[Federal Register Volume 69, Number 216 (Tuesday, November 9, 2004)]
[Notices]
[Pages 64962-64964]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-24871]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2004D-0466]


Draft Guidance for Industry: Substantiation for Dietary 
Supplement Claims Made Under Section 403(r)(6) of the Federal Food, 
Drug, and Cosmetic Act; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a draft guidance entitled ``Guidance for Industry: 
Substantiation for Dietary Supplement Claims Made Under Section 
403(r)(6) of the Federal Food, Drug, and Cosmetic Act.'' This draft 
guidance describes the amount, type, and quality of evidence that FDA 
recommends a manufacturer have to substantiate a claim under section 
403(r)(6) of the Federal Food, Drug, and Cosmetic Act (act). FDA is 
also announcing its decision not to publish additional guidance on 
applying the structure/function rule at this time.

DATES: Submit written or electronic comments on the draft guidance and 
the collection of information provisions by January 10, 2005, to ensure 
adequate consideration in preparation of any final guidance document. 
General comments on agency guidance documents are welcome at any time.

ADDRESSES: Submit written comments on the draft guidance document and 
the collection of information provisions to the Division of Dockets 
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, 
rm. 1061, Rockville, MD 20852. Submit electronic comments on the draft 
guidance and the collection of information to http://www.fda.gov/dockets/ecomments. See the SUPPLEMENTARY INFORMATION section for 
electronic access to the draft guidance document.

FOR FURTHER INFORMATION CONTACT: Vickey Lutwak, Center for Food Safety 
and Applied Nutrition, Food and Drug Administration, 5100 Paint Branch 
Pkwy., College Park, MD 20740, 301-436-2375, fax: 301-436-2636, e-mail: 
[email protected]

SUPPLEMENTARY INFORMATION:

I. Background--Substantiation Draft Guidance

    Section 403(r)(6) of the act (21 U.S.C. 343(r)(6)) requires that a 
manufacturer of a dietary supplement making a nutritional deficiency, 
structure/function, or general well-being claim have substantiation 
that the claim is truthful and not misleading.\1\
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    \1\ Under section 403(r)(6)(A) of the act (21 U.S.C. 
343(r)(6)(A)), such a statement is one that ``claims a benefit 
related to a classical nutrient deficiency disease and discloses the 
prevalence of such disease in the United States, describes the role 
of a nutrient or dietary ingredient intended to affect the structure 
or function in humans, characterizes the documented mechanism by 
which a nutrient or dietary ingredient acts to maintain such 
structure or function, or describes general well-being from 
consumption for a nutrient or dietary ingredient.''
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    This draft guidance document is intended to describe the amount, 
type, and quality of evidence FDA recommends a manufacturer have to 
substantiate a claim under section 403(r)(6) of the act. This draft 
guidance document is limited to issues pertaining to substantiation 
under section 403(r)(6) of the act; it does not extend to 
substantiation issues that may exist in other sections of the act.
    FDA intends to apply a standard for substantiating claims for 
dietary supplements that is consistent with the Federal Trade 
Commission's (FTC's) standard for dietary supplements and other health 
related products of ``competent and reliable scientific evidence.'' FDA 
seeks comments on this draft guidance only as they relate to FDA's use 
and application of the standard and approach that are described in the 
guidance. We (FDA) are not seeking comment on FTC's application, use, 
or interpretation of their standard.
    The agency has adopted good guidance practices (GGPs) that set 
forth the agency's policies and procedures for the development, 
issuance, and use of guidance documents (21 CFR 10.115). The draft 
guidance document is being issued as a Level 1 guidance consistent with 
FDA's GGPs. The draft guidance document represents the agency's current 
thinking on the amount, type, and quality of evidence FDA recommends a 
manufacturer have to substantiate a claim under section 403(r)(6) of 
the act. It does not create or confer any rights for or on any person 
and does not operate to bind FDA or the public. An alternative method 
may be used as long as it satisfies the requirements of the applicable 
statutes and regulations.

II. Paperwork Reduction Act of 1995--Substantiation Draft Guidance

    This draft guidance document contains information collection 
provisions that are subject to review by the Office of Management and 
Budget (OMB) under the Paperwork Reduction Act of 1995 (the PRA) (44 
U.S.C. 3501-3520). Under the PRA, Federal agencies must obtain approval 
from the OMB for each collection of information they conduct or 
sponsor. ``Collection of information'' is defined in 44 U.S.C. 3502(3) 
and 5 CFR 1320.3 and includes agency requests or requirements that 
members of the public submit reports, keep records, or provide 
information to a third party. Section 3506(c)(2)(A) of the PRA (44 
U.S.C. 3506(c)(2)(A)) requires Federal agencies to provide a 60-day 
notice in the Federal Register concerning each proposed collection of 
information before submitting the collection to OMB for approval. To 
comply with this requirement, FDA is hereby publishing notice of the 
proposed collection of information set forth in this document.
    FDA invites comments on: (1) Whether the proposed collection of 
information is necessary for the proper performance of FDA's functions, 
including whether the information will have practical utility; (2) the 
accuracy of FDA's estimate of the burden of the proposed collection of 
information, including the validity of the methodology and assumptions 
used; (3) ways to enhance the quality, utility, and clarity of the 
information to be collected; and (4) ways to minimize the burden of the 
collection of information on respondents, including through the use of 
automated collection techniques, when appropriate, and other forms of 
information technology.
Draft Guidance for Industry: Substantiation for Dietary Supplement 
Claims Made Under Section 403(r)(6) of the Federal Food, Drug, and 
Cosmetic Act; Availability
    Section 403(r)(6) of the act requires that a manufacturer of a 
dietary supplement making a nutritional deficiency, structure/function, 
or general well-being claim have substantiation that the statement is 
truthful and not misleading. This draft guidance document is intended 
to describe the amount, type, and quality of evidence FDA recommends a 
dietary supplement manufacturer have to

[[Page 64963]]

substantiate a claim under section 403(r)(6) of the act. This guidance 
does not discuss the types of claims that can be made concerning the 
effect of a dietary supplement on the structure or function of the 
body, nor does it discuss criteria to determine when a statement about 
a dietary supplement is a disease claim.
    FDA estimates the burden for this information collection as 
follows:

                                                         Table 1.--Estimated Reporting Burden\1\
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                                                                                                        Total
                         Claim type                                No. of         Annual Frequency      Annual         Hours per          Total Hours
                                                                 Respondents        per Response      Responses        Response
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Widely known, established                                                  667                   1          667                   1                 667
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Pre-existing, not widely established                                       667                   1          667                 120              80,040
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Novel                                                                      667                   1          667                 120              80,040
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Annual one time burden hours                                                                                                                    160,747
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\1\ There are no capital costs or operating and maintenance costs associated with this information collection.

    Dietary supplement manufacturers will only need to collect 
information to substantiate their product's nutritional deficiency, 
structure/function, or general well-being claim if they chose to place 
a claim on their product's label. Gathering evidence on their product's 
claim is a one time burden; they collect the necessary substantiating 
information for their product as required by section 403(r)(6) of the 
act.
    The standard discussed in the guidance for substantiation of a 
claim on the labeling of a dietary supplement is consistent with 
standards set by the FTC for dietary supplements and other health 
related products that the claim be based on competent and reliable 
scientific evidence. This evidence standard is broad enough that some 
dietary supplement manufacturers may only need to collect peer-reviewed 
scientific journal articles to substantiate their claims; other dietary 
supplement manufacturers whose products have properties that are less 
well documented may have to conduct studies to build a body of evidence 
to support their claims. It is unlikely that a dietary supplement 
manufacturer will attempt to make a claim when the cost of obtaining 
the evidence to support the claim outweighs the benefits of having the 
claim on the product's label. It is likely that manufacturers will seek 
substantiation for their claims in the scientific literature.
    The time it takes to assemble the necessary scientific information 
to support their claims depends on the product and the claimed 
benefits. If the product is one of several on the market making a 
particular claim for which there is adequate publicly available and 
widely established evidence supporting the claim, then the time to 
gather supporting data will be minimal; if the product is the first of 
its kind to make a particular claim or the evidence supporting the 
claim is less publicly available or not widely established, then 
gathering the appropriate scientific evidence to substantiate the claim 
will be more time consuming.
    FDA assumes that it will take only about an hour to assemble 
information needed to substantiate a claim on a particular dietary 
supplement when the claim is widely known and established. These are 
likely products whose claimed effects have been long studied and the 
results of the studies are widely available in credible textbook and 
reference books, therefore making the substantiation burden minimal. 
FDA believes it will take closer to 120 hours to assemble supporting 
scientific information when the claim is novel or when the claim is 
pre-existing but the scientific underpinnings of the claim are not 
widely established. These are claims that may be based on emerging 
science, where conducting literature searches and understanding the 
literature takes time. It is also possible that references for claims 
made for some dietary ingredients or dietary supplements may primarily 
be found in foreign journals and in foreign languages or in the older, 
classical literature where it is not available on computerized 
literature databases or in the major scientific reference databases, 
such as the National Library of Medicine's literature database, all of 
which increases the time of obtaining substantiation.
    In the final rule on statements made for dietary supplements 
concerning the effect of the product on the structure or function of 
the body (structure/function final rule (65 FR 1000, January 6, 2000)), 
FDA estimated that there were 29,000 dietary supplement products 
marketed in the United States (65 FR 1000 at 1045). Assuming that the 
flow of new products is 10 percent per year, then 2,900 new dietary 
supplement products will come on the market each year. The structure/
function final rule estimated that about 69 percent of dietary 
supplements have a claim on their labels, most probably a structure/
function claim (65 FR 1000 at 1046). Therefore, we assume that 
supplement manufacturers will need time to assemble the evidence to 
substantiate each of the 2,001 claims (2,900 x 69%) made each year. If 
we assume that the 2,001 claims are equally likely to be pre-existing 
widely established claims, novel claims, or pre-existing claims that 
are not widely established, then we can expect 667 of each of these 
types of claims to be substantiated per year. Row 1 of Table 1 of this 
document shows that the annual burden hours associated with assembling 
evidence for claims is 160,747 (667 x 1hr, 667 x 120 hrs, and 667 x 120 
hrs).
    There are no capital costs or operating and maintenance costs 
associated with this information collection.

III. Guidance on Applying the Structure/Function Rule

    On January 6, 2000, FDA published a final rule, often referred to 
as the ``structure/function rule,'' implementing section 403(r)(6) of 
the act concerning the types of statements that can be made regarding 
the effect of a dietary supplement on the structure or function of the 
body (65 FR 1000). This rule, codified in Sec.  101.93(f) (21 CFR 
101.93(f) and (g)), distinguishes between disease claims and structure/
function claims. As discussed in Sec.  101.93, if the label or labeling 
of a product marketed as a dietary supplement bears a disease claim as 
defined in that rule, the product will be subject to regulation as a 
drug unless the claim is an authorized health claim for which the 
product qualifies.

[[Page 64964]]

    In the preamble to the final rule, FDA stated that it intended to 
publish a guidance on applying this rule. In a notice published in the 
Federal Register on February 22, 2001 (66 FR 11172), FDA invited public 
comments on the topics that should be included in such a guidance. FDA 
agrees with the comments that were submitted stating that the preamble 
to the structure/function rule and the numerous courtesy letters that 
the agency has issued since the enactment of section 403(r)(6) provide 
considerable guidance to dietary supplement manufacturers about the 
types of claims that the agency considers to be disease claims. 
Therefore, FDA has decided not to issue such a guidance at this time. 
FDA will continue to monitor dietary supplement manufacturers' 
compliance with section 403(r)(6) of the act and Sec.  101.93, take 
enforcement action where appropriate, and reconsider the possibility of 
issuing guidance if future developments warrant.

IV. Comments

    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES) written or electronic comments regarding the 
substantiation draft guidance document. (FDA is not specifically 
seeking comment on its decision not to publish additional guidance on 
the structure/function rule.) Two copies of mailed comments are to be 
submitted, except that individuals may submit one paper copy. Comments 
are to be identified with the docket number found in brackets in the 
heading of this document. The draft guidance and received comments are 
available for public examination in the Division of Dockets Management 
between 9 a.m. and 4 p.m., Monday through Friday.

V. Electronic Access

    Persons with access to the Internet may obtain the document at 
http://www.cfsan.fda.gov or http://www.fda.gov/dockets/ecomments. Once 
on this site, select 2004D-0466 ``Guidance for Industry: Substantiation 
for Dietary Supplement Claims Made Under Section 403(r)(6) of the 
Federal Food, Drug, and Cosmetic Act'' and follow the directions. 
Copies of this draft guidance may be obtained on the Internet from the 
CFSAN homepage at http://www.cfsan.fda.gov.

    Dated: October 25, 2004.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 04-24871 Filed 11-4-04; 8:45 am]
BILLING CODE 4160-01-S