[Federal Register Volume 59, Number 2 (Tuesday, January 4, 1994)]
[Rules and Regulations]
[Pages 433-437]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 93-31817]


[[Page Unknown]]

[Federal Register: January 4, 1994]


DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration
[Docket No. 93N-0481]
RIN 0905-AB67

 

Food Labeling: Health Claims and Label Statements; Folate and 
Neural Tube Defects

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing that, in 
accordance with the Nutrition Labeling and Education Act of 1990 (the 
1990 amendments), as amended by the Dietary Supplement Act of 1992 (the 
DS act), the regulation proposed on October 14, 1993 (58 FR 53254), to 
authorize the use of a health claim about the relationship between 
folate and the risk of neural tube defects (NTD's) is now considered a 
final regulation for dietary supplements of vitamins, minerals, herbs, 
and other similar nutritional substances (dietary supplements). The 
proposed regulation set out the information that must be included in 
such a health claim to ensure that it is an accurate representation of 
the effect of intake of folic acid on the risk of NTD's, and that any 
claims that are made are understandable, informative, and not 
misleading.

DATES: The final regulation will become effective on July 1, 1994.

FOR FURTHER INFORMATION CONTACT: Judith W. Riggins, Office of Policy 
(HF-23), Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 
20857, 301-443-2831.
    or
Jeanne I. Rader, Center for Food Safety and Applied Nutrition (HFS-
175), Food and Drug Administration, 200 C St. SW., Washington, DC 
20204, 202-205-5375.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing that, in accordance with section 3(b)(1)(A)(ii), 
(b)(1)(A)(x), and (b)(2) of the 1990 amendments as amended by the DS 
act (Pub. L. 102-571), the regulation proposed on October 14, 1993 (58 
FR 53254), to authorize the use of a health claim about the 
relationship between folate and the risk of NTD's is now considered a 
final regulation for dietary supplements of vitamins, minerals, herbs, 
and other similar nutritional substances (dietary supplements).

II. Passage of 1990 Amendments

    The 1990 amendments to the Federal Food, Drug, and Cosmetic Act 
(the act) (Pub. L. 101-535) gave the Secretary of Health and Human 
Services (the Secretary), and by delegation FDA, the authority to issue 
regulations authorizing health claims on the labels and in the labeling 
of foods. Section 403(r)(1)(B) of the act (21 U.S.C. 343(r)(1)(B)) 
provides that a product is misbranded if it bears a claim that 
characterizes the relationship of a nutrient to a disease or health-
related condition, unless the claim is made in accordance with 
procedures and standards established under section 403(r)(3) and 
(r)(5)(D) of the act (21 U.S.C. 343(r)(3) and (r)(5)(D)).
    The 1990 amendments also directed the Secretary to determine 
through rulemaking whether claims regarding 10 nutrient-disease 
relationships met the requirements of the act. The relationship of 
folic acid and NTD's was among those 10 topics (section 3(b)(1)(A)(x) 
of the 1990 amendments).

III. Chronology of Regulatory and Other Activities Related To 
Folate and Ntd's

A. The 1991 Proposed Rule

    In the Federal Register of November 27, 1991 (56 FR 60537), FDA 
proposed to not authorize a health claim on folic acid and NTD's. The 
agency tentatively concluded that the available evidence did not 
establish that the standard that FDA had proposed for health claims for 
dietary supplements under section 403(r)(5)(D) of the act was met, that 
is, that there was not significant scientific agreement, based on the 
totality of publicly available scientific evidence, that the claim is 
valid.

B. The Public Health Service Recommendations

    In September 1992, the Public Health Service (PHS) issued a 
recommendation that all women of childbearing age in the United States 
who are capable of becoming pregnant should consume 0.4 milligram (mg) 
of folic acid/day for the purpose of reducing their risk of having a 
pregnancy affected with spina bifida or other NTD's. The recommendation 
was based on data suggesting that folic acid, when given at a high dose 
(4 mg), can reduce the risk of recurrence of NTD's and on a synthesis 
of information from studies that used multivitamins containing folic 
acid at dose levels from 0 to 1,000 micrograms/day. The PHS 
recommendation identified approaches and identified outstanding issues, 
including the appropriate intake of folate, the potential role of other 
nutrients in reduction of risk of NTD's, safety concerns, and the 
``folate-preventable'' fraction of NTD's.

C. The Dietary Supplement Act of 1992

    In October 1992, the DS act was enacted. This statute imposed a 
moratorium on FDA's implementation of the 1990 amendments with respect 
to dietary supplements until December 15, 1993. The DS act directed FDA 
to issue proposed rules to implement the 1990 amendments with respect 
to dietary supplements by June 15, 1993, and to issue final rules based 
on these proposals by December 31, 1993. The DS act also amended the 
so-called ``hammer'' provision of the 1990 amendments, section 3(b)(2) 
of the 1990 amendments, to provide that if the agency did not meet the 
established December 31, 1993, timeframe for issuance of final rules, 
the proposed regulations would be considered final regulations.

D. The 1993 Final Rules for Health Claims for Foods in Conventional 
Food Form

    On January 6, 1993 (58 FR 2606), FDA published a final rule to not 
authorize a health claim for folic acid and NTD's. However, the agency 
reaffirmed its support of the PHS recommendation that all women of 
childbearing age in the United States who are capable of becoming 
pregnant should consume 0.4 mg of folic acid daily to reduce their risk 
of having a pregnancy affected with spina bifida or other NTD's. The 
agency noted, however, that unresolved questions about the safe use of 
folate remained. The agency concluded that it could not authorize a 
health claim until these questions were resolved. Because of the DS 
act, FDA took no final action with respect to the use of a health claim 
on folic acid and NTD's on dietary supplements.

E. The 1993 Proposal to Authorize a Health Claim on Folic Acid and 
NTD's

    On October 14, 1993, FDA published a proposed rule to authorize the 
use of a health claim about the relationship of folate and NTD's on the 
labels of foods in conventional food form and dietary supplements (58 
FR 53254). FDA provided 60 days for comment on this proposed action. 
The comment period closed on December 13, 1993.
    Section 3(b)(2) of the 1990 amendments, as amended by section 
202(a)(2)(B)(ii) of the DS act, provides that if the Secretary does not 
promulgate final regulations on any of the health claims applicable to 
dietary supplements in a timely manner, the proposed regulations shall 
be considered final regulations but not until December 31, 1993. FDA 
did not issue a final regulation on the use of a health claim on folic 
acid and NTD's on dietary supplements by December 31, 1993. Therefore, 
FDA is issuing this document announcing that by operation of the law, 
the proposal to authorize a health claim about the relationship of 
folate and NTD's published in the Federal Register of October 14, 1993, 
is now considered a final regulation applicable to the labels and 
labeling of dietary supplements only. The agency proposed that 21 CFR 
part 101 be amended as follows:

PART 101--FOOD LABELING

    2. Section 101.71 Health claims: claims not authorized is amended 
by removing paragraph (c) and by redesignating paragraphs (d) through 
(f) as (c) through (e), respectively.

    3. New Sec. 101.79 is added to subpart E to read as follows:


Sec. 101.79  Health claims: folate and neural tube defects.

    (a) Relationship between folate and neural tube defects--(1) 
Definition. Neural tube defects are serious birth defects of the brain 
or spinal cord that can result in infant mortality or serious 
disability. The birth defects anencephaly and spina bifida are the most 
common forms of neural tube defects and account for about 90 percent of 
these defects. These defects result from failure of closure of the 
covering of the brain or spinal cord during early embryonic 
development. Because the neural tube forms and closes during early 
pregnancy, the defect may occur before a woman realizes that she is 
pregnant.
    (2) Relationship. The available data show that diets adequate in 
folate may reduce the risk of neural tube defects. The strongest 
evidence for this relationship comes from an intervention study by the 
Medical Research Council of the United Kingdom that showed that women 
at risk of recurrence of a neural tube defect pregnancy who consumed a 
supplement containing 4 milligrams (mg) (4,000 micrograms (g)) 
folic acid daily had a reduced risk of having a child with a neural 
tube defect. (Products that contain this level of folic acid are 
drugs.) In addition, based on its review of a Hungarian intervention 
trial that used a multivitamin and multimineral preparation containing 
800 g (0.8 mg) of folic acid, and its review of the 
observational studies that reported use of multivitamins containing 0 
to 1,000 g of folic acid, the Food and Drug Administration 
concluded that most of these studies had results consistent with the 
conclusion that folate, at levels attainable in usual diets, may reduce 
the risk of neural tube defects.
    (b) Significance of folate--(1) Public health concern. Neural tube 
defects occur in approximately 0.6 of 1,000 live births in the United 
States (i.e., about 2,500 cases among 4 million live births annually). 
Neural tube defects are believed to be caused by many factors. The 
single greatest risk factor for a neural tube defect-affected pregnancy 
is a personal or family history of a pregnancy affected with a such a 
defect. However, about 90 percent of infants with a neural tube defect 
are born to women who do not have a family history of these defects. 
The available evidence shows that diets adequate in folate may reduce 
the risk of neural tube defects but not of other birth defects.
    (2) Populations at risk. Prevalence rates for neural tube defects 
have been reported to vary with a wide range of factors, including 
genetics, geography, socioeconomic status, maternal birth cohort, month 
of conception, race, nutrition, and maternal health, including maternal 
age and reproductive history. Women with a close relative (i.e., 
sibling, niece, nephew) with a neural tube defect, those with insulin-
dependent diabetes mellitus, and women with seizure disorders who are 
being treated with valproic acid or carbamazepine are at significantly 
increased risk compared with women without these characteristics. Rates 
for neural tube defects vary within the United States, with lower rates 
observed on the west coast than on the east coast.
    (3) Those who may benefit. Based on a synthesis of the results of 
several observational studies, the Public Health Service has estimated 
that about 50 percent of neural tube defect-affected pregnancies in the 
United States (e.g., about 1,250) may be averted annually if all women 
consume adequate amounts of folate daily (i.e., 0.4 mg) throughout 
their childbearing years.
    (c) Requirements. The label or labeling of food in conventional 
food form or dietary supplements may contain a folate/neural tube 
defect health claim provided that:
    (1) General requirements. The health claim for a food or supplement 
meets all of the general requirements of Sec. 101.14 for health claims, 
except that a food or dietary supplement may qualify to bear the health 
claim if it meets the definition of the term ``good source.''
    (2) Specific requirements--(i) Nature of the claim--(A) 
Relationship. A health claim that women who are capable of becoming 
pregnant and who consume adequate amounts of folate daily during their 
childbearing years may reduce their risk of having a pregnancy affected 
by spina bifida or other neural tube defects may be made on the label 
or labeling of foods in conventional food form or of dietary 
supplements provided that:
    (B) Specifying the nutrient. In specifying the nutrient, the claim 
shall use the terms ``folate,'' ``folic acid,'' ``folacin,'' ``folate, 
a B vitamin,'' ``folic acid, a B vitamin,'' or ``folacin, a B 
vitamin.''
    (C) Specifying the condition. In specifying the health-related 
condition, the claim shall identify the birth defects as ``neural tube 
defects,'' ``birth defects, spina bifida, or anencephaly,'' ``birth 
defects of the brain or spinal cord anencephaly or spina bifida,'' or 
``spina bifida or anencephaly, birth defects of the brain or spinal 
cord;''
    (D) Multifactorial nature. The claim shall state that neural tube 
defects have many causes and shall not imply that folate intake is the 
only recognized risk factor for neural tube defects.
    (E) Prevalence. In specifying the prevalence of neural tube defects 
among women in the general population, the claim shall state that such 
birth defects ``which, while not widespread, are extremely 
significant'' or ``* * * birth defects * * * that, while not 
widespread, are extremely significant.''
    (F) Reduction in risk. The claim shall not attribute any specific 
degree of reduction in risk of neural tube defects, including mention 
of the Public Health Service estimate that 50 percent of neural tube 
defects may be averted annually, to maintaining an adequate folate 
intake throughout the childbearing years. The claim shall state that 
some women may reduce their risk of a neural tube defect pregnancy by 
maintaining adequate intakes of folic acid during their childbearing 
years.
    (G) Safe upper limit of daily intake. Claims on fortified foods in 
conventional form and on dietary supplements that contain more than 25 
percent of the RDI for folate (100 g per serving or per unit) 
shall state that 1 mg folate per day is the safe upper limit of intake 
(e.g., ``Folate consumption should be limited to 1,000 g per 
day from all sources.'')
    (H) The claim. The claim shall not state that a specified amount of 
folate (e.g., 400 g in a dietary supplement) is more effective 
in reducing the risk of neural tube defects than a lower amount (e.g., 
100 g in a breakfast cereal or from diets rich in fruits and 
vegetables).
    (ii) Nature of the food--(A) Requirements. The food or supplement 
shall meet or exceed the requirements for a good source of folate as 
defined in Sec. 101.54;
    (B) Diets adequate in folate. The claim shall identify diets 
adequate in folate by using phrases such as ``* * * diets that include 
2 to 4 servings per day of fruits) including citrus fruits and juices), 
3 to 5 servings of vegetables (including dark green leafy vegetables 
and legumes), 6 to 11 servings of enriched grain products (such as 
breads, rice, and pasta) and fortified cereals. Such diets provide many 
essential minerals and vitamins, including folate. Women who do not eat 
well-balanced diets or who may be concerned about their diets may 
choose to obtain folate from dietary supplements.''; or ``Adequate 
amounts of folate, a B vitamin, can be obtained from diets rich in 
fruits, including citrus fruits and juices, vegetables, including dark 
green leafy vegetables and legumes, enriched grain products, including 
breads, rice, and pasta, fortified cereals, or a dietary supplement.''; 
or ``Adequate amounts of folate, a B vitamin, can be obtained from 
diets rich in fruits, dark green leafy vegetables and legumes, enriched 
grain products, fortified cereals, or from dietary supplements.''
    (C) Dietary supplements. Dietary supplements shall meet the United 
States Pharmacopeia (U.S.P.) standards for disintegration and 
dissolution, except that if there are no applicable U.S.P. standards, 
the folate in the dietary supplement shall be shown to be bioavailable 
under the conditions of use stated on the product label.
    (iii) Limitation. The claim shall not be made on foods in 
conventional food form or dietary supplements that contain more than 
100 percent of the RDI for vitamin A as retinol or preformed vitamin A 
or vitamin D.
    (iv) Nutrition labeling. The nutrition label shall include 
information about the amount of folate in the food. This information 
shall be declared after the declaration for iron if only the levels of 
vitamin A, vitamin C, calcium, and iron are provided, or in accordance 
with Sec. 101.9(c)(8) and (c)(9) if other optional vitamins or minerals 
are declared.
    (3) Optional information--(i) Risk factors. The claim may 
specifically identify risk factors for neural tube defects;
    (ii) Relationship between folate and neural tube defects. The claim 
may include statements from paragraphs (a) and (b) of this section that 
summarize the relationship between folate and neural tube defects and 
the significance of the relationship except for information 
specifically prohibited from the claim.
    (iii) Personal history of a neural tube defect-affected pregnancy. 
The claim may state that women with a history of a neural tube defect 
pregnancy should consult their physicians or health care providers 
before becoming pregnant.
    (iv) Daily value. The claim may identify the daily value level of 
400 g of folate per day as the target intake goal.
    (d) Model health claims. The following are examples of model health 
claims that may be used in food labeling to describe the relationship 
between folate and neural tube defects:
    (1) Example 1. Women who consume adequate amounts of folate, a B 
vitamin, daily throughout their childbearing years may reduce their 
risk of having a child with a neural tube birth defect. Such birth 
defects, while not widespread, are very serious. They can have many 
causes. Adequate amounts of folate can be obtained from diets rich in 
fruits, dark green leafy vegetables and legumes, enriched grain 
products, fortified cereals, or a supplement. Folate consumption should 
be limited to 1,000 g per day from all sources.
    (2) Example 2. Women who consume adequate amounts of folate daily 
throughout their childbearing years may reduce their risk of having a 
child with a birth defect of the brain and spinal cord. Such birth 
defects, while not widespread, are very serious. They can have many 
causes. Adequate amounts of folate, a B vitamin, can be obtained from 
diets rich in fruits, dark green leafy vegetables and legumes, enriched 
grain products, fortified cereals, or a supplement. Women who have had 
a child with a spinal cord birth defect should consult a physician 
before becoming pregnant. Folate consumption should be limited to 1,000 
g per day from all sources.
    (3) Example 3. Women who take steps to ensure that their folate 
intake is adequate throughout their childbearing years may reduce their 
risk of having a child with a neural tube defect. Such birth defects, 
while not widespread, are very serious. They can have many causes. 
Adequate amounts of folate, a B vitamin, can be obtained from diets 
rich in citrus fruits and juices, dark green leafy vegetables and 
legumes, enriched grain products such as breads, rice, and pasta, 
fortified cereal, or a supplement. Folate consumption should be limited 
to 1,000 g per day from all sources.
    (4) Example 4. Women who take steps to ensure that their folate 
intake is at least 400 g daily throughout their childbearing 
years may reduce their risk of having a child with spina bifida or 
anencephaly, birth defects of the brain or spinal cord that, while not 
widespread, are very serious. These birth defects can have many causes. 
Adequate amounts of folate, a B vitamin, can be obtained from diets 
rich in fruits, including citrus fruits and juices, vegetables, 
including dark green leafy vegetables and legumes, enriched grain 
products, including breads, rice, and pasta, fortified cereals, or from 
a supplement. Women who have had a pregnancy affected with a neural 
tube defect should consult a physician before becoming pregnant. Folate 
consumption should be limited to 1,000 g per day from all 
sources.

    (5) Example 5. Some women who consume the Daily Value of folate 
(400 g) throughout their childbearing years may reduce their 
risk of having a child affected with spina bifida or anencephaly, birth 
defects of the brain or spinal cord that, while not widespread, are 
very serious. These birth defects can have many causes. Women of 
childbearing age should choose well-balanced diets that include 2 to 4 
servings per day of fruits (including citrus fruits and juices), 3 to 5 
servings of vegetables (including dark green leafy vegetables and 
legumes), 6 to 11 servings of enriched grain products (such as breads, 
rice, and pasta) or fortified cereals throughout their childbearing 
years. Such diets provide many essential minerals and vitamins, 
including folate. Women who may be concerned about their diets may 
choose to obtain folate from a supplement. Folate consumption should be 
limited to 1,000 g per day from all sources.

    (e) Effective date. For fortified foods, this regulation is 
effective on the date the food additive regulation on the use of folic 
acid that was proposed on October 14, 1993, becomes effective.

    The 1990 amendments state that FDA is to promptly publish notice of 
the new status of the proposed regulations in the Federal Register. 
This notice is issued in response to that requirement. The agency 
emphasizes, however, that this regulation is deemed to be a final 
regulation only with respect to dietary supplements.

    The agency notes that this document is part of a separate 
rulemaking contemplated by Congress if the final regulation was not 
issued by December 31, 1993. This rulemaking bears a separate docket 
number from the one assigned to the October 14, 1993 rulemaking to 
distinguish it from that rulemaking, which is ongoing. The agency 
intends to continue its rulemaking with respect to folic acid and 
neural tube defects and to issue a final rule as quickly as possible.

    In this regard, FDA recognizes that clarification with respect to 
the legal status of claims about folic acid and NTD's on foods in 
conventional food form is appropriate. FDA advises that, given the PHS 
recommendation and the results of FDA's preliminary review of the 
evidence on this claim, at this time it has no intention of taking 
action against foods in conventional food form that are naturally high 
in folate that bear a claim on this nutrient-disease relationship, so 
long as the claim fully complies with the provisions of the regulation 
that has become final for dietary supplements by operation of law.
    However, for foods fortified with folic acid, the agency has more 
significant concerns. As explained in the health claim proposal on 
folic acid and NTD's (58 FR 53254 at 53288) and the proposal to amend 
the food additive regulation on folic acid that published in the 
Federal Register on October 14, 1993 (58 FR 53312), there appears to be 
a rather narrow range of safe use of folic acid in food. Based on this 
tentative view, FDA would be very concerned, at least until it reached 
a final determination in those proceedings, if manufacturers began 
adding folic acid to their products, or increasing the amount of folic 
acid in their products, to qualify for a claim. Therefore, FDA strongly 
discourages the use of a health claim about folic acid and NTD's on any 
such fortified products pending the issuance of a final rule on this 
nutrient-disease relationship.
    As stated above, FDA intends to issue a final rule in the 
proceeding on a health claim on folic acid and NTD's that it began on 
October 14, 1993, in the near future. FDA is in the process of 
evaluating the comments that it has received in that proceeding, 
including the results of an advisory committee meeting held on October 
14 and 15. FDA will attempt to resolve the issues in that ongoing 
proceeding as soon as possible.

    Dated: December 23, 1993.
David A. Kessler,
Commissioner of Food and Drugs.
Donna E. Shalala,
Secretary of Health and Human Services.
[FR Doc. 93-31817 Filed 12-29-93; 8:45 am]
BILLING CODE 4160-01-F