Federal Register: April 29, 1998 (Volume 63, Number 82)
Notices
Page 23633-23637
From the Federal Register Online via GPO Access wais.access.gpo.gov
DOCID:fr29ap98-127
 
 
 
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, IBernste@oc.fda.gov.
 
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:
because 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
 
Page 23636
 
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