
ORPHAN BIOLOGICAL PRODUCT DESIGNATIONS
January 1, 1985 through Narch 15, 1985
(Approved for :larketiny*)
(Exclusive Approval **)
BIOLOGICAL PRODUCT DESIGNATIONS
Proposed Use
Hereditary AT-Ill deficiency
PAGENO="0740"
lame of Drug
Generic-antipyrine
iP569-not established
Gener ic-flumecinol
Trade-Zixoryn
Gener ic-glucocerebros idase/
8B6R~lucosidase (placenta-
derived)
Trade-not established
Generic-human epidercial
~F3~E, factor (urogastrone)
Trade-not established
Generic-human superoxide
3T68O6aue (hSOD)
Trade-not establ ished
Antipyrine test as an index
of hepatic drug-metabolizing
capacity
Hyperbi I irubinernia
in newborn infants
unresponsive to phototherapy
Replacement therapy in patients
with Gaucher's Disease Type I
Promotion of cutaneous
wound healing in extreme
burn treatment protocols
Protection of donor organ
tissue from damage or injury
mediated by oxygen-derived free
radicals that are generated
during the necessary periods of
ischemia (hypoxia, anoxia), and
especially reperfusion, associated
with the operative procedure
Treatment of heroin addicts
suitable for maintenance on
opiate agonists
Sponsor's Name
and Address
Upoher-Snith Laboratories, Inc
14905 23rd Avenue North
Minneapolis, MN 55441
Farmacon, Inc.
P.O. Box 536
Westport, CT 06381
Genzyme Corporation
75 Kneeland Street
Boston, MA 02111
Chiron Corporation
4560 Horton Street
Erneryville, CA 94608
Chiron Corporation
4560 Horton Street
Emeryville, CA 94608
Dixon and Williams
Pharmaceutical Cs, Inc.
43 Old (sod Road
Bernardsville, N.J. 07924
734
ORPHAN DRUG PRODUCT DESIGNATIONS
1985
(Approved for Marketing*)
(Exclusive Approval **)
ORPHAN DRUG DESIGNATIONS
Proposed line
Generic-l-al pha-acetyl-
i6~tlli08l (LAAM)
Trade-not established
PAGENO="0741"
735
ORPHAN DRUG DESIGNATIONS (Continued)
Prooosed Use
Sponsors Name
Name of Drug and Address
Generic-naltrexone HC1 Blockade of the pharmacological Du Punt Pharmaceuticals, Inc..
TBBTrexan effects of exogenously 1000 Stewart Avenue
administered opioids as an Garden City, New York 11530
adjunct to the maintenance of the
opioid-free state in detoxified
formerly opioid-dependent
individuals
Generic-oxymorphone For severe intractable pain Du Pont Pharmaceuticals, Inc.
~i~tency in narcotic-tolerant patiento P.O. Box 12
Trade-Dilaudid H.P. !anati, Puerto Rico 00701
Generic-physostigmine Friedreicho and other ONeal, Jones and Feldman
iBTTE~Tate inherited ataxias Pharmaceuticals
Trade-Antilirism 2510 Hetro Doslevard
lIaryland ieighto, 10 54043
Generic-sodium garna Narcolepsy and the auxiliary Sigma F end 0
~a~butyrate (GHB) symptoms of cataplexy, sleep Division, Ltd.
Trade-not established paralysis, hypnagogic Sigma Chemical Co.
hallucinations and automatic 3050 Spruce Street
behavior St Louis, 110 53103
Generic-thyrotropin- Amyotrophic lateral Abbott Laboratories
F5T~ing hormone (TRH) sclerosis (ALS) North Chicamo, CL 60054
Trade-not established
PAGENO="0742"
736
SUBMISSION FOR THE RECORD/ORPHAN DRUG HEARING 3/20/85
ORPHAN DRUGS AND DEVICES SPONSOR COMNITMENTS
DRUG SPONSOR DISEASE DATE OF COMMITMENT
Trien MSD Wilson's Disease October 1982
(triethylene
tetramifle
dihydrochloride)
NP-59 Mallinckrodt Adrenal Cortical June 1982
(6-beta-l9- Imaging (Presentation to PMA
iodonorcholesterol) Commission
Hematin Abbott Hepatic Porphyria May 1982; (licensed
July 1983)
Amiodarone Ives Cardiac Arrhythmias October 1982
Indium1~ Amersham Platelet Imaging December 1982
Oxine
Methacholine Cl Roche Diagnosis of March 1982
occult bronchial
asthma
Pimozide McNeil * Tourette's November 1982 (Approved
Syndrome for marketing July 1984)
Bacitracin A.L. Labora- Pseudomembranous August 1982
tories Enterocol itis
Hydroxy-Ethyl American WBC Harvesting August 1982
starch Critical Care
L-5 Hydroxy- Bolar Postanoxic June 1982
tryptophan Myoclonus
Vitamin E Roche Neuromuscular October 1982
Disorders secondary
to cholestatic
disease in Vitamin £
deficient patients
Pentamidine LyphoMed P. Carinli Approved for marketing
Pneumonia October 1984
L-Carnltlne McGaw Carnltine July 1982
Deficiency
Ethanolamine Glaxo, Inc. Bleeding December 1982
Oleate Esophageal Varices
PAGENO="0743"
i131_~i_
I odobenzyl-
guanidine
(I 13l-tIIBG)
Moctan
(monooctanoin)
Confidential
Citric acid,
gluconic acid,
magnesium hydroxy-
carbonate, mag-
nesium acid citrate,
calcium carbonate
solution
Furamide
(diloxide
furoate)
Mitronal
(cinnarlz me)
Confidential
Lamprene
(clofazimine)
Glycopyrrolate
Ismel in
(guaneth idine) IV
Quinacrine HC1
SPONSOR DISEASE
Confidential Certain patients
with Parkinson's
disease
Confidential Confidential
Confidential Confidential
Hall inckrodt Adrenal
medullary
imaging agent
Ascot Cholesterol
gallstone
dissolution
Confidential
Dissolution of
urinary tract
calculi and preven-
tion and treatment
of encrusted in-
dwelling urinary
tract catheters
Boots Pharma- Asymptomatic
ceuticals Inc. intestinal
amebiasis
G.D. Searle Hereditary
angloneurotic
edema
Confidential Pain
Ciba-Geigy Leprosy
A. H. Robins
Ciba-Geigy
LyphoMed
(Sterling Drug
will provide
Information
for product
development)
Upsher-Smith
Laboratories
Chelsea
Laboratories
Confidential
Tn Hawk Inter-
national Inc.
737
DRUG
Deprenyl
Confidential
Confidential
Confidential
Guardian
Chemical
DATE OF COMtIITtIENT
January 1983
January 1983
December 1982
March 1983
July 1983
September 1983
November 1983
January 1984
January 1984
January 1984
February 1984
March 1984
July 1984
September 1984
October 1984
Frey syndrome
Causalgia
Prevention of
recurrence of
pneumothorax in
patients at high
risk of recurrence
Use of oral anti-
pyrine in the
Antipyrine Test in
patients to monitor
the drug-metabolizing
capacity of the liver
Confidential
Selected cases of
corneal perforation
Antipyrine
Confidential
Histoacryl
January 1985
January 1985
PAGENO="0744"
738
SUBMISSION FOR THE RECORD/ORPHAN DRUG HEARING 3/20/85
ORPHAN DRUGS AND DEVICES APPROVED
JUNE 1982 - DEC. 1984
HEMATIN - ERYTHROPOIETIC PROTOPORPHYRIA
AFP DIAGNOSTIC KIT FOR TESTICULAR CARCINOMA
ORAP (PIMOZIDE) - TOURETTE~S DISORDER
GONADORELIN - DIAGNOSTIC FOR EVALUATION OF
HYPOTHALMIC-PITUITARY GONADOTROPIC FUNCTION
ACETOHYDROXAMIC ACID - FOR UREASE SPLITTING
URINARY TRACT INFECTIONS
HYDROMORPHONE HIGH POTENCY - CHRONIC PAIN
CHENODEOXYCHOLIC ACID - DISSOLUTION OF RADIOLUCENT
GALLSTONES IN POOR-SURGICAL-RISK PATIENTS
ETOPOSIDE - TESTICULAR CANCER
CYCLOSPORINE - IMMUNOSUPPRESSANT TO PREVENT
ORGAN TRANSPLANT REJECTION
DESMOPRESSIN - MODERATE HEMOPHILIA
SODIUM CELLULOSE PHOSPHATE - HYPERCALCIURIA
AND RECURRENT CALCIUM NEPHROLITHIASIS
PENTAMIDINE ISETHIONATE -
P. CARINII PNEUMONIA
NALTREXONE - NARCOTIC ADDICTION
MODRASTANE (TRILOSTANE) - GUSHING'S SYNDROME
PRISCOLINE (TOLAZOLINE HCL) - PERSISTENT
PULMONARY HYPERTENSION IN THE NEWBORN
PAGENO="0745"
739
SUBMISSION FOR THE RECORD/ORPHM DRUG HEARING 3/20/85
Grant Awards
Office of Orphan Products Development
Food and Drug Administration
September and November 1983
The amounts listed are for first year funding.
ROCKEFELLER UNIVERSITY (New York) - $112,109 - Dr. 0. Martin Carter
Phenytoin for Recessive Dystrophic Epidermolysis Bullosa
ROCKEFELLER UNIVERSITY (New York) - $60,575 - Dr. Charles Peterson
Evaluation of WR 2721 as Treatment for Cystinuria
UNIVERSITY OF MICHIGAN (Ann Arbor) - $65,952 - Dr. Jess Thoene
Pantethine Therapy of Nepropathic Cystinosis
UNIVERSITY OF ~1ICHIGAN (Ann Arbor) - $45,235 - Dr. Brahm Shapiro
131 I-MIBG: Evaluation of Efficacy in Diagnosis and Therapy
ADRIA LABORATORIES, INC. (Columbus, Ohio) - $50,362 - Dr. James Luce
Mesna to Prevent Cystitis from High Dose Cyclophosphamide
NYS PSYCHIATRIC INSTITUE (New York) - $92,000 - Dr. Joaquim Puig-Antich
Imipramine in Pre-Pubertal Major Depression
UNIVERSITY OF CALIFORNIA (Los Angeles) - $50,417 - Dr. Edward Ritvo
Safety & efficacy of Fenfluramine in Autism
MT. SINAI SCHOOL OF MEDICINE (New York) - $22,350 -. Dr. Melvin Van Woert
Therapeutic Trial of Harmaline in Cerebellar Disorders
UNIVERSITY OF IOWA (Iowa City) - $79,967 - Dr. Daniel Furst
Analysis of Controlled Trial of Chiorambucil vs Placebo in Progressive
Systemic Sclerosis
CHILDREN'S HOSPITAL RESEARCH FOUNDATION (Cincinnati, Ohio) - $50,625 -
Mrs. Helen Berry - VIL - A Hew Treatment for Phenylketonuria
CASE WESTERN RESERVE UNIVERSITY (Cleveland, Ohio) - $44,776 -
Dr. Gary Brittenham - Carbonyl Iron Therapy for Iron Deficiency Anemia
JOHN F. KENNEDY INSTITUTE (Baltimore, MD) - $54,555 - Dr. Julian Chisholm
Efficacy of DMPS in Therapy of Childhood Lead Poisoning
PAGENO="0746"
740
GRANT AWARDS
Office of Orphan Products Development
Food and Drug Administration
(September 1984)
CHILDREN'S HOSPITAL, Buffalo, New York, Clara Ambrus, M.D., Ph.D.
Use of Enzyme-Reactors for Management of Phenylketonuria
BOSTON UNIVERSITY, Boston, Massachusetts, Michael E. Osband, M.D.
Treatment of Histiocytosis-X with Suppressin A
THE WISTAR INSTITUTE, Philadelphia, Pennsylvania, Stanley A. Plotkln, M.D.
Live Attenuated Cytomegalovirus Vaccine in Patients Receiving Renal Transplants
BAYLOR COLLEGE OF PIEDICINE, Houston, Texas, Earl J. Brewer, M.D.
Methotrexate in Severe Juvenile Rheumatoid Arthritis
UNIVERSITY OF FLORIDA, Gainesville, Florida, William N. Williams, Ph.D.
Treating Palatal Insufficiency by Teflon
A. L. LABORATORIES, INC., Englewood Cliffs, New Jersey, Bernard B. Brown, Ph.D.
Bacitracin for Therapy of Pseudomembranous Colitis
JAYE-BOERN LABORATORIES, INC., Northbrook, Illinois, Joel E. Bernstein, M.D.
Topical Capsaicin Treatment of Post-Herpetic Neuralgia
PAGENO="0747"
741
SUBMISSION FOR THE RECORD/ORPHAN DRUG HEARING 3/20/85
I. EXECUTIVE SUMMARY
BACKGROUND
Orphan Drugs is the first annual report on the status of orphan drug
development as coordinated within the Department by the Orphan Products Board
(OPB). This report Is submitted by the Secretary of the Department of Health
and Human Services to the Committee on Labor and Human Resources of the Senate
and the Committee on Energy and Commerce of the House of Representatives,
pursuant to Section 227 of the Public Health Service Act. This report is due
on June 1, 1984. It was prepared at an estimated cost of ~75,SOO. It
presents the results of a survey of all Department activities with respect to
the development of orphan drugs.
As specified by statute, the report is organized around four major themes:
o ActIvities of the Orphan Products Board
o Orphan Product Development Activities of the Department
o Marketing Commitments by Sponsors of Orphan Drugs
o Rare Disease Research Activities of the Department
Fourteen tables and five appendices on orphan product research and development
activities are also presented.
FINDINGS
Orphan drugs are drugs or biological products for the diagnosis, treatment or
prevention of a rare disease or condition which occurs so infrequently in the
United States that there is no expectation that the cost of developing the
product and making it available in the United States will be recovered from
the sales of that product in the United States.
The Orphan Drug Act (Public Law 97-414) establIshed within the Department of
Health and Human Services (OHHS) the Orphan Products Board (OPB). The Orphan
Products Board is chaired by the Assistant Secretary for Health. It includes
members representing those agencies within the Depamtment which function to
develop, identify, approve, distribute, or provide reimBursement for drug
products. At the Board's regular meetings and the two public hearings, it
identified and developed positions on major policy issues that affect orphan
product availability. These areas of interest are presented below.
Product Liability Related to Orphan Products Development
Concern has been expressed that increased product liability costs would
prevent the development of orphan drugs. To explore this concern, the Orphan
Products Board conducted a brief survey of the Chief Zxecutive Officers or
Presidents of several Pharmaceutical Manufacturers Association (PHA) member
firms and the President of the Generic Pharmaceutical industry Association
(GPIA). The results of this survey indicated that most firms are not deterred
from developing and marketIng orphan drugs by liability considerations. Also,
firms that have marketed orphan drugs have had no increase in insurance costs
as a result of this activity.
The Bcard will continue to monltcr the ava:labillty of orphan urugs aid
determine if liability Is a major obstruction to the development of orpnan
drugs.
PAGENO="0748"
742
Orphan Drug Designation
FDA developed interim procedures to implement Section 526 of the Federal Food,
Drug and Cosmetic Act to designate drugs for rare diseases or conditions.
These interim procedures will help speed up the development of orphan products
by encouraging research activities with the availability of incentives after a
drug receives the orphan designation.
The requirements in a request for designation as an orphan drug include
information on the estimated costs for the development and distribution of the
drug as well as the expected sales in the U.S. This information is necessary
to Indicate there is no reasonable expectation that the total costs for drug
development and distribution will be recovered from sales of the drug.
Assistance to Soonsors on Orphan Drug Research Protocols
To assist In the development of research protocols and provide guidance to
these sponsors FDA developed interim procedures to implement Section 525 of
the Federal Food, Drug and Cosmetic Act. These procedures require FDA to
provide written reconmmendations for the pre-clinical and clinical
investigations that are required prior to marketing approval to those sponsors
of drugs who submit a request for assistance in the design of the study
protocol.
Information Center for Rare Diseases and Orphan Dr'~gp
The possibility of developing an improved mechanism for disseminating
informatibn about orphan drugs and rare diseases or conditions to patients,
physicians and voluntary patient associ~tions was discussed at the first
publlc.meeting of the OPB. A public meeting was held in December, 1983 to
discuss this in greater detail. Participants at the public meeting were asked
to identify information gaps in the area of orphan drugs or rare diseases ano
possible sources of information for patients and their families, physisiars,
or researchers. Existing clearinghouses, information centers and voluntary
associations discussed their activities with respect t3 the transfer of
information to requestors. The Board continues to work on this issue.
CHHS ORPHAN PRODUCTS DEVELOPMENT ACTIVITIES
Introduction
The 0P8 conducted a survey of the 12 research Institutes and Divisions that
comprise NIH, the three ADA~fl~A Institutes, FDA, CCC, and HCFA to determine the
extent of research activities with respect to orphan drugs.
Ten Federal agencies reported direct involvement in research and/cr
distribution activities to increase the availability of over 80 products. The
FDA reported that aoproximately 300 products are currently under study, either
within the Federal government or in the private sector. Sixty percent of
these drugs are available to patient populations through treatment and
compassionate Investigational New Drug (IND5) exemptions. The drugs represent
treatments for a broad range of rare conditions, including neurologic,
hematologic, metabolic and oncologic disorders, as well as infectious diseases.
PAGENO="0749"
743
Some important indicators of specific orphan drug development efforts among
the surveyed organizations follow:
o Nine organizations and CCC are involved to varying degrees in the
development of orphan products. In addition CDC and Nd selectively
distribute several of these drugs, and FDA performs a monitoring
role. Twenty-one products are available to physicians and patients
through treatment INDs.
o Eleven NIH Institutes have issued an omnibus grant announcement
- requesting for ap~plications to conduct research projects on orphan
products;
o Ten organizations have funded research projects for orphan drugs;
while some products required no Federal funding, the expenditures for
others have ranged as high as 3 million dollars;
o Six organizations engaged in activities to seek sponsors for the
development and/or marketing of orphan products; and
o Six organizations currently pursue and/or plan future intramural
research activities to support the development of orphan products.
ORPHAN DRUG DEVELOPMENT AND MARKET!NG COMMITMENTS BY SPONSORS OF ORPHAN CRUGS
Many orphan drugs are without a commercial sponsor to guarantee the continued
availability of the product to the general public or clinicians involved in
the treatment of a rare disease or condition. The Act provides incentives
such as tax credits for expenses incurred by required clinical studies,
exclusive marketing privileges and assistance in developing a protocol for the
study of a particular product. In spite of inducements made available by the
Act, many products remain unavailable.
Sponsor commitments are obtained in several ways. Most are the result of a
direct approach by means of invitations for sponsorship published in the
Federal Register, or requests to firms that are making a drug available under
a compassionate IND or that have specific expertise in the manufacture of a
certain type of product. The remainder are obtained by working with the PMAs
Commission on Drugs for Rare Diseases or S?!As Institute- for Orphan Drugs.
Twenty-one products received commitments in l983 from sponsors to pursue
further investigations prior to submitting a New Drug Application.
The work on orphan drugs in the private sector has been augmented by the
efforts of the PMA Commission on Drugs for Rare Diseases and the G?IA
Institute for Orphan Drugs. Each of these associations has workeo with
ADAIO-iA, CCC, FDA, and NIH to identify potential treatments for rare diseases
and then to Identify sponsors of these drugs, thus allowing the treatments to
become more readily available to the patient popula~ions.
RARE DISEASE RESEARCH ACTIVITIES OF THE DEPARTMENT
The Act directs the Secretary to make grants to and enter into contracts with
public and private entities mo individuals to assist ~n r~ducirg the cc~ts of
clinical testing expenses incurred in the development of drugs for rare
PAGENO="0750"
SUBMISSION FOR THE RECORD/ORPHAN DRUG HEARING 3/20/85
ORPHAN DRUGS AND MEDICAL DEVICES
Drug and Device Exclusivity Grant
Orphan Sponsor Marketing Applications Approval Applications
Program Designations Coniuitments Submitted Approved Applications Funded
5/82 - 12/82 0 14 (13)4* 2 0 0
Orphan
Drug Act 1/83 - 6/83 0 3 5 2 0 0
7/83 - 12/83 1 3 5 5 0 12
1/84 - 6/84 16 5 3 2 1 0
Act
Amended 7/84 - 12/84 23 3 6 5 6 7
1/85 - Present 15 3 2 1 10 0
* 4 submitted between 5/82 - 12/82
9 submitted before 5/82
PAGENO="0751"
745
Mr. WAXMAN. I would like to now call forward Dr. Jess G.
Thoene, president-elect, National Organization for Rare Disorders,
who will be accompanied by Abbey S. Meyers, chairperson, Govern-
ment-Industry liaison committee, National Organization for Rare
Disorders, director, Family and Professional Services, Tourette Syn-
drome Association; and Dr. Dilip P. Shah, vice president, regula-
tory affairs, LyphoMed, and Mr. William Baird, president of the
American Narcolepsy Association.
I want to welcome you to our subcommittee hearing today and
tell you that your prepared statements will be made a part of the
record in full.
We would like to ask you to summarize those statements in
around 5 minutes if you could possibly do it.
Dr. Thoene.
STATEMENTS OF JESS G. THOENE, M.D., PRESIDENT-ELECT, NA-
TIONAL ORGANIZATION FOR RARE DISORDERS, ACCOMPANIED
BY ABBEY S. MEYERS, CHAIRPERSON, GOVERNMENT-INDUS-
TRY LIAISON COMMITTEE, DIRECTOR, FAMILY AND PROFES-
SIONAL SERVICES, TOUREVfE SYNDROME ASSOCIATION; DILIP
0. SHAH, PH.D., VICE PRESIDENT, REGULATORY AFFAIRS,
LYPHOMED, INC.; AND WILLIAM BAIRD, PRESIDENT, AMERI-
CAN NARCOLEPSY ASSOCIATION
Dr. THOENE. Thank you, Mr. Chairman, and my thanks to the
members of this committee for giving us this additional opportuni-
ty to address you on this important issue.
As you know, the Orphan Drug Act has been a vital first step in
the struggle to provide the fruits of the American biomedical-indus-
trial complex to sufferers of rare disorders. The committee knows
that until the institution of this act, there was little interest on the
part of industry in developing treatment for these diseases.
Since passage of the act, the Office of Orphan Products Develop-
ment of the Food and Drug Administration has made a number of
research grants to investigators attempting to develop treatment
for rare diseases.
We are delighted with this first step and pleased with the results
of some of these investigations which have led to the availability of
treatment for rare disorders which otherwise have no hope of ame-
lioration.
It is essential, therefore, that the act be reauthorized and that
continuing research funds be made available for preclinical trials
and clinical investigations in the treatment of rare disorders.
In responding to the conversation just a moment ago, these funds
are essential, in my view, because without them the data necessary
to generate interest on the part of industry for the development of
treatment for rare disorders will not be available.
The National Organization of Rare Disorders therefore requests
that the $4 million appropriation for the Orphan Drug Act be reau-
thorized but with the following change: that funding for Orphan
Drug research grants should be appropriated by the Agricultural
Subcommittee directly to the Food and Drug Administration's
Office of Orphan Products Development.
PAGENO="0752"
746
This is because the Orphan Products Board is not funded by any
congressional committee, and during the past 3 years, funding for
orphan drug research grants has been appropriated through the
House Agricultural Subcommittee. This resulted in some confusion
and dilution of funding efforts.
In 1985, as was noted, an additional $1 million was appropriated
through the National Institute of Child Health and Human Devel-
opment and then transferred to FDA's Office for Orphan Products
Development.
Language in the reauthorization should restrict the use of the
funds to extramural research grants, and the money should not be
used for FDA's intramural research, administrative costs, or other
ongoing projects.
Insofar as it is possible in these times of domestic budgetary re-
striction, the National Organization of Rare Disorders would like to
emphasize that this $4 million appropriation for rare disorder re-
search should not be obtained at the expense of funding for the Na-
tional Institutes of Health.
I echo Dr. Young's statement. The National Organization of Rare
Disorders recognizes the essential nature of the infrastructure pro-
vided by basic research funded by the National Institutes of
Health. To subtract moneys from these vital research efforts to
fund the Orphan Drug Program would only rob Peter to pay Paul.
Our feeling is the entire research enterprise must go forward with
augmented funding.
The National Organization of Rare Disorders notes that under
current regulations, during the time a drug is approved for market-
ing but not actually released to the market, the drug may not be
distributed to consumers. We believe that the act should allow for
drug companies to continue distribution of an orphan drug which
was under IND status during the transition between approval for
marketing and actual licensing.
In some cases this period can last between 6 months to a year.
We feel it unconscionable to allow patients with rare disorders to
suffer for lack of a drug they were previously receiving just be-
cause of the way a regulation is written.
The National Organization of Rare Disorders also supports inclu-
sion of medical devices within the purview of the act insofar as
these devices will truly benefit persons with orphan conditions.
We believe that the 7-year exclusive marketing rights provision
of the act is essential to encourage corporations to undertake
orphan drug development. However, we also feel some abuse of this
exclusive marketing period may occur, conceivably, if a company
holding a patent for a given agent continually pursues, under pro-
visions of the act, a marketing application for an orphan indica-
tion.
Serial repetition could provide an unfair advantage to the patent
holder for an indefinite amount of time. We suggest a limit of no
more than 1 year during which the Secretary cannot issue approv-
al for a generic form of the drug.
Finally, the NORD is concerned that the Department of the
Treasury be directed to publish tax incentive regulations of the act
within 6 months of enactment. Both patients with rare disorders
and those of us in this field of research are heartened by the con-
PAGENO="0753"
747
tinued interest of this committee-and I mean that sincerely-and
we hope that the recommendations made today will further en-
hance the prospects of sufferers of rare disorders to obtain treat-
ment.
Thank you.
Mr. WAXMAN. Thank you very much.
Dr. Shah.
STATEMENT OF DILIP P. SHAH, PH.D.
Mr. SHAH. Thank you, Mr. Chairman and members of the sub-
committee.
I am indeed honored today to have this opportunity to share with
the committee a view of the Orphan Drug Program from the per-
spective of the small pharmaceutical company.
I would like to use my allotted time today to mention briefly Ly-
phoMed's experience with orphan drugs and also to focus on specif-
ic suggestions which I feel would serve to advance this worthwhile
program.
LyphoMed, Inc., is headquartered in a suburb 25 miles outside of
Chicago and employs approximately 420 persons. Sales for fiscal
year 1984 have reached $31.4 million. We are a leading producer
and distributor of critical care micronutrients in small volume par-
enteral dosage form.
These micronutrients consist of a wide range of multivitamins,
trace elements and electrolytes. In addition, we manufacture anti-
biotics, anticoagulants, diuretics, steroids and hormones. In the
near future, we will enter the anticancer market, which will serve
to strengthen our leadership position in the area of critical care
parenteral drugs.
In 1983 the Centers for Disease Control, CDC, approached several
pharmaceutical companies, including LyphoMed, with the purpose
of securing a manufacturer for the drug Pentamidine Isethionate.
This product is used in the treatment of an often fatal pneumonia
in patients with suppressed immune system, including those with
acquired immune deficiency syndrome, commonly known as AIDS.
Due to the dramatic increase in the number of requests for Pent-
amidine and the uncertain availability of the overseas supply, the
CDC found it necessary to recruit a domestic manufacturer. In
view of LyphoMed's commitment to and concern for the specialized
needs of the critically ill, we agreed to produce and distribute the
drug.
Since there are less than 7,000 AIDS patients in the country, a
fact that would make commercial success unattainable, we sought
and received orphan drug status for Pentamidine. A decision was
then made to file a new drug application with the FDA.
Within a remarkably short time of 6 months, the drug was ap-
proved. Along with that approval, I am very proud to say, the first
7-year manufacturing and marketing exclusivity for an orphan
drug was granted to our product, Pentam 300.
Presently we are the sole supplier of this critical drug to virtual-
ly every major medical institution in the country. A 24-hour hot-
line has been instituted to ensure product distribution within a
matter of hours. The hotline is also an effective channel of commu-
PAGENO="0754"
748
nication for disseminating clinical and technical information to the
health care professional.
Pentam 300 can, no doubt, be called an orphan drug success
story. Through the combined efforts of the CDC, various divisions
of the FDA, and especially the Orphan Drug Division of Dr. Finkel,
and LyphoMed, the ultimate goal of providing a life-saving drug to
AIDS victims was accomplished.
From our vantage point, both agencies offered invaluable support
and guidance throughout this project, and for that, we at Ly-
phoMed are most grateful. Our positive experience with Pentam
300 has served to reinforce the company's commitment to the
Orphan Drug Program.
Within the last 5 months, LyphoMed has filed and received
orphan drug designations for two more drugs, and several others
are now being considered as possible candidates.
As LyphoMed becomes more involved with the activities of the
program, we have perceived that certain improvements can be
made in order to assist those already involved in the program and,
at the same time, help in attracting additional participants.
These suggestions are as follows: One, increase the amount of
funding to support clinical trials regarding safety and efficacy of
orphan products. To obtain a new drug approval for our orphan
drug quinacrine hydrochloride, LyphoMed will need to finance clin-
ical studies.
Although expected sales of the drug over a 7-year period would
total $350,000, the cost for the required studies alone would
amount to well over half a million dollars. To a company of our
size, the loss of revenue from such an undertaking is difficult to
justify.
Presently the maximum amount of funds through the grant pro-
gram for the purpose of clinical investigation is $70,000 per year
per grant. An increase in available moneys would serve a dual pur-
pose. First, it would help offset the high cost of the required safety
and efficacy studies, and second, help to encourage additional par-
ticipation from small pharmaceutical companies like ours.
Second, once orphan drug status is granted, certain funds could
be earmarked for clinical studies for the specific drug. In this way,
availability of funds to finance the study would be guaranteed. This
would make disbanding of a study due to lack of funds less likely.
Perhaps a matching fund program would be one means of provid-
ing this type of specific funding.
Third, the greatest obstacle we encountered recently with the
Orphan Drug Program was finding researèhers who were interest-
ed and qualified to undertake clinical studies. After numerous
phone calls, false leads and negative responses, sponsorship was
eventually acquired.
We suggest that, along with publication of the list of orphan
product designation in the Federal Register, an invitation for par-
ticipation in specific clinical studies be extended. In this manner,
interested parties would have the opportunity to contact the spon-
sor directly, serving to expedite the entire process.
LyphoMed has been given this opportunity to make a significant
contribution to the area of critical care medicine. Without the vari-
ous incentives offered through the program, a company of our size
PAGENO="0755"
749
would not have been able to develop and make available a life-ex-
tending drug such as Pentam 300.
We are most eager to continue our involvement in the develop-
ment of orphan products, and therefore, we wholeheartedly support
reauthorization of the Orphan Drug Program.
Thank you.
Mr. WAXMAN. Thank you very much, Dr. Shah.
Mr. Baird.
STATEMENT OF WILLIAM BAIRD
Mr. BAIRD. I would like to give you a demonstration of your suc-
cess. There was a police officer, a motorcycle cop, going down the
highway, and he spied a woman driving a station wagon. Believe
me, this is relevant to why I am here. In the back of the station
wagon were a bunch of penguins, so he pulled the station wagon
over and he said to the lady, "What's with all the penguins?"
She says, "Nothing, officer. I'm just out for a drive."
He says, "This is not the thing you should be doing with pen-
guins. Now, going down the highway here, there is a zoo. I want
you to take the penguins to the zoo."
So she went off and he went off, and the next day he is going
down the highway and he spies the same station wagon, and in the
back, a bunch of penguins, and they are all wearing sunglasses.
So he pulls her over, and he said, "Lady, I thought I told you to
take those penguins to the zoo."
And she said, "I did, and they enjoyed it so much, today we are
going to go to the beach."
I have told that so many times that by now, I am feeling like
everyone in the world must have heard that joke, but a year ago I
couldn't have told it. Just thinking about telling it to someone
would have triggered a cataplectic attack because I have narcolep-
sy.
That cataplectic attack would have caused my eyes to be a little
difficult to focus. My muscles would have been hard to maintain. I
would have sort of slumped down slowly until I actually slid off the
chair onto the floor, and as long as I continued to think about
trying to tell that joke, as long as I still had that emotional feeling,
I would be awake but unable to move, unable to control my mus-
cles.
Now, as part of a drug being tested because of the orphan drug
legislation, I can do that. I can have those emotions. I can experi-
ence humor, laughter, joy, anger, elation, all the things that we
value most highly because they make life really why life is worth
living because of its emotional content.
At this point, we still need well-controlled clinical trials, I under-
stand, to demonstrate the effectiveness of this particular medica-
tion, and I understand that. For me, I don't need any proof. I just
don't fall down. I tell jokes and I am still standing. I know that it
works for me.
But I recognize that you can't do things that way. The áontinu-
ation of the orphan drug legislation and the continuation of fund-
ing, though, becomes ever more vital and important to me and to
the hundreds of people that I know.
PAGENO="0756"
750
I am president of the American Narcolepsy Association, I get to
write in our newsletter, and I get to do newspaper interviews. I got
to be on 60 Minutes. For 60 Minutes, I just fell down to show them
what happens, and they thought I did well enough so they let me
talk on Nightline.
But I am afraid to mention that I've got a medication that's
doing well because of what it would do to the expectations of all
those people who have narcolepsy and have suffered the symptom
of cataplexy. Just to tell them that there's something that's work-
ing for me and that it might not be made available to them would
be a very cruel thing to do.
I have talked to people in Canada who have used it. They have
said great things about it. I have talked to other people in the
United States. I mean, this really looks like it's going to be some-
thing special. But then, of course, not all jokes are equally funny.
And the setting here today might have been such that I would
have been too tense to really enjoy telling the joke.
So maybe it's a bit misleading to say that I couldn't have told it.
It might have gotten me by here, but I couldn't have told it with
the confidence that I can get through the entire joke, and hit the
punch line and not hit the floor.
So from a very personal standpoint, and for the thousands of
people who suffer from this, the continuation of the program and
continuation of the funding is absolutely vital. And I think it
would be tragic if we didn't look at the success that we have al-
ready had and attempt to build upon that, and the potential for the
future.
Mr. WAXMAN. Thank you very much, Mr. Baird. Your testimony
and your story is very heartening, and I want to thank you very
much for it.
I think also, Dr. Thoene and Dr. Shah, let me ask the four of you
this question. Do we have sufficient funds for grants? If not, do you
know what types of applications are not being funded?
Ms. MEYERS. Yes; the $4 million appropriation was never fully
appropriated. In the first year or two, we had less than $1 million,
and this year there will be more money because of the National In-
stitute of Child Health and Human Development which is transfer-
ring $1 million to FDA.
We know that every year Dr. Finkel gets a substantial number of
research proposals and she can only fund a small amount. And in
the 3 years since the Orphan Drug Act became law, I believe ac-
cording to that chart, only 19 grants have been funded so far.
Dr. Finkel told me that she felt that 18 of those grants would
lead to the approval of new drugs, and that's really quite a mark.
But of course, more money is needed, and some of these studies
like the narcolepsy drug, if there was more money the two con-
trolled studies could have been funded this year, and maybe 2 or 3
years from now the drug would be approved. But with only one
study funded, we have to wait another few years to start the
second controlled study.
Mr. WAXMAN. Should FDA have the discretion to award funds
for animal studies in addition to its current authority to fund
human testing?
PAGENO="0757"
751
Ms. MEYERS. I think the basic need right now has been in the
clinical studies because so many orphan drugs are out there and
we had substantial evidence that they would be safe and effective.
But in future years, the toxicology and the animal studies will be
absolutely essential for the drugs which are not yet fully developed.
So we have really been touching the top of the iceberg, and in
order to get further down on the iceberg we need money for pre-
clinical testing.
Mr. WAXMAN. Should the act be expanded to cover medical de-
vices? Members of the panel, anybody who wants to respond.
Ms. MEYERS. Yes; I would like to respond. FDA has done some-
thing with two or three devices without statutory authority to do
so, and we are absolutely delighted that they have. But I think to
clarify, in the future, since the act is up for reauthorization, de-
vices should definitely be added to the act so there is no question in
the future. And of course, they should be eligible for the clinical
research grants.
Mr. WAXMAN. Mr. Whittaker, any questions?
Mr. WHIrFAKER. No questions.
Mr. WAXMAN. Mr. Leland.
Mr. LELAND. Thank you, Mr. Chairman.
Dr. Shah, are these incentives in the Orphan Drug Act sufficient
to tempt companies to sponsor orphan drugs?
Mr. SHAH. That definitely helps to make a decision to take the
project.
Mr. LELAND. Let me ask all of you, would you comment on the
capabilities of the National Information Center on Orphan Drugs
and Rare Diseases?
Ms. MEYERS. Well, we are absolutely delighted that this clearing-
house was funded by the Government because certainly, the worst
problem with~ having a rare disease is that you can't get any infor-
mation about it. And even your doctor tells you that he doesn't
know much about it. So it's important to have some central area to
do this.
Of course, NORD is a voluntary agency and has been doing this,
and we saw how it is agonizingly slow to get information. Some-
times it takes 2 or 3 weeks to find information about a disease.
We were hoping when the clearinghouse was funded that it
would be computerized so that it could be speeded up, and we could
not only find information on the disease but where the current re-
search projects are being conducted. And we were quite disappoint-
ed in the way the project was awarded. There was no competition
for the contract. And we knew at least two universities and one
corporation that would have applied for it.
And I'm sure that if there was competition, probably a better
clearinghouse would have been set up. But we have no complaints
about the current clearinghouse right now. We just feel that it
could have been computerized.
Mr. LELAND. Anybody else?
Mr. SHAH. As I mentioned in the testimony, we had a difficult
time finding the clinical researchers for the quinacrine hydrochlo-
ride. Some kind of funding should be available to centralize the
data and really be available, which would help expedite the proc-
ess.
PAGENO="0758"
752
Mr. BAIRD. We have been receiving the transmittal of requests,
and we answer as quickly as we can but it does take some time.
But I had been surprised at the number that we have suddenly
been getting on their forms.
Mr. LELAND. Very good. Thank you. Thank you, Mr. Chairman.
Mr. WAXMAN. Thank you, Mr. Leland.
Mr. Nielson.
Mr. NIELSON. No questions.
Mr. WAXMAN. Well, let me thank the members of this panel very
much for your testimony, and we look forward to working with you
on the reauthorization of this legislation.
I would like to now call forward Dr. John Simon representing
the American Academy of Ophthalmology and assistant professor,
ophthalmology and pediatrics, Albany Medical College of Union
University, Albany, NY; and Larry Martin, president, Florida Med-
ical Device Association, general counsel, Neuromed, Inc., Fort Lau-
derdale, FL.
STATEMENTS OF JOHN W. SIMON, M.D., ON BEHALF OF AMERI-
CAN ACADEMY OF OPHTHALMOLOGY; AND LARRY H. MARTIN,
PRESIDENT, FLORIDA MEDICAL DEVICE ASSOCIATION, AND
GENERAL COUNSEL, NEUROMED, INC.
Dr. SIMoN. Good morning, Chairman Waxman and members of
the subcommittee. My name is John W. Simon, M.D. I am assistant
professor of ophthalmology and pediatrics at the Albany Medical
College in Albany, NY. I am pleased to present the views of the
American Academy of Ophthalmology regarding the need to
amend the Orphan Drug Act of 1983.
Let me summarize a few key elements of my written testimony,
which I believe you have. The American Academy of Ophthalmolo-
gy is the largest national professional society of medical doctors
specializing in medical and surgical care of the eyes. Our 13,500
members include not only the vast majority of all board-certified
ophthalmologists in this country, but also a significant proportion
of the leading researchers in virtually every subspecialty of eye re-
search and eye care.
The academy has worked closely with the Office of Orphan Prod-
ucts in the Food and Drug Administration to designate and obtain
sponsorship for a number of ophthalmic products which meet
orphan product criteria under the act. Most of these ophthalmic
products are classified as devices.
Because of this classification, these products do not enjoy the
ease of orphan product designation or the incentives for sponsor-
ship accorded drugs under the act. These two factors have ham-
pered the approval process and have evoked considerable frustra-
tion, some examples of which I will describe. We hope that the
Congress will be able to address this inequity.
Cyanoacrylate is one such ophthalmic device. The academy has
issued a policy on cyanoacrylate tissue adhesive which is attached
to my statement. Briefly, cyanoacrylate tissue adhesives appear to
be a useful, safe method of treatment of corneal perforations and
impending perforations, common complications of injuries and in-
fections.
PAGENO="0759"
753
These require immediate treatment to preserve sight. The use of
cyanoacrylate provides a safer alternative to standard surgical
treatments. Application of the tissue adhesive results in closure of
the perforation site and reformation of the anterior chamber. The
Academy has recommended that this product be made available
under the Orphan Drug Act because a true medical need exists for
this product for a very limited number of patients. The develop-
ment of this product will require considerable cost, and the antici-
pated profit will be small.
Under present provisions of the Orphan Drug Act, efforts to clas-
sify this ophthalmic device as an orphan product have been bur-
densome. Last year, Congress amended the Orphan Drug Act to es-
tablish a presumption that drugs intended for diseases or condi-
tions with a prevalence of less than 200,000 patients in the United
States are orphans. Unfortunately, because devices were not in-
cluded under this amendment, designation of orphan status re-
mains cumbersome and time consuming. In addition, sponsorship
for devices remains difficult to obtain.
I would like now to relate my own personal and professional ex-
perience with another ophthalmic orphan device: A specific kind of
contact lens designed for children. I am a pediatric ophthalmol-
ogist. That means that I care for the medical and surgical condi-
tions affecting infants and children.
As a pediatric ophthalmologist, I have a special interest in child-
hood cataracts. Now, cataracts are a condition that most of us are
attuned to thinking occur only in old people, but in fact, they rep-
resent the most common treatable cause of childhood blindness.
Fortunately, they remain uncommon with an incidence of approxi-
mately 3 in 10,000 births, accounting for perhaps 1,200 new cases
each year in the United States.
We have made impressive surgical advances during the past 10
years, but it is important to realize that refractive correction is es-
sential if these babies are going to be able to obtain and maintain
clear vision. Unfortunately, there have been insurmountable prob-
lems with most available types of optical correction, including
glasses and conventional contact lenses.
Especially in monocular cases, babies with only one eye involved,
we have come to expect failure in the treatment of the refractive
error that always happens after we remove a cataract in a baby.
Until about 2 years ago, the situation was grim. About that time,
we began in Albany and in other centers around the country to
work with a silicone contact lens that was specifically made for
babies.
The long and short of it is that it works. Perhaps because of the
specific material that's involved in the manufacture, with its en-
hanced oxygen transmissability, we have been able, in my own per-
sonal praétice, to fit successfully 59 of 60 children, that we have at-
tempted.
The superiority of this particular lens was recognized at a na-
tional meeting of pediatric eye surgeons just last week in a unani-
mous resolution, which I think you have a copy of.
Again, let me emphasize the importance of refractive correction.
If one of the members of the committee or anyone else in this room
were to remove his glasses or his contact lenses for a day or a week
PAGENO="0760"
754
or a year and then replace that optical correction, the vision would
return immediately. Not so in babies. Because of the condition
technically known as amblyopia and commonly referred to as "lazy
eye," visual loss without correction occurs daily. And within a
short time, it can become permanent.
It had been common to see eyes which had excellent surgical re-
sults which were nevertheless, unfortunately, legally blind because
of amblyopia. We thought we had that problem solved because of
the silicone contact lens.
In December and January, however, the Dow Corning Corp. an-
nounced that they had decided, because the lens was not profitable,
that they were going to discontinue production of the silicone con-
tact lens. That decision was a blow to me and, more important to
the parents of the children I care for.
With their help, we were able to mobilize a media and letterwrit-
ing campaign announcing publicly that this decision would consign
children to a lifetime of blindness. That campaign was finally suc-
cessful, and Dow Corning, under pressure, agreed temporarily to
continue production of the contact lens.
The decision was limited, however, and the lenses that they
agreed to continue making will not be applicable for children with
high degrees of nearsightedness or with certain other parameters
that used to be available. We are particularly concerned that Dow
Corning, when they do finally get out of the contact lens business,
which they certainly intend to do as soon as they can, will simply
dump this technology onto the shoulders of a smaller or less image-
conscious company who will not be amenable to this kind of public
pressure.
The Academy sees its role in this matter as an advocate for our
patients. In our estimation, the need is clear. We must provide
companies with sufficient economic incentives to maintain the
supply of these sight-saving devices.
I thank the subcommittee for your attention.
Mr. WAXMAN. Thank you very much.
[The prepared statement of Dr. Simon follows:]
PAGENO="0761"
755
® AMERICAN ACADEMY OF OPHTHALMOLOGY
Testimony of
The American Academy of Ophthalmology
Before the
Subcommittee on Health and the Environment
of the
U.S. House Committee on Energy and Commerce
on
The Orphan Drug Act
March 20, 1985
Good Morning, Chairman Waxman and members of the Subcommittee.
My name is John W. Simon, M.D. lam Assistant Professor of
Ophthalmology at the Albany Medical College of Union University,
Albany, New York. I am pleased to present the views of the
American Academy of Ophthalmology regarding the need to amend the
Orphan Drug Act of 1983.
My Curriculum Vitae is attached to this statement. However,
please allow me to summarize at the outset a few key elements of
the Academy's collective experience, and my own experience, with
this issue. The American Academy of Ophthalmology is the largest
national professional society of medical doctors specializing in
medical and surgical care of the eyes. Our 13,500 member
physicians include not only the vast majority of all board
certified ophthalmologists in the country, but also a significant
proportion of the leading researchers and virtually every
1833 Fillmore / P.O. Box 7424 / San Francisco / California 94120-7424 / (415) 921-4700
52-266 0-85-25
PAGENO="0762"
756
subspecialty of eye researôh and eye care.
As Director of the Pediatric Ophthalmology and Strabismus service
of the Department of Ophthalmology at the Albany Medical College,
I have been intimately involved with infants and children whose
sight depends on an ophthalmic product - pediatric high-powered
contact lenses following cataract removal - whose manufacture and
production has been threatened with termination because the
process has not been profitable. I will address this acute
problem later in my testimony.
The Academy has worked closely with the Office of Orphan Products
in the Food and Drug Administration to designate and obtain
sponsorship for a number of ophthalmic products which meet orphan
product criteria under the Act. Most of these ophthalmic
products are classified as devices. Because of this
classification, these products do not enjoy the ease of orphan
product designation nor the incentives for sponsorship accorded
drugs under the Act. These two factors have hampered the
approval process and have evoked a great deal of frustration,
some examples of which I shall describe. We hope Congress will
address this inequity.
Cyanoacrylate is one such ophthalmic device. The Academy has
issued a policy on cyanoacrylate tissue adhesive which is
attached to this statement. Briefly, cyanoacrylate tissue
adhesives appear to be a useful, safe method of treatment of
PAGENO="0763"
757
corneal perforations and impending perforations. These
perforations, which are common complications of infective
processes, require immediate treatment. The use of cyanoacrylate
provides a safer alternative to standard methods of treatment
which include conjunctival flaps, patch grafts and penetrating
keratoplasty. Application of the tissue adhesive results in
closure of the perforation cite and reformation of the anterior
chamber. The Academy has recommended that this product be made
available under the Orphan Drug Act because a true medical need
exists for this product for a limited number of patients. The
development of this product will require considerable cost and
the anticipated profit will be small.
Under present provisions of the Orphan Drug Act, efforts to
classify this ophthalmic device as an orphan product have been
burdensome. Last year Congress amended the Orphan Drug Act to
establish a presumption that drugs intended for diseases or
conditions with a prevalence of less than 2ø~,SøG patients in the
United States are orphans. Unfortunately, because devices were
not included under this amendment, designation of orphan status
remains cumbersome and time consuming. In addition, sponsorship
for devices remains difficult to obtain.
Present incentives under the Act to attract sponsors for orphan
products include special tax credits for clinical trials, a seven
year period of marketing exclusivity for a non patentable product
and a grants program. Except for the grants program offered by
PAGENO="0764"
758
the FDA these incentives are not now available for devices under
the Act.
I would like to relate my personal and professional experience
with an ophthalmic product which would be a likely candidate for
orphan status under the Act. Like cyanoacrylate, the high
powered contact lens for pediatric aphakic patients is a medical
device. These lenses may represent the only viable alternative
to a lifetime of legal blindness for infants and children who
have undergone cataract surgery. The corrective surgery and
lenses provide immediate restoration of a clear, focused image
and have given pediatric ophthalmologists hope that we may be
able to improve our results in unilateral congenital cataracts
where deprivation amblyopia has been such a problem. These
lenses have been manufactured and distributed by one company
which until recently held a patent on the silicone which
comprises the lens material. The company notified the ophthalmic
community in December, 1984 that it intended to discontinue the
production and manufacture of the silicone contact lens.
Although there are alternative corrections for adults on the
market, infants and children with cataracts and high degrees of
nearsightedness have come to rely on this product. The reaction
from the ophthalmic community, particularly among pediatric
ophthalmologists, was rapid and intense. (We would be pleased to
furnish materials relevant to this situation to the Committee).
As a result of intense lobbying on the part of the pediatric
ophthalmology community, the company has temporarily rescinded
PAGENO="0765"
759
its decision and instead is continuing the manufacture and
production of these lenses on a limited basis. I again emphasize
that this solution is temporary. The tenuous nature of the
decision has resulted in a "run" on the lenses with the result
that not all lens powers are now available.
Interesting another company in assuming the manufacture of this
lens may be difficult because the company announced that the lens
is not a commercially profitable product. The lens would appear
to be an appropriate product for orphan status under the Act.
However, the present Act does not contain incentives to encourage
this particular company to continue sponsoring this device.
It is the hope of the Academy that Congress will address the
issue of what incentives are appropriate in order to encourage
sponsorship of these products and others, so necessary for a
small portion of our population. The Academy sees its role in
this issue as an advocate for the medical needs of our patients
in order to encourage and stimulate the availability of these
necessary medical products.
Thank you for your time and attention.
PAGENO="0766"
760
Attachment I
® AMERfCAN ACADEMY OF OPHTHALMOLOGY
CYANOACRYLATE TISSUE ADHESIVE
I. INTRODUCTION
Perforations and impending perforations (desmetoceles), which are common complica-
tions of infective processes and melting conditions, require immediate treatment.
Standard methods of treatment include conjunctival flaps, patch grafts and penetrating
keratoplasty. However, such surgery on these inflamed or infected eyes, has a poor
prognosis because of the risk of infection, synechiae formation, and/or graft rejection.
The use of adhesives with, or without, a bandage contact lens provides a safe alternative.
The application of the tissue adhesive results in closure of the perforation site, and
reformation of the anterior chamber. Sometimes this is all that is needed. However, if
surgery (conjunctival flap or penetrating keratoplasty) is necessary, it can be done at a
later time under more optimal conditions.
Unfortunately, the investigational status of the material has prevented its
widespread use so other methods of treatment of corneal perforations continue to be
used.
II. ETIOLOGY OF CORNEAL PERFORATIONS
Over half of the cases of corneal perforations are due to herpes simplex ulcers,
bacterial ulcers, and corneal melting syndromes associated with rheumatoid arthritis.
These are common conditions, in which treatment is not always effective, so one can
anticipate an increasing incidence of comical perforations.
111. TYPES OF TISSUE ADHESIVES
The first tissue adhrive that was introduced in ophthalmology was Eastman 910
(methyl 2-cyanoacrylate). Initially there was much enthusiasm because of its rapid
bonding action quickly sealed perforations; the liquid monomer polymerized within a few
seconds ~fJer contact with the cornea. However, it was associated with mild ocular
toxicity. ` Following topical application, hyperemia of the conjunctive, and a transient
mild stromal haze, occurred. When injeete~I intralamellarly into rabbit corneas, after two
weeks, corneal neovascularization occurred.
New materials, which are less toxic have been introduced.5'6 These include isobutyl
cyanoacrylate~ and n-butyl cyanoacrylate**. Isobutyl is distributed by Ethicon* as
"Bucrylate", and n-butyl cyanoacrylate is distributed by Trikhawk as "Histacryl".
Isobutyl 2-cyanoacrylate (IBC) is also referred to as "Bucrylate". It does not have a
pharmacologic action; it does not react with tissues. Upon polymerization, it simply acts
as a physical barrier. It c~oes not have a bacteriostatic or bactericidal action. When
first introduced, one study demonstrated that cyanoaci~rlate, when added to blood agar
plates, inhibited the growth of bacteria. A later study indicated that the cyanoacrylate
monomers are neither bacteriostatic nor bacteriocidal regardless of the form of the
bacteria, whether vegetative or spore.
*Ethiocn Company, Somerville, New Jersey, USA
**T1.ihawk, Montreal, Quebec, Canada
1833 Fillmore / P.O. Box 7424 / San Francisco / California 94120-7424 / (415) 921-4700
PAGENO="0767"
761
IV. METHOD OF ACTION
Unlike most conventional adhesives that function by the application of heat and
pressure, addition of a polymerization initiator ("catalyst"), or evaporation of a solvent,
the cyanoacrylate tissue adhesives are converted from a liquid to a solid ~tate by
polymerization when simply pressed into a thin film between moist tissue. When
Bucrylate is spread on corneal tissue, at room temperature, the monomer very quickly
(15-30 seconds) polymerizes to a water proof film. This results in a reasonably strong
bond between the tissues that. maintain wound apposition while stromal healing occurs.
Often a free tissue patch is placed over the perforations, and then the adhesive is
applied. The use of a soft b~nfl~ge lens over the adhesive protects the patch from lid
trauma and holds it in place.
V. RESULTS
Recent studies have conclusively dem1~strated the efficacy of this mode of
treatment. In a study by Hirst LW, et al, the authors contrasted the experience at
their institution prior to 1974, and after 1974 (when tissue adhesives were introduced).
Prior to 1974, the enucleation rate for perforations was 19%. After 1974, when corneal
perforations were treated by tissue e~hesives, the enucleation rate had decreased to 6%.
In another study by Weiss JL, et al, the use of tissue adhesives lowered the
enucleation/evisceration rate to 7%.
VI. COMPLICATIONS
It is difficult to determine if complications ~e due to the adhesive or to the
disease process. In the study by Weiss JL, et al, complications occurred in nine of
eighty (11%) of patients. The complications included a significant increase in intraocular
pressure (2 patients) and corneal infiltrates (7 patients). The cases of elevated
intraocular pressure were easily controlled by antiglaucoma medication. Of the cases of
corneal infiltrates, 5 were proven by culture to the bacterial infections. These infections
could have been a complication of the tissue adhesive, the extended wear bandage lens,
or the disease process itself. As mentioned previously, the tissue adhesive is neither
bacteriostatic or bacteriocidal, but it appears unlikely to be a source of infection. These
complications did not affect the eventual outcome. All nine eyes eventually had a
satisfactory result.
VII. SAFETY
Ocular toxicity has not proven to be a significant problem with the newer tissue
adhesives. Conjunctival hyperemia has not been a significant problem. Anterior chamber
reaction has been minimal. (Due to the very rapid polymerization, in all likelihood very
little, or no, monomer enters the anterior chamber.)
The tissj~e 1~dhesives have been used for sealing corneo-s~eral wounds,15 chloriodal
holes, scleral ` buckling procedures, eye muscle operations, etc. There have been no
instances of ocular toxicity when cyanoacrylate comes into contact with choroidal,
scleral, or muscle tissue.
VIII. SUMMARY
Cyanoacrylate tissue adhesives, as presently available, appear to be a useful,
safe method of treatment of corneal perforations and impending perforations. The
small complication rate is of little importance as contrasted to the lower
enucleation/evisceration rate. It behooves the FDA to make this material available
for general use. Furthermore, since the development of this product has
considerable cost, and the anticipated profit will be small (because only a small
number of patients will require this treatment), companies that distribute such
tissue adhesives should be permitted to participate in the available tax incentives
for "orphan drugs"
Developed by: Research and Regulatory Agencies
Committee
Reviewed by: Committee on Ophthalmic Procedures
Assessment
Approved by: Board of Directors, June 1, 1984
PAGENO="0768"
762
REFERENCES
1. Bloomfield S, Barnett A, Kanter PD: The use of Eastman 910 monomer as
an adhesive in ocular surgery. Biological effects on ocular tissue.
American Journal of Ophth. 55:742, 1963.
2. Straatsma BR, Allen RA, et al: Experimental studies employing adhesive
compounds in ophthalmic surgery. Trans. Am. Acad. Ophth. Otolarng.
67:320, 1963.
3. Refojo Miguel, MS.: Surgical adhesives in ophthalmology. Journal Macro-
molecular Science and Chemistry 3:667, 1970.
4. Hanna C, Shibley S: Tissue reaction to intracorneal silicone rubber (sliastic
ARTV 382) and methyl 2-cyanoacrylate (Eastman 910 adhesive). American
Journal of Ophth. 6:323, 1965.
5. Gasset AR, Hood CI, Ellson ED, Kaufman HE: Ocular tolerance to
cyanoacrylate monomer tissue adhesive analogs. Investigative Ophth. 9:3,
1970.
6. Refojo MF, Dohlman DH, Koliopoulus J: Adhesives in ophthalmology: A
review. Surgery of Ophthalmology 15:217, 1971.
7. Lehman RAW, West RL, Leonard F: Toxicity of alkyl 2-cyanoacrylate U
Bacterial growth. Archives of Surgery 93:447, 1966.
8. Matsumoto T, Dobek AS, Paul KC, Kovaric JJ, Hamit HF: Bacteriological
study of cyanoacrylate tissue adhesives. Archives of Surgery 97:527, 1968.
9. Ginsberg SP, Polack FM: Cyanoacrylate tissue adhesive in ocular disease.
Ophthalmic Surgery 3:126, 1972.
10. Hyndiuk RA, Hal DS, Kinyoun JL: Free tissue patch and cyanoacrylate in
corneal perforations, Ophthalmic Surgery 5:2, 1974.
11. Boruchoff SA, Refojo MF, Slansky HH, et al: Clinical application of
adhesives in corneal surgery. Trans of American Acad. of Ophth. &
Otolaryn. 73:449, 1969.
12. Fogle JA, Kenyon KR, Foster CS: Tissue adhesive arrests stromal melting
in the human cornea. American Journ. of Ophth. 89:795-802, 1980.
13. Hirst LS, Stark WJ, Jensen AD: Tissue adhesive: New prospects in corneal
perforations. Ophthalmic Surgery 10:58, 1979.
14. Hirst LW, Sinitty WE, Stark WJ: Corneal perforations. Changing methods
of treatment 1960-1980. Ophthalmology 89:630, 1982.
15. Weiss JL, Williams P, Lindstrom RL, Doughman DJ: The use of tissue
adhesives in corneal perforations. Ophthalmology May 610, 1983.
16. Price JA, Wadsworth JAC: The evaluation of adhesive in cataract wound
closure. American Journal of Ophth. 68:663, 1969.
17. Calabria GA, Pruett RC, Refojo MF: Further experience with sutureless
scleral buckling materials 11. Cyanoacrylate tissue adhesive. Arch. Ophth.
86:82, 1971.
18. Vygantas CM, Kanter PJ: Experimental buckling with homologous sclera and
cyanoacrylate. Arch. Ophth. 91:126-129, 1974.
19. Dunlap EA, Dunn M, Rossomondo R: New uses of ocular adhesives.
Archives of Ophthalmology 82:756, 1969.
PAGENO="0769"
Board of Directors
Forrest D. Ellis, M.D.
Eugene R.. Folk. M.D.
Thomas D. France, M.D.
Hiram H. Hardesy. M.D.
John Prsts'Johnson. MB.
Arthur L. Rosenbaum. M.D.
Wjlljasn E. Scott. M.D.
President
Eugene R. Folk. M.D.
President.EIecz
Thomas D. France. M.D.
Secietary.Treasarer
Arthur L. Rosenbaum. M.D.
Jules Stein Eye Institute
UCLA School of Medicine
Los Angeles, CA 90024
Telephone (213) 823-2572
At the annual business meeting of the American Association of Pediatric
Ophthalmology and Strabismus held in Dorado, Puerto Rico on March 4, 1985,
the complex problem of production of soft lenses for aphakic children was
discussed by Dr. John Simon. Dr. John Baker mode the following motion:
Moved. Whereas there remain substantial difficulties and concerns with the
availability of pediatric silicon contact lenses, the American Association
of Pediatric Ophthalmology and Strabismus resolve the following:
1. That extended wear silicon contact lenses of both high plus and high minus
powers must be available to infants and children with special problems to allow
normal visual development.
2. That there must be an adequate supply of necessary powers while other
manufacturing arrangements are mode.
3. That a dependable long-term supplier must be developed or found.
Lure! .4#onerenrrnz Chatnegn. 1905 Secrrrgeyfar P96gtoth. 190546
Roe Vauqude. M.D. WOtison B. Sooct. M.D.
Thou Sto'ons.Posrat. Coordinator Doparonsoc of chulmolouy
P.O. Son 13132 Uojenuiy tdosp6als
Rhihenood, VA 23225 teen Oct. *52242
416)997.6225 Tdopboom (319) 336.2215
763
THE AMERICAN ASSOCIATION
FOR
PEDIATRIC OPHTHALMOLOGY
AND
STRABISMUS
Resolution
f
Lure! .4erontome,uo Chormen,r. 1906
Malcolm B. log. M.D.
Kapiolnol Children, Med. Co.
1319 Puoahou In.. 11110
Honolulu, HI 96026
(000) 955.5951
PAGENO="0770"
764
4. That an Ad Hoc committee of the American Association of Pediatric Ophthalmology
and Scrabismus be appointed to interact with appropriate representatives of the
American Academy of Ophthalmology and can jointly meet with Dow Corning officials
to resolve this crisis.
5. That the president of the American Association of Pediatric Ophthalmology and
Strabismus be kept informed by the membership of other potential orphan products
affecting pediatric and stràbismic eye care.
A general discussion was held. The motion was passed unanimously.
STATEMENT OF LARRY H. MARTIN
Mr. MARTIN. Thank you, Mr. Chairman and members of the com-
mittee.
I would like to take this opportunity today to comment on the
current status of the Orphan Drug Act with respect to the medical
device industry and recommend amendments to the act that would
provide the same incentives that are accorded the drug industry
today. -
It would appear that although the act was intended medical as-
sistance for orphan diseases, using whatever medical modalities
were available, drug or device, in implementation, only drug devel-
opment has prospered. Sponsors of medical devices for the same
diseases, at present, cannot enjoy the benefits which have been ac-
corded sponsors of orphan drugs.
I am confident that the intent of the legislation was to make new
treatments available to the public, whether it be drug or device.
There is strong evidence to support the belief that promising
orphan devices will not be developed unless changes are made in
the current laws to help defray costs and provide commercial in-
centives for developing such devices.
It is in the public interest to provide these incentives, so that the
patient population can receive the same benefit of available ad-
vanced technologies which could be developed and applied to medi-
cal devices.
The act does provide that the Orphan Product Board shall func-
tion to promote the development of drugs and devices, so that it
will appear that the original drafters of the act intended the de-
vices to have some, if not all, the benefits. However, it is clear that
the guidelines issued by the Orphan Products Board and the imple-
mentation of the act, that they have overlooked the device indus-
try. Medical devices were not officially designated as orphan prod-
ucts under the act. Nevertheless, the orphan products may be es-
sential and vital to the afflicted patient group which could benefit
from their development.
From my experience, both with Neuromed and as president of
the Florida Medical Device Association, it is apparent that unless
the same treatment is accorded the device industry, that the pre-
PAGENO="0771"
765
1980 pace and experience in the drug industry with orphan product
development will be fostered.
Furthermore, medical device companies, different from drug
companies, do not generally possess the same resources that the
drug companies have established over the past decades. Very few
medical device companies have other products that are, so to
speak, the bread and butter of such companies to support orphan
product development. In my experience, it is the smaller entrepre-
neurial company, with a particular motivation, be that of a family
member or friend, that is a developer of new medical technology.
It is clear that high technology products will be developed by the
medical industry on a fast track, as has occurred in all other forms
of society today. For example, I am associated with Neuromed,
whose primary focuS, is on the development of electrical neurosti-
mulator devices for the treatment of some very rare diseases-
namely, dystonia, tortiocollis, Friedreich's ataxia, and other motor
dysfunctions.
The company presently manufactures an implantable spinal cord
stimulator that is being investigated for the beneficial treatment of
some neurological motor dysfunctions. The broad range of stimulat-
ing parameters, multichannel capability, percutaneous implanta-
tion techniques are a direct result of new technologies which did
not exist when the medical device amendments were enacted in
1976.
How will the act spur development for the medical device indus-
try? Being imminently involved in such a company and associated
with many other companies in the trade association, I can speak
from experience that these incentives would increase research and
development substantially.
For example, in a small company, you cannot afford the clinical
research staff necessary to prepare and carry out more than one
study at a time. Quite often, companies rely on consultants and do
not have an in-house regulatory affairs person at all.
The cost of device clinicals are not the same as drug trials, but in
most cases, the device clinical costs far exceed the associated drug
costs when taking a product to market. Many medical device clini-
cals require extensive hospitalization to use and test the device.
Not only is there a high cost in developing the product, but the
high cost of hospital care necessary to prove the safety and efficacy
of the device is an added burden as well.
A comparative overview of the medical industry today will un-
equivocally demonstrate that it is the device area where the great
medical strides are being made today. Moreover, it's obvious from
the media covering the well-publicized Jarvik-7 Heart, as compared
to the Phoenix Heart, that a problem exists in funding medical
device technology. There are many other devices of equal promise,
including those for rare diseases, such as Neuromed's, whose
growth will not be as fast as could be.
When Lee Majors and Lindsey Wagner played the "Bionic Man"
and "Bionic Woman" in the TV series, many people thought that
to be of a futuristic world, but today the bionic persons is a reality.
From artificial ears, eyes, and limbs to electrical stimulation, de-
vices will be able to correct, replace, and regulate the diseased and
injured.
PAGENO="0772"
766
These important and relevant technologies to treat those in need
cannot be ignored in today's world, especially that in the orphan
product field. The chemist pioneer of yesterday has been replaced
by the mechanical and electrical engineers of today.
I strongly recommend that the act be amended to treat medical
device companies no differently than the pharmaceutical industry.
Thank you for your time.
[The prepared statement of Mr. Martin follows:]
PAGENO="0773"
767
TESTIMONY OF LARRY H. MARTIN
I'd like to take this opportunity today to comment upon the
current status of the Orphan Drug Act with respect to the medical
device industry and to recommend amendments to the Act that would
provide the same incentives that are accorded the drug industry.
The Orphan Drug Act, Public Law 97-414, was passed by
Congress over two years ago to facilitate the development of
products for the treatment of rare diseases or conditions. The Act
established financial and other incentives to encourage sponsors
of drugs to conduct research and to pursue marketing of these
drugs while failing to provide the same incentives to the medical
device industry.
One of the most important incentives of the Act provides that
drugs designated as Orphan Drugs under Section 525. of the Act and
for which a U.S. Patent may not be issued are entitled to an
exclusive marketing status, 21 U.S.C. 527. Other incentives
include research and development tax credits, research grants,
relaxation of the Food And Drug Administration's extensive testing
requirements and a procedure to determine requirements for Orphan
Drug status under the Act. The Act also established a process
whereby sponsors of orphan drugs may seek recommendations for the
clinical and nonclinical investigations of drugs for rare diseases
or conditions. Additionally, the Orphan Product Board was
established under this Act to promote the development of drugs and
devices for rare diseases and to coordinate the various agencies
PAGENO="0774"
768
in carrying out their respective functions related to the
development of such products.
Unfortunately, the Act has had negligible effect on device
development over the past two years. In fact, no medical device
has gained recognition or assistance under the Act. It would
appear that although the Act was dntended to provide medical
assistance for orphan diseases using whatever medical modalities
were available--drug or device--in implementation only drug
development has prospered. Sponsors of medical devices for the
same diseases, at present, cannot enjoy the benefits which are
accorded sponsors of orphan drugs. I am confident that the intent
of the legislation was to make new treatments available to the
public whether it be via drug or device.
There is strong evidence to support the belief that promising
orphan devices will not be developed unless changes are made in
the current laws to help defray costs and provide commercial
incentives for developing such devices. It is in the public
interest to provide these incentives so that the patient
population can receive the benefit of available advanced
technologies which could be developed and applied to medical
devices.
As referred to previously, the Act does provide that the
Orphan Product Board shall function to promote the development of
drugs and devices so it would appear that the original drafters of
the legislation intended devices to have some, if not all, of the
benefits. However, it is clear that in the guidelines issued by
PAGENO="0775"
769
the Orphan Product Board and the implementation of the Act they
have ignored the device industry. Medical devices, while not
officially designated as orphan products under the Act,
nevertheless, may be orphan products essential and vital to an
afflicted patient group which could benefit from their
development.
The medical device industry is dramatically different in size
and capability from that of the drug industry as a whole. The
majority of medical device companies are small entrepreneurial
businesses engaged in the development of technologies for personal
medical necessities resulting from their own experiences. These
companies are part of a relatively young industry and lack the
capability to develop new products in the same manner required for
new drugs. The Food and Drug Administration's Medical Device Act
fully recognized the differing capabilities and requirements of
these industries. However, it did not address the use of medical
devices for orphan diseases.
From my experience, both with Neuromed, Inc. and as President
of the Florida Medical Device Association, it is apparent that
unless the same treatment is accorded the device industry, that
the same lackadaisical attitude impugned in the drug companies for
orphan product development will be fostered. Furthermore, medical
device companies, different from drug companies, do not generally
possess the resources that the drug companies have established
over the past decades. Very few medical device companies have
other products that are, so-to--speak, the bread and butter of such
PAGENO="0776"
770
companies to support orphan product development. In my experience,
it is the smaller entrepreneurial company with a particular
motivation, be that of a family member or friend, that isa
developer of new medical technology. It is clear that high
technology products will be developed by the medical industry on a
fast track as has occurred in all other areas of society.
It does not seem logical that the drafters of the Orphan
Product Act would have recommended arbitrary and capricious
legislation if they had been aware of the improved medical
technologies that exist today.
For example, I am associated with NEUROMED, INC., whose
primary focus is on the development of neurostimulator devices for
the treatment of some very rare diseases; namely, dystonia,
torticollis, cerebral palsy, Friedreich's ataxia and other motor
disorders. The company presently manufactures an implantable
spinal cord stimulator system, MULTISTIM,tm that is being
investigated for the beneficial treatment of such neurological
motor dysfunctions. The system consists of an electrode connected
to a programmable neurostimulator receiver implanted in the
patient. By the use of a R.F linked transmitter, various electrical
signals can be transmitted to the spinal cord. The broad range of
stimulating parameters, multichannel capability, and percutaneous
implantation technique are a direct result of new technologies
which did not exist when the Medical Device Amendments were
enacted in 1976. Implants for motor dysfunctions are presently
conducted under an FDA approved investi9ational device exemption;
PAGENO="0777"
771
however, due to the cost of the Medical Device Act and the
requirements promulgated/thereunder, the road to developing the
product and obtaining approval from the FDA continues to be a
long, arduous, and expensive one.
How will the Act spur development for the medical device
industry? Being imminently involved in such a company and
associated with other companies in the trade association, I can
speak from experience that these incentives would increase
research and development substantially.
For example, in a small company, you cannot afford the
Clinical Research staff necessary to prepare and carry out more
than one study at a time. Quite often,companies rely on
consultants and do not have an in-house Regulatory Affairs person
at all. The cost of device clinicals are not the sane as drug
trials, but in most cases, the device clinical costs far exceed
the associated drug costs when taking *a product to market. Many
medical device clinicals require extensive hospitalization to use
and test the device; not only is there a high *cost in developing
the product, but the high cost of hospital care necessary to prove
the safety and efficacy of the device is an added burden as well.
A comparative overview of the medical industry will
unequivocally demonstrate that it is the device area where the
great medical strides are being made today. Moreover, it is
obvious from the media covering the well-publicized Jarvik-7
Heart, compared to the Phoenix Heart, that a problem exists in
funding medical device technology . There are many other d~vices
PAGENO="0778"
772
of equal promise including those for rare diseases such as
Neuromed's, whose growth will be hampered due to extensive legal,
financial, and regulatory requirements. These companies do not
have the publicity or support that the large institutions possess.
One could argue that it is not the governmental incentives
that the Act provides which are necessary, but independent
motivations or desires that may be even more compelling. However,
if that were solely the case, it would be hard to justify the
Orphan Drug Act as it relates to the drug industry. For there, it
was the multimillion dollar conglomerates that were unable to
justify the cost of developing such products without governmental
incentives. Obviously, the medical device industry, a fledgling in
comparison, has the same problems as the drug companies magnified
many times over. I would venture to say that if the same
incentives were available to the device industry, that the
advances in technology would be faster paced than that achieved by
the drug industry.
When Lee Majors and Lindsey Wagner played the Bionic Man and
Woman in the T.V. series, many people thought that to be of a
futuristic world, but today the bionic person is a reality. From
artificial ears, eyes and limbs to electrical stimulation; devices
will be able to correct, replace and regulate the diseased and
injured. These important and relevant technologies to treat those
in need cannot be ignored in today's world. The chemist pioneer of
yesterday has been replaced by the mechanical and electrical
engineers of today.
I strongly recommend that the Act be amended to treat medical
device companies no differently than the pharmaceutical industry.
PAGENO="0779"
773
Mr. WAxN. Thank you both very much.
What are the most important actions that Government can take
to encourage the availability of orphan medical devices?
Mr. MARTIN. I think one of the biggest spurs currently could be
basically in amending the act to initiate and spur the same type of
incentives that the drug companies have today. I think in the medi-
cal device industry, you are dealing, from my experience, with a lot
smaller companies. That is not to say that there are not large med-
ical device companies around, but from my experience, they are
not presently interested in the smaller product for the afflicted
groups.
Mr. WAXMAN. Dr. Simon, have you worked with FDA on the pe-
diatric contact lens that you need from Dow Corning, and if so,
what has FDA done?
Dr. SIMON. I have had no experience with FDA at all.
Mr. WAXMAN. Why is that?
Dr. SIMON. I kind of stumbled into this, Mr. Chairman. I found
out about the decision that Dow Corning had made, and I, under a
time pressure, acted outside of Government agencies as quickly as I
could to try to reverse that decision. I did write my Congressman
who did forward a copy of my. letter to the FDA, and I got a reply
that said that under the current act, there was nothing they could
do.
Mr. WAXMAN. Well, we want to work with you on that issue.
Mr. Whittaker.
Mr. WHITTAKER. Thank you, Mr. Chairman.
Dr. Simon, do you believe the reason the company proposed dis-
continuance of the manufacturing of the silicone lens is because of
the limited market that existed, as it presently stood, and if so, was
that related to gaining approval for use on a wider market than
just in the pediatric field?
Dr. SIMON. I don't think that a major part of the problem had to
do with FDA. I think that they had a great deal of difficulty mar-
keting the silicone contact lens for adults. It was a big money loser
for a variety of reasons. It just so happened that the part of the
market which could not be supplanted by another contact lens;
that is, the pediatric contact lens, was a very, very small part of
the total business, and that's what allowed me to put pressure on
them to continue production at all.
They have made a firm decision to get out of the contact lens
business in general, because it has lost money for them. They have
decided to continue making a very limited number of parameters of
contact lenses for babies only.
What I would like to see is for Dow Corning or probably some-
body else on a smaller scale to make the kinds of contact lenses
that these children need.
Mr. WHITTAKER. In your testimony, Dr. Simon, you indicated
that until recently, they had held what would appear to be an ex-
clusive patent, but now recently it is not held totally by them.
Do you think that will open other markets for the silicone
lenses?
Dr. SIMoN. There is more than one patent involved, and I think
that Dr. Finkel alluded to this kind of problem. There is a patent
on the silicone material itself, which I understand has expired, and
PAGENO="0780"
774
that has opened up. It's my understanding that the surface treat-
ment of the lens is every bit as important in order to make the con-
tact lens usable, and that there are still patent concerns in that
area.
Mr. WHITTAKER. Well, I would echo the chairman's sentiment.
We would be most anxious to work with you.
Dr. SIMoN. Thank you.
Mr. WAXMAN. Mr. Leland.
Mr. LELAND. I have no questions, Mr. Chairman, but I am, too,
very happy that you have brought this matter before us, and I am
very supportive of the chairman's leadership in this whole thing.
Mr. WAXMAN. Mr. Nielson.
Mr. NIELSON. I'd like to ask Mr. Martin, I guess I missed the
point on the comparison between the Jarvik Heart and the Phoe-
nix Heart. What point were you trying to make there?
Mr. MARTIN. The point I was trying to make there is, in products
that may not be considered even orphan products, you have the
Jarvik Heart, which was sponsored by a substantial medical device
company and outside funds, and then you have the Phoenix Heart,
which is an individual who was self-motivated to develop a heart,
and as was recently played in the newspaper, he was unable to
carry forth his research, and the FDA requirements because of a
lack of funds.
It had no relevancy as to which may have been the better prod-
uct, but only dealt with who had the funds to push it through,
pointing out that in the medical device industry, most of the com-
panies involved in it are individual entrepreneurial-type people.
Mr. NIELSON. Was that because the Phoenix people did not seek
FDA approval, whereas the University of Utah did? Is that the
reason?
Mr. MARTIN. The people that had the Phoenix heart was an indi-
vidual who lacked the funds to progress down the road of FDA ap-
proval.
Mr. NIELSON. The University of Utah also lacked the funds, but
they went through FDA approval, which took them a number of
years.
Mr. MARTIN. They raised a substantial amount of money through
companies, I think several million dollars, to accomplish that.
That's a private foundation.
Mr. NIELSON. But we are talking here about which one had the
approval that it be used and so on. I think one went the route, and
one did not; isn't that true?
Mr. MARTIN. That's correct. But I was merely using that to dem-
onstrate that in the device industry, many of the small companies
that are involved in it do not have the funds, as compared to the
larger companies. It was merely an analogy that I was making.
Mr. NIELSON. Let me ask this question: Would the Phoenix Heart
ever have been developed, had there not been the primary effort at
the Jarvik level? Wasn't it the fact that Jarvik-7 was acted on for a
number of years; they used the caps and so on long before they
used the perfected one? Wasn't the Phoenix a result of the coopera-
tion between FDA and the university?
Mr. MARTIN. I'm not that familiar with the Phoenix Heart. I was
merely reiterating what had been recently in the media and how
PAGENO="0781"
775
they were describing it as an individual who lacked the funds and
capability to progress.
I believe the Phoenix Heart had been around since about-I
don't know the timeframe on that.
Mr. NIELSON. Thank you, Mr. Chairman.
Mr. WAXMAN. Thank you, Mr. Nielson.
Dr. Simon and Mr. Martin, thank you very much for being with
us, and we are going to work with both of you on this bill and
other things we can do to be of help.
That concludes our business for today. Therefore, the subcommit-
tee stands adjourned.
[Whereupon, at 11:25 a.m., the subcommittee was adjourned.]
[The following statement was submitted for the record:]
PAGENO="0782"
776
STATEMENT OF THE AMERICAN PHARMACEUTICAL ASSOCIATION
The American Pharmaceutical Association, the national professional
society of pharmacists, is pleased to have this opportunity to present
its views on the matter of the reauthorization of the Orphan Drug Act..
A number of years ago the problem of inadequate resources and insufficent
economic interest in research, development, and distribution of certain
needed drugs or potential drugs was the subject of increasing public,
private and professional concern. As the cost of new drug development
soared, this problem grew proportionally more acute. The continually
increasing economic break-even point meant that drugs needed to achieve a
higher volume of usage in the marketplace than in the past in order to
justify the expenditures of resources in the development process.
The free enterprise marketplace was failing to operate in the case of
drugs for rare diseases precisely because they were intended to treat a
relatively low incidence population. With the potential market for such
drugs so small, strategic decisions were made not to enter into the
research and development efforts necessary to produce those drugs. As
early as 1979 an Interagency Task Force to the Secretary of Health,
Education and Welfare released its report titled "Sufficient Drugs of
Limited Consumer Value" and in September, 1979 the Drug Regulation Reform
Act carried provisions to support drugs of limited commercial value.
In mid-1980 representative Elizabeth Holtzman introduced a bill to
establish an office at the National Institutes of Health to assist in the
development of drugs and diseases of low incidence. However, it was not
.0024A/1
PAGENO="0783"
777
until the 96th Congress that consensus was reached regarding the nature
of the solution. The full spectrum of view points regarding the
appropriate way to address the needs of those Americans with rare
diseases finally achieved consensus with the passage of the Orphan Drug
Act. Since the passage of that Act we have observed a number of
activities whose thrust consistently points to making available products
for those with rare diseases.
The activities of those involved in orphan drug development since the
passage of the Act just over two years ago have been numerous and the
efforts of many should be noted here. First, the pharmaceutical
industry, through ~he Pharmaceutical Manufacturers Association Commission
on Rare Diseases and through the Generic Pharmaceutical Industry
Association have consistently sought to promote an awareness of the need
for research for orphan drugs, the adoption of those products once they
were developed, and the rapid distribution of those products. Second,
the activities of the Federal government through the programs of the
Department of Health and Human Services and especially through the
activities of the Orphan Products Board have consistently sought to
maintain a high level of basic and clinical research in the most
promising areas. They also have addressed other needs (such as the need
for increase public information and patient information) in the Orphan
Drug areas. Third, Universities and individual researchers have
continued their efforts, not only in the development of new knowledge
through basic and clinical studies, but also by conducting seminars and
conferences which sought to built networks among re2earchers to promote
PAGENO="0784"
778
their knowledge of developmental efforts. Finally, and certainly among
the most important, are the efforts of those patients and their families
that suffer from rare diseases. These individuals and groups have been.
active in maintaining th~e visibility and awareness of the nature of their
diseases. On more than one occasion, they have been significant
contributers to the conferences held by universities and hearings held by
the Department of Health and Human Services Orphan Products Board as~~
matters of importance related to rare diseases were discussed.
Now, as the committee considers the reauthorization of this legislation
the American Pharmaceutical Association would like to recommend a number
of items relevant to your deliberations.
First, APhA supports the reauthorization of the legislation. This
support is in keeping with our earlier policy statements calling for
legislation or regulation to provide incentives to manufacturers,
private foundations, academic and public institutions and others for
the development, manufacture and distribution of needed drugs of
limited commercial value.
Second, APhA supports the extension of current Orphan Drug Act
incentives to other therapeutic technology including those relating
to medical foods and devices.
PAGENO="0785"
779
Third, APhA believes that funds authorized under the Orphan Drug Act
should be available for animal pre-clinical studies. The current
Orphan Drug Act precludes the use of its funds for pre-clinical
animal studies. It is now clear that other disincentives for animal
research exist as well and that resources are needed in this area.
We believe the Secretary should have sufficient flexibility in the
allocation of those resources to assure that no drug limited -
commercial value will fail to be developed because of an inability to
conduct early clinical phase testing.
APhA appreciates this opportunity to present its views before this
committee, and looks forward to future opportunities to be of
assistance. The American Pharmaceutical Association was among the first
organizations to study this topic of needed drugs for rare diseases and
adopted a policy in this regard at its House of Delegates Meeting as
early as 1981. The Association will continue to press its efforts on
behalf of those with rare diseases and locks forward to the day when the
needs of those individuals are so sufficiently met that no special
programs will be needed.
PAGENO="0786"
780
STATEMENT
Submitted for the Record by Dr. Theodore Cooper
Chairman, PMI\ Commission on Drugs for Rare Diseases
Subcommittee on Health and Environment
House Energy and Commerce Committee
March 20, 1985
Mr. Chairman and Members of the Subcommittee, We are pleased to have
the opportunity to participate in this oversight hearing on the implementation
of the Orphan Drug Act and appreciate the invitation to do so. Due to prior
and firm commitments which could not be changed, neither I as Chairman of the
PMA Commission, nor Dr. John Adams, Executive Director of the Commission, were
able to appear at the hearing to personally present this statement and to
respond to any questions you or members of the Subcommittee may have directed
to us. We, nevertheless, deem it of importance to submit this statement for
inclusion in the record, and I shall be pleased to respond in writing to any
questions you may have concerning its content or other aspects of the Commissions
activities. It is my opinion that the dialogue generated between the Commission
and the Subcommittee as the result of our earlier testimony was most constructive,
and it is in this spirit that we shall be pleased to personally testify at any
future hearings.
Based on the invitation extended to me, it is my understanding that
one of the principal reasons for this hearing is to consider the need for
reauthorization of the pertinent section of the Orphan Drug Act which provides
for an appropriation of $4,000,000 per year for a three-year period to fund
clinical research. It is our opinion as evidenced by support for the passage
of the Orphan Drug Act, that this provision offers important incentives for
PAGENO="0787"
781
academic investigators engaged in rare disease research. Wore importantly,
this provision provides a means to encourage additional investigators to enter
the field and thus increase our knowledge of the causes and possible prevention
or treatment of these diseases. It is for these reasons that the Commission
endorses a reauthorization of the appropriations provisions of the Act. We
believe that provisions for orphan drug designation and peer review of research
proposals will assure the prudent and effective use of these funds.
In our testimony last March, we commented on several other aspects in
the implementation of the Orphan Drug Act, some of which are worthy of repetition
and further comment.
To the best of our knowledge, regulations or rules to implement the
tax incentive provisions of the Act have never been published. Despite this
hiatus, a number of firms have applied for orphan drug designation and have
undertaken the research necessary for NDA approval without any clear assurance
that they will be eligible for the tax credit. We have received numerous
inquiries regarding these provisions from firms who have applied for orphan
product designation or are considering doing so, but we obviously cannot provide
definitive answers. Our only recourse is to suggest that these firms communicate
directly with the Internal Revenue Service to obtain the detailed procedures
required in applying for the tax credit. One of the most frequently asked
questions is whether the statutory definition of a rare disease and orphan
product designation are a sufficient basis for qualifying for the tax credit,
or whether IRS rules will impose additional requirements as embodied in the
definition in the Act as it was originally passed. We are not aware of any
PAGENO="0788"
782
firms that have filed or received a tax credit under provisions of the Act.
Such information may be considered ofa confidential nature with the IRS, but
it may be of interest to the Subcommittee to seek the information as a means
of measuring the impact of the Act on commercial research and development.
The fact that a number of firms have applied for orphan product designation is
encouraging, but the number might be increased if specific IRS rules were
published.
We also stated in last year's testimony that there was a need for
expanded sources of information on rare diseases and orphan drugs and for a
system to effectively communicate such information to patients, practicing
physicians, and to the scientific community. Such efforts are underway as
evidenced by the Compuserve system established by the National Organization
for Rare Disorders and the more recently established National Information
Center on Orphan Drugs and Rare Diseases announced by the HHS Orphan Products
Board. Both of these initiatives will do much to increase awareness of the
needs and opportunities in the field of rare diseases. It will take some time
to develop a comprehensive data base on all aspects of the problem, but an
important start has been made. One of the early problems in the field of rare
diseases was to assess the magnitude of the problem. Little was known concerning
research in progress or available therapies. Great progress has been achieved
in the past few years due in large part to the efforts of this Subcommittee,
the FDA, the HHS Orphan Products Board and the voluntary health agencies such
as NORD, the GPIA Institute and the PMA Commission. Much remains to be done,
however, in order to expand the data base through imputs from government and
voluntary health agencies, the scientific community and industry.
PAGENO="0789"
783
An important corollary of comprehensive information systems will be an
educational program to encourage the necessary inputs. I am pleased to report
that the PMA Commission is currently considering the ways in which it can
assist in such efforts. While solicitation of proposals for commercial
development of promising experimental compounds remains the principal mandate
of the Commission's charter, we are not unmindful of the other needs in the
field, particularly the needs for information and education. We are therefore
prepared to suggest changes in the charter of the Commission to the PMA Board
of Directors that would authorize the Commission to engage in studies and
other educational programs.
There is reason to believe that the decline in the submission of formal
proposals to the Comission, which we reported at the March, 1984 hearing and
which has continued during the balance of 1984, may be reversed in the near
future. This prediction is based on the number of grants and contracts awarded
by FDA, MCI and NINCDS during the past year for early clinical evaluation of
drugs for rare diseases. It is assumed that investigators will be advised to
submit proposals to the PMA Comission for purposes of commercial development
if the outcome of these preliminary studies is favorable.
It also should be noted that contributions by industry to the commercial
research and development of orphan drugs, as evidenced by the FDA lists of
orphan drug designation and commercial sponsor commitments from 1982 to the
present, have been impressive. In our opinion, this record presents strong
evidence that the industry has been responsive to the challenge largely set in
motion by this Subcommittee and by dedicated members of voluntary health organizations
PAGENO="0790"
784
and other interested persons. We are confident that industry will continue to
sponsor commercial development of drugs for rare diseases on its own volition
or as the result of favorable recommendations by the PMI\ Commission.
In closing these brief coniiients, I wish to reemphasize that commercial
drug development cannot proceed in a vacuum. It is completely dependent on an
infrastructure of basic and clinical science that has traditionally been provided
by academic, government and private research institutions. The degree to which
these institutions are funded will largely determine the quality and quantity
of research on rare diseases and the concomitant increase or decrease in orphan
drug development.
0