[Federal Register: January 6, 2000 (Volume 65, Number 4)]
[Rules and Regulations]
[Page 999-1050]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr06ja00-17]
[[Page 999]]
Part IV
Department of Health and Human Services
_______________________________________________________________________
Food and Drug Administration
_______________________________________________________________________
21 CFR Part 101
Regulations on Statements Made for Dietary Supplements Concerning the
Effect of the Product on the Structure or Function of the Body; Final
Rule
[[Page 1000]]
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 101
[Docket No. 98N-0044]
RIN 0910-AB97
Regulations on Statements Made for Dietary Supplements Concerning
the Effect of the Product on the Structure or Function of the Body
AGENCY: Food and Drug Administration, HHS.
ACTION: Final rule.
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SUMMARY: The Food and Drug Administration (FDA) is issuing final
regulations defining the types of statements that can be made
concerning the effect of a dietary supplement on the structure or
function of the body. The regulations also establish criteria for
determining when a statement about a dietary supplement is a claim to
diagnose, cure, mitigate, treat, or prevent disease. This action is
intended to clarify the types of claims that may be made for dietary
supplements without prior review by FDA and the types of claims that
require prior authorization as health claims or prior approval as drug
claims.
DATES: The final rule will become effective February 7, 2000.
FOR FURTHER INFORMATION CONTACT: Ann Marlin Witt, Office of Policy,
Planning, and Legislation (HF-11), Food and Drug Administration, 5600
Fishers Lane, Rockville, MD 20857, 301-827-0084.
SUPPLEMENTARY INFORMATION:
I. Introduction
In the Federal Register of April 29, 1998 (63 FR 23624), FDA
proposed regulations to identify the types of statements that may be
made without prior FDA review about the effects of dietary supplements
on the structure or function of the body (``structure/function
claims''), and to distinguish these claims from claims that a product
diagnoses, treats, prevents, cures, or mitigates disease (disease
claims). FDA received over 235,000 submissions in response to the
proposed rule. Many of these were form letters, but over 22,000 were
individual letters from the dietary supplement industry, trade
associations, health professional groups, and consumers. Almost all the
comments from the dietary supplement industry and from individuals,
which made up the vast majority of the comments, objected to all or
part of the proposed rule, arguing that it inappropriately restricted
the structure/function claims that could be made for dietary
supplements. Most of the comments from health professional groups and
groups devoted to particular diseases supported the proposed rule, or
believed it did not go far enough in limiting structure/function claims
for dietary supplements.
After reviewing the comments, FDA concluded that the comments had
raised significant questions about some of the key provisions of the
proposal such that a public meeting was warranted. In the Federal
Register of July 8, 1999 (64 FR 36824), FDA announced a public meeting
to be held on August 4, 1999, at which representatives of the dietary
supplement industry, consumer groups, and health professionals were
asked to address three major issues raised by the comments. The three
issues, described in the Federal Register notice, were: (1) Whether to
finalize the proposed definition of ``disease'' or retain a 1993
definition of ``disease or health-related condition'' that was in
effect at the time the Dietary Supplement Health and Education Act
(DSHEA) was enacted; (2) whether to modify one of the proposed criteria
for assessing disease claims to permit structure/function claims
related to certain conditions associated with natural states, such as
hot flashes associated with menopause and decreased sexual function
associated with aging; and (3) whether to permit implied disease claims
structure/function claims. The July 8, 1999, notice also reopened the
comment period until August 4, 1999, to receive written comments on
these three issues.
This document addresses the comments received on the proposed
rule, as well as comments received in response to the July 8, 1999,
Federal Register notice. A few comments raised issues that are beyond
the scope of this rule and generally will not be addressed in this
document.
A. Highlights of the Final Rule
Like the proposed rule, the final rule contains criteria to
determine when a labeling statement made about a dietary supplement
constitutes a structure/function claim for which no prior FDA review is
required and when it constitutes a disease-related claim that requires
either authorization of a health claim or review under the drug
provisions of Federal Food, Drug, and Cosmetic Act (the act). FDA has,
however, made several important changes in the final rule in response
to comments.
First, the agency has deleted the proposed definition of
``disease.'' Rather than creating a new definition of disease, FDA will
use the preexisting definition of ``disease or health-related
condition'' in Sec. 101.14(a)(5) (21 CFR 101.14(a)(5)) (formerly
Sec. 101.14(a)(6)), which was issued as part of the implementation of
the health claims provisions of the Nutrition Labeling and Education
Act (NLEA). This change has been made in response to the large number
of comments that objected to the proposed definition and urged that FDA
retain the NLEA definition.
Second, FDA has revised the criterion that applies to conditions
associated with such natural states or processes as menopause, aging,
adolescence, and pregnancy. The proposed rule stated that menopause,
aging, and pregnancy are not themselves diseases but that certain
conditions associated with them are diseases if they are recognizable
to consumers or health professionals as abnormal. Many comments
objected to classifying as diseases such common conditions as hot
flashes, premenstrual syndrome (PMS), and decreased sexual function
associated with aging. In response to these comments, FDA has revised
proposed Sec. 101.93(g)(2)(iii). Common conditions associated with
natural states or processes that do not cause significant or permanent
harm will not be treated as diseases under the final rule. For example,
hot flashes, common symptoms associated with the menstrual cycle,
ordinary morning sickness associated with pregnancy, mild memory
problems associated with aging, hair loss associated with aging, and
noncystic acne will not be treated as diseases under this provision.
Uncommon or serious conditions like senile dementia, toxemia of
pregnancy, severe depression associated with the menstrual cycle, and
cystic acne will continue to be treated as diseases under the final
rule.
Third, FDA has revised the criterion that relates to the use in
labeling of the titles of publications that refer to diseases. In
response to comments objecting that, as proposed, this criterion would
hamper manufacturers from providing consumers with information
substantiating their claims, FDA has revised this criterion. Under the
revised criterion, the use in labeling of a publication title that
refers to a disease will be considered a disease claim only if, in
context, it implies that the product may be used to diagnose, treat,
mitigate, cure, or prevent disease. Highlighting, bolding, using large
type size, or prominent placement of a citation that refers to a
disease use in the title could suggest that the product has an effect
on disease. Placing a citation to a scientific reference that refers to
a disease in the title on the
[[Page 1001]]
immediate product label or packaging will be considered a disease claim
for that product. The agency will also consider whether the cited
article provides legitimate support for the express structure/function
statement made for that dietary supplement. Enhancing the bibliography
with citations to scientific references that refer to a disease in the
title and that have no reasonable relation to the statement made will
be considered a disease claim. Similarly, the agency will consider
whether citations are to bona fide research.
B. Background
DSHEA created a new regime for the regulation of dietary
supplements. These products were previously regulated either as foods
or as drugs, depending upon whether they had the attributes of food and
upon their intended uses. Before the passage of DSHEA, a dietary
supplement for which a health-related claim was made was regulated
either as a drug, which had to be shown to be safe and effective before
marketing, or as a food, for which prior authorization to make a health
claim was required if the claim concerned a disease or health-related
condition. If the claim concerned a non-disease-related effect on the
structure or function of the body and the claimed effect derived from a
food attribute, such as nutritive value, the claim was considered a
food claim, and prior authorization was not required. Under section
201(g)(1)(B) and (g)(1)(C) of the act (21 U.S.C. 321(g)(1)(B) and
(g)(1)(C)), a drug is defined as ``an article intended for use in the
diagnosis, cure, mitigation, treatment, or prevention of disease,'' or
``an article (other than food) intended to affect the structure or any
function of the body.'' Section 505 of the act (21 U.S.C. 355) requires
that new drugs (see section 201(p) of the act) be shown to be safe and
effective for their intended uses before marketing. Under sections
403(r)(1)(B) and (r)(5)(D) of the act (21 U.S.C. 343(r)(1)(B) and
(r)(5)(D)) and Sec. 101.14, prior authorization is required to make a
health claim for a dietary supplement. A health claim is a claim that
``characterizes the relationship of any nutrient * * * in the food to a
disease or health-related condition'' (section 403(r)(1)(B) of the act;
see Sec. 101.14(a)(1)).
DSHEA specifically authorized certain types of claims about the
uses of dietary supplements, including some claims that formerly would
have required review by FDA before the claim is made. Section 403(r)(6)
of the act, added by DSHEA, allows dietary supplement labeling to bear,
among other types of statements, a statement that ``describes the role
of a nutrient or dietary ingredient intended to affect the structure or
function in humans'' or that ``characterizes the documented mechanism
by which a nutrient or dietary ingredient acts to maintain such
structure or function.'' Such statements are generally referred to as
``structure/function claims.'' Because many of these claims would
previously have been covered by the drug definition in section
201(g)(1)(C) of the act, section 201(g)(1) was amended by DSHEA to
provide that a dietary supplement ``for which a truthful and not
misleading statement is made in accordance with section 403(r)(6) is
not a drug under clause (C) solely because the label or the labeling
contains such a statement.''
Although a dietary supplement manufacturer who wishes to make a
statement permitted under section 403(r)(6) of the act need not obtain
prior review of the statement, the manufacturer must possess
substantiation that the statement is truthful and not misleading, and
must include in the statement the following disclaimer: ``This
statement has not been evaluated by the Food and Drug Administration.
This product is not intended to diagnose, treat, cure, or prevent any
disease.'' DSHEA also requires the manufacturer of a dietary supplement
bearing a statement under section 403(r)(6) of the act to notify FDA,
no later than 30 days after the first marketing of the dietary
supplement with the statement, that such a statement is being made for
the product. Regulations implementing these requirements were published
in the Federal Register of September 23, 1997, and are codified at
Sec. 101.93 (21 CFR 101.93) (62 FR 49883 at 49886, September 23, 1997).
DSHEA did not alter the statutory treatment of dietary supplement
claims related to disease (``disease claims''). Section 403(r)(6) of
the act, specifically provides that statements permitted under that
section ``may not claim to diagnose, mitigate, treat, cure, or prevent
a specific disease or class of diseases,'' except that such statements
may claim a benefit related to a classical nutrient deficiency disease,
provided that they also disclose the prevalence of the disease in the
United States. Consistent with the quoted provision, Congress did not
modify section 201(g)(1)(B) of the act to exclude disease claims for
dietary supplements from use as evidence of intended use as a drug, as
it had done for section 201(g)(1)(C) of the act. Thus, dietary
supplements ``intended for use in the diagnosis, cure, mitigation,
treatment, or prevention of disease'' remain within the definition of a
``drug.'' In enacting DSHEA, Congress also maintained the requirement
of prior authorization of a claim that characterizes the relationship
of a nutrient in a dietary supplement to a disease (section
403(r)(1)(B) and (r)(5)(D) of the act). An interested person may submit
a petition to FDA requesting the agency to issue a regulation
authorizing the health claim (see Sec. 101.70 (21 CFR 101.70)). The
petitioner must demonstrate, among other things, that the use of the
substance at levels necessary to justify the claim is safe and that
there is ``significant scientific agreement'' among qualified experts
that the claim is supported by the totality of publicly available
scientific evidence (Sec. 101.14(b)(3)(ii) and (c)). The agency notes
that for health claims to be used on conventional foods, an interested
person may submit to FDA a notification of an authoritative statement
by one of certain designated scientific bodies concerning the
substance-disease relationship to which the claim refers (see section
403(r)(3)(C) of the act). Unless FDA issues a regulation modifying or
prohibiting the claim, or a Federal district court finds that
applicable statutory requirements have not been met, the claim may be
used 120 days after the notification has been submitted (see section
403(r)(3)(C)(ii) and (r)(3)(D) of the act). This alternative
authorization procedure does not apply to dietary supplements by
statute, but FDA has proposed to extend it to dietary supplements by
regulation (see 64 FR 3250, January 21, 1999).
Although FDA believes that dietary supplements have potential
benefits for consumers, dietary supplements labeled with unproven
disease claims, i.e., those that have not met the requirements for
health claim authorization or new drug approval, can pose serious
risks. Such claims may encourage consumers to self-treat for a serious
disease without benefit of a medical diagnosis or treatment. They may
also cause consumers to substitute potentially ineffective products for
proven ones, foregoing or delaying effective treatment for serious and
life-threatening illnesses. Reliance on disease prevention claims may
encourage consumers to feel sufficiently protected from developing
serious diseases (e.g., cancer or human immunodeficiency virus (HIV)
infection) that they delay or forego regular screening, and forfeit the
opportunity for early medical treatment that may be critical to
survival. Finally, use of dietary supplements to treat
[[Page 1002]]
disease may increase the risk of adverse reactions due to the
interaction of the dietary supplement with other compounds a consumer
is taking for that disease or for other conditions, e.g., prescription
medications.
This final rule is intended to apply only to structure/function
claims and disease claims within the meaning of section 403(r)(6) of
the act. DSHEA, generally, and section 403(r)(6) of the act,
specifically, apply only to dietary supplements for human consumption
and were enacted to provide a unique regulatory regime for these
products. Thus, this rule is neither intended to apply to products
other than dietary supplements for human consumption nor to interpret
other provisions of the act.
The final rule establishes criteria for determining whether a
statement made about a dietary supplement is acceptable as a structure/
function claim under section 403(r)(6) of the act. The rule is neither
intended to establish whether any particular structure/function claim
is appropriate for any specific product, nor whether the claim would be
permitted under other provisions of the act. Like the labeling of any
other FDA-regulated product, the labeling of dietary supplements must
comply with all applicable requirements of the act and regulations. For
example, an otherwise acceptable structure/function claim might
nevertheless be false or misleading for other reasons, causing the
product to be misbranded under section 403(a)(1) of the act.
C. The Proposed Rule
The proposed rule defined criteria for determining when a
statement about a dietary supplement is a claim to diagnose, cure,
mitigate, treat, or prevent disease (``disease claim''), and thus
requires prior approval as a drug or prior authorization as a health
claim. The proposed rule included a definition of ``disease,'' which
was to replace a definition of ``disease or health-related condition''
issued for implementation of the health claims regulations, and 10
criteria for identifying express or implied disease claims. FDA
proposed to treat a statement about a dietary supplement as a disease
claim if the statement claimed, explicitly or implicitly, that the
product: (1) Has an effect on a specific disease or class of diseases;
(2) has an effect, using scientific or lay terminology, on one or more
signs or symptoms that are recognizable to health care professionals or
consumers as being characteristic of a specific disease or of a number
of different specific diseases; (3) has an effect on a consequence of a
natural state that presents a characteristic set of signs or symptoms
recognizable to health care professionals or consumers as constituting
an abnormality of the body; (4) has an effect on disease through one or
more of the following factors: (a) The name of the product; (b) a
statement about the formulation of the product, including a claim that
the product contains an ingredient that has been regulated by FDA as a
drug and is well known to consumers for its use in preventing or
treating a disease; (c) citation of a publication or reference, if the
citation refers to a disease use; (d) use of the term ``disease'' or
``diseased;'' or (e) use of pictures, vignettes, symbols, or other
means; (5) belongs to a class of products that is intended to diagnose,
mitigate, treat, cure, or prevent a disease; (6) is a substitute for a
product that is a therapy for a disease; (7) augments a particular
therapy or drug action; (8) has a role in the body's response to a
disease or to a vector of disease; (9) treats, prevents, or mitigates
adverse events associated with a therapy for a disease and manifested
by a characteristic set of signs or symptoms; or (10) otherwise
suggests an effect on a disease or diseases.
Claims that did not fall within the proposed criteria for disease
claims and that otherwise complied with the notification and disclaimer
provisions of Sec. 101.93(a) through (e) were to be eligible for use as
structure/function claims. The proposed rule also provided examples of
claims that would be permitted as structure/function claims and those
that would require prior review as disease claims under each of the 10
criteria.
The basis for the proposed rule was the agency's experience in
implementing section 403(r)(6) of the act, and the final report (the
report) of the President's Commission on Dietary Supplement Labels
(Ref. 1), which included a number of recommendations for distinguishing
structure/function and disease claims and suggested that FDA issue
further guidance on acceptable structure/function claims.
II. Comments
A. General Comments
(1.) Many comments focused on the impact of the rule on consumers.
Many comments opposing the proposed rule said that consumers should be
able to receive truthful and non-misleading information and that the
proposed rule would curtail or restrict such information or restrict
the focus of dietary supplements to preventive care and wellness. Some
comments added that DSHEA, through the dissemination of truthful and
non-misleading information on health and promotion and disease
prevention, makes consumers responsible for their own health. Other
comments said that FDA should let the public educate itself. Other
comments suggested that FDA simply adopt a ``truthful and non-
misleading'' standard. Some comments added that full disclosure of all
pertinent information (such as the preliminary status of scientific
studies substantiating the claim) would be sufficient. Another comment
questioned whether consumers would, as the preamble to the proposed
rule stated, benefit from not having to search for information and from
getting appropriate information. The comment argued that consumers
would receive less information under the rule and would have to search
more extensively for information.
Many comments supporting the proposed rule, including comments
from nutrition counselors and health professionals, said that the
proposal would reduce confusion among patients, prevent consumers from
being misled, diminish the number of inappropriate disease claims, and
help consumers decide when to seek medical attention. One comment added
that, while it supported the need for consumers to have choice
regarding dietary supplements, the choice should be made based on
accurate information that is supported by appropriate scientific
investigations. One comment argued that in the absence of valid
effectiveness data, which does not exist for most dietary supplements,
it is not possible to provide ``truthful'' information about the
effects of these products. Some comments said that the proposal would
protect consumers from harmful or potentially harmful products and save
consumers from needless suffering and financial loss; others expressed
concern that inappropriate statements would expose consumers to
potentially harmful drug-supplement interactions, create ``false
hopes,'' and lead consumers to stop complying with advice from health
care professionals or to avoid proven treatments.
FDA agrees that DSHEA encourages the dissemination of truthful and
non-misleading information about the uses of dietary supplements to
affect the structure or function of the body, and encourages full
disclosure of information about claims authorized by the statute. To
the extent that truthful and non-misleading information is being
withheld from consumers in the context of structure/function claims for
dietary supplements, it is the statute that, in the first instance,
precludes
[[Page 1003]]
certain information from being included in such claims. Section
403(r)(6) of the act permits dietary supplement labels to carry
structure/function claims without meeting the requirements for drug
approval or health claim authorization, but precludes them from
carrying unreviewed claims that the product diagnoses, treats,
mitigates, cures, or prevents disease. (The statute does not ultimately
prevent dissemination of information about disease uses to the consumer
in labeling claims or otherwise. Instead, it requires that claims about
disease uses meet certain standards of substantiation and undergo
agency review.) This final rule differentiates between structure/
function claims authorized by section 403(r)(6) of the act and disease
claims that may not be made in dietary supplement labeling under the
authority of section 403(r)(6). The agency notes that, in response to
comments, the final rule classifies many more claims as structure/
function claims than would have been so classified under the proposed
rule, thus increasing the amount of information available to the
consumer without prior FDA review.
The agency also declines to adopt a ``truthful and non-
misleading'' standard instead of the final rule. Section 403(a)(1) of
the act already subjects all food claims, including structure/function
claims on dietary supplements, to the ``truthful and non-misleading''
standard, so promulgating the same standard through regulations is
unnecessary. In addition, section 403(r)(6)(B) of the act already
requires dietary supplement manufacturers to have substantiation that
their statements are truthful and non-misleading. Finally a fundamental
problem with this approach is that a ``truthful and non-misleading''
standard, unlike the final rule, would not provide any criteria for
differentiating between structure/function claims and disease claims.
(2.) Some comments focused on product safety. One comment said that
regulation of claims is unnecessary because dietary supplements are
safe. Similarly, another comment claimed that ``one million peer-
reviewed studies'' showed that dietary supplements provide benefits,
whereas a recent medical journal reported deaths and other injuries to
patients who use prescription drugs. Other comments declared that
dietary supplements are safer than most regularly-used drug products.
In contrast, other comments argued that the safety of many dietary
supplements is unknown, and that risks have been documented with some
supplements. Some comments claimed that dietary supplements pose risks
because they can cause consumers to avoid or delay more effective
treatment. One comment stated that there is a substantial potential for
public harm because of the unknown or unregulated source materials for
many dietary supplements, the variety of suppliers, and the lack of
regulatory production standards and quality control.
Although this final rule may not appear to be a safety measure
because it addresses the labeling of dietary supplements rather than
their composition, protecting consumer health and safety is one of its
major purposes. Because structure/function claims are not subject to
the new drug approval standard or the health claim authorization
standard and do not undergo FDA review before marketing, FDA believes
it is important to ensure that such claims do not promote products for
disease treatment or prevention claims. Disease treatment or prevention
claims can pose serious risks to consumers if they induce consumers to
substitute ineffective or less effective treatments for proven ones,
especially if the disease involved is serious or life-threatening.
Therefore, the agency believes that ensuring that such claims cannot be
made without a demonstration of safety and effectiveness will protect
and promote public health.
FDA also believes that the safety and the effectiveness of
products intended to promote health, including both dietary supplements
and drugs, cannot be viewed independently of each other. FDA agrees
that prescription drugs can and do cause adverse reactions. It is
important to remember, however, that ``safety'' is relative. Products
that are capable of treating diseases have powerful effects on the body
and frequently carry risks. Before prescription drugs are marketed,
both their risks and their benefits must be carefully investigated and
documented in adequately designed clinical trials. Prescription drugs
are permitted to be marketed only when the agency concludes that their
documented benefits outweigh their known and potential risks. Those
with significant risks are approved for marketing only if the benefits
warrant those risks. And they are marketed as ``prescription'' drugs to
ensure that health professionals manage their risks. Even over-the-
counter (OTC) drugs are evaluated for both benefits and risks and are
permitted to be marketed only when their established benefits outweigh
their risks. There is no comparable testing and approval process for
dietary supplements marketed with structure/function claims. The
manufacturer must have substantiation of the structure/function claim,
but this substantiation is not reviewed before the product is marketed
with the claim. Contrary to the suggestion in the comment, few dietary
supplements have been the subjects of adequately designed clinical
trials.
This does not mean that dietary supplements are unsafe or that
they do not have benefits. Some have already been shown to be safe and
to have benefits, and the safety and effectiveness of others are likely
to be shown in the future. At this time, however, many marketed
supplements have not been the subjects of adequate studies to establish
whether or not they are safe or effective, or the nature of the
benefits they may provide.
(3.) Many comments asserted that FDA had no authority to issue the
proposed rule because it was inconsistent with DSHEA and congressional
intent, in that it restricted rather than increased the amount of
information given to consumers. Some comments said that Congress
enacted DSHEA to reverse FDA's ``overly restrictive'' approach towards
health claims and to increase the dissemination of truthful and non-
misleading health information and that Congress repeatedly expressed
its displeasure with FDA's regulatory approach. One comment said FDA
must determine whether a proposed action is consistent with its
statutory authority before it takes any regulatory action. The comment
cited excerpts from congressional documents ``condemning the agency's
repeated penchant'' for restricting statements on dietary supplement
labels and labeling, and said that, given congressional intent and the
act's language, FDA has no authority to proceed with rulemaking without
a grant of authority from Congress. One comment cited section 403B of
the act (21 U.S.C. 343-2) as evidence that Congress, by exempting
certain publications from the definition of labeling, barred FDA from
restricting in ``any way whatsoever'' the dissemination of such
publications and information.
FDA agrees that DSHEA was intended to authorize the dissemination
of more truthful and non-misleading information in dietary supplement
labeling without the need for prior agency review. In response to
comments that the proposed rule was too restrictive, FDA has modified
the final rule to incorporate many of the changes requested by the
comments, including a return to the preexisting definition of ``disease
or health-related condition,'' and a less restrictive interpretation of
the types of structure/function claims
[[Page 1004]]
that can be made about conditions associated with such natural states
as aging, pregnancy, and the menstrual cycle. The final rule classifies
many more claims as structure/function claims than the proposed rule
would have.
The agency does not agree, however, that section 403(r)(6) of the
act authorizes dissemination of any and all information about dietary
supplements without prior review. That section authorizes statements
about the effects of dietary supplements on the structure or function
of the body, but not statements that claim to diagnose, mitigate,
treat, cure, or prevent a specific disease or class of diseases.
Section 403B of the act exempts from being considered labeling certain
balanced, third-party publications that are physically separate from
product labeling and do not promote a particular brand or product. This
provision does not authorize dietary supplement manufacturers to ignore
the restrictions in section 403(r)(6) of the act on what structure/
function claims may be made by a manufacturer about its product on the
product label and in materials that are indisputably part of the
product's labeling.
The agency also disagrees with the assertion that separate
congressional authority is needed for this rulemaking. FDA issued the
proposed rule, and this final rule, to implement section 403(r)(6) of
the act. No independent authority to issue these regulations is
necessary because section 701(a) of the act (21 U.S.C 371(a)) expressly
gives FDA ``the authority to promulgate regulations for the efficient
enforcement of this Act, except as otherwise provided in (section 701
of the act) * * *.'' The proposed rule identified section 701(a) of the
act as being part of the agency's legal authority (see 63 FR 23624 at
23628 and 23631), and there is no exception in the act that restricts
or limits, either expressly or impliedly, the agency's ability to issue
regulations to implement section 403(r)(6) of the act. Therefore, the
rule is authorized by law and consistent with FDA's statutory
authority.
(4.) Some comments contended that FDA did not provide a sufficient
justification for issuing the rule. Two comments challenged FDA's
assertion that the rule would reduce substantial confusion among
manufacturers. The comments referred to statements in the preamble to
the proposed rule which said FDA received approximately 2,300
notifications of structure/function claims and sent objection letters
to approximately 150 notifications. One comment said the low objection
rate did not indicate ``substantial confusion'' among manufacturers,
while the other comment hypothesized that, if FDA objected to a small
number of claims in each notification, the number of objectionable
claims was very small. Other comments contended that the Commission
report did not support the proposed rule. These comments were divided
in their reasons. Some comments argued that the Commission exceeded its
statutory mandate under section 12 of DSHEA or failed to perform its
statutory obligations. Thus, the comments stated, FDA cannot base any
regulation on the Commission's findings, guidance, or recommendations
and has no authority to proceed with the rulemaking. Other comments
stated that FDA relied on statements from individual Commission members
rather than the report itself, that the report did not suggest that FDA
issue regulations, and that the report did not suggest that FDA issue a
new definition of disease. One comment said that the Commission did not
support a need for regulations. Another comment noted that the
Commission did not recommend regulations and asserted that FDA had
publicly said that DSHEA is self-implementing.
FDA does not agree that there is insufficient support for this
rule. FDA's experience, the Commission report, and FDA's authority
under section 701(a) of the act to issue regulations implementing
statutory requirements provide more than adequate support for the rule.
The preamble to the proposed rule referred to substantial confusion
among manufacturers and consumers, rather than manufacturers alone.
Comments received from other sources, particularly physicians,
dieticians, and health professional organizations, agreed that
consumers are confused and misled by claims. In addition, the number of
objection letters is not the sole indicator of manufacturer confusion,
for three reasons. First, manufacturers and consumers have asked FDA to
provide clarification on structure/function and disease claims, and
such requests for clarification would not necessarily have resulted in
an objection letter from FDA. Second, the agency has repeatedly said
that the absence of an objection letter does not necessarily indicate
acceptance of the claim. Third, there are apparently a large number of
marketed dietary supplement products making claims for which FDA has
not received 30-day notification letters under section 403(r)(6) of the
act. (In the proposed rule, FDA estimated that approximately 22,500
dietary supplement labels carried structure/function claims. FDA had
received 2,300 notifications at the time of the proposed rule. While
some notifications contain more than one claim, they do not average 10
claims per notification.)
FDA also does not agree that the Commission report was necessary
to provide support for this rule. The proposal was based not only on
the Commission report, but also on the agency's experience in reviewing
30-day notification letters submitted under section 403(r)(6) of the
act (63 FR 23624 at 23625). Although FDA believes the rule is
consistent with the views expressed in the Commission report, the
Commission report was not a necessary prerequisite for the agency to
issue the rule. FDA issued the proposal under section 403(r)(6) of the
act (section 6 of DSHEA) and the rulemaking authority of section 701(a)
of the act, not under section 12 of DSHEA. FDA takes no view on whether
the Commission met its statutory obligations in issuing its report. To
the extent that the report is beyond the Commission's authority, FDA's
experience and section 701(a) of the act provide adequate support for
the rule. Thus, whether or not the Commission exceeded its mandate is
irrelevant to the validity of the rule.
With regard to the issues raised about the consistency of the
agency's approach with the Commission report, it is true that the
Commission did not specifically recommend regulations, but the
Commission did express the view that FDA guidance on claims under
section 403(r)(6) of the act would be ``appropriate and helpful in
clarifying the appropriate scope'' of such claims (the report, p. 38).
As to the agency's public statements that DSHEA is self-
implementing, the comment took those statements out of context. When
DSHEA was passed, there was confusion in the industry about whether the
types of statements permitted by section 403(r)(6) of the act could be
made under the authority of the statute alone, in the absence of
implementing regulations. To clear up this confusion, at least one
agency official publicly said that DSHEA was ``self-implementing.''
Agency statements to this effect were intended to clarify that
manufacturers were not required to wait for FDA to issue implementing
regulations before making claims under section 403(r)(6) of the act;
however, they were in no way intended to imply that the agency lacked
authority to issue implementing regulations.
Contrary to the suggestion in one of the comments, FDA did not
rely on the views of individual Commission members, but on the official
7-point
[[Page 1005]]
``guidance'' developed by the Commission ``as to what constitutes an
acceptable statement of nutritional support of the structure function
type'' (the report at pp. 38 and 39). The criteria developed by FDA are
highly consistent with the Commission's guidance. FDA also agrees that
the Commission did not make any findings or recommendations on the
definition of disease. As described elsewhere in this rule, the final
rule does not modify the existing definition of disease found in FDA's
health claims regulations.
(5.) One comment said that FDA should have admitted that there is
and will be some overlap between disease and structure/function claims
and that the agency should have drafted a rule to prevent extreme
overlap between structure/function claims and drug or health claims.
FDA disagrees with this comment. In the proposed rule, FDA
recognized that section 403(r)(6) of the act leaves open questions
concerning the distinction between structure/function claims and
disease claims. Diseases cause, and can be characterized as,
abnormalities in the structure or function of the body. It would
therefore be possible to describe almost all products intended to treat
or prevent disease in terms of their effects on the structure or
function of the body, without mentioning the disease itself.
The language of DSHEA, however, does not support treating those
structure/function claims that are also disease claims as statements
permitted under section 403(r)(6) of the act. As noted above, section
403(r)(6) of the act contains two passages that indicate Congress'
intent to exclude from the scope of structure/function claims any claim
that is also a disease claim. Section 403(r)(6) of the act provides
that structure/function statements ``may not claim to diagnose,
mitigate, treat, cure, or prevent a specific disease or class of
diseases.'' It also requires structure/function claims to be
accompanied by a disclaimer stating that the product ``is not intended
to diagnose, treat, cure, or prevent any disease.''
In light of the statutory framework, FDA concluded in the preamble
to the proposed rule that section 403(r)(6) of the act authorizes
claims related to the effect of a product on the structure or function
of the body only if they are not also disease claims. FDA's conclusion
was consistent with the policy guidance offered by the President's
Commission on Dietary Supplement Labels. In the report the Commission
offered general guidance on structure/function claims, including the
following:
3. Statements indicating the role of a nutrient or dietary
ingredient in affecting the structure or function of humans may be
made when the statements do not suggest disease prevention or
treatment.
(The report, p. 38)
Accordingly, FDA believes that it is appropriate to define the
universe of permitted structure/function claims by first identifying
those claims that should be considered disease claims. Remaining claims
about the effect of a dietary supplement on the structure or function
of the body may be acceptable structure/function claims under section
403(r)(6) of the act, provided that they are consistent with the
requirement in section 201(ff)(1) of the act that a dietary supplement
be ``intended to supplement the diet.''
(6.) Some comments, particularly those received at the public
hearing or during the reopened comment period, argued that it is
difficult or impossible to draw principled distinctions between
structure/function claims and disease claims. Some of these comments
said that section 403(r)(6) of the act, which is premised on such a
distinction, is not scientifically based. Other comments argued that it
is not necessary or practical to draw clear lines between disease
claims and structure/function claims, and that dietary supplement
labeling should instead focus on educating consumers about the
conditions for which a product may be used. According to these
comments, if there are disease conditions that might be implied by a
particular claim, the labeling should, for example, inform consumers of
the symptoms of such conditions, the importance of seeking medical
attention for them, and their health-related consequences. Other
comments argued that consumers reading the labels of dietary
supplements will incorrectly assume that the information provided
therein has been reviewed by the government and that the claims,
express or implied, are supported by the kind of scientific evidence
that supports drugs with similar claims.
FDA agrees that it may be very difficult to draw clear lines
between structure/function claims and disease claims. Despite the
difficulty, implementing section 403(r)(6) of the act requires the
agency to draw these lines. FDA would not be carrying out its statutory
obligations if it abdicated responsibility for distinguishing between
the two types of claims, and instead permitted dietary supplements to
disseminate information about specific disease states. FDA agrees that
scientifically valid information about diseases is helpful to
consumers, if it is delivered consistently and accurately, but does not
agree that section 403(r)(6) of the act authorizes such dissemination.
FDA strongly believes that the dissemination of such information on
dietary supplement labels increases the likelihood that consumers will
believe that the supplements are intended to treat or prevent the
diseases described in the labeling. Therefore, it is important that any
disease claims in dietary supplement labeling continue to be subject to
prior FDA review to evaluate the safety and effectiveness of the
product for the use described or suggested by the claim.
The agency also notes that there may be important health-related
consequences associated with taking a dietary supplement, even if the
product does not bear disease claims. For the labeling of a dietary
supplement to be considered truthful and non-misleading (see sections
403(a) and (r)(6) and 201(g)(1) of the act), it must include all
information that is material in light of the claims made for the
product and the consequences that may result from its use (see section
201(m)) of the act.
(7.) Many comments discussed the rule's effect on scientific
research. Some comments argued that the proposal would discourage
scientific research on dietary supplements. One comment contended that
such research might prompt FDA to consider a dietary supplement to be a
drug. Another comment said the proposal would ``chill'' the
availability of third-party information on dietary supplements.
The agency disagrees with the comments. The comments provided no
evidence, and the agency is aware of none, that establishing criteria
for distinguishing structure/function claims and disease claims will
adversely affect the conduct or use of scientific research. In the
agency's experience, establishing regulatory standards has generated
more research rather than less. As described below, some comments from
pharmaceutical companies and from patient organizations expressed the
contrary concern that allowing dietary supplements to make disease
claims without FDA review would undermine incentives for rigorous
scientific research. The agency also notes that nothing in this rule
would treat scientific research or the publication of research results
in a scientific journal as evidence that a product is marketed as a
dietary supplement or is a drug.
(8.) Several comments addressed the relationship between dietary
supplements and drug products, and the effects of this regulation on
drug products and drug development. Some comments suggested that the
proposal represented an attempt by FDA to
[[Page 1006]]
regulate dietary supplements in a manner that benefits pharmaceutical
interests or to regulate dietary supplements in a manner that is
similar to European regulatory systems that apply drug requirements to
such products.
In contrast, other comments expressed concern over the negative
effects of DSHEA and the proposed rule on incentives for pharmaceutical
drug development. One comment asked FDA to provide an ``unambiguous
demarcation'' that would preserve research and development incentives
for drug products and permit evaluation of opportunities in the dietary
supplement marketplace. According to this comment, section 403(r)(6) of
the act, and DSHEA generally, were intended to create ``parity''
between the dietary supplement and food industries without undermining
research and development incentives for the pharmaceutical industry and
to address a perceived failure by FDA to implement the health claims
provision for dietary supplements in section 403(r)(5)(D) of the act.
The comment contended that section 403(r)(6) of the act is intended to
provide a limited statutory safe harbor for certain dietary supplements
that might otherwise be subject to regulation under the health claim
rules for food or as unapproved new drugs, but it does not permit any
and all structure/function statements for dietary supplements. Thus,
the comment said FDA should have ``parallel interpretations'' of
sections 201(g)(1)(C) and 403(r)(6) of the act. The comment suggested
that FDA enforce the requirement of a ``documented mechanism'' imposed
in section 403(r)(6)(A) of the act, which permits claims that
``characterize the documented mechanism by which a nutrient or dietary
supplement acts to maintain'' structure or function and that FDA limit
claims to ``maintaining,'' rather than ``promoting'' or ``improving''
structure or function.
FDA does not agree that this rule was designed to benefit the
pharmaceutical industry or to establish rules that are consistent with
European regulation of dietary supplements. As noted above, some
pharmaceutical companies believe that the rule will harm them by
permitting competition by products that have not had to undergo
rigorous testing or review. Other pharmaceutical companies already
produce dietary supplements and expressed the same reservations about
the rule as other dietary supplement manufacturers. There was also no
attempt to model this rule after European regulation of dietary
supplements.
FDA recognizes the importance of maintaining incentives for
research and product innovation. By establishing criteria for
determining when a statement may be a disease claim, the final rule
indirectly contributes towards preserving the incentives for
pharmaceutical research and development by ensuring that products
marketed for treatment or prevention of diseases must all meet the same
regulatory standards. As stated below, FDA believes that if the rule
were to permit dietary supplements to carry implied disease claims, the
incentives for new drug development could be significantly undermined.
FDA agrees with the comment that the structure/function provisions
of sections 403(r)(6) and 201(g)(1)(C) of the act are similar in scope.
FDA also agrees that to make a statement about the mechanism by which a
dietary supplement maintains structure or function, the mechanism of
action must be ``documented.'' FDA does not agree, however, that this
is the only provision under which a dietary supplement may claim to
maintain healthy structure or function. Maintenance claims also can be
made under the provision that authorizes statements that ``describe the
role'' of a supplement ``intended to affect the structure or function''
of the body (section 403(r)(6)(A) of the act).
In response to the comment asking FDA to limit claims to
``maintaining,'' rather than ``promoting'' or ``improving,'' structure/
function, the agency agrees that ``improving'' often suggests some
abnormality or deficiency that can be treated, so a claim to
``improve'' a structure or function of the body would be more likely to
be a disease claim. On the other hand, a claim to improve memory or
strength would be a permitted structure/function claim, unless disease
treatment were implied. Use of the term ``promote'' may be acceptable
under the portion of section 403(r)(6)(A) of the act which authorizes
claims that ``describe[] the role of a * * * dietary ingredient
intended to affect the structure or function.'' Whether a claim for
``promoting'' structure or function is a disease claim will depend on
the context and nature of the claim. For example, a claim that a
product ``helps promote digestion'' would be a structure/function claim
because it does not refer explicitly or implicitly to an effect on a
disease state, but a claim that a product promotes low blood pressure
would be considered a disease claim. Both the preamble to the proposed
rule and the Commission recognized that statements using the word
``promote'' can be appropriate when the statements do not suggest
disease prevention or treatment or use for a serious health condition
that consumers cannot evaluate (see 63 FR 23624 at 23626).
(9.) A few comments objected to the statement that a dietary
supplement bearing an appropriate structure/function claim may be
subject to regulation as a drug if there is other evidence that it is
intended for the diagnosis, cure, mitigation, treatment, or prevention
of disease. One comment argued that many dietary supplements are used
for medicinal purposes and it would be ``easy'' for FDA to find
evidence that they were intended for this purpose based on consumer use
of the product.
Although FDA's longstanding interpretation of section 201(g)(1)(B)
of the act authorizes the agency to rely on evidence outside the
labeling and advertising of a product to establish its intended use,
FDA does not rely on such evidence alone except in unusual
circumstances. For example, the courts have suggested that if the
agency seeks to rely solely on evidence that consumers use a product
for a particular purpose to support a finding of intended use for that
purpose, consumers must use the product predominantly or nearly
exclusively for that purpose. (See, e.g., Action on Smoking and Health
(ASH) v. Harris, 655 F.2d 236, 239-240 (D.C. Cir. 1980); National
Nutritional Foods (NNFA) v. Weinberger, 512 F.2d 688, 702 (2d Cir.
1975), cert. denied, 423 U.S. 827 (1975).) The fact that some consumers
used a dietary supplement for medicinal purposes would not by itself be
sufficient to establish intended use as a drug, if use for medicinal
purposes was not the predominant use.
FDA reiterates, however, that in appropriate circumstances, FDA
may find that a dietary supplement for which only structure/function
claims are made in labeling may nevertheless be a drug if there is
other evidence of intended use to prevent or treat disease.
(10.) Some comments discussed the ``disclaimer'' statement
required by section 403(r)(6)(C) of the act. The disclaimer reads as
follows: ``This statement has not been evaluated by the Food and Drug
Administration. This product is not intended to diagnose, treat, cure,
or prevent any disease.'' One comment said the disclaimer resolves any
consumer confusion between dietary supplement claims and drug claims.
Another comment said the proposed rule showed that FDA was implicitly
rejecting the disclaimer's meaning because the proposed rule would
restrict the amount of information flowing to consumers. One comment
said the disclaimer reflects
[[Page 1007]]
Congress' understanding of a tension between structure/function and
disease claims, while another comment asserted that the disclaimers
required on a label are an attempt to decrease the amount of space on a
label for a structure/function claim.
Section 403(r)(6) of the act requires dietary supplement
manufacturers who wish to make a structure/function statement to
include the disclaimer, and, since 1997, FDA regulations regarding the
disclaimer have been codified at Sec. 101.93. However, the disclaimer's
role does not eliminate the need for this final rule to establish
criteria for determining whether a statement is a disease claim.
Section 403(r)(6) of the act provides that a statement for a dietary
supplement that is made under section 403(r)(6) ``may not claim to
diagnose, mitigate, treat, cure, or prevent a specific disease or class
of diseases.'' Had Congress thought the disclaimer, alone, was
sufficient to distinguish between structure/function claims and disease
claims, it would not have enacted the restriction against disease
claims in section 403(r)(6) of the act.
FDA does not agree with the assertion that the disclaimer, which
is expressly required by the act, is a scheme to decrease the space for
structure/function claims on a label. FDA believes that the disclaimer
is intended to make sure that consumers understand that structure/
function claims, unlike health claims and claims that appear on the
labels of drugs, are not reviewed by FDA prior to marketing, and to
caution consumers that dietary supplements bearing such claims are not
for therapeutic uses.
(11.) Several comments sought additional statements or language on
product labels. One comment supported the marketing of dietary
supplements and other substances whose effectiveness has not been
established and that have no appreciable toxicity as long as the
product's label stated that effectiveness had not been proven. Another
comment said precautions, such as adverse reactions and
contraindications to certain diseases and medications, are important
information for labels. The comment also sought a description of a
dietary supplement product's contents as a percentage of a person's
recommended daily intake (RDI) and in actual units.
FDA declines to revise the rule as suggested by the comments. With
regard to the marketing of dietary supplements with a label statement
that the product's effectiveness has not been proven, the agency
advises that dietary supplements that do not do what they claim to do
are misbranded. The act forbids false and misleading labeling and
advertising claims and requires businesses to have substantiation for
any structure/function claims they make for dietary supplements in
labeling (see section 403(a) and (r)(6)(B)) of the act). The presence
of a disclaimer indicating that effectiveness has not been established
cannot vitiate these statutory obligations. Therefore, it would be
inappropriate for FDA to sanction the use of effectiveness disclaimers.
Although the act does not prescribe any specific statements
concerning adverse reactions or contraindications that dietary
supplements must carry, the agency notes that dietary supplement
labeling, like the labeling of all other FDA-regulated products, is
required to include all information that is material in light of
consequences that may result from the use of the product or
representations made about it (see sections 403(a)(1) and 201(n) of the
act).
As for requiring information on the percentage of RDI and actual
units for dietary ingredients in dietary supplements, FDA agrees that
such information is useful. In fact, FDA's nutrition labeling
regulations for dietary supplements generally require the percentage of
the RDI or daily reference value (DRV) that a dietary supplement
contains to be given for dietary ingredients that have an RDI or DRV
(see Sec. 101.36(b)(2)(iii) (21 CFR 101.36(b)(2)(iii))). In addition,
the amount in units must be given, regardless of whether an RDI or DRV
has been established (see Sec. 101.36(b)(2) and (b)(3) (21 CFR
101.36(b)(2) and (b)(3)). This information can be found on the
Supplement Facts panel of dietary supplements.
(12.) One comment objected to referring to structure/function
statements as ``claims.'' The comment said that, under section
403(r)(6) of the act, such statements must be truthful and non-
misleading, so they should be called ``statements'' instead of
``claims.''
FDA has traditionally used the term ``claim'' to refer to any
statement made by a manufacturer that recommends or suggests a
particular use of a product. This term is used for all products
regulated by FDA, including drugs, foods, devices, and dietary
supplements. Use of the term ``claim'' is not intended to suggest that
a statement is untrue or misleading in any way.
(13.) One comment said that any substance used with
``pharmacologic intent'' should be classified as a drug or biologic in
order to ensure the efficacy, potency, and purity of medicines. The
comment explained that such substances have a potential for therapeutic
benefit as well as harm, and suggested that existing and new dietary
supplements that are marketed with health-related claims be required to
provide scientific evidence of their safety and efficacy as a condition
of their being marketed as a drug or biologic.
FDA declines to adopt the comment's suggestion. Section 403(r)(6)
of the act expressly authorizes certain structure/function claims for
dietary supplements. Many of these claims may be said to be ``health-
related.'' (The agency is uncertain what is meant by ``pharmacologic
intent.'') Thus, the act does not require all substances with health-
related claims to be classified as a drug or biologic.
Regarding safety and effectiveness evidence for dietary
supplements that bear health-related claims, FDA agrees that such
evidence should continue to be required where the claim is a health
claim within the meaning of Sec. 101.14(a)(1) or a claim that subjects
the product to regulation as a drug under section 201(g)(1)(B) of the
act. With regard to health-related claims that are authorized by
section 403(r)(6) of the act, section 403(r)(6)(B) does require
manufacturers to have substantiation for their claims. However, the act
does not generally require dietary supplement manufacturers that make
claims for their products under section 403(r)(6) of the act to provide
a premarket demonstration of safety and effectiveness to FDA.
(14.) One comment recommended that FDA not finalize the proposed
rule because it claimed that the proposal's criteria were based on a
subjective evaluation of claims and not on objective information from
market research studies to determine whether consumers are confused by
the claim. The comment also argued that FDA did not provide data and
information regarding consumer confusion, and that all interested
parties should be able to evaluate and comment on any data before FDA
finalizes the proposal. The comment asserted that a significantly
revised and limited final rule could provide a basic regulatory
definition of disease and a ``construct'' for structure/function claims
so that detailed regulatory criteria would be unnecessary.
The act does not require market research studies to determine
whether a particular statement is a structure/function claim or disease
claim, and it would be both impractical and inefficient to require such
studies to decide the status of every possible claim that could be made
under section 403(r)(6) of the act. FDA also does not
[[Page 1008]]
believe that market research studies are necessary to provide a
reasonable basis for the agency's determinations concerning the meaning
of labeling claims. The agency has extensive experience in interpreting
such claims. The agency has, however, modified the second criterion in
Sec. 101.93(g)(2)(ii) to eliminate reference to recognition of signs
and symptoms by consumers or health professionals because many comments
objected that this standard would appear to require consumer testing.
FDA has replaced the recognition standard with an objective standard.
(15.) One comment said that it would be inappropriate for FDA to
issue any regulation that restricted the scope of statements of
nutritional support related to a nutrient content claim or claims
pertaining to a classical nutrient deficiency-related disease. The
comment said that claims such as ``calcium builds strong bones'' are
acceptable and that FDA should clarify this fact in the final rule.
FDA agrees that dietary supplements may carry structure/function
statements concerning the relationship of nutrients and the structure
or function of the body, such as ``calcium builds strong bones.'' The
preamble to the proposed rule also specifically acknowledged that
although statements under section 403(r)(6) of the act generally may
not claim to diagnose, mitigate, treat, cure, or prevent a specific
disease or class of diseases, ``such statements may claim a benefit
related to a classical nutrient deficiency disease, provided that they
also disclose the prevalence of the disease in the United States'' (63
FR 23624). The final rule codifies this exception at Sec. 101.93(g)(2),
which states that ``FDA will find that a statement about a product
claims to diagnose, mitigate, treat, cure, or otherwise prevent disease
(other than a classical nutrient deficiency disease) * * *'' (emphasis
added). Classical nutrient diseases are also specifically excluded from
the definition of disease in Sec. 101.93(g)(1). Thus, because the final
rule already contains the exception, no change to the rule is
necessary.
(16.) Many comments suggested that FDA issue a guidance document
instead of regulations. Some of the comments stated that regulations
are neither desirable nor necessary. Others stated that a guidance
document would be appropriate because it would permit new information
to support new structure/function claims or because it would enable FDA
to conduct consumer research and industry outreach programs before
imposing new rules. Some comments also requested separate guidance
documents for specific claims or recommended that FDA create or use
advisory committees to help draft guidance documents. Two comments said
that the Commission report only provided guidance and suggestions, so
FDA did not have to issue the proposed rule. Another comment said that
publishing a guidance document would consume fewer agency resources and
that a rule is unnecessary because the industry already knows the
permissible scope of statements for dietary supplements.
FDA disagrees with the comments. The final rule creates uniform,
enforceable requirements for structure/function claims. By doing so,
the final rule establishes a ``level playing field'' for all members of
the dietary supplement industry, and permits rational use of FDA's
limited enforcement resources. In contrast, guidance documents,
although they represent FDA's best advice on a particular matter, are
not binding on any party. Relying solely on guidance documents would
not be as effective in achieving consistency in the regulation of
structure/function claims on dietary supplements and would lead to
case-by-case enforcement.
FDA does, however, intend to issue a guidance document to provide
additional information regarding structure/function and disease claims.
The guidance document would complement, rather than substitute for, the
final rule.
As for those comments stating that a guidance document would
permit new information to support new structure/function claims or that
outreach programs are necessary, FDA notes that interested persons may
generate such information regardless of the rule. FDA may also conduct
research or other programs or consult advisory committees or other
persons if such actions would be helpful. In short, gathering more
information or conducting research and other programs is not dependent
on whether FDA issues a guidance document instead of a rule.
(17.) A few comments stated that FDA should enforce existing laws
and regulations, remove unsafe products from the market, take action
against dietary supplements that make ``extravagant, unsubstantiated''
claims, or promote educational activities instead of issuing
regulations. One comment suggested that FDA resources would be better
spent reviewing notices sent to the agency instead of issuing
regulations. Another comment suggested that FDA continue to clarify
issues on a case-by-case basis.
FDA disagrees with the comments. Regulations offer several
important advantages that case-by-case clarification, individual
enforcement actions, and educational activities generally cannot. For
example, when FDA develops a regulation, it provides notice, obtains
public comment, considers alternatives, and evaluates the rule's
potential impacts, costs, and benefits. Individual enforcement actions
and educational activities are not subject to these considerations.
Regulations also establish uniform, industry-wide requirements in
a single administrative proceeding (rulemaking). In contrast,
individual enforcement actions focus on distinct facts that may not
lend themselves to uniform application to an entire industry. Moreover,
enforcement actions are resource-intensive and require multiple steps,
such as inspections, warning letters, and sometimes litigation, before
they are completed. Educational activities may deal with general topics
and provide valuable opportunities for discussing issues with FDA, but
they do not create uniform requirements.
Regulations are also easier to locate because they are published
in the Federal Register when they are issued, are codified and
published in the Code of Federal Regulations (CFR) and can be found in
libraries and on government Internet sites (such as the Government
Printing Office's website at www.gpo.gov). In contrast, agency
correspondence and results of individual enforcement actions are not as
widely available and may be difficult for some regulated entities and
consumers to obtain.
Thus, when it comes to establishing uniform, industry-wide
requirements, conserving agency resources, and providing public notice
and an opportunity to comment, regulations are preferable to individual
enforcement actions and educational activities.
(18.) A comment suggested that FDA adopt an approach like hazard
analysis critical control point (HACCP) instead of issuing the rule.
FDA disagrees with the comment. HACCP is best suited for issues
relating to how a product is manufactured. Here, the principal issue is
the claims made for a product rather than how the product is made.
(19.) A comment stated that FDA lacks the expertise to determine
whether a botanical is a drug or a dietary supplement. The comment
explained that botanicals can be used for medicinal purposes, but that
they can also be used for promoting general well being and supporting
the structure or function of the body. According to the
[[Page 1009]]
comment, FDA declared Yellowdock, an herb, to have medicinal purposes
only, when the herb also had a long history of use as a food source.
The comment may have misinterpreted the rule. The focus of this
rule is not on whether a substance has a history of use as a food but
on claims made in the product's labeling. The rule defines the types of
statements that may be made concerning a dietary supplement's effect on
the structure or function of the body. FDA has many years of experience
in regulating and interpreting health-related product claims.
(20.) One comment said other countries (naming several European
nations) and the World Health Organization have established lists of
ingredients and botanical products that are safe and permitted for
therapeutic purposes. The comment suggested that FDA consider
assembling a committee to establish a similar list for the United
States.
A list of dietary ingredients and botanical products and their
therapeutic uses might provide valuable information. Nevertheless,
section 403(r)(6) of the act permits only structure/function claims for
dietary supplements that are not also disease claims, and so such a
list would not be relevant to this rulemaking.
(21.) Two comments suggested that FDA list examples of structure/
function claims in order to reduce confusion. Another comment would
have FDA describe both disease claims and structure/function claims.
FDA intends to issue a guidance document that will provide
examples of claims that would and would not be considered disease
claims. This final rule also includes many examples of structure/
function and disease claims.
B. Permitted Structure/Function Statements (Sec. 101.93(f))
Proposed Sec. 101.93(f) stated that dietary supplement labels and
labeling may bear structure/function statements that are not disease
claims within the meaning of proposed Sec. 101.93(g) and that otherwise
comply with the notification and disclaimer provisions of
Sec. 101.93(a) through (e). FDA is revising Sec. 101.93(f) on its own
initiative to make it clear that a dietary supplement may bear a
disease claim if it is the subject of an authorized health claim, but
that otherwise disease claims will subject the product to regulation as
a drug.
C. Definition of Disease (Sec. 101.93(g)(1))
To assist in describing what constitutes a disease claim, the
proposed rule contained a definition of ``disease.'' The proposed
definition was based on standard medical and legal definitions of the
term (Refs. 2, 3, 4, and 5). Proposed Sec. 101.93(g)(1) defined
``disease'' as:
any deviation from, impairment of, or interruption of the
normal structure or function of any part, organ, or system (or
combination thereof) of the body that is manifested by a
characteristic set of one or more signs or symptoms, including
laboratory or clinical measurements that are characteristic of a
disease.
The proposed definition would have replaced an earlier definition
issued in 1993 as part of the regulations implementing the health
claims provisions of NLEA. The implementing regulations require dietary
supplement manufacturers to obtain prior authorization of any labeling
statement that characterizes the relationship between a substance in
the supplement to a ``disease or a health-related condition'' (section
403(r)(1)(B) of the act; Sec. 101.14(a)(1)). The phrase ``disease or
health-related condition'' was defined in those regulations as:
damage to an organ, part, structure, or system of the body such
that it does not function properly (e.g., cardiovascular disease),
or a state of health leading to such dysfunctioning (e.g.,
hypertension); except that diseases resulting from essential
nutrient deficiencies (e.g., scurvy, pellagra) are not included in
this definition * * *.
Section 101.14(a)(5) (formerly Sec. 101.14(a)(6)). The definition was
redesignated as Sec. 101.14(a)(5) effective March 23, 1999 (see 62 FR
49859, 49867).
FDA tentatively concluded that it did not want to retain the older
health claims definition because its use of the term ``damage'' could
be interpreted to limit the definition to serious or long-term
diseases, and could imply that there needed to be pathological evidence
of damage, which is not always present. For example, most mental
illnesses have no evidence of anatomic damage, yet are clearly
diseases.
In the July 8, 1999, Federal Register notice announcing a public
meeting and reopening the comment period, FDA requested additional
comment on the definition of disease. The notice listed four questions
on which it sought specific comment: (1) What are the consequences,
with respect to the range of acceptable structure/function claims, of
adopting: (a) The 1993 definition in Sec. 101.14(a)(5), or (b) the
definition in the proposed rule? (2) If FDA were to retain the 1993
definition, does the reference to ``damage'' exclude any conditions
that are medically understood to be diseases? Please provide examples.
(3) If it does not exclude any such conditions, is the 1993 definition
otherwise consistent with current medical definitions of disease? (4)
If it does exclude conditions that are medically understood to be
diseases, could it be revised in a way that would include such
conditions?
(22.) Almost all of the comments from the dietary supplement
industry and from individuals objected to the new definition of
disease. Most of these comments argued that the new definition is too
broad, sweeping in many minor deviations or abnormalities that are not
diseases. (Many of these comments did not appear to have understood
that the definition required not only a deviation, but one that ``is
manifested by a characteristic set of one or more signs or symptoms.'')
One comment said that under the new definition wrinkles and gray hair
would qualify as diseases. Some comments objected to the fact that the
proposed definition was not limited to adverse deviations from normal
structure or function. Other comments argued that the breadth of the
proposed definition is inconsistent with the intent of DSHEA. Some
comments objected to the distinction between normal and abnormal
functions, and argued that Congress did not intend to limit structure/
function claims to normal structure or function. Some comments
contended that the definition of disease should not include the phrase
``structure or function.'' Other comments said that Congress should be
presumed to have been aware of the 1993 definition of ``disease or
health-related condition'' and to have intended FDA to use that
definition. Several comments argued that the new definition of
``disease or health-related condition'' for health claims would
inappropriately broaden the scope of health claims for conventional
foods and concomitantly narrow the scope of acceptable structure/
function claims for foods. One comment said that redefining ``disease
or health-related condition'' in Sec. 101.14(a)(5) would undermine the
existing definition of ``statement of nutritional support,'' and would
violate DSHEA and the First Amendment. Most of the comments from the
dietary supplement industry and from individuals recommended that FDA
return to the 1993 definition.
Most of the comments from health professional groups and groups
devoted to specific diseases, including those who participated in the
August 4, 1999, public meeting, supported the new definition of disease
as more consistent with a medical understanding of disease than the
NLEA definition. Some of these
[[Page 1010]]
comments criticized the 1993 definition because of its reliance on
``damage'' and dysfunction and because of its failure to refer to signs
and symptoms. While many comments from the dietary supplement industry
said that no recognized diseases would be excluded by requiring
evidence of ``damage,'' comments from health professionals pointed out
a number of recognized disease conditions for which it is not currently
possible to identify physical damage to an organ, part, or system of
the body, including most psychiatric diseases (depression, bipolar
disorder, schizophrenia, and obsessive compulsive disorder, among
others), and the early stages of certain metabolic diseases, including
diabetes, genetic diseases, and nutritional deficiency diseases.
A few comments offered alternative definitions of disease. A major
medical association contended that the proposed definition would be
improved by the addition of the phrase ``or a state of health leading
to such deviation, impairment, or interruption.'' An OTC drug and
dietary supplement trade association offered the following alternative
definition of disease, which would modify the proposed definition:
A disease is any adverse deviation from, or impairment of, or
interruption of the normal structure or function of any part, organ,
or system (or combination thereof) of the body that is manifested by
a characteristic set of one or more signs or symptoms that are not
characteristic of a natural state or process.
According to this comment, the addition of the word ``adverse''
appropriately narrows the nature of the deviation, ``laboratory or
clinical measurements'' are appropriately deleted because they are
already included under the concept of ``signs,'' and the exclusion of
natural states ``encompasses Congress' intent to allow health
promotion/maintenance claims.'' One comment suggested that, if FDA were
to retain the 1993 definition, it add the word ``impairment'' after
``damage'' to cover those recognized disease conditions for which
evidence of damage is missing. A pharmaceutical trade association urged
FDA to convene a small workshop of physicians, patients, and other
stakeholders to develop a consensus on the distinction between disease
claims and structure/function claims.
In response to the comments, FDA has reconsidered the proposed
definition of disease in Sec. 101.93(g)(1), and has concluded that it
is not necessary to change the 1993 health claims definition, because
it can be construed in a manner that covers conditions that are
medically understood to be diseases. In light of Congress' desire to
increase the number of claims that could be made for dietary
supplements without subjecting them to drug regulation, FDA is
persuaded that it is therefore appropriate to retain a narrower
definition of disease at this time.
FDA has concluded that the older health claims definition, read as
a whole, will not exclude any significant conditions that are medically
understood to be diseases. For example, the requirement of ``damage to
an organ, part, structure, or system of the body such that it does not
function properly'' indicates that a condition may be considered a
disease if there is direct evidence of structural damage to an organ,
part, structure, or system of the body, or indirect evidence of damage,
indicated by the failure of the organ, part, structure, or system of
the body to function properly. This interpretation is appropriate
because otherwise well-recognized psychiatric diseases, migraine
headaches, hypertension, blood lipid disorders, and many other well-
accepted diseases, could be excluded from coverage due to the lack of
direct evidence of physical damage. The reference to ``a state of
health leading to such dysfunctioning'' also permits the agency to look
at evidence other than actual damage to an organ, part, structure, or
system of the body.
FDA does not believe that it would be constructive to defer a
decision on the definition of disease and seek a ``consensus'' of
stakeholders. The agency believes that it is unlikely that diverse,
strongly-held views expressed in written comments and at the public
hearing could be forged into a consensus on this issue. FDA also
believes that it is important to reach a decision as soon as possible
to permit the issuance of clear, uniform rules that will apply to all
dietary supplement labeling.
Accordingly, the final rule does not include a new definition of
disease, but incorporates the definition of ``disease or health-related
condition'' in Sec. 101.14(a)(5). If experience shows a public health
need for a different or broader definition, however, FDA will consider
initiating a rulemaking to amend that definition.
(23.) One comment argued that it is unnecessary for FDA to define
disease at all, but that the agency should use a ``common sense''
approach to distinguishing structure/function claims from disease
claims. According to this comment, dietary supplements should be
allowed to make any claim that does not contain express references ``to
specific diseases * * * or which can only be reasonably interpreted to
refer to a specific disease (e.g., `helps prevent tumors').''
FDA does not agree that a definition of disease is unnecessary.
The comment that made this argument went on to use the term disease in
its ``common sense'' principle, apparently assuming that there is some
common sense understanding of the term. FDA is not aware of any common
sense understanding of ``disease,'' and the diversity of comments
received in this rulemaking on the appropriate definition of disease
supports FDA's view that a definition is needed if FDA is to enforce
section 403(r)(6) of the act fairly and consistently.
(24.) One comment argued that any definition of disease should
exclude symptoms or diseases that do not normally require a drug or
doctor's care because these states could be considered part of
``normal'' living.
FDA does not agree that DSHEA was intended to permit structure/
function claims about diseases that can normally be treated without a
physician's care. Nothing in the statute or its legislative history
suggests that Congress intended to accord different treatment to this
subset of diseases. Diseases that do not ordinarily require a
physician's care are generally those for which drugs may be sold over
OTC. (OTC drug claims include both disease claims and structure/
function claims.) Drugs carrying OTC claims are already regulated under
rules different from those applicable to prescription drugs. FDA has
undertaken a comprehensive review of OTC drug claims and published
monographs on these claims. Had Congress intended to permit dietary
supplements to make all OTC claims (both disease claims and structure/
function claims) without prior review, it could easily have so
indicated. Because Congress did not do so, FDA does not believe that
there is support for treating this subset of diseases differently from
other diseases. As discussed elsewhere in this document, the structure/
function claims made for OTC drugs also may be made, in appropriate
circumstances, for dietary supplements under section 403(r)(6) of the
act.
(25.) One comment argued that it was irrelevant whether the 1993
definition excluded conditions that were medically understood to be
diseases. According to this comment, the definition of disease should
be based on consumer understanding rather than medical understanding,
because DSHEA was intended to educate consumers.
FDA does not agree that its interpretation of a medical term like
``disease'' should ignore medical definitions of the term, unless there
is
[[Page 1011]]
clear guidance from Congress that it intended a nonmedical definition
of the term. In any case, the comment provided no argument or evidence
that the 1993 definition was based on, or reflects, consumer
understanding of the term ``disease.''
D. Disease Claims (Sec. 101.93(g)(2))
(26.) Many comments agreed with the statement in proposed
Sec. 101.93(g)(2) that, in determining whether a statement is a disease
claim, it is appropriate to consider the context in which the claim is
presented. One comment argued, however, that language of the regulation
and preamble showed that FDA was biased because the agency would only
consider the context of a claim to convert a dietary supplement to a
drug.
FDA does not agree that it will consider context only to convert
an otherwise acceptable structure/function claim to a disease claim.
The context in which a claim appears can provide evidence in either
direction.
(27.) One comment argued that the rule should have only the
following three criteria: (1) The words ``diagnose,'' ``prevent,''
``treat,'' ``cure,'' and ``mitigate'' should not be used in a
structure/function claim; (2) the words ``stimulate,'' ``maintain,''
``support,'' ``regulate,'' and ``promote''--or other similar words--may
be used in a structure/function claim to distinguish the claim from a
specific disease claim; and (3) clinical endpoints that are
recognizable to health professionals or consumers as being related to a
disease may be used in a structure/function claim.
FDA does not believe that the three suggested criteria provide a
sufficient basis to distinguish between structure/function claims and
disease claims. Nothing in these criteria would prevent a structure/
function claim from discussing a specific disease, explicitly or
implicitly, as long as the claim did not contain the specific verbs
``diagnose,'' ``prevent,'' ``treat,'' ``cure,'' or ``mitigate.''
(28.) Several comments from medical and consumer groups supported
the establishment of criteria for structure/function claims, but were
concerned that the criteria in the proposed rule were too vague and
would fail to protect consumers from misleading claims. A major medical
association contended that some of the structure/function claims listed
as acceptable in the proposal were debatable and expressed doubt that
the public health would be adequately protected. Some of these comments
expressed the view that some of the structure/function claims listed in
the proposal in fact imply disease prevention. For example, some of
these comments argued that health maintenance claims imply disease
prevention. On the other hand, a comment from a major dietary
supplement trade association argued that the overall impact of the
criteria restricts the value of structure/function claims in providing
consumers with useful information about dietary supplements.
FDA agrees that consumers should have access to, and be allowed to
evaluate for themselves, as much truthful information about dietary
supplements as is possible, consistent with the statutory restrictions
on disease treatment and prevention claims. FDA believes that the
criteria in this rule strike a reasonable balance between these
competing goals. Undoubtedly, the criteria will not satisfy everyone.
For example, some of the claims considered to be structure/function
claims may imply specific disease prevention to some consumers. Because
of the importance of the context in which a claim is presented, it will
not always be possible to draw a line between structure/function and
disease claims in this rule with great specificity. FDA believes that,
within these constraints, the criteria, as finalized, adequately
distinguish between structure/function claims and disease claims. In
developing final criteria, the agency has tried to pay particularly
close attention to claims that might relate to serious health
conditions that patients cannot safely evaluate on their own. The
question of whether health maintenance claims necessarily imply disease
prevention is discussed in more detail below.
(29.) One comment, from a Commission member, said the ``dietary
relationship'' of a structure/function claim is relevant in considering
whether such a claim is appropriate. The comment said that statements
for dietary ingredients should ``relate to the role of the dietary
ingredient in the diet in achieving effects like those associated with
the effects of foods.'' The comment added that the claim ``should be
for an effect that is similar to the non-disease effects of a food on
the body'' and ``phrased to indicate the role of the dietary ingredient
in the diet in maintaining or supporting the ordinary functioning of
the body in a manner similar to that achieved through foods.'' Thus,
the comment would consider a claim such as ``promotes relaxation'' to
be appropriate ``only if it is indicated to be similar to the effects
achieved from foods, such as by indicating that it provides a relaxing
calming effect like a cup of tea.'' While the preamble to the proposed
rule considered the claim of ``improves absentmindedness'' to be a
structure/function claim, the comment viewed the same claim as a
disease claim ``because of the association of absentmindedness with
Alzheimer's disease.'' The comment continued, ``That claim should not
be permissible for the same reason that a claim that a dietary
supplement is an `oral contraceptive' is not permissible--the claim is
simply not one for the effects of a dietary ingredient.''
FDA agrees that dietary supplements must be ``intended to
supplement the diet'' (section 201(ff) of the act). In interpreting
section 403(r)(6) of the act, however, FDA believes that it is
appropriate to focus on the claims made for the product. Unlike section
201(g)(1)(C) of the act, section 403(r)(6) of the act does not limit
authorization to make structure/function claims (without triggering
drug approval requirements) to substances that are ``food.'' FDA notes
that it is developing an overall dietary supplement strategy and will,
when a document incorporating the strategy is released, state how the
agency plans to address the requirement that dietary supplements be
``intended to supplement the diet.''
(30.) One comment said FDA should develop a list of ``acceptable
subclinical, pre-disease, and normal states'' that may be used in
structure/function claims.
FDA declines to adopt the comment's suggestion. However, this rule
contains many examples of acceptable structure/function claims and FDA
intends to issue further guidance listing acceptable claims.
(31.) One comment argued that all statements about effects on
structure or function should be deemed permissible unless they are
already approved drug claims. The comment noted that ``reduces joint
pain'' and ``relieves headache'' would not be structure/function claims
because they are OTC monograph claims.
FDA does not agree that such a criterion would appropriately
discriminate between structure/function claims and disease claims. One
kind of valid drug claim is a claim related to the effect of the
product on the structure or function of the body (section 201(g)(1)(C)
of the act) but not related to disease prevention or treatment. In
other words, not all drug claims are disease claims. Congress
specifically provided that structure/function claims authorized by
section 403(r)(6) of the act do not, in themselves, subject a dietary
supplement to regulation as a drug under 201(g)(1)(C) of the act. It
thus would not be appropriate to exclude
[[Page 1012]]
from the scope of acceptable structure/function claims OTC monograph
claims or other approved claims for products classified as drugs under
section 201(g)(1)(C) of the act.
(32.) A national pharmacy group stated that the examples of
structure/function and disease claims in the proposal were reasonable
and based on good science and logic, but should be evaluated and
revised as necessary over time.
FDA agrees that it will be necessary to evaluate the examples over
time and to revise them as experience dictates.
(33.) Some comments argued that the types of claims permitted
under the proposal may discourage serious approaches to substantiation
because the terms used are not scientifically verifiable. Stating that
the preferred method of substantiation is an adequate and well-
controlled trial, one comment contended that the claims permitted under
the rule are not amenable to such proof. According to this comment,
this rule may preclude companies from meeting the substantiation rules
of the Federal Trade Commission (FTC). A few comments said that
manufacturers cannot substantiate claims that a product maintains
healthy status. One of these comments stated that it was impossible to
show by adequate studies that ``cranberry extract supports healthy
urinary tract functioning,'' and that companies should instead be able
to show that cranberry extract reduces frequency of urinary tract
infections in susceptible people. Similarly, because it is
``impossible'' to test whether St. John's Wort ``supports mood'' in the
general population, companies need to be able to test its effect on
depressed people.
FDA agrees that some structure/function claims that are acceptable
under DSHEA may be difficult to substantiate. For example, some
structure/function claims currently in the marketplace use terms that
do not have clear scientific meaning. Other claims concern health
maintenance in the general population and therefore could require
studies in a large population for substantiation. FDA believes,
however, that such claims are within the intended scope of section
403(r)(6) of the act. Difficulty in substantiating them does not alter
the terms of the statute. Manufacturers are responsible for determining
whether claims for their products can be appropriately substantiated,
and to use only those claims for which they have substantiation. FDA
does not agree that difficulty in substantiating a particular claim
justifies the use of express or implied disease claims for which
methods of substantiation may be more straightforward. Such an approach
would turn section 403(r)(6) of the act on its head.
FDA also does not agree that it is impossible to substantiate the
claims described in the comments. For example, to substantiate the
claim ``supports mood,'' it is not necessary to study the effects of a
substance on clinical depression. Instead, it is quite possible to
assess the effects of a substance on mood changes that do not
constitute clinical depression.
E. Effect on Disease or Class of Diseases (Sec. 101.93(g)(2)(i))
Under proposed Sec. 101.93(g)(2)(i), a statement would be
considered a disease claim if it explicitly or implicitly claimed an
effect on a specific disease or class of diseases. FDA included the
following examples of such disease claims: ``Protective against the
development of cancer,'' ``reduces the pain and stiffness associated
with arthritis,'' ``decreases the effects of alcohol intoxication,'' or
``alleviates constipation.'' FDA included the following examples of
claims that do not refer explicitly or implicitly to an effect on a
specific disease state: ``Helps promote urinary tract health,'' ``helps
maintain cardiovascular function and a healthy circulatory system,''
``helps maintain intestinal flora,'' and ``promotes relaxation.'' FDA
proposed to treat both express and implied disease claims as disease
claims that could not be made for dietary supplements without prior
review either as health claims or as drug claims. Implied disease
claims do not mention the name of a specific disease, but refer to
identifiable characteristics of a disease from which the disease itself
may be inferred. There are many possible ways to imply treatment or
prevention of disease, from listing the characteristic signs and
symptoms of the disease to providing images of people suffering from
the disease. Nine of the 10 criteria proposed by FDA for identifying
disease claims could be considered methods of implying disease
treatment or prevention.
In the July 8, 1999, Federal Register notice announcing a public
meeting and reopening the comment period, FDA sought additional comment
on the applicability of the rule to implied disease claims. The
discussion in the notice offered three examples of possible implied
disease claims: (1) ``shrinks tumors of the lung'' or ``prevents
development of malignant tumors'' (``treats cancer'' would be the
corresponding express claim); (2) ``prevention of seizures''
(``treatment of epilepsy'' would be the corresponding express claim);
(3) ``relief of sneezing, runny nose, and itchy watery eyes caused by
exposure to pollen or other allergens'' (``treatment of hayfever''
would be the corresponding express claim). The notice listed four
questions related to implied disease claims on which the agency sought
specific comments: (1) If implied disease claims should be permitted,
has FDA correctly drawn the line between what constitutes an express
disease claim and what constitutes a permitted implied claim? (2) If
such claims should be permitted, what are representative examples of
the types of implied disease claims that should be permitted without
prior review? (3) Are the examples of implied claims mentioned in the
July 8 notice appropriate structure/function claims? (4) Is a claim
that a product ``maintains healthy function'' an implied disease claim
in all cases? If not, under what circumstances is such a claim not an
implied disease claim?
(34.) Many comments agreed with proposed Sec. 101.93(g)(2)(I) that
structure/function statements should not explicitly or implicitly
mention specific diseases or class of diseases. These comments
contended that consumers cannot distinguish between implied and express
disease claims and that permitting implied disease claims poses
significant dangers to consumers with diseases. According to these
comments, permitting implied disease claims on dietary supplements may
cause consumers to delay or forego effective treatment for serious
diseases without assurance that the dietary supplement that has been
substituted is safe or effective for the disease. Some comments also
argued that permitting implied disease claims on dietary supplements
will undermine the drug approval process by permitting dietary
supplement manufacturers to market products for essentially the same
indications for which pharmaceutical companies have spent millions of
dollars obtaining approval.
Many other comments objected to treating implied disease claims as
disease claims, arguing that dietary supplements should be allowed to
carry any truthful claim that does not explicitly refer to a specific
disease. Some comments argued that Congress intended consumers to have
access to as much information about supplements as possible. Other
comments contended that barring implied disease claims eliminates any
meaningful claims for dietary supplements. Other comments argued that
treating implied claims as disease claims gives FDA ``unlimited
discretion'' to treat structure/function
[[Page 1013]]
claims as disease claims. Some comments, however, agreed that disease
claims may be implied as well as express, and said that it is
appropriate to consider a structure/function statement in context to
determine whether it conveys a disease claim.
FDA continues to believe that structure/function claims should not
imply disease treatment or prevention. Most disease treatment or
prevention claims, including claims about serious and life-threatening
diseases, can be described in a manner that will be easily understood
by consumers without express reference to a specific disease. The
following examples of implied disease claims demonstrate that it is not
difficult to convey prevention or treatment of a specific disease or
class of diseases without actually mentioning the name of the disease,
which are given in parentheses: ``Relieves crushing chest pain''
(angina or heart attack), ``prevents bone fragility in post-menopausal
women'' (osteoporosis), ``improves joint mobility and reduces joint
inflammation and pain'' (rheumatoid arthritis), ``heals stomach or
duodenal lesions and bleeding'' (ulcers), ``anticonvulsant''
(epilepsy), ``relief of bronchospasm'' (asthma), ``prevents wasting in
persons with weakened immune systems'' (AIDS) (acquired immune
deficiency syndrome), ``prevents irregular heartbeat'' (arrhythmias),
``controls blood sugar in persons with insufficient insulin''
(diabetes), ``prevents the spread of neoplastic cells'' (prevention of
cancer metastases); ``antibiotic'' (infections), ``herbal Prozac''
(depression). The distinction between implied and express disease
claims is thus, in many cases, a semantic one that has little, if any,
practical meaning to consumers. The argument that Congress intended to
encourage the free flow of information about dietary supplements and
therefore intended to permit implied disease claims is illogical. If
Congress wanted to ensure that consumers receive information about how
these products can treat or prevent diseases, it is difficult to
imagine why it would have specifically denied the right to make such
claims expressly, and allowed manufacturers to make the claims only by
implication.
There are also serious public health questions raised by implied
disease claims. Treatment and prevention of disease are serious
matters, and the statute reflects a congressional judgment that
consumers deserve to have claims for such uses reviewed by experts for
proof of safety and effectiveness. In addition, permitting dietary
supplement manufacturers to make implied disease claims without prior
review would allow them to compete unfairly with prescription and OTC
drugs, which are required to establish their safety and effectiveness
for disease treatment and prevention before being marketed.
Pharmaceutical manufacturers, faced with this competition, might be
less likely to undertake future research and development, compromising
one of the nation's most important sources of therapeutic advances. Had
Congress intended to allow implied disease claims when it authorized
dietary supplement manufacturers to make structure/function claims
without prior review, it could easily have made clear its intention
through express statutory language or legislative history. As discussed
below, Congress did not do so.
FDA does not agree that the final rule eliminates all meaningful
claims for dietary supplements. FDA believes that there are many
meaningful structure/function claims that can be made without implying
disease treatment or prevention, and has listed a number of such claims
in this preamble.
FDA does not agree that treating implied claims as disease claims
gives the agency unfettered discretion to treat all structure/function
claims as disease claims. The purpose of this rule is to clarify which
claims are structure/function claims permitted under section 403(r)(6)
of the act and which are disease claims. Both in the proposed rule and
in this final rule, FDA has provided many examples of specific claims
that would be acceptable structure/function claims.
(35.) Many comments pointed to three provisions of DSHEA as
evidence that Congress intended to include implied disease claims among
structure/function claims permitted under section 403(r)(6) of the act.
First, the ``Findings'' section of DSHEA refers to the relationship
between dietary supplements and disease prevention. Many comments
argued that Congress would not have made statutory findings linking
dietary supplements to disease prevention if it intended that FDA could
prohibit such references.
Second, section 403(r)(6) of the act states that structure/
function statements may not ``claim'' to treat or prevent disease, and,
according to the comments, this term should be read to refer only to
express claims. Some comments noted that section 403(r)(6) of the act
does not use the word ``implied'' to qualify the term ``claims,'' and
contrasted the language of the drug definition in section 201(g)(1)(B)
of the act (``articles intended for use in the diagnosis, cure,
mitigation, treatment, or prevention of disease'') with the language of
section 403(r)(6)(C) of the act, which states that a structure/function
statement may not ``claim'' to diagnose, cure, mitigate, treat, or
prevent disease. One comment agreed with the proposal's statement that
while DSHEA authorizes structure/function claims that are not also
disease claims, but nevertheless asserted that the statute authorizes
structure/function claims that imply ``some protection against
disease.'' This comment reasoned that the act, as amended by DSHEA,
allows dietary supplements to be ``intended'' to affect the structure
or function of the body, provided that the product does not ``expressly
claim to prevent, etc. disease'' (emphasis in original) and the product
bears ``an express, formal disclaimer of an intent to prevent, etc.
disease.'' The comment also said that the Commission report only
referred to express claims.
Third, DSHEA requires structure/function claims to be accompanied
by a disclaimer that reads, in part: ``[T]his product is not intended
to diagnose, treat, cure, or prevent any disease.'' According to some
comments, Congress understood that specific disease treatment or
prevention effects can also be described as effects on the structure or
function of the body, and resolved the tension by requiring the
disclaimer. In contrast, however, another comment argued that the drug
definition in section 201(g)(1)(B) of the act still applies to dietary
supplements because the exemption for dietary supplements added to
section 201(g)(1) applies only to the structure/function definition in
section 201(g)(1)(C). Many comments argued generally that DSHEA was
intended to promote the free flow of truthful information about dietary
supplements, and that prohibiting implied disease claims is contrary to
this legislative goal.
FDA does not agree that DSHEA authorizes dietary supplement
manufacturers to make implied disease claims without prior review of
the claims. There is no express provision of DSHEA that authorizes
implied disease claims, and a construction of DSHEA that permitted such
claims would be fundamentally incompatible with important provisions of
the act that were squarely before Congress when it passed DSHEA,
including the definitions of ``drug'' and ``new drug'' and the health
claims provisions of NLEA.
As described above, Congress created a partial exemption for
dietary supplements from the definition of drug in section 201(g)(1)(C)
of the act by providing that truthful and non-misleading claims under
section
[[Page 1014]]
403(r)(6) of the act do not in themselves trigger drug regulation.
Congress did not, however, create any exemption from section
201(g)(1)(B) of the act for dietary supplements. Thus, dietary
supplements that are ``intended for use in the diagnosis, cure,
mitigation, treatment, or prevention of disease'' are subject to
regulation as drugs under the act. It has been FDA's longstanding
interpretation of section 201(g)(1)(B) of the act that the phrase
``intended for use'' refers to the objective intent of the
manufacturer, which is not limited to a manufacturer's express
representations. See Sec. 201.128 (21 CFR 201.128); NNFA v. Weinberger,
557 F.2d 325, 334 (2d Cir. 1977) (``the FDA is not bound by the
manufacturer's subjective claims of intent,'' but may establish intent
``on the basis of objective evidence''). Evidence of objective intent
can come from a variety of sources, and may include both implied and
express claims (United States v. Undetermined Quantities * * * Pets
Smellfree, 22 F.3d 235 (10th Cir. 1994); United States v. Storage
Spaces Designated Nos. ``8'' and ``49'', 777 F.2d 1363, 1366 (9th Cir.
1985) (``intent may be derived or inferred from labeling, promotional
material, advertising, or any other relevant source''), cert. denied,
479 U.S. 1086 (1987); United States v. Kasz Enterprises, Inc. 855 F.
Supp. 534, 539, 543-44 (D.R.I. 1994), modified on other grounds, 862 F.
Supp. 717 (D.R.I. 1994); United States v. Articles of Drug * * *
Neptone, 568 F. Supp. 1182 (N.D. Ca. 1983); United States v. * * *
Vitasafe, 226 F. Supp. 266 (D.N.J. 1964); United States v. 14 105 Pound
Bags * * * Mineral Compound, 118 F. Supp. 837 (D.C. Idaho 1953); United
States v. 43 1/2 Gross Rubber Prophylactics, 65 F. Supp. 534, 535 (D.
Minn. 1946), aff'd sub nom. Gellman v. United States, 159 F.2d 881 (8th
Cir. 1947); 59 FR 6084, 6088 (February 9, 1994) (terms
``antibacterial,'' ``antimicrobial,'' ``antiseptic,'' or ``kills
germs'' constitute implied drug claims that cause products carrying
them to be drugs); 58 FR 47611, 47612 (September 9, 1993) (labeling
indicating that ``hormones'' are present in a product constitutes
implied drug claim); 58 FR 28194, 28204 (May 12, 1993) (products
carrying term ``sunscreen'' are drugs because ``sunscreen'' implies
disease prevention, even if not expressly promoted for prevention of
skin cancer)).
Thus, interpreting section 403(r)(6) of the act as permitting
implied disease claims would be irreconcilable with FDA's longstanding
interpretation of section 201(g)(1)(B) of the act, which treats such
claims as drug claims.
Permitting implied disease claims as structure/function claims
would also conflict with the health claims scheme established in
section 403(r)(1) through (r)(1)(5) of the act, which requires food and
dietary supplement manufacturers to obtain health claim authorization
before making a claim ``which expressly or by implication''
characterizes the relationship of a nutrient to a disease or health-
related condition. Under this provision, a claim that characterized, by
implication, the relationship between a dietary supplement ingredient
and a disease would require authorization as a health claim.
Interpreting section 403(r)(6) of the act as permitting the same
implied claim without authorization of a health claim directly
conflicts with 403(r)(1) through (r)(1)(5) of the act.
None of the statutory provisions relied on by the comments
provides persuasive support for the conclusion that structure/function
claims can imply disease treatment or prevention.
FDA agrees that the Findings section of DSHEA includes statements
linking dietary supplements and disease prevention. However, in
addition to the types of claims authorized for dietary supplements in
section 403(r)(6) of the act, the act specifically authorizes dietary
supplements to bear health claims. Health claims are expressly
described in the statute as claims that characterize the link between a
nutrient and a disease or health-related condition (section
403(r)(1)(B) of the act). The statements in the ``Findings'' section of
the DSHEA are entirely consistent with this scheme and do not compel
the conclusion that claims linking dietary supplements and disease
prevention may be made as structure/function claims.
The use of the word ``claim'' rather than ``intended for use'' in
section 403(r)(6) of the act also does not show that Congress intended
to permit implied disease claims. First, the comment cites no
authority, and FDA is aware of none, for the proposition that the
meaning of the word ``claim'' is limited to ``express claim.'' More
importantly, section 403(r)(6) of the act does not stand by itself. As
Congress recognized when it provided that dietary supplements making
appropriate claims under section 403(r)(6) of the act do not thereby
become drugs under section 201(g)(1)(C) of the act, section 403(r)(6)
must be read in conjunction with section 201(g)(1). As described above,
section 201(g)(1)(B) of the act continues to apply to dietary
supplements and treats them as drugs if they are ``intended for use in
the diagnosis, cure, mitigation, treatment, or prevention of disease.''
FDA has interpreted section 201(g)(1)(B) of the act to cover both
express and implied claims for more than 50 years. Had Congress
intended 403(r)(6) of the act to permit any claims covered by section
201(g)(1)(B) of the act, it would have had to provide an exemption from
the latter section.
Further, FDA does not agree that the Commission report referred
only to express claims. In its guidance on statements under section
403(r)(6) of the act, the Commission specifically said that such
statements ``should be distinct from NLEA health claims in that they do
not state or imply a link between a supplement and prevention of a
specific disease or health-related condition'' (the report, p. 38)
(emphasis added). In addition, the Commission cautioned that claims
using terms such as, e.g., ``support,'' ``maintain,'' or ``promote''
are appropriate only if they do not ``suggest disease prevention or
treatment or use for a serious health condition that is beyond the
ability of the consumer to evaluate'' (the report, p. 38) (emphasis
added). Clearly, the Commission was concerned about implied claims as
well as express claims.
FDA also does not agree that the required disclaimer demonstrates
an intention to permit implied claims. To the contrary, FDA believes
that the disclaimer language (``This product is not intended to
diagnose, treat, cure, or prevent any disease''), which is virtually
identical to the language of section 201(g)(1)(B) of the act, provides
further evidence that Congress did not intend section 403(r)(6) of the
act claims to overlap section 201(g)(1)(B) claims. As a practical
matter, it is unreasonable to interpret section 403(r)(6) of the act as
inviting a communication to consumers like the following: ``This
product prevents bone fractures in post-menopausal women due to bone
loss. This product is not intended to diagnose, treat, cure, or prevent
any disease.'' The comments suggested that the addition of the
disclaimer would somehow clarify the product's purpose to consumers.
The comments provided no support, however, for their view that
consumers reading the disclaimer would interpret it as eliminating
implications in the remainder of the labeling that the product treats
or prevents disease. FDA believes that the two statements simply
contradict one another and could confuse consumers. Indeed, FDA is
concerned that juxtaposing two such contradictory statements is likely
to cause consumers to ignore the disclaimer required by section
403(r)(6) of the act, undermining its effectiveness.
[[Page 1015]]
(36.) A few comments addressed the examples of implied claims
listed in the July 8, 1999, Federal Register notice. Some comments said
that all of the examples were appropriate structure/function claims.
Two comments suggested that ``shrinks tumors,'' ``prevents development
of malignant tumors,'' and ``prevents seizures'' are express disease
claims because they employ ``synonyms'' for specific diseases.
According to these comments, ``tumor'' is a synonym for cancer, and
``seizure'' is a synonym for epilepsy. Another comment said that FDA
should treat as implied disease claims only those claims ``where there
is a direct causal relationship between the structure/function
parameter identified in the claim and a specific known disease.''
According to this comment, a tumor is a ``direct manifestation of
cancer'' and therefore reference to a tumor is a disease claim. In
contrast, risk factors for disease, in which the comment includes
elevated cholesterol, are not direct manifestations of a disease, and
therefore may be the subject of structure/function claims. Another
comment contended that disease claims should be limited to express
claims and to terms or measurements that are ``surrogates for the
disease itself.'' According to this comment, tumors are a surrogate for
cancer, but elevated cholesterol is not a surrogate for heart disease.
One comment argued that ``relief of sneezing, runny nose, and itchy
watery eyes caused by exposure to pollen or other allergens'' is an
acceptable structure/function claim, but did not explain why.
FDA has considered these comments, but does not believe that any
of them have provided a principle that distinguishes between claims
that consumers will understand as disease claims and those that will
not be understood as disease claims. According to the comments, some of
the claims that FDA offered as examples of implied disease claims
should not be allowed as structure/function claims. FDA agrees that
claims that refer to synonyms for disease, direct manifestations of
disease, and surrogates for disease are disease claims. Each of these
principles, however, would permit many types of implied disease claims
that would be clearly understood by consumers as disease claims, e.g.,
``Herbal Prozac'' and ``antibiotic.''
(37.) Some comments argued that it is impossible to construct a
structure/function claim that does not imply disease prevention or
treatment. Several of these comments claimed that health promotion
claims inevitably imply disease prevention.
FDA does not agree that every structure/function claim implies
disease prevention or treatment. In the proposed rule, FDA provided
examples of many types of claims that the agency would not consider
implied disease claims, and has expanded that list in the final rule.
(38.) Some comments disagreed with FDA's examples of disease
claims in the proposed rule. These comments stated that intoxication
and constipation are not in and of themselves diseases, and that these
conditions are not readily understood by consumers as diseases. A few
comments argued that alcohol intoxication is a ``self-induced
condition'' and not a disease.
FDA continues to believe that alcohol intoxication, like all
poisonings (mushroom, digitalis, or any drug overdose), meets the
definition of disease, albeit a transient disease. The definition in
Sec. 101.14(a)(5), which FDA is incorporating in this rule, states, in
part, that a disease is ``damage to an organ, part or structure, or
system of the body such that it does not function properly * * *'' All
poisonings, like alcohol intoxication, cause dose-related
dysfunctioning and damage, ranging from mild impairments to death.
Alcohol intoxication causes temporary damage to brain function, causing
impairments of judgment, attention, reflexes, and coordination. The
fact that it is ``self-induced'' does not remove it from the definition
of disease. Deliberate barbiturate overdoses are also self-induced, but
clearly meet the definition of disease.
FDA has considered the comments on constipation and agrees that
certain constipation claims should not be treated as disease claims.
Constipation has a variety of causes, many of them unrelated to
disease. For example, constipation can be caused by changes in diet and
schedule, and by travel. Constipation can also, however, be a symptom
of such serious diseases as bowel obstruction and irritable bowel
syndrome. FDA is aware that there may be differences of opinion about
whether occasional constipation, alone, constitutes a disease, but
believes that treating it as a disease would not be consistent with the
intent of DSHEA. ``For relief of occasional constipation'' would
therefore not be considered a disease claim under the rule. The
labeling of a product that claimed to treat occasional constipation
should make clear, however, that the product is not intended to be used
to treat chronic constipation, which may be a symptom of a serious
disease.
(39.) One comment questioned whether a claim that begins,
``According to the National Cancer Institute'' would be a disease claim
because it used the word ``cancer.''
Although the National Cancer Institute (NCI) is associated with
the treatment and prevention of cancer, such a statement will be
considered a disease claim only if, within the context of the total
labeling, the statement can be reasonably understood to relate the
product to the disease listed in the organization's name, e.g., cancer.
For example, FDA would regard as a disease claim ``According to the
National Cancer Institute, ingredient X protects smokers' lungs.''
F. Signs or Symptoms of Disease (Sec. 101.93(g)(2)(ii))
Under proposed Sec. 101.93(g)(2)(ii), a statement would be
considered a disease claim if it explicitly or implicitly claimed an
effect (using scientific or lay terminology) on one or more signs or
symptoms that are recognizable to health care professionals or
consumers as being characteristic of a specific disease or of a number
of diseases. FDA provided as examples of such disease claims:
``Improves urine flow in men over 50 years old,'' ``lowers
cholesterol,'' ``reduces joint pain,'' and ``relieves headache.''
Stating that claims of an effect on symptoms that are not recognizable
as characteristic of a specific disease or diseases would not
constitute disease claims, FDA provided the following examples of
acceptable structure/function claims: ``Reduces stress and
frustration,'' ``inhibits platelet aggregation,'' and ``improves
absentmindedness.'' The agency also stated that if the context did not
suggest treatment or prevention of a disease, a claim that a substance
helps maintain normal function would not ordinarily be a disease claim.
Examples included: ``Helps maintain a healthy cholesterol level,'' or
``helps maintain regularity.''
FDA specifically requested comment on the distinction between
maintaining normal function, which is potentially the basis for an
acceptable structure/function claim, and preventing or treating
abnormal function, which is potentially a disease claim. FDA noted that
the members of the Commission were divided on this issue, but that the
final report concluded that ``statements that mention a body system,
organ, or function affected by the supplement using terms such as
`stimulate,' `maintain,' `support,' `regulate,' or `promote' can be
appropriate when the statements do not suggest disease prevention or
treatment or use for a serious health condition that is beyond the
ability of the consumer to evaluate'' (the report, p. 38). Recognizing
that
[[Page 1016]]
claims relating to maintaining healthy cholesterol levels raise
particularly difficult issues, FDA sought specific comment on these
claims.
(40.) Many comments from manufacturers and individuals objected to
proposed Sec. 101.93(g)(2)(ii). Some of these comments argued that
basing the criterion on which signs and symptoms were ``recognizable''
to health care professionals or consumers was too vague, and that it
was unclear what proportion of health care professionals or consumers
would be necessary to establish recognition. Some comments asked
whether FDA expected manufacturers to conduct consumer surveys. Other
comments urged that FDA itself conduct consumer surveys to determine
which signs and symptoms were recognizable to consumers as implied
disease claims. Other comments argued that the proposed provision would
create a moving target because ``as soon as consumers understood that
certain signs and symptoms are characteristic of a disease--that is, as
soon as consumers understood why they should take a particular
supplement--FDA could * * * prohibit a product label from bearing the
substantive claims information.''
FDA agrees with these comments that the proposal's focus on
recognition of signs and symptoms by consumers or health professionals
might have made the provision difficult to apply, both for
manufacturers and for the agency. Accordingly, the agency has
substituted a more objective criterion. The final rule eliminates the
reference to recognition, and focuses simply on whether the labeling
suggests that the product will produce a change in the characteristic
signs or symptoms of a specific disease or class of diseases. FDA
believes that it will be easier for manufacturers to verify whether
symptoms are in fact characteristic of a disease. FDA and manufacturers
may look to medical texts and other objective sources of information
about disease to determine whether a label implies treatment or
prevention of disease by listing the characteristic signs and symptoms
of a disease or class of diseases.
FDA notes that the standard in the rule may be met if
characteristic signs and symptoms are referred to either in technical
or lay language. It also would not be necessary to mention every
possible sign or symptom of a disease to meet this standard. Instead,
the standard focuses on whether the labeling suggests that the product
will produce a change in a set of one or more signs or symptoms that
are characteristic of the disease.
FDA does not agree with the comment that objected to the
recognition standard because it would prohibit a claim ``as soon as
consumers understood that certain signs and symptoms are characteristic
of a disease--that is, as soon as consumers understood why they should
take a particular supplement * * *.'' This comment assumes that the
only reason people take dietary supplements is to treat or prevent
disease and that it is appropriate to market supplements by implying
that they can do so. Many people take dietary supplements for health-
related reasons that do not involve treatment or prevention of specific
diseases. As discussed elsewhere in this document, FDA does not believe
that the act permits structure/function claims to imply treatment or
prevention of specific diseases.
(41.) Several comments contended that the recognition standard was
too restrictive because all signs or symptoms relating to the structure
or function of the body are potentially recognizable to health care
professionals and educated consumers as characteristic of some specific
disease. Another comment argued that the proposal to treat references
to signs and symptoms as disease claims was arbitrary and artificial.
The comment said that specific examples of disease claims used in the
proposal could as easily refer to nondisease states, e.g., ``reduces
joint pain'' could refer to over-exercise. Conversely, ``stress and
frustration'' could refer to anxiety and depression. Another comment
contended that ``reduces joint pain'' is an acceptable structure/
function claim if other language or graphics in the labeling clearly
communicated treatment of conditions unrelated to arthritis. One
comment asked whether ``helps support cartilage and joint function''
would constitute a permissible structure/function claim. Some comments
said that references to signs and symptoms should not be evidence of a
disease claim because signs and symptoms can be associated with a
number of varying conditions. One comment claimed that ``inhibits
platelet aggregation'' does not mean anything to most consumers. On the
other hand, some medical groups, groups devoted to specific diseases,
and others expressed concern that the examples of structure/function
claims provided by FDA permitted references to signs or symptoms that
imply disease treatment or prevention. According to one comment,
``inhibits platelet aggregation'' could be interpreted to mean
``prevents heart attack,'' and ``improves absentmindedness'' could be
interpreted as a treatment for Alzheimer's disease.
FDA believes that removing the reference to recognition by
consumers or health professionals from Sec. 101.93(g)(2)(ii) will
permit a clearer distinction between those signs and symptoms that
imply a disease and those that do not. The focus will be on whether
specific signs or symptoms are characteristic of a disease, based on
objective sources. FDA does not believe that ``improves
absentmindedness'' or ``relieves stress and frustration'' are
characteristic of the specific diseases mentioned in the comments. FDA
agrees that some signs and symptoms are associated with such a wide
variety of diseases and nondisease states that they may not imply a
specific disease or class of diseases. For example, FDA would not
interpret ``improves absentmindedness'' as implying treatment of
Alzheimer's disease because absentmindedness is not as serious as the
t