[Federal Register Volume 63, Number 82 (Wednesday, April 29, 1998)]
[Notices]
[Pages 23633-23637]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-11293]



  Federal Register / Vol. 63, No. 82 / Wednesday, April 29, 1998 / 
Notices  

[[Page 23633]]



DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration
[Docket No. 98N-0048]
RIN 0910-AA59


Dietary Supplements; Comments on Report of the Commission on 
Dietary Supplement Labels

AGENCY: Food and Drug Administration, HHS.

ACTION:  Notice.

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SUMMARY:  The Food and Drug Administration (FDA) is announcing its 
views on recommendations and guidance of the Commission on Dietary 
Supplement Labels, as presented in the Commission's Final Report. The 
document also responds to recommendations and guidance directed to FDA. 
Elsewhere in this issue of the Federal Register, FDA is issuing a 
proposed rule that responds to guidance in the Commission Report 
concerning statements about the effect of dietary supplements on the 
structure or function of the body.

ADDRESSES: Submit written comments to the Dockets Management Branch 
(HFA-305), Food and Drug Administration, 12420 Parklawn Dr., rm. 1-23, 
Rockville, MD 20857.

FOR FURTHER INFORMATION CONTACT: Ilisa B.G. Bernstein, Office of Policy 
(HF-23), Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 
20857, 301-827-3380, IB[email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    Section 12 of the Dietary Supplement Health and Education Act of 
1994 (the DSHEA) (Pub. L. 103-417) established an independent agency 
within the Executive Branch known as the Commission on Dietary 
Supplement Labels (the Commission). The Commission was charged with 
conducting a study on, and providing recommendations for regulating 
label claims and statements for dietary supplements, including the use 
of literature in connection with the sale of dietary supplements and 
procedures for evaluating such claims.
    The Commission was appointed in October 1995 and convened its first 
meeting in February 1996. Interested persons presented oral and written 
testimony at several Commission meetings. A draft report of the 
Commission was released for public comment on June 24, 1997. On 
November 24, 1997, the final report of the Commission (Commission 
Report) was released.
    Under section 12(d)(3) of the DSHEA, within 90 days of issuance of 
the Commission's final report, the Secretary of Health and Human 
Services is required to publish in the Federal Register
a notice of any recommendation of [the] Commission for changes in 
regulations of the Secretary for the regulation of dietary 
supplements and shall include in such notice a notice of proposed 
rulemaking on such changes together with an opportunity to present 
views on such changes. Such rulemaking shall be completed not later 
than 2 years after the date of issuance of such report.
    The Commission divided its conclusions into three categories: 
Findings, guidance, and recommendations. The Commission Report did not 
contain any recommendations for changes to FDA's ``regulations * * * 
for the regulation of dietary supplements.'' The Commission made only 
two recommendations directed to FDA. These recommendations pertain to 
botanicals and are discussed in section VIII of this document. Neither 
of the two recommendations suggests changes in regulations governing 
dietary supplements. Therefore, there are no recommendations subject to 
the deadlines imposed under section 12 of the DSHEA. In this document 
the agency is announcing its views on the Commission's recommendation 
and guidance, as well as a description of the actions the agency 
intends to take because of these recommendations and guidance. In 
addition, based on guidance set forth in the Commission Report, the 
agency is issuing a proposed rule elsewhere in this issue of the 
Federal Register concerning statements about the effects of dietary 
supplements on the structure or function of the body.
    This document addresses only guidance and recommendations made in 
the Commission Report that are addressed to FDA or relevant to its 
responsibilities.

II. Safety of Dietary Supplements

    The Commission Report states that existing postmarket surveillance 
systems for dietary supplements could be improved. The Commission 
Report notes that there is no mandatory requirement for industry, 
consumers, or health care professionals to report adverse events 
resulting from consumption of foods and dietary supplements, and 
specifically states that the Commission is not recommending such a 
requirement. However, the Commission Report does urge FDA, industry, 
the scientific community, and consumer groups to work together 
voluntarily to improve passive postmarketing surveillance systems.
    The agency agrees that greater cooperation among FDA, industry, and 
other interested parties to enhance the effectiveness of current 
surveillance systems would improve the ability of these systems to 
identify potential safety problems and thereby improve their public 
health utility. FDA currently collects reports of adverse events 
associated with the use of dietary supplements through its MedWatch 
system, which accepts voluntary reports of adverse events from health 
professionals and consumers for serious adverse events related to FDA-
regulated products. FDA also receives reports of adverse events 
associated with the use of dietary supplements through the Center for 
Food Safety and Applied Nutrition (CFSAN) Adverse Event Monitoring 
System. All reports FDA receives concerning adverse events associated 
with dietary supplements are entered into CFSAN's Special Nutritionals 
Adverse Event Monitoring System database for evaluation and monitoring.
    The agency intends to respond to the Commission Report's guidance 
by initiating a process to further cooperation among interested 
parties. The agency has asked the FDA Foods Advisory Committee 
(composed of outside experts who advise the agency on food issues) to 
consider the issue of postmarket surveillance and particularly, how 
best to collect and share surveillance information. The Foods Advisory 
Committee (FAC) considered these issues at its February 1998 meeting 
and referred them to a FAC internal working group to develop 
recommendations for consideration by the full FAC.
    The Commission Report strongly suggests that dietary supplement 
manufacturers include appropriate warning statements in product 
information where necessary. Although no corresponding guidance or 
recommendation to the agency was made, the agency intends to work with 
the FDA Foods Advisory Committee and industry in developing guidance on 
the use of warning statements on dietary supplement labeling.
    Also related to safety of dietary supplements, the Commission 
Report urges FDA to use its authority under the DSHEA to take swift 
enforcement action to address potential safety issues. The agency takes 
seriously its mission to promote and protect the public health. When 
the agency becomes aware of the presence of harmful dietary supplements 
in the marketplace, it is

[[Page 23634]]

committed to taking timely action, within the legal limits of its 
authority, to remove unsafe products from the market or to take other 
steps to protect consumers from adverse health effects that may result 
from the use of unsafe dietary supplements.

III. Nutritional Labeling and Education Act (NLEA) Claims in 
Dietary Supplement Labeling (Health Claims)

     A health claim is ``any claim made on the label or in labeling of 
a food, including a dietary supplement, that expressly or by 
implication * * * characterizes the relationship of any substance to a 
disease or health-related condition'' (21 CFR 101.14(a)(1) 
(Sec. 101.14(a)(1)). The Federal Food, Drug, and Cosmetic Act (the act) 
provides that FDA may authorize a health claim for a conventional food 
only if the agency determines,
    based on the totality of publicly available scientific evidence 
(including evidence from well-designed studies conducted in a manner 
which is consistent with generally recognized scientific procedures 
and principles), that there is significant scientific agreement, 
among experts qualified by scientific training and experience to 
evaluate such claims, that the claim is supported by such evidence.
21 U.S.C. 343(r)(3)(B)(i)).
    Any person may petition FDA to authorize a particular health claim 
by regulation; however, the health claim may not be made until 
authorized by regulation. Current regulations at 21 CFR 101.14 and 
101.70 set forth general requirements for health claims on the labels 
or in the labeling of conventional foods and dietary supplements. These 
regulations apply the same standard (i.e., ``significant scientific 
agreement'') and set forth the same process (i.e., petition process) 
for health claims for dietary supplements as for health claims for 
conventional foods.
    The Commission Report states that the significant scientific 
agreement standard is appropriate and serves the public interest. The 
Commission Report also states that the scientific standard and approval 
process for health claims for dietary supplements should be the same as 
for conventional foods, which is an endorsement of FDA's current 
regulations for health claims on dietary supplements. The Commission 
Report does not recommend any changes in FDA's health claim regulations 
for dietary supplements.
    The Commission Report does suggest, however, that ``FDA should 
ensure that broad input is obtained to ascertain the degree of 
scientific agreement that exists for a particular health claim.'' FDA 
agrees. The agency has considered and will continue to consider the 
opinions of scientific experts outside the agency in its deliberations 
on whether there is significant scientific agreement supporting the 
validity of a particular disease-substance relationship. For example, 
FDA considered and relied on data and opinions from several other 
governmental agencies and professional organizations in deciding to 
authorize a health claim for folate and neural tube defects. See 58 FR 
53254 at 53262-63. The agency is open to input from interested parties 
as to how to improve its process for considering proposed health 
claims.
    On November 21, 1997, 3 days before the Commission Report was 
issued, the President signed into law the ``Food and Drug 
Administration Modernization Act of 1997'' (FDAMA) (Pub. L. 105-115). 
FDAMA, among other things, amended the health claims provisions of the 
act in several respects. The Commission Report does not discuss the 
provisions of the FDAMA as enacted, although it mentions the 
predecessor House and Senate bills. The effect of the FDAMA on health 
claim requirements for dietary supplements is beyond the scope of this 
document. FDA will address such issues during the rulemaking process to 
implement the FDAMA.

IV. Scope of Structure/Function Statements for Dietary Supplements

    The DSHEA added section 403(r)(6) (21 U.S.C. 343(r)(6)) to the act. 
If certain conditions are met, section 403(r)(6) of the act permits 
several categories of statements to be made for dietary supplements, 
including statements that ``describe[] the role of a nutrient or 
dietary ingredient intended to affect the structure or function in 
humans [or] characterize[] the documented mechanism by which a nutrient 
or dietary ingredient acts to maintain structure or function,'' also 
known as ``structure/function'' claims. The Commission Report contains 
general guidance for what would constitute an acceptable structure/
function claim. Elsewhere in this issue of the Federal Register the 
agency is proposing regulations, consistent with the Commission's 
guidance, that describe the types of statements that can be made by a 
manufacturer of a dietary supplement concerning the effect of the 
dietary supplement on the structure or function of the body in 
accordance with section 403(r)(6) of the act.

V. Notification Letters for Statements of Nutritional Support 
(Statements made under section 403(r)(6) of the act)\1\
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    \1\ The Commission Report refers to statements under section 
403(r)(6) of the act as ``statements of nutritional support.'' As 
noted in the September 23, 1997, final rule regarding labeling 
claims for dietary supplements, FDA no longer uses the term 
``statements of nutritional support'' because ``many of the 
substances that can be the subject of this type of claim have no 
nutritional value. Thus, the term `statement of nutritional support' 
is not accurate in all instances.'' 62 FR 49859 at 49863.
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    The act, as amended by the DSHEA, requires the manufacturer of a 
dietary supplement bearing a statement made under section 403(r)(6) of 
the act to notify the Secretary no later than 30 days after the first 
marketing of the dietary supplement with the statement. In the Federal 
Register of September 27, 1996 (61 FR 50771), the agency proposed 
procedures for such notifications. A final rule was issued September 
23, 1997 (62 FR 49883). The regulations set forth the requirements for 
when and where such a notification is to be made and what information 
the notification must contain (see 21 CFR 101.93(a)).
    The Commission Report suggests that manufacturers include certain 
information in the notification letter, including some information not 
required by FDA's regulations. Specifically, the Commission Report 
suggests that the notification letter include the following: A 
statement of the purpose of the notification letter, including the 
exact wording of the statement that is the subject of the notification; 
the name, address, and telephone number of the manufacturer or 
distributor; the trade name of the product, the common or usual name of 
the product, and a description of the product; a copy of the product 
label or label mock-up, if labels have not yet been printed; the 
identity of individual ingredients or combinations of ingredients for 
which the statement is being made, including, for botanicals, the 
common or usual name, the Latin binomial and its scientific authority, 
and the part(s) of the plant(s) used; and a statement of intended use, 
including the recommended dosage and appropriate contraindications or 
warnings. The Commission Report also suggests that, either in the 
notification letter or in a separate public notice, the manufacturer 
affirm that it has substantiation that the statement made under 
403(6)(r) is truthful, not misleading, and scientifically valid and 
that the product does not present a significant or unreasonable risk of 
illness or injury under the conditions of use recommended or suggested 
in the

[[Page 23635]]

labeling. The Commission Report notes that these are suggestions and 
expresses the view that the rulemaking process need not be reopened at 
this time. The agency agrees with the guidance in the Commission 
Report. The agency also agrees that the rulemaking need not be reopened 
at this time, but will reconsider the need to do so in the future if 
experience warrants.
    The Commission Report also suggests that the notification letters 
continue to be made available to the public. The agency will continue 
making these notification letters publicly available by placing them in 
Docket No. 97S-0162 at FDA's Docket Management Branch (address above). 
In addition, the agency will consider other mechanisms to make these 
submissions available.

VI. Substantiation Files for Statements of Nutritional Support 
(Statements made under section 403(r)(6) of the act)

    Section 403(r)(6) of the act requires the manufacturer of a dietary 
supplement making a statement of nutritional support to have 
substantiation that such statement is truthful and not misleading. 
Section 403(r)(6) of the act, however, does not specify what 
constitutes adequate substantiation. The Commission Report includes 
guidance on what quantity and quality of evidence should be used to 
substantiate claims made under section 403(r)(6) of the act. The 
Commission Report also includes guidance on the content of 
substantiation files for statements made under section 403(r)(6) of the 
act, including the notification letter, identification of the product's 
ingredients, evidence to substantiate the statements, evidence to 
substantiate safety, assurances that good manufacturing practices were 
followed, and the qualifications of the person(s) who reviewed the data 
on safety and efficacy. The agency agrees with the guidance.

VII. Publications Exempt From Classification as Labeling When Used 
in Connection With Sales

    The DSHEA added section 403B of the act (21 U.S.C. 343-2). This 
provision exempts certain publications used in connection with the sale 
of dietary supplements from the definition of ``labeling'' in section 
201(m) of the act (21 U.S.C. 321(m)). Under section 403B of the act, a 
``publication'' will be exempt when it:
    (1) is not false or misleading; (2) does not promote a 
particular manufacturer or brand of a dietary supplement; (3) is 
displayed or presented, or is displayed or presented with other such 
items on the same subject matter, so as to present a balanced view 
of the available scientific information on a dietary supplement; (4) 
if displayed in an establishment, is physically separate from the 
dietary supplements; and (5) does not have appended to it any 
information by sticker or any other method.
21 U.S.C. 343-2.
    The Commission Report supports the requirement that information 
about the uses of dietary supplements be balanced and truthful and 
advises the dietary supplement industry to strictly observe the five 
requirements necessary to qualify for the exemption from the labeling 
definition for publications used in connection with the sale of dietary 
supplements. The Commission Report states that:
[b]ecause more experience with the implementation of this provision 
may provide additional information about the use of publications in 
connection with a sale, the Commission suggests that proactive 
monitoring of practice in this area be undertaken by FDA as 
resources permit and that regulatory guidance be developed if 
necessary.
    The agency agrees with the suggestion that it should proactively 
monitor the use of publications in connection with the sale of dietary 
supplements and provide guidance, as necessary, to the industry. The 
agency intends to monitor the use of publications under section 403B of 
the act. Consistent with FDA's practice with claims made under section 
403(r)(6) of the act, the agency intends to continue assisting industry 
in complying with the requirements of this section. If experience 
demonstrates a need for regulatory guidance, the agency will develop 
such guidance in the future.

VIII. Botanical Products

    As previously noted, the DSHEA's charge to the Commission 
encompassed the regulation of label claims. The Commission intrepreted 
this charge to include the marketing of botanical products as over-the-
counter (OTC) drugs when a preventive or therapeutic claim is made.
    The Commission Report recommends that botanical products should 
continue to be available to consumers as dietary supplements when 
properly labeled as such in compliance with the requirements of the 
DSHEA. The Commission did not recommend any changes to FDA's regulation 
of botanical products that are marketed as dietary supplements.
    The Commission Report, however, did note that there may be 
instances in which consumers would be better served by having certain 
botanical products marketed as OTC drug products, so that statements 
regarding the prevention or treatment of disease may accompany the 
product. As the Commission Report also notes, some botanical 
ingredients are recognized for specific preventive and therapeutic 
uses, and botanical pharmacopeias have been established in a number of 
developed countries. Yet, as the Commission observed, in the United 
States, many botanicals are being labeled with statements of 
nutritional support that suggest only indirectly the type of 
therapeutic use that is traditionally associated with the product.
    To address this concern, the Commission Report advises that a study 
is needed ``regarding the establishment of some alternative system for 
regulating botanical products that are used for purposes other than to 
supplement the diet but that cannot meet OTC drug requirements.'' In 
addition, the Commission Report states that a comprehensive evaluation 
is needed of the regulatory systems that other countries have adopted 
to regulate botanicals with preventive or therapeutic uses. While the 
U.S. drug regulatory system ``as it currently exists'' may allow some 
botanical remedies to be marketed OTC, the Commission Report suggests 
that existing FDA requirements might preclude others from entering the 
OTC drug market.
    Finally, the Commission Report recommends ``that FDA promptly 
establish a review panel for OTC claims for botanical products that are 
proposed by manufacturers for drug uses,'' and suggests that FDA ``give 
special attention to the feasibility of approving botanical remedies 
for OTC uses in which sufficient evidence is available.''
    For several years, FDA has been engaged in discussions with experts 
within the Government, academia, and industry, regarding the regulatory 
status of botanical products. FDA has actively participated in symposia 
and workshops sponsored by the National Institutes of Health (NIH) and 
the Drug Information Association (DIA), which focused on topics such as 
identification and characterization of botanical products, the safety 
and efficacy evaluation of botanical products, the various regulatory 
pathways to market that a botanical product could take, and the 
necessary information that would be required for a particular 
regulatory route.
    Since 1994, FDA has reviewed the relevant laws and regulations, 
policies and, in some cases, draft policies, from regulatory and 
advisory authorities around the world. Although the agency agrees that 
a much more comprehensive evaluation would be helpful, the project

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as outlined by the Commission would be costly and resource-intensive. 
Unfortunately, because resources have not been allocated for such a 
comprehensive study, FDA is unable to act on its own to implement the 
Commission's suggestion at this time. Agency personnel, however, are 
available to work with persons interested in conducting such a study on 
study design features to provide other technical assistance.
    With respect to the Commission Report's points regarding evaluating 
botanicals under FDA's OTC drug review, under FDA's existing statutory 
framework, a drug product may avoid ``new drug'' premarket approval 
requirements and may be eligible for marketing under an OTC drug 
monograph if (1) the product is generally recognized as safe and 
effective under the conditions for use for which it is labeled; and (2) 
if the product has been used to a material extent and for a material 
time under those conditions. See section 201(p) of the act. (21 U.S.C. 
321(p)). FDA recognizes, however, the need to clarify the criteria for 
eligibility under the OTC drug review for certain additional OTC drug 
active ingredients, indications, dosage forms, dosage strengths, routes 
of administration, and combinations. The agency has interpreted section 
201(p)(2) of the act to mean use in the United States (see 61 FR 51625, 
51626 (October 3, 1996)).
    In the Federal Register of October 1996, FDA issued an advance 
notice of proposed rulemaking (ANPRM) seeking comment on eligibility 
requirements and, among other matters, whether OTC marketing experience 
abroad could be used to establish ``material time'' and ``material 
extent'' requirements (61 FR 51625, October 3, 1996). For many 
botanical products, the history of use is based on marketing experience 
outside the United States.
    Based on the comments received in response to the October 1996 
ANPRM, the agency expects to issue a proposed rule setting forth 
criteria for eligibility in the OTC drug monograph system, including 
definitions of the terms ``material extent'' and ``material time.'' 
Unless and until regulations are in place that would allow FDA to 
accept foreign marketing experience, it may be difficult for many 
botanical products to qualify for inclusion in the existing OTC 
monograph system. Consequently, establishing an OTC advisory panel to 
evaluate therapeutic and preventive drug claims for botanical products, 
as the Commission recommends, would be premature at this time. The 
agency, however, intends to work expeditiously on rulemaking for this 
issue.
    In the interim, if there were a situation in which the scientific 
evidence and marketing experience submitted to the agency are 
sufficient to allow a botanical ingredient to be considered under the 
existing framework, then the agency would work expeditiously to assess 
whether the submitted data and experience supports marketing under an 
OTC drug monograph.
    In addition, recognizing the need for guidance for manufacturers 
seeking to develop botanicals as either OTC or prescription drug 
products, and recognizing the unique nature of botanical products, the 
agency currently is developing a draft guidance for industry that 
discusses the kinds of data necessary to satisfy drug regulatory 
requirements based on existing statutes and regulations. The draft 
guidance will be made available for public comment before a final 
guidance is issued.

IX. Information for Consumers and Health Professionals

    As required by the DSHEA, the Commission considered how best to 
ensure that consumers receive information that is truthful, 
scientifically valid, and not misleading so that they may make informed 
and appropriate health choices. The Commission Report calls for 
consumer research to determine whether consumers want and can use the 
information provided to them under the DSHEA, existing FDA regulations, 
and the recommendations of the Commission. Because advice from health 
professionals can be critical in helping consumers to make appropriate 
decisions about dietary supplement use, the Commission Report also 
states that health care and nutrition professionals should become more 
knowledgeable about these products. Additionally, the Commission Report 
urges manufacturers to develop balanced and nonmisleading summaries of 
the evidence substantiating any statements made under section 403(r)(6) 
of the act and of the evidence substantiating product safety for the 
intended use at the recommended dosage. The Commission Report further 
suggests that manufacturers make these summaries publicly available.
    FDA agrees that a better understanding of consumer information 
needs is desirable. The agency has asked the FDA Foods Advisory 
Committee (FAC) to consider how best to gather data on how consumers 
use information on dietary supplement labels to make decisions on 
whether a dietary supplement is appropriate for them. FDA has also 
asked the FAC to consider the development of guidelines or criteria 
that could be used by the dietary supplement industry and others to 
conduct consumer research studies or to evaluate the results of 
consumer research studies. FAC considered these issues at its February 
1998 meeting and referred them to a FAC internal working group to 
develop recommendations for consideration by the full FAC.

X. Research

    The Commission Report addresses various issues related to research 
about dietary supplements. The Commission Report states that the public 
interest would be served by more research to assess the relationships 
between dietary supplements and the maintenance of health and/or 
prevention of disease. Additionally, the Commission Report states that 
incentive mechanisms should be developed to encourage the dietary 
supplement industry to invest in research on these products. To that 
end, the Commission Report suggests that FDA consider a ``mechanism for 
review of research conducted to validate a statement of nutritional 
support so that the label disclaimer mandated by DSHEA could be 
modified or removed.'' The Commission Report notes that consideration 
is needed of ways to provide FDA with sufficient resources to make it 
possible for the agency to take on such an additional responsibility.
    FDA agrees that additional research should be undertaken in the 
public and private sector to assess the relationships between dietary 
supplements and the maintenance of health and/or prevention of disease. 
The agency has provided, and will continue to provide, assistance and 
guidance to industry and other Federal agencies in designing studies 
for these types of assessments. Additionally, the agency has worked 
closely, and will continue to work, with NIH's Office of Dietary 
Supplements.
    With regard to the Commission Report suggestion that FDA consider 
reviewing research to validate structure/function claims and other 
statements made under section 403(r)(6) of the act so that the 
currently required disclaimer could be removed, the agency notes that 
current law prevents it from adopting this suggestion. Because the 
disclaimer requirement is statutory, FDA cannot permit the disclaimer 
to be removed unless Congress amends section 403(r)(6)(C) of the act 
accordingly.


[[Page 23637]]


    Dated: April 22, 1998.
Michael A. Friedman,
Lead Deputy Commissioner for the Food and Drug Administration.
Donna E. Shalala,
Secretary of Health and Human Services.
[FR Doc. 98-11293 Filed 4-24-98; 4:27 pm]
BILLING CODE 4160-01-F