MINI B R I E F NUMBER M B 8 2 2 4 4
Science Policy Research Division
THE LIBRARY OF CONGRESS
CONGRESSIONAL RESEARCH SERVICE
MAJOR I S S U E S S Y S T E M
FOR ADDITIONAL INFORMATION CALL 287-5700
In the spring of 1982, congressional concern focused for the second time
i n 3 years on an infant formula that was deficient i n a required nutrient.
In 1979 infant formulas deficient in chloride
(Neo-Mull-Soy and Cho-Free,
manufactured by Syntex Laboratories, Inc. of California)
had been recalled
from the market, following reports of illness among children who consumed the
Congressional hearings thereafter led to passage of the Infant
Formula Act of 1980, which was designed to prevent future problems of
deficiencies in these products.
The regulations promulgated under this Act
had not been finalized, however, when a second incident of infant formula
On Mar. 3 , 1982, the Food and Drug Administration (FDA)
and Wyeth Laboratories announced the recall of a n infant formula
(Nursoy i n
both concentrated liquid and ready-to-eat
forms) that lacked vitamin B 6
This soy-based product is available :or
infants who may be
allergic to cow's milk formulas.
In the week
following the Nursoy recall
announcement, a second brand of formula, S M A , which
is also produced by
Wyeth, was recalled.
Since these specialized formulas can be the sole source
of nourishment for infants, concern has mounted about the possible health
consequences of deficiencies.
In the vitamin B 6 deficiency incident,
congressional attention focused on the delay in completing the final
regulations for nutrient composition, product testing and recall procedures
required under the Infant Formula Act of 1980.
Although breastfeeding is the feeding of choice for the human infant,
historical records show that mothers have long sought substitutes.
substitutes can be advantageous if the mother
i s disinclined
(either physiologically or psychologically)
the child is
unable to breastfeed or has special nutritional needs; or the child is
physically separated from the biological mother.
It was not until late in the 19th century, however, that alternative
feeding methods started to be fairly safe and reliable. The discovery of the
need to pasteurize (heat-treat) cow's milk and modify its composition to be
suitable for infant feeding, and the concomitant development of sanitary
standards and techniques for milk handling permitted safe bottle feeding.
the late 1800s, milk-based
feedings were formulated and prescribed
pediatricians who had begun to study the complex problems of feeding infants.
Modern infant formulas evolved from these earlier mixtures.
The composition of infant formula is important since early infancy is the
most critical period for growth and development.
It is the one time i n life
to provide virtually all
that the individual relies on a single product
Progress from the early carbohydrate-modified cow's miik
mixtures to formulas closer in nutrient composition to human milk became
possible as a result of the advances in overall nutritional knowledge, modern
clinical studies that revealed the complexities of infant needs for various
nutrients, ant3 technological developments that enabled large-scale production
of wholesale formulas with standard composition.
When used a s directed,
these formulas provide protein; fat, carbohydrate, Vitamins, minerals and
water a t the appropriate caloric density and in a form physiologically suited
for the infant. Formulas provide an adequate nutritional substitute for
human milk i n the support of infant growth and development.
Another major benefit of the development of infant formulas has been the
evolution of special formulas for infants with
problems can include allergy to milk
gastrointestinal disease and/or diarrhea, low birth weight, or inborn errors
Formulas have evolved from carbohydrate-modified
milk products to milkor whey-based
formulas, and most recently, to
all of which can meet special dietary
lactose-free and .elemental formulas
proteinhydrolyzate, or meat base.
Other major ingredients include corn syrup
solids, sucrose and vegetable oils, as well as all vitamins and minerals
known to be essential to the infant.
Soy-based formulas were the first of
the lactose-free formulas developed for infants intolerant to milk
either due to a n allergy to milk protein or a temporary deficiency of the
enzyme, lactase (which is necessary to break down the sugar, lactose).
According to census data in 1980, there were 3.5 million children aged one
year or younger in the United States. Recent data reported on infants at one
week of age indicated that in 1980 about 51% received commercially prepared
infant formulas compared to 77% receiving formulas in 1971.
occurred due to a significant increase in the number of mothers who chose to
breastfeed their infants.
Data on feedings received by infants 5 to 6 months
of age indicated that 61% were using commercially prepared formulas in 1980
compared to 28% in 1971. The change i n use in this age group primarily
represents a shift away from formulas made with evaporated and cow's milk
use of commercial formulas, coupled
The 1979 recall of the Neo-Mull-Soy and Cho-Free formulas was a result of
inadequate chloride content.
Chloride exists in the body almost entirely a s
the chloride ion.
It is primarily located in the extracellular fluid, with a
small amount in red blood cells.
The ion i s important in the regulation of
osmo.tic pressure, Water balance, and acid-base balance.
Chloride ions are
linked to hydrogen ions to provide the acid medium which promotes digestion
in the stomach.
Chloride is also an activator of saliva, -which begins the
digestion of food in the mouth.
A minimum daily requirement of chloride has not been determined.
average intake of sodium chloride (salt) assures that more than
amounts are consumed under normal conditions.
Most of the chloride
comes from salt used in food processing and preparation.
Severe losses or deficiency of chloride can lead to metabolic alkalosis.
This condition is characterized by a pH (degree of acidity or alkalinity)
the blood and other body fluids above the normal pH of 7.0.
The rise above
7.0 can be clue to an excess of alkalies or the withdrawal of acids or
chlorides from the blood.
Onset of the condition is commonly the result of a
loss of acid from excessive vomiting, but also can result from a loss of
-potassium or ingestion of excessive amounts of sodium bicarbonate.
and signs include
occas-ionally tetany (tonic spasms of muscles).
Infants experience a f a i l ~ r e
to gain weight, loss of appetite, lethargy and constipation.
includes correction of the primary disorder and administration of
sodium o r
Neo-Mull-Soy and Cho-Free are two brands of infant formula that have been
produced by Syntex Laboratories for a decade.
At the time of the 1979
recall, it was estimated that these two products represented
10-12% of the
infant formula market in the United States and that about 20,000 children
were consuming these special products.
In recent years the medical profession, along with
consumer groups, has
supported the position that the addition of salt in baby foods is not good
for the health of children.
In 1974 the American Academy of Pediatrics (AAP)
recommended that the s a l t s i n infant foods, particularly formulas, be reduced
to lessen the risk of elevated blood pressure in children.
Along with other
companies which had modified the salt content of their infant food products,
Syntex removed salt (sodium chloride) from Neo-Mull-Soy and Cho-Free in 1978.
Coincidental to the removal of salt from the formulas, a decision was made t o
drop routine chloride assaying of Syntex formulas.
The decreased amount of
chloride in the formulas caused by the removal of the sodium chloride from
the products resulted in metabolic alkalosis in some children fed either of
the formulas as their sole source of nourishment.
In July 1979 the manufacturer began to receive reports from doctors of
cases of metabolic alkalosis occurring in
The company notified physicians across the country about the
problem with the product.
FDA was also apprised of the situation.
Late i n
July, the company convened a panel of experts to review the available data o n
the reported cases.
On Aug. 1 , 1 9 7 9 , Syntex decided to recall voluntarily
the Neo-Mull-Soy and Cho-Free formulas. Notification of the product recall
was sent to physicians and pediatric nurses.
The notification included a
description of the symptoms of children who had suffered problems, provided
information concerning appropriate corrective medical measures, and asked
that all cans of the formulas be quarantined.
A statement was released to
the news media nationwide to alert mothers and other consumers to the recall.
Under the procedures of FDA's enforcement policy, the company attempted to
retrieve all cans of the product.
First, food brokers, wholesalers,
retailers and hospitals were notified.
Then the company embarked upon a
program to conduct checks in order to verify the effectiveness of the recall.
The company reportedly contacted almost all of its customers through
visits made by the company's sales force.
In total, over 2 million
the formula were destroyed.
In the isolated cases where cans were found on
store shelves, it was reportedly due to the failure of store owners and
middlemen to follow instructions to remove the formula.
Following the incident, Syntex reformulated Neo-Mull-Soy
appropriate levels of all ingredients, including chloride.
In addition, the
company initiated a program to conduct tests for nutrient content on all
infant formulas that they manufactured.
Finally, the company has supported
the follow-up study of all children reported to have had adverse reactions t o
~ e o - ~ u l l - s o yand ~ h o - ~ r e e . This follow-up is being conducted by
independent team of experts.
In a related issue, a nonprofit organization asked Syntex for the
deficient in chloride t o be donated to their overseas food program.
asked FDA for permission to donate the formula. FDA refused this request on
the grounds that formula unfit for U.S. -babies would also be unfit for human
infants in foreign countries. -
The 1982 recall of the Nursoy formula was a result if inadequate vitamin
Vitamin B6 is not a single substance, hut rather a collective term for
the naturally-occurring compounds pyridoxine, pyridoxal, and pyridoxamine.
The vitamin is essential for cellular function and the proper metabolism
protein and fats. Consequently, the vitamin complex is important for the
proper function of the blood, central nervous system (CNS), and skin.
~ e c o m m e n d e d 'Dietary Allowance (RDA) of adults is about 2 mg. daily.
deficiency is rare in humans since most foods contain the compound.
best sources are muscle and organ meats, fish, vegetables, and whole grain
cereals.] Secondary deficiencies may result in cases of malabsorption,
chemical inactivation by drugs, excessive losses, and increased metabolic
Experimental deficiency in man
leads to clinical evidence of
dermatitis, inflammation in the oral cavity, cheilosis (scaling of the lips
and angular areas of the mouth),
depression, confusion and
electroencephalograms (EEG), followed by convulsiorfs.
of vitamin B 6 daily is
For infants under 6 months of age, 0.3 mg.
The vitamin B6 stores of the normal newborn are
sufficient to meet requirements for a month after birth even if the diet i s
totally devoid of vitamin B6. A daily allowance of 0.6 mg. of vitamin B6 i s
recommended for the older infant (0.5 to 1 year) consuming a mixed
General experience with commercial formulas
requirements for the vitamin are met if vitamin B6 is present in amounts of
0.15 mg./gm of protein or 0.04 mg./100 kilocalories provided by the formula.
In documented cases of vitamin B6 deficiency in infants, the reported cause
supplementation of breastfed infants of
was either (1) a lack of vitamin
poorly nourished mothers, or (2) destruction of the pyridoxine content of
infant formula during processing.
For infants, dietary deprivation of
vitamin B 6 may result i n epileptic-type convulsions, weight loss, abdominal
distress, vomiting and hyperirritability.
The lack of vitamin B6 in the Nursoy infant formula was identified by the
manufacturer, Wyeth Laboratories. The incident occurred when an employee
mistakenly placed a canister of vitamin B1 (thiamin) into a container labeled
for vitamin B6.
As a result, the batch of defective formula - contained no
vitamin B6 and too much vitamin B1.
The recalled lots of formula were
manufactured by Wyeth between Jan. 26 and Feb.
1 1 , 1982.
The lots were
distributed nationwide and were available for sale in retail stores beginning
the first week of February 1982.
the recall affected 265,000
13-02. cans of the concentrated liquid and 306,000 32-02.
cans of the
ready-to-use infant formula. However, on Mar. 1 1 , 1982, it was announced
that an additional 567,000 cans of SMA brand formula would also need to berecalled.
(SMA is a second brand of formula produced by this company).
announcement was followed by a third recall on Mar.
1 2 , 1982, for a n
additional 1.8 million cans of SMA.
In each case the deficiency of vitamin
B6 in the formulas was picked up on routine nutrient analysis, a procedure
performed by the company for all batches of the infant formula.
company's batch analysis, however, is performed after the formula has been
In an earlier case (1952), about 2000 infants, who took another Wyeth
formula in which the ,vitamin B6 had been destroyed inadvertently i n
processing, had experienced COnVUlSiVe seizures.
Some of these infants have
been reported to have suffered permanent brain damage, in the form of
In the 1982 incident, no actual cases of vitamin B6
deficiency have been reported to date from use of the Nursoy or SMA brands of
formula.- It is not known in the present case how many infants were fed the
defective formula, nor whether any permanent brain damage occurred in those
infants who were not yet taking any other foods.
Two additional recalls of nutrient-deficient products have occurred
the Infant Formula Act went into effect in 1980.
In August 1983 Loma Linda
Foods (Riverside, California) recalled about 274,000 cans of its Soyalac
Powder when it was discovered that the formula had a loss of vitamin A
In September 1983 Sunrise and Rainbow (Los Angeles) recalled about
7,000 cans and 1 , 0 0 0 packets of its Naturlac Infant Formula Powder when it
was determined that the product was deficient in copper, vitamin B6, and
that is, the minimum amount required for each nutrient by the Act
was not present in the formula when it was analyzed.
Congressional interest in this issue began with reports of the link
the use of certain baby formulas and the medical
disorder, metabolic alkalosis.
A hearing was held by the Subcommittee on
Oversight and Investigations of the House Committee on Interstate and Foreign
Commerce Nov. 1 , 1979, to examine the adequacy of the existing law and
regulations concerning the manufacture of infant formulas, and the recall
procedures when a product is determined to be defective.
hearing, several bills were introduced to provide
specific provisions for
infant formulas in the Federal Food, Drug and Cosmetic Act
A number of hearings were held in both the House and Senate to
examine the various provisions of the bills.
law on Sept. 26, 1980 (P.L. 96-359).
The Infant Formula Act of 1980 created a new section for infant formulas
in the FD&C Act, Sec. 412.
The term "infant formulaw was defined under Sec.
201 (a) to mean w a food which purports to be or is represented for special
dietary use solely a s a food for infants by reason of its simulation of human
milk or its suitability a s a complete or partial substitute for human milk".
The new provisions established minimum, a n 8 where appropriate maximum, levels
for nutrient requirements in formula. A formula is deemed to be a d ~ l ~ e r a t e d
if it does not provide nutrients in accordance with levels stated in the law,
or if it does not meet the quality control standards for processing.
Secretary is permitted to revise the nutrient requirements, a s it becomes
On an-Lnterim basis t h e - Act .required the manufacturer
to notify the
Secretary every 90 days of the nutrient composition of his product until the
quality control procedures to be promulgated by the Secretary were in effect.
The final regulations require the manufacturer t o notify the- Secretary not
less than 9 0 days before the first processing of any infant formula that the
formula provides nutrients and meets quality control requirements
accordance with the law. The Secretary is also to be notified of any changei? the formulation or processing of a formula to be sure that the product
complies With the provisions of the law.
In the case where a manufacturer
has any knowledge that a formula is not in compliance and presents a risk t o
human health, the manufacturer has to notify the Secretary.
Under the permanent provisions of the Act, in situations where a recall i s
required, regulations are to be promulgated to prescribe the scope and extent
of recalls necessary and appropriate for the degree of risk to human health
presented by the formula subject to the recall.
The Secretary i s to review
the effectiveness of the manufacturer's
recall to determine whether i t
complies with the regulations. Manufacturers are required to keep records on
the distribution of their products for use in the event of a recall.
The law exempts from the nutrient and notification requirements any infant
formula that is represented and labeled for use by an infant who has an
inborn error of metabolism, a low birth weight, or who otherwise has an
Unusual medical or dietary problem.
The Secretary may, by regulation,
establish terms and conditions for the exemption of these special infant
1 1 , 1982, ,the House Committee on Energy
Subcommittee on Oversight and Investigations held a hearing on the rgcall of
the Nursoy and SMA formulas. The purpose of the hearing was to determine (1)
surrounding the vitamin B6 deficiency i n the Wyeth
products; (2) the status of the FDA regulations concerning infant formula
recall and quality control being promulgated as a result of the Infant
Formula Act of 1980; and (3) the ability of FDA to carry out the monitoring
of su'ch recalls given present budgetary constraints.
Congressional. oversig'ht has continued in this area to monitor
effectiveness of the new law and its accompanying regulations i n preventing
future incidents of defective infant formulas.
On July 26, 1979, the Center for Disease Control
(CDC) first began to
investigate reports of defective formulas when the agency was notified by
local health authorities in Tennessee of three cases of metabolic alkalosis
CDC notified FDA of the reported cases associated with the
formulas on the same day.
On July 31, 1979, CDC notified FDA that 26 cases
of metabolic alkalosis associated with the SynteX products had
By Aug. 31, 1979, there were 115 cases listed in the CDC
On Aug. 1 , 1 9 7 9 , Syntex notified FDA of its plans for recall of the
products and for public notification.
Simultaneously with initiation of the
recall, FDA inspected the firm's three manufacturing plants in a n effort to
determine the cause of the problem and to prevent future
Information obtained during the inspections revealed that two formulation
may have substantially- reduced-the chloride content of the products:
in March 1978 Syntex reduced the sodium content by reducing the salt
chloride); and in June 1978 the soy protein isolate
(protein source) was
changed. Another contributing factor may have been a change i n the water
supply to one of the plants.
Inspections a l s o ' r e v e a l e d that the firm had
By October 1979 Syntex had reformulated its Neo-Mull-Soy
planned to begin marketing it. However, FDA asked Syntex to refrain from
the modified product until FDA was assured that the newly
formulated product was safe and would be manufactured
in accordance with
accepted nutrient standards and good manufacturing practices.
FDA's recall actions followed the established procedures a t that time.
However, misinterpretation of recall instructions within FDA caused a delay
in monitoring the Syntex recall.
In the case of a manufacturer-initiated
recall, FDA recall procedures require the agency to confirm the health
hazard, evaluate the adequacy of the firm's recall strategy, and classify the
The FDA's Health Hazards Evaluation Board rated the Syntex situation
H a significant
as "life-threatening, subacute," meaning that it presented
probability of deathn over an extended period of time.
The situation was
classified as requiring a class 2 recall, based on the opinion that "the risk
of death was not immediate and that there would be no irreversible health
consequencesw if chloride was restored.
While FDA's Bureau of Foods intended
its instructions to require a 10% level of recall audit to be done by the
agency, these instructions were misinterpreted
the FDA San Francisco
office to mean that the minimum
level of audit requirement was to be
undertaken by the manufacturer.
When reports revealed that cans of the
defective formulas were still on store shelves, the agency notified Syntex of
the'problem, began its own effectiveness checks, and issued a memorandum
all FDA bureaus and District offices clarifying recall procedures.
As a follow-up.to the incident, FDA took several actions.
the manufacturers of all infant formula products to express concern about the
recent incident and urged all companies to test their formulas
FDA also conducted its own tests to determine
whether infant formulas currently on the market contained the amounts of the
ingredients declared on the label. The National Institute of Child Health
and Human Development in cooperation with FDC and CDC, initiated a 5-year
follow-up study to assess the long-term health problems associated with use
of the two defective Syntex formulas.
Early in 1980 FDA convened two public meetings to discuss various aspects
of the infant formula problem.
The first was held on Feb. 19-20, to discuss
quality assurance and quality control procedures; manufacturing, packaging
and labeling; and clinical tests as they relate to infant formulas.
second proceeding on Mar. 12-13 was a public hearing
concerned with the
possible nutrient composition of infant formulas and possible revisions of
existing regulation on infant formulas.
Prior to these meetings, FDA
contracted with the Federation of American Societies for Experimental Biology
(FASEB) to prepare a paper on the various topics related to infant formulas
and provide background information for the two public proceedings.
The agency then proposed revision of Statutory authority and regulations
on infant formulas to require manufacturers to perform certain types of tests
and maintain both test records and results to be available to FDA upon
On Mar. 1 8 , 1980, FDA publishe'd in the Federal Register interim
guidelines for the nutrient Composition and nutrient levels of infant
formulas. The recommendations on standards for nutrient levels in infant
for the American Academy
for-mulas +made by -the Commi,ttee- OR Nutrition
Pediatrics (AAP) in 1976 were to be followed by infant formula manufacturers
as interim guidelines until revisions in the existing infant formula
regulations were completed. T h e AAP guidelines for the nutrient composition
of infant formulas are based on a consensus of experts on the nutrient
requirements of infants and the bioavailability of'nutrients
sources used i n infant formulas.
(Bioavailability is the degree to which a
substance becomes available to the target tissue after administration).
During the interim, manufacturers were to notify the Secretary
every 9 0 days that their formulas were in compliance with the interim
guidelines for nutrient standards.
In accordance with the Infant Formula Act of 1980, the
regulations for infant formula quality control procedures were published i n
%he Federal Register on Dec. 3 0 , 1980. The comment period, which was to end
by Mar. 2 , 1981, was extended to May I , 1981. The final rules, which were
published on Apr. 20, 1982, established quality control procedures for -the
manufacture of infant formulas to assure that formulas contain the necessary
nutrients at the levels specified in the Act.
The rules require each
manufacturer to establish a quality control system, but permits each firm to
adopt the system that is best suited to its needs.
The final regulations
require that a n infant formula not be shipped by a manufacturer until the
company's own laboratory results establish that certain nutrients are present
in the product a t the required levels.
The previous regulations had allowed
an infant formula product to be distributed once the processing was complete
without any requirement for testing for nutrient composition.
Prior to the
Infant Formula Act o'f 1980, there were no regulatory
standards for the
nutrient composition of infant formulas, and formulas were regulated under
the good manufacturing
(GMP) regulations applicable to food
sanitation and requirements of low-acid canned foods. Under Title 21, new
part 106 subpart A of the c6de of Federal Regulations
(21 CFR 106A) for
infant formula quality control procedures, regulations are established for:
the Status and applicability of the quality control procedures regulation;
ingredients control; in-process
evaluation; coding; records; and new formulations.
The regulations became
effective July 201 1982.
In December 1982, a suit was filed against FDA by several consumer groups
who claimed that the FDA's infant formula regulations fail to carry out the
mandate of the 1980 law.
In January 1982, FDA proposed regulations for recall procedures to be
followed by infant formula manufacturers
in accordance. with the Infant
Formula Act of 1980.
These regulations were designed to facilitate the
removal of products from the market which do not provide the nutrients
required or are otherwise adulterated
or misbranded according to the
provisions and definitions of the Act.
The recall procedures contained in
new part 7, subpart d l of 21 CFR specify: the scope and effect, elements,
reports, termination, revision, and compliance for a infant formula recall.
The final regulations were published in the Federal Register on Apr.
1982, and became effective June 1 , 1982, creating specific procedures for
infant formulas. Previously infant formulas were recalled under the general
enforcement procedures for any food product.
On July 1 2 , 1983, FDA proposed in the Federal Register two additional
rules pertaining to infant formula. One proposed rule dealt with exemptions
to the Act for specialty formulas intended for use by infants with
medical or dietary needs.
Under this regulation, FDA proposed to establish
the terms'a-nd conditions.under-which those infant formulas would continue to
The Act exempted these formulas from requirements set forth in
the law until special rules could be promulgated for specialty formulas.
s proposal would also establish quality control, nutrient, and labeling
uirements for exempt infant formulas.
The second rule, published July 1 2 ,
concerned with revising the labeling requirements for infant formula.
The proposal would require the label to provide a declaration
required, expiration date, and directions for preparation and use.
rule, if adopted, will provide necessary information for health care
professionals and consumers in the appropriate preparation and use of infant
The comment period for both rules closed Sept. 1 2 , 1983.
On Apr. 1 1 , 1984, FDA published in the Federal Register a proposal to
revise the infant formula nutrient requirements of the Infant Formula Act of
1980 to ensure that infant formula products . a r e adequate i n meeting the
normal infant's total nutritional requirements.
The proposed rules would
codify most of the nutrients and nutrient levels specified in the Act without
It would revise the minimum levels for calc.ium and phosphorus, set
maximum levels for iron and iodine, and establish the minimum level for
It would also require that any added vitamin K be in the form of
phyllogluinone, the only form of the vitamin permitted i n foods.
proposal is based on the recommendations of the Committee on Nutrition of the
American Academy of Pediatrics, the Codex Alimentarius Commission's standard
for infant formulas, and other sources.
Although the Infant Formula Act of 1980 became law and the regulations
promulgated under the
interpretation of the law remain unclear.
Changes in the knowledge of
nutrient needs for infants may require frequent modification
standaras in both the law and the regulations.
It is unclear a t the present
time how the law will be interpreted with
regard to special formulas
classified under the exemption provision and whether the new rules will
prevent future incidents of quality control problems with infant formulas.