[Federal Register Volume 65, Number 4 (Thursday, January 6, 2000)]
[Rules and Regulations]
[Pages 1000-1050]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-53]
[[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
Federal Register / Vol. 65, No. 4 / Thursday, January 6, 2000 / Rules
and Regulations
[[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
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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
type of memory loss characteristically suffered by Alzheimer's
patients; absentmindedness is, in fact, suffered predominantly by
people who do not have Alzheimer's disease or any other disease. Stress
and frustration, while associated with some anxiety disorders, are not
the characteristic symptoms of those disorders; in addition, these
symptoms are equally associated with many other nondisease states.
The agency does agree, however, with the comment that ``inhibits
platelet aggregation'' is an implied disease treatment or prevention
claim. Although platelet aggregation is a normal function needed to
maintain homeostasis, inhibiting or decreasing platelet aggregation is
a well-recognized therapy for the prevention of stroke and recurrent
heart attack (see, e.g., 63 FR 56802, October 23, 1998 (final rule for
professional labeling of aspirin for cardiovascular, cerebrovascular,
and rheumatologic uses); 53 FR 46204, November 16, 1988, (internal
analgesic tentative final monograph)). Inhibiting or decreasing
platelet aggregation is the mechanism of action of a number of drug
products approved for the treatment or prevention of stroke and heart
attack. Thus, the agency would consider a claim to inhibit normal
platelet function to be an implied claim to treat or prevent these
disease conditions.
FDA also believes that ``joint pain'' is characteristic of
arthritis. According to the Merck Manual, joint tenderness is the most
sensitive physical sign of rheumatoid arthritis (Ref. 6). The claim
``helps support cartilage and joint
[[Page 1017]]
function,'' on the other hand, would be a permissible structure/
function claim, because it relates to maintaining normal function
rather than treating joint pain.
(42.) One comment suggested that claims about a physiologic marker
or symptom should be regarded as disease claims in two situations: (1)
If the physiologic marker or symptom of a disease is described as being
quantifiably linked to that disease in an official government health
agency summary statement or consensus report, or (2) if most clinicians
treating patients with the condition prescribe prescription drugs to
modify the marker and historically do so without including nutritional
or dietary intervention as part of the treatment. According to this
comment, references to cholesterol lowering or blood pressure reduction
would be regarded as disease claims under the first suggested
criterion, and white cell counts and fever would be disease claims
under the second. This comment also suggested that FDA develop a list
of disease markers and symptoms that fall under each of the proposed
criteria.
FDA agrees in part and disagrees in part with this comment. The
agency agrees that references in dietary supplement labeling to
physiologic markers or symptoms of a disease that are quantifiably
linked to that disease in an official government health agency summary
statement or consensus report would be appropriately treated as implied
disease claims. Indeed, in the cases described, elevated blood pressure
(hypertension) and elevated cholesterol (hypercholesterolemia) are
diseases themselves, with subsequent events (heart attack, stroke) the
late consequences of those diseases. Although FDA agrees that fever and
elevated white cell counts are almost always evidence of a disease, FDA
does not agree that the second criterion appropriately describes the
remaining circumstances in which references to signs or symptoms should
be treated as disease claims. The appropriate test is whether: (1) The
condition to be treated or prevented is a disease and (2) the signs and
symptoms referred to in the labeling, in context, are characteristic of
a disease and thus permit the inference that the product is intended to
treat or prevent the disease. The second criterion offered by the
comment does not provide information on either of these elements.
(43.) Some comments that objected to the proposed definition of
disease argued that the inclusion of ``signs or symptoms'' as part of
the definition of disease should not mean that a reference to the signs
and symptoms of a disease in dietary supplement labeling constitutes a
disease claim. Another comment argued that because signs and symptoms
do not appear in the definition of ``drug,'' FDA is not authorized to
treat a reference to characteristic signs and symptoms as a drug claim.
The health claims definition of ``disease or health-related
condition'' in Sec. 101.14(a)(5), which is being adopted as the
definition of ``disease'' in this regulation, does not include
reference to the signs and symptoms of disease. Nonetheless, dietary
supplement labeling that refers to the characteristic signs or symptoms
of a specific disease or class of diseases will still be considered to
have made an implied disease claim. Labeling that claims a product
``prevents bone fragility in post-menopausal women,'' clearly implies
that the product prevents osteoporosis. Similarly, labeling that claims
a product ``prevents shortness of breath, an enlarged heart, inability
to exercise, generalized weakness, and edema'' has made a congestive
heart failure claim.
The basis for determining whether such a reference to signs or
symptoms constitutes an implied disease claim is not whether the
definition of disease includes mention of signs or symptoms. Rather,
FDA looks at whether the objective evidence shows that the product is
``intended for use in the diagnosis, cure, mitigation, treatment, or
prevention of disease'' within the meaning of section 201(g)(1)(B) of
the act and Sec. 201.128, or the claim constitutes a health claim
within the meaning of section 403(r)(1)(B) of the act and
Sec. 101.14(a)(1). For example, Sec. 201.128 provides that the
objective intent of those responsible for the labeling of drugs ``is
determined by such persons' expressions or may be shown by the
circumstances surrounding the distribution of the article.'' Section
101.14(a)(1) provides that ``[i]mplied health claims include those
statements, symbols, vignettes, or other forms of communication that
suggest, within the context in which they are presented, that a
relationship exists between the presence or level of a substance in the
food and a disease or health-related condition.'' Both of these
provisions permit FDA to look at whether a reference to the
characteristic signs or symptoms of a disease constitute an implied
disease claim.
(44.) Many comments argued that the distinction between claims
that a product maintains healthy function and that it prevents or
treats abnormal function is artificial, and that consumers understand
both types of claims as disease treatment or prevention claims.
Comments from dietary supplement manufacturers and some consumer groups
argued that both types of claims should be permitted either because
they are not implied disease claims or because implied disease claims
are permissible. Conversely, most of the comments from health
professional groups, groups devoted to specific diseases,
pharmaceutical companies, and other consumer groups argued that neither
type of claim should be permitted, because permitting implied disease
claims to be made without prior review would jeopardize the public
health by encouraging substitution of unproven remedies for proven
ones. One comment argued that analysis of health maintenance claims is
no different than analysis of any other structure/function claim: They
are disease claims if they imply disease prevention or treatment.
According to this comment, health maintenance claims are permissible
unless they relate to endpoints that are understood to be disease
markers, such as blood pressure and cholesterol. Comments from a former
Commission member and from a consumer group argued that many health
maintenance claims will be perceived as disease treatment or prevention
claims, and urged that FDA follow the Commission's guidelines, under
which the seriousness of the condition and the ability of the consumer
to evaluate it are key factors in deciding whether a disease claim has
been made. One comment argued that FDA may not prohibit a claim that a
dietary supplement ``maintains normal function'' even if it implies a
disease claim because 403(r)(6)(A) of the act expressly authorizes such
claims.
One comment said that the proposed rule would frustrate the
``orphan drug'' process. The comment contended that if dietary
supplement labeling may claim to promote or maintain ``healthy''
endpoints that are related to signs and symptoms of specific diseases,
then incentives to conduct research on orphan drugs would be
undermined. The comment explained that dietary supplements do not
require the same financial investment as drugs do (because drugs must
be approved as safe and effective for their intended uses and meet
quality controls), and could undercut sales of a more heavily regulated
and more expensive approved drug. The comment said that a dietary
supplement manufacturer's ability to make a disease prevention claim by
characterizing the product as promoting good health ``cannot become a
license to sell an active ingredient in a product
[[Page 1018]]
that is functionally a drug but is labeled as a dietary supplement.''
FDA has carefully considered these comments and has concluded that
the distinction drawn in the proposal between maintaining normal
function and treatment or prevention of abnormal function is supported
by the statute and the Commission report. FDA does not agree that
health maintenance claims must always be treated as implied disease
claims. Section 403(r)(6)(A) of the act demonstrates that Congress
intended to treat as structure/function claims some claims concerning
maintenance of normal structure or function, because it expressly
permits statements that ``characterize the documented mechanism by
which a nutrient or dietary ingredient acts to maintain such structure
or function.''
FDA also believes that many claims concerning the maintenance of
``normal'' or ``healthy'' structure or function do not imply disease
prevention in the context of dietary supplement labeling, unless other
statements or pictures in the labeling imply prevention of a specific
disease or class of diseases. There may be cases, however, in which a
statement of health maintenance can be understood only as a claim of
prevention of a specific disease, in which case it will be considered a
disease claim. Thus, any reference to ``maintaining a tumor-free
state'' would be a disease claim. Similarly, a claim to ``maintain
normal bone density in post-menopausal women'' is a disease claim
because post-menopausal women characteristically develop osteoporosis,
a disease whose principal sign is decreased bone mass.
FDA has added a sentence to Sec. 101.93(g)(2) clarifying that the
criteria in that paragraph are not intended to preclude structure/
function claims that refer to the maintenance of healthy structure or
function, unless they imply disease treatment or prevention.
For the reasons described elsewhere in this document, however, FDA
does not believe that DSHEA permits claims concerning treatment or
prevention of abnormal function, where such abnormal function implies a
specific disease or class of diseases. Accordingly, FDA believes that
the statutory scheme is consistent with treating many health
maintenance statements as structure/function claims, while treating as
health claims or new drug claims statements that imply disease
treatment or prevention by reference to an effect on abnormal structure
or function.
The Commission report also supports the distinction drawn by FDA
between maintaining healthy function and preventing or treating
abnormal function. The report's Guidance states:
4. 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.
5. Statements should not be made that products ``restore''
normal or ``correct'' abnormal function when the abnormality implies
the presence of disease. An example might be a claim to ``restore''
normal blood pressure when the abnormality implies hypertension.
(Report at pp. 38 and 39.)
FDA agrees that if a health maintenance claim implies disease
treatment or prevention, it would not be acceptable. (In FDA's view, a
claim promoting ``use for a serious health condition that is beyond the
ability of the consumer to evaluate'' is simply one form of implied
disease claim.) FDA believes that many health maintenance claims are
acceptable. In some cases, a health maintenance claim could use terms
that are so closely identified with a specific disease or that so
clearly refer to a particular at-risk population that FDA would
consider the claim to be an implied disease prevention claim, e.g.,
``maintains healthy lungs in smokers'' would imply prevention of
tobacco-related lung cancer and chronic lung disease. ``Maintains
healthy lung function,'' alone, however, would be an acceptable
structure/function claim.
In response to the comment contending that dietary supplements
undercut sales of orphan drugs by making health promotion claims for
active ingredients already approved as orphan drugs, FDA notes that
section 201(ff)(3) of the act excludes from the definition of ``dietary
supplement'' articles that have been approved as drugs or for which
substantial clinical investigations conducted under an investigational
new drug application (IND) have been made public, before they were
marketed as dietary supplements or foods.
(45.) Many comments responded to FDA's specific request for
comment on whether it is appropriate to treat ``maintains healthy
cholesterol levels'' as a permissible structure/function claim, while
treating ``lowers cholesterol'' as a disease claim. A few comments
supported the distinction drawn in the proposed rule. Many did not,
however. One comment from a major trade association claimed that the
distinction between lowering and maintaining cholesterol levels is
ambiguous, asking ``What is a healthy cholesterol level, but a lower
cholesterol level?'' Another comment from a food industry group
contended that ``cholesterol'' itself is a sign or symptom, and thus
that both types of claims refer to a sign or symptom of disease.
Several comments argued that lowering cholesterol is inextricably
linked to cardiovascular disease. Some comments argued that the
distinction between maintaining normal cholesterol and lowering
cholesterol is arbitrary because both have as their purpose preventing
heart disease, and consumers link cholesterol levels with disease
prevention. Other comments, however, argued that cholesterol claims do
not imply disease prevention. A comment from an organization devoted to
prevention and treatment of heart disease argued that if any
cholesterol claims were to be permitted, a claim like ``promotes
cholesterol clearance'' would be a more accurate structure/function
statement than ``maintains healthy cholesterol'' and less likely to
imply disease prevention. Two comments contended that changing a claim
from ``lowers cholesterol'' to ``maintains healthy cholesterol levels''
does not change the effect of the product or its use. Some comments
argued that ``lowers cholesterol'' claims should be permitted for
cholesterol levels that are not ``abnormal'' or are below
hypercholesterolemia.
FDA does not agree that claims concerning maintenance of normal
cholesterol levels necessarily constitute implied disease claims.
Although an elevated cholesterol level is a sign of
hypercholesterolemia and an important risk factor for heart disease, a
cholesterol level within the normal range is not a sign or risk factor
for disease. Moreover, maintaining cholesterol levels within the normal
range is essential to the structure and function of the body for
reasons other than prevention of heart disease. Although many people
think of cholesterol solely in terms of the negative role of elevated
cholesterol in heart disease, normal cholesterol levels play a positive
role in maintaining a healthy body. Cholesterol is a necessary
constituent of cell membranes and of myelin, the sheath that coats
nerves. Cholesterol is also required for the synthesis of steroid
hormones, which are essential for life. Finally, cholesterol is
required for the production of bile in the liver, making possible
absorption of dietary fat and fat soluble vitamins. Thus, a claim that
a dietary supplement helps maintain cholesterol levels that are already
within the normal range does not necessarily imply disease
[[Page 1019]]
treatment. FDA also believes that Congress intended to permit dietary
supplements to carry claims of this type under section 403(r)(6)(A) of
the act.
The agency has concluded, however, that references to ``healthy''
cholesterol may be misleading to consumers because the phrase ``healthy
cholesterol'' is now frequently used to refer to high density
lipoproteins (HDL), a specific cholesterol fraction believed to be
beneficial. To avoid this confusion, FDA has concluded that an
appropriate structure/function claim for maintaining cholesterol would
be ``helps to maintain cholesterol levels that are already within the
normal range.''
FDA continues to believe that ``lowers cholesterol,'' however
qualified, is an implied disease claim. As many comments argued,
lowering cholesterol is inextricably linked in the public mind with
treating elevated cholesterol and preventing heart disease. The agency
also believes that ``promotes cholesterol clearance'' is an implied
disease claim because it is directed at lowering cholesterol rather
than maintaining levels already determined to be within a normal range.
FDA will review all cholesterol claims to determine whether the
labeling as a whole implies that the product is intended to lower
elevated cholesterol levels. In such cases, FDA would consider the
labeling to create an implied disease claim.
(46.) A comment from a former Surgeon General of the United States
argued that, given the importance of preventing cardiovascular disease,
dietary supplements should be permitted to make claims for cholesterol
reduction, because ``our citizens deserve the opportunity to know when
safe and effective dietary supplements are available to lower
cholesterol.'' A comment from the Nutrition Committee of the American
Heart Association argued that current scientific evidence does not
support added benefits of dietary supplementation with nutritive
substances for prevention of cardiovascular disease in the general
population, and expressed concern that dietary supplements also carry
risks.
FDA agrees that prevention of heart disease is an extremely
important public health goal. Lowering cholesterol with certain drugs
has been conclusively shown to be effective in reducing mortality from
coronary artery disease. Indeed, the evidence linking the lowering of
elevated cholesterol with preventing heart disease is so strong that
identifying and using effective therapies to lower cholesterol in
patients with elevated cholesterol levels has become of compelling
importance. With this in mind, use of possibly ineffective therapies in
persons with elevated cholesterol, which can delay or prevent effective
treatment, poses significant public health risks. Although DSHEA
requires that manufacturers who make structure/function claims have
substantiation, manufacturers are not currently required to submit that
substantiation to FDA for premarket review, nor does FDA have the
resources to inspect and review the quality of the substantiation in
most cases. For this reason, FDA does not believe that permitting
``lowers cholesterol'' claims on dietary supplements without prior
review serves the public health.
(47.) A few comments argued that FDA may not prohibit ``lowers
cholesterol'' claims because the agency had earlier issued an advisory
letter permitting such claims if the claim stated that the product was
useful in the context of a healthy diet. One of these comments
contended that the agency may not change its advice or guidance because
it has cited no studies in this rulemaking to support the view that
``lowers cholesterol'' implies disease treatment.
FDA does not agree that it may not change its position on whether
particular cholesterol claims imply disease treatment. The record and
analysis in this rulemaking, as well as FDA's experience in
implementing DSHEA, provide an ample basis for the conclusions that the
agency has reached on cholesterol claims.
G. Conditions Associated With Natural States (Sec. 101.93(g)(2)(iii))
The proposed rule stated that natural states such as aging,
menopause, pregnancy, and the menstrual cycle, are not themselves
diseases, but can be associated with abnormal conditions that are
diseases. FDA proposed in Sec. 101.93(g)(2)(iii) to treat as a disease
claim a statement that a product had an effect on a condition
associated with a natural state if the condition presented ``a
characteristic set of signs or symptoms recognizable to health care
professionals or consumers'' as an ``abnormality.'' FDA provided as
examples of such abnormal conditions the following: Toxemia of
pregnancy; premenstrual syndrome; hot flashes; and presbyopia,
decreased sexual function, and Alzheimer's disease associated with
aging.
In the July 8, 1999, Federal Register notice announcing a public
meeting and reopening the comment period, FDA asked for additional
comment on this provision of the proposed rule. The agency sought
specific comment on the following three questions: (1) If FDA were to
treat some conditions associated with natural states as diseases (e.g.,
toxemia of pregnancy and Alzheimer's disease) but not others (e.g., hot
flashes, common symptoms associated with the menstrual cycle, and
decreased sexual function associated with aging), what would be an
appropriate principle for distinguishing the two groups? (2) For
example, would it be appropriate to consider the severity of the health
consequences if the condition were to go without effective treatment?
(3) If so, how should ``severity'' be defined?
(48.) Although some comments from disease-specific organizations
and health professionals supported this provision, most of the comments
strongly objected to classifying common conditions associated with
natural states as diseases. None of the objecting comments argued that
toxemia of pregnancy or Alzheimer's disease are not diseases. Almost
all of these comments, however, contended that PMS, hot flashes, and
various conditions associated with aging, such as decreased sexual
function, are so common that they should be considered neither abnormal
nor diseases. Some comments argued that any condition suffered by more
than 50 percent of the population should be considered normal and not a
disease, and gave as an example benign prostatic hypertrophy. Other
comments cited prevalence rates for conditions such as PMS and hot
flashes, and contended that the cited rates were too high for these
conditions to be considered abnormal. A large number of comments
asserted that the proposed rule would treat pregnancy, menopause, and
aging as diseases. A few comments argued that if menopause, aging, and
pregnancy are not diseases, then signs and symptoms associated with
these states cannot be diseases. One comment argued that conditions
related to natural states are not diseases but ``health-related
conditions'' and that DSHEA permits statements about health-related
conditions.
In response to the questions in the July 8, 1999, Federal Register
notice, many comments argued that the severity of the condition
associated with a natural state was not an appropriate principle for
distinguishing diseases from nondiseases. These comments generally
argued that the severity of the symptoms (rather than the severity of
the consequences of going without effective treatment) was not an
adequate basis to distinguish diseases from nondiseases. One comment
from a food industry group argued that this was an inappropriate
principle because ``all
[[Page 1020]]
natural states can have severe consequences if left unattended.'' This
comment suggested that conditions that were ``universal'' should not be
treated as diseases. This comment and one other also suggested that the
distinguishing principle was whether the cause of the condition was
``pathological.''
FDA has reconsidered proposed Sec. 101.93(g)(2)(iii), and has
concluded that it is not appropriate, under DSHEA, to treat certain
common, nonserious conditions associated with natural states as
diseases. There are a wide variety of conditions representing impaired
function of an organ or system that are associated with particular
stages of life or normal physiologic processes. These stages and
processes include adolescence, the menstrual cycle, pregnancy,
menopause, and aging. (FDA notes that, contrary to the comments, the
proposed rule would not have classified these stages or processes
themselves as diseases; it classified only certain abnormal conditions
associated with these stages or processes as diseases.) The conditions
associated with these stages or processes can vary from common,
relatively mild abnormalities, for which medical attention is not
required, to serious conditions that can cause significant or permanent
harm if not effectively treated.
For example, pregnancy is associated with common and mild
abnormalities such as morning sickness and leg edema that cause no
permanent harm if left untreated, as well as with such serious
conditions as hyperemesis gravidarum, toxemia of pregnancy, and acute
psychosis of pregnancy, which can be life-threatening if not
effectively treated. The menstrual cycle is commonly associated with
mild mood changes, edema, and cramping that do not cause significant or
permanent harm if left untreated, but also, more rarely, with serious
cyclical depression that can result in significant harm if not
effectively treated. Aging is almost invariably associated with
characteristic skin and scalp changes, such as wrinkles and hair loss,
which do not need medical attention. It is also, however, associated
with serious diseases that will result in significant, often
irreversible damage, many of which can be effectively treated. These
diseases include osteoporosis, glaucoma, and arteriosclerotic diseases
of coronary, cerebral, and peripheral vessels. Adolescence is commonly
associated with mild acne, which does not cause significant or
permanent harm if not treated, and, rarely, with cystic acne, which can
produce severe physical and psychological scars if not effectively
treated.
Whether all of these conditions represent diseases is, in part, a
matter of definition and, in part, depends on the consequences of the
conditions if not effectively treated, and on how commonly they occur,
i.e., whether they may be considered ``normal.'' Although most people
consider the more serious or infrequent conditions referred to above to
be diseases, views vary with respect to the common, milder conditions.
FDA has reconsidered the position it took in the proposed rule and
agrees with the comments that treating as diseases the common, mild
symptoms associated with normal life stages or processes would not be
consistent with the intent of DSHEA.
FDA does not believe that the frequency with which a condition
associated with a natural state occurs is, by itself, sufficient to
distinguish diseases from nondiseases. The severity of the consequences
of disease, as well as the consequences of ineffective treatment, must
also be considered. As noted above, whether common, minor conditions
associated with natural states are diseases is a matter of debate, but
FDA has decided not to treat them as diseases because the agency
believes this approach is consistent with the intent of DSHEA. FDA does
not, however, believe that DSHEA was intended to permit unreviewed
claims about serious conditions that could cause significant or
permanent harm, particularly where effective treatment is available.
FDA also does not agree that ``all natural states can have severe
consequences if left unattended.'' FDA has listed a large number of
conditions associated with natural states that commonly do not have
serious consequences even if not effectively treated. FDA also does not
agree that it is helpful in this context to distinguish between
diseases and nondiseases by asking which have a ``pathological'' basis.
The term ``pathological'' is itself defined by reference to disease,
namely, ``caused by or involving disease; morbid'' (Ref. 7).
Accordingly, for purposes of this rule, mild conditions commonly
associated with particular stages of life or normal physiological
processes will not be considered diseases. Therefore,
Sec. 101.93(g)(2)(iii) now states that a statement will be considered a
disease claim if it claims that the product ``has an effect on an
abnormal condition associated with a natural state or process, if the
abnormal condition is uncommon or can cause significant or permanent
harm.'' Ordinarily, FDA would follow the suggestion in the comments
that conditions associated with a stage of life or a normal
physiological process be considered common if they occur in more than
one-half of those experiencing that stage or process.
The following are examples of conditions about which structure/
function claims could be made under Sec. 101.93(g)(2)(iii): (1) Morning
sickness associated with pregnancy; (2) leg edema associated with
pregnancy; (3) mild mood changes, cramps, and edema associated with the
menstrual cycle; (4) hot flashes; (5) wrinkles; (6) other signs of
aging on the skin, e.g., liver spots, spider veins; (7) presbyopia
(inability to change focus from near to far and vice versa) associated
with aging; (8) mild memory problems associated with aging; (9) hair
loss associated with aging; and (10) noncystic acne. The following are
examples of conditions that would remain disease claims: (1) Toxemia of
pregnancy; (2) hyperemesis gravidarum; (3) acute psychosis of
pregnancy; (4) osteoporosis; (5) Alzheimer's disease, and other senile
dementias; (6) glaucoma; (7) arteriosclerotic diseases of coronary,
cerebral or peripheral blood vessels; (8) cystic acne; and (9) severe
depression associated with the menstrual cycle.
FDA has not included benign prostatic hypertrophy (BPH) on either
of these lists, because the agency does not believe that BPH should be
considered a consequence of aging. Like many other diseases, e.g.,
diabetes, prostate cancer, and heart disease, the incidence of BPH is
much higher among older men. This does not mean that BPH or prostate
cancer is caused by the aging process. Even if BPH were considered a
direct consequence of aging, however, claims to treat or prevent it
would still be treated as disease claims because failure to obtain
effective treatment can cause significant or permanent harm.
FDA notes that it does not base the exclusion of the mild common
conditions associated with natural states from Sec. 101.93(g)(2)(iii)
on the argument advanced by one of the comments that these are
``health-related conditions'' and that DSHEA permits structure/function
claims about health-related conditions. FDA believes that a ``health-
related condition'' is a state of health leading to disease. As FDA has
said previously, ``diseases'' and ``health-related conditions'' are
``so closely related that no bright-line distinction is practicable''
(58 FR 2478, 2481 January 6, 1993). There is nothing in DSHEA, its
legislative history, or in the definition of ``disease or health-
related condition'' that would suggest that common conditions
associated with natural states
[[Page 1021]]
are ``health-related conditions'' within the meaning of section
403(r)(1)(B) of the act. Further, FDA does not agree that section
403(r)(6) of the act authorizes structure/function claims about
``health-related conditions.'' Had Congress intended to authorize
structure/function claims about ``health-related conditions'' it could
easily have used that terminology, but did not.
(49.) Some comments concerned specific claims under proposed
Sec. 101.93(g)(2)(iii). One comment sought concurrence that the
following are acceptable structure/function claims: ``supports a
normal, healthy attitude during PMS'' and ``supportive for menopausal
women.'' Another comment argued that a statement that a product
provides nutrients that diminish the normal symptomatology of
premenstrual syndrome or menopause is a permissible structure/function
claim. Another comment asked whether ``helps to maintain normal urine
flow in men over 50 years old'' is a permissible structure/function
claim. One comment urged that only products proven safe when used as
directed should be permitted for sale for enlarged prostate and that
such products should recommend that a man see his physician. Another
comment argued that the claim ``for men over 50 years old,'' which FDA
had proposed as an acceptable structure/function claim, is vague and
ambiguous and is of no use to consumers.
FDA agrees that ``supports a normal, healthy attitude during PMS''
and ``supportive for menopausal women'' are appropriate structure/
function claims. ``Supports a normal, healthy attitude during PMS'' is
acceptable because PMS is generally a common, mild condition associated
with a normal physiologic process. ``Supportive for menopausal women''
is acceptable because it is a general statement that does not refer to
symptoms of any conditions at all. Claims about diminishing the normal
symptomatology of premenstrual syndrome or menopause would also be
acceptable structure/function claims, if they did not suggest, for
example, prevention or treatment of osteoporosis, or another disease
associated with these states. ``Helps to maintain normal urine flow in
men over 50 years old,'' however, is an implied disease claim because,
as many comments pointed out, the average or ``normal'' state in men
over 50 years old is diminishing urine flow, in most cases due to BPH,
so that the apparent ``maintenance'' really represents a claim of
improvement (treatment).
H. Generally (Sec. 101.93(g)(2)(iv))
Under proposed Sec. 101.93(g)(2)(iv), FDA stated that a statement
would be considered a disease claim if it claimed explicitly or
implicitly to have an effect on disease through one or more of the
following factors: (1) The name of the product (e.g., ``Carpaltum''
(carpal tunnel syndrome), ``Raynaudin'' (Raynaud's phenomenon),
``Hepatacure'' (liver problems)). Names that did not imply an effect on
a disease, such as ``Cardiohealth'' and ``Heart Tabs,'' would not
constitute disease claims; (2) statements about the formulation of the
product, including a claim that the product contained an ingredient
that has been regulated by FDA predominantly as a drug and is well
known to consumers for its use in preventing or treating a disease
(e.g., aspirin, digoxin, or laetrile); (3) citation of a publication or
other reference, if the citation refers to a disease use. For example,
labeling for a vitamin E product that included a citation to an article
entitled ``Serial Coronary Angiographic Evidence That Antioxidant
Vitamin Intake Reduces Progression of Coronary Artery
Atherosclerosis,'' would create a disease claim under this criterion;
(4) use of the term ``disease'' or ``diseased;'' or (5) otherwise
suggesting an effect on disease by use of pictures, vignettes, symbols,
or other means (e.g., electrocardiogram tracings, pictures of organs
that suggest prevention or treatment of a disease state, or the
prescription symbol (Rx)). The proposed rule stated that a picture of a
body would not constitute a disease claim under this criterion.
(50.) A few comments stated that the phrase ``has an effect on''
in proposed Sec. 101.93(g)(2)(iv) is vague and could be interpreted by
the agency to mean almost anything. Some of these comments argued that
disease claims should include only those that use the specific terms
``diagnose,'' ``prevent,'' ``treat,'' ``mitigate,'' or ``cure.''
FDA does not agree that the phrase ``has an effect on'' is
inappropriately vague. FDA believes that it is necessary to use a
phrase that encompasses synonyms for the terms ``diagnose,''
``prevent,'' ``treat,'' ``mitigate,'' or ``cure.'' If disease claims
were limited to those that used the specific terms in the statute, it
would be possible to make obvious and explicit disease claims simply by
using terms that are similar in meaning to the statutory terms, e.g.,
``relieves arthritis pain'' rather than ``treats arthritis pain,'' or
``eliminates the risk of cancer'' rather than ``prevents cancer.''
I. Product Name (Sec. 101.93(g)(2)(iv)(A))
(51.) One comment observed that there is an inconsistency between
the statement in the proposed rule that ``Heart Tabs'' does not imply
an effect on a disease and Sec. 101.14(a)(1), which states that:
Health claim means any claim made on the label or in the
labeling of a food, including a dietary supplement, that expressly
or by implication, including ``third party'' references, written
statements (e.g., a brand name including a term such as ``heart''),
symbols (e.g., a heart symbol) characterizes the relationship of any
substance to a disease or health-related condition * * *
and requested clarification.
FDA agrees, in part, and disagrees, in part, with the comment. FDA
does not agree that Sec. 101.93(g)(2)(iv)(A) and Sec. 101.14(a)(1) are
inconsistent. Section 101.14(a)(1) was issued in 1993 to implement the
health claims provisions of NLEA. In Sec. 101.14(a)(1), use of the term
``heart'' in a brand name and use of the heart symbol in labeling are
offered as examples of health claims, if in the context of the labeling
as a whole, the word or symbol suggests that there is a relationship
between the product and a disease or health-related condition. Thus,
according to the preamble to that final rule (58 FR 2478 at 2486), the
heart symbol might appropriately appear in the labeling of a food
product if, in context, it did not suggest a relationship to heart
disease, e.g, in conjunction with ``Hey, Fudge Lovers.'' If, however,
the heart symbol appeared alone on a food, without further explanation
from context, consumers might conclude that the food was beneficial for
reducing the risk of developing cardiovascular disease (id.).
Following the issuance of Sec. 101.14(a)(1), Congress enacted
DSHEA. DSHEA created a special regulatory regime for dietary
supplements. That regime, while closely related to the regime for food,
was not identical to the food regime. Section 403(r)(6) of the act
specifies certain types of structure/function claims and general well-
being claims that may be made for dietary supplements without first
obtaining new drug approval or health claim authorization. The types of
claims listed in section 403(r)(6) of the act are similar, but not
identical to the claims permitted for foods under section 201(g)(1)(C)
of the act. Under Nutrilab v. Schweiker, 713 F.2d 335 (7th Cir. 1983),
conventional food claims are limited to structure/function effects that
derive from the taste, aroma, or nutritive value of the food. Dietary
supplement claims are not subject to that limitation. Had Congress
intended the scope of the permitted claims to be identical, it
[[Page 1022]]
could simply have declared that dietary supplements are ``foods.'' In
light of Congress' intent to expand the types of claims authorized for
dietary supplements in DSHEA, FDA interprets Sec. 101.14(a)(1) as
permitting dietary supplements to have brand names that include the
word ``heart'' or other organs, if, in the context of the labeling as a
whole, the name does not imply disease treatment or prevention.
FDA does agree, however, that under .Sec. 101.14(a)(1), a dietary
supplement name that included the word ``heart'' could be a health
claim, depending on the context. Thus, a dietary supplement could be
called ``HeartTabs'' if its claim was ``to maintain healthy
circulation,'' or some other role related to the structure or function
of the heart that did not imply treatment or prevention of disease. If,
however, the product name was not qualified by any further claim in the
labeling, the product could be considered, under Sec. 101.14(a)(1), to
be intended for treatment or prevention of cardiovascular disease.
FDA also believes that the heart symbol has become so widely
associated with prevention of heart disease that its use in the
labeling of a dietary supplement would be ordinarily considered an
implied heart disease prevention claim. Consistent with the examples
provided in the January 6, 1993, Federal Register document on health
claims (58 FR 2486), however, there may be unusual cases in which, in
context, the use of a heart symbol does not imply heart disease
prevention.
(52.) Several comments agreed with proposed
Sec. 101.93(g)(2)(iv)(A) that product names that imply an effect on
disease, including implying cure or treatment of a disease, should not
be allowed. The comments, however, requested that the agency provide
further guidance as to what types of product names are acceptable and
what types are not. Some comments questioned whether product names such
as ``CarpalHealth,'' ``HepatoHealth,'' ``HepataCare,'' ``CircuCure,''
or ``Soothing Sleep'' would be acceptable under proposed
Sec. 101.93(g)(2)(iv)(A). Other comments disagreed with the agency's
examples and stated that it is difficult to distinguish the reasoning
behind some of the examples cited. For example, a few comments stated
that both ``Cardiohealth'' and ``Heart Tabs'' imply that the product
prevents heart disease.
Two principles formed the basis for the distinctions in the
proposed rule between product names that were considered structure/
function claims and those that were considered disease claims. First,
the name should not contain the name, or a recognizable portion of the
name, of a disease. Second, the name should not use terms such as
``cure,'' ``treat,'' ``correct,'' ``prevent'' or other terms that
suggest treatment or prevention of a disease. Thus, ``CarpalHealth''
and ``CircuCure'' would be considered disease claims. In some cases, to
determine whether a product name implies an effect on disease, the
agency will need to consider the context in which a term is presented
in the labeling as a whole. Thus, ``Soothing Sleep'' could be
considered a claim to treat insomnia, unless the labeling made clear
that the product was intended only for occasional sleeplessness.
``HepataCare'' and ``HepataHealth'' could also be considered disease
claims because ``Hepata'' could be read as a reference to hepatitis,
unless the labeling made clear that the product was intended for
general liver health and not intended to treat or prevent hepatitis.
The agency notes that in the near future, FDA will issue for
public comment a draft guidance to provide additional clarification and
examples of claims that would and would not be considered disease
claims under the final rule. FDA will include in the draft guidance
examples of product names.
(53.) Another comment stated that proposed
Sec. 101.93(g)(2)(iv)(A) would prohibit the use of the name of the
``dispensing institution'' if it had the word ``Cancer'' in it because
the agency would interpret the labeling as implying an effect on
disease, when in fact the product was listing the institution where the
product was dispensed, e.g., ABC Cancer Institute. Other comments were
concerned that the proposed rule would prohibit the use of their
company trade name, which includes the use of the word ``prescription''
and its abbreviation ``Rx.''
The agency reiterates that it will view the name in the context of
the entire labeling to determine whether a disease claim is being made.
However, a manufacturer may not circumvent the requirements of the act,
DSHEA, or this final rule by using the name of an institution or the
manufacturer to imply a disease claim.
The agency agrees that the use of the word ``prescription'' or its
abbreviation ``Rx'' in the name of the product should not automatically
be interpreted as a disease claim. Although these terms imply that the
product is a prescription drug, some prescription drugs are intended
for nondisease conditions. Therefore, if nothing else in the labeling
suggests a disease use, the agency will not consider the use of
``prescription'' or ``Rx'' to be an implied disease claim. The agency
notes, however, that the use of these terms on dietary supplement
products may deceive consumers into thinking that they are purchasing a
prescription drug without a prescription. Thus, use of the terms
``prescription'' or ``Rx'' is misleading and will misbrand the product
under section 403(a)(1) of the act if, in the context of the labeling
as a whole, the terms imply that the product is a prescription drug.
(54.) A few comments cited in a proposed rule published in the
Federal Register of March 27, 1974 (39 FR 11298), in which FDA stated
that it would challenge brand names only in situations where clarifying
language is incapable of rectifying FDA's concern with the brand name
and that excision of a brand name should be a last resort and should be
pursued only when all other methods of qualifying the name have failed.
The agency notes that the proposed rule cited in this comment was
never finalized and was withdrawn on December 30, 1991 (56 FR 67440),
as part of an FDA initiative to reduce the backlog of outstanding
proposed rules that have never been finalized. The policies outlined in
the March 27, 1974, Federal Register notice are not in effect.
(55.) Several comments sought a statement from FDA that if a
product brand name becomes synonymous over time with use for prevention
or treatment of a disease, it will still be permitted. As an example,
the comments claimed that Kleenex has become synonymous with treatment
of nasal congestion, but did not provide support for this assertion.
FDA does not believe that Kleenex is synonymous with treatment of
nasal congestion and, absent any supportive data, has no reason to
believe that consumers believe them to be synonymous. The agency would
agree that Kleenex has become synonymous with ``tissue,'' and that both
are used in conjunction with nasal congestion. Neither tissue nor
Kleenex, however, treat, prevent, or otherwise affect nasal congestion
in any way. Because the agency was not presented with any specific
examples of, nor is it aware of any, names of products that are not
intended to treat disease but that have become synonymous with disease
treatment or prevention, it does not have reason to believe that there
is a real basis for concern.
J. Product Formulation (Sec. 101.93(g)(2)(iv)(B))
(56.) Several comments questioned whether the inclusion of a
dietary ingredient in the ingredient list of a
[[Page 1023]]
dietary supplement would be interpreted as a disease claim under
proposed Sec. 101.93(g)(2)(iv)(B). They argued that to provide truthful
labeling, this information must be included. Another comment stated
that the proposal fails to distinguish between true claims and false
claims. Several comments further argued that ingredient information may
be of value to consumers to alert them to potential adverse effects or
drug interactions. One comment urged that the presence of a constituent
that is naturally occurring in a plant and is also regulated as a drug
does not automatically classify the substance as a drug. The comment
asserted that 45 percent of drugs are derived from plants, which,
according to the comment, would classify a number of dietary
ingredients as drugs.
Listing a dietary ingredient in the ingredient list of a dietary
supplement will not be considered to imply an effect on disease unless
the ingredient is one that has been regulated primarily by FDA as a
drug and is well-known to consumers for its use or claimed use in
preventing or treating a disease. (In the proposed rule, the agency
gave as examples aspirin, digoxin, and laetrile.) Very few dietary
ingredients meet this test. The agency agrees that a certain percentage
of drug products are derived from plants. However, only a handful of
these drugs are well-known to consumers under the name of the plant or
natural plant ingredient from which they were derived. Instead, they
are known to consumers under a brand name or generic name, e.g.,
aspirin. Thus, FDA does not believe that listing dietary ingredients
that happen to be related to well-known drugs will fall under this
provision, except in unusual circumstances. In those cases where a
manufacturer does add a drug ingredient that is well-known to treat or
prevent disease to its product and label its presence, however, FDA may
consider it a disease claim. The fact that the labeling is truthful
does not necessarily mean that it falls within the scope of claims
authorized by section 403(r)(6) of the act. For example, the agency
believes that there are many dietary ingredients that could be shown to
treat or prevent diseases, and for which it could thus be truthful to
state that the product treats or prevents a specific disease. Under the
act, however, if a manufacturer wants to label its product to treat or
prevent disease, it must do so under the drug approval provisions or
the health claim provisions of the act. It may not do so under section
403(r)(6) of the act. In drafting section 403(r)(6) of the act to
exclude disease claims, Congress made a judgment that the public health
will be served by requiring premarket review of such claims.
FDA agrees that it is important to inform consumers about
potential adverse effects or drug interactions for specific dietary
supplement ingredients. In fact, dietary supplement labeling, like the
labeling of other FDA-regulated products, is required to include all
facts that are material in light of consequences that may result from
use of the product or representations made about it (sections 403(a)(1)
and 201(n) of the act). This provision is not intended in any way to
preclude truthful adverse event or drug interaction information from
appearing in a dietary supplement's labeling.
(57.) A dietary supplement manufacturer asked FDA to clarify the
effect of Sec. 101.93(4)(ii) on a dietary ingredient found in common
food(s), whose biological activity is first characterized in a food
context, but which is subsequently approved as a drug. The comment
asked whether, if indole-3-carbinol, a compound discovered in broccoli
and other vegetables, were to be approved as a breast cancer drug,
claims to the effect that a vegetable-based dietary supplement product
contains indole-3-carbinol would be permitted as structure/function
claims under the proposed rule. The comment claimed that the proposed
rule would classify such claims as disease claims even if the
biological activity of this dietary ingredient were first identified in
the food context.
Where an ingredient has been approved as a drug, section
201(ff)(3) of the act prohibits marketing of the ingredient as a
dietary supplement unless the ingredient itself was previously marketed
as a food (including a dietary supplement), or unless a food containing
the ingredient was previously marketed for the presence of the
ingredient. In the example provided in the comment, the isolated
ingredient indole-3-carbinol could not be marketed as a dietary
supplement, unless a food containing the ingredient had been marketed
for the presence of the ingredient before the drug was approved or was
the subject of substantial investigations that had been made public.
However, to avoid a conflict between this provision and section
201(ff)(3) of the act in a situation where the ingredient was marketed
as a food first, FDA has revised Sec. 101.93(g)(2)(iv)(B) to exclude
claims about an ingredient that is an article included in the
definition of ``dietary supplement'' under section 201(ff)(3) of the
act.
(58.) One comment misunderstood Sec. 101.93(g)(2)(iv)(B) and
believed that this provision only applies to the listing of OTC drug
ingredients recognized by consumers.
This provision is not limited to the listing of OTC drug
ingredients. For purposes of Sec. 101.93(g)(2)(iv)(B), the agency may
consider as a disease claim a claim that the product contains an
ingredient that has been regulated by FDA as a drug, whether marketed
over-the-counter or by prescription, and that is well known for its use
in preventing or treating a disease.
K. Citation of Publication Titles (Sec. 101.93(g)(2)(iv)(C))
(59.) Many comments objected to this proposed criterion or sought
clarification. Many comments said that the proposed criterion
undermines DSHEA by prohibiting the use of most journals, is not
required by DSHEA, or is contrary to section 403B of the act (21 U.S.C.
343-2), which, the comment said, exempts scientific publications from
labeling rules and is intended to allow consumers to be more informed
by reading scientific studies. Other comments said that Congress
intended to encourage the dissemination of scientific research and
truthful, non-misleading information, so FDA should not prohibit titles
of scientific studies. Some comments stated that the issue should not
be whether a publication's title refers to a disease use, but rather
whether, on balance, the entire presentation, including the product
label, package insert, and other labeling, represents a disease claim.
These comments supported the use of complete citations to scientific
literature, including the titles of scientific articles. Some comments
suggested that the proposal contradicted earlier FDA positions. One
comment referred to the September-October 1998 issue of FDA Consumer
which, the comment stated, suggested that consumers contact companies
to obtain scientific articles that the company might have to
substantiate a claim. Another comment said the proposal was contrary to
FDA policy to recognize and accept valid science. Several comments
questioned how to provide substantiation of labeling claims, in
compliance with 403(r)(6)(B) of the act, if the supporting articles
cannot be cited. One comment stated that there will be more fraud and
deception in the marketplace because companies will not cite scientific
support for their statements. Several comments stated that the proposed
rule will restrict
[[Page 1024]]
access by consumers and the medical community to important new research
results and discourage companies from investing in research. A dietary
supplement manufacturer suggested revising the provision to permit
companies to cite ``bonafide'' textbooks and peer-reviewed scientific
journals that mention a disease in the title. Another dietary
supplement manufacturer suggested revising this provision to permit
citation of a publication or reference if the citation ``is necessary
to present a balanced discussion of the documented mechanism by which a
nutrient or dietary ingredient acts to maintain the structure or
function of the body.''
FDA agrees that in enacting DSHEA, Congress intended to encourage
the dissemination of scientific research and truthful, non-misleading
information. FDA also agrees that consumers can benefit from reviewing
the scientific support used to substantiate a statement made for a
dietary supplement under section 403(r)(6) of the act. In keeping with
these goals, FDA has modified Sec. 101.93(g)(2)(iv)(C) to narrow the
circumstances under which citation to a scientific reference will be
considered a disease claim. Based on Congress' explicit prohibition in
section 403(r)(6) of the act of claims to affect disease, however, FDA
does not believe that Congress intended to permit scientific references
to be used in a way that constitutes an implied disease claim.
Consequently, Sec. 101.93(g)(2)(iv)(C) has been revised to state that
citation of a title referring to a disease will be treated as a disease
claim, if, in the context of the labeling as a whole, the citation
implies treatment or prevention of a disease, e.g., through placement
on the immediate product label or packaging, inappropriate prominence,
or lack of relationship to the product's express claims.
The agency continues to believe that placing a citation to a
scientific reference that mentions a disease in the title on the
immediate product label or packaging should be considered a disease
claim for that product, because of the unusual and unnecessary
prominence of such placement. For citations to scientific references
that refer to a disease use in the title and that are included in other
types of labeling (i.e., other than the product label or packaging) the
agency will consider the context in which the citation is presented.
FDA agrees with the comments that the totality of all available
labeling should be considered to determine the context. One element
that the agency will look at is the prominence of the citation in the
labeling. If, for example, the citation is simply listed in the
bibliography section of the labeling among other titles, it will
generally not suggest an implied disease claim. On the other hand,
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. The agency will also consider
whether the cited article provides legitimate support for a 403(r)(6)
of the act statement that appears in the labeling of the 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.
FDA also agrees that it is important to provide a balanced
discussion of the scientific literature regarding the claim. FDA
encourages manufacturers to cite references that provide a balanced
discussion of the evidence supporting a structure/function claim.
The agency believes that the final rule strikes a reasonable
balance between encouraging the dietary supplement industry to inform
consumers about the substantiation for their claims and preventing
abuses of section 403(r)(6) of the act.
(60.) Several comments challenged the basis for the proposed
restriction of scientific references. One comment from industry said
the proposed restriction on titles is outside DSHEA because the act
refers to statements. The comment said titles could be prohibited if
they were misleading, but said the rule should not contain a blanket
prohibition.
The comment is apparently referring to section 403(r)(6) of the
act, which prescribes the terms under which a ``statement'' may be made
for a dietary supplement. FDA believes that the comment's reading is
too literal, however. A ``statement'' does not have to be a declaratory
sentence but rather is fairly read to include other kinds of
statements, such as citations of scientific authority. In keeping with
DSHEA's purpose to broaden the scope of labeling claims that may be
made for dietary supplements without subjecting them to regulation as
drugs, FDA believes that Congress intended ``statement'' to refer to
any claim made that recommends or suggests a particular use of a
dietary supplement. In addition to being under inclusive, a narrower
interpretation would not benefit the dietary supplement industry
because it would limit the scope of claims authorized under section
403(r)(6) of the act.
(61.) A few comments stated that the agency did not provide any
support for the assumption that citations are disease claims rather
than substantiation for a claim.
FDA believes that a citation of a title that refers to a specific
disease can serve both as a disease claim and as substantiation for a
claim. A citation of a publication title that links the product to a
particular disease could lead consumers to believe that the product can
be used to diagnose, prevent, mitigate, treat, or cure a disease, even
if the title also provides substantiation for the product claims.
As stated above, citation of a scientific reference will not be
treated as a disease claim if, in the context of the labeling as a
whole, the reference lacks prominence and if it is appropriate support
for the product claim.
(62.) One comment sought clarification of the effect of this
provision on multi-ingredient products. The comment asked whether a
disease claim for the entire product would be created if the labeling
cited an article about only one ingredient of a multi-ingredient
product.
Generally, if a citation is presented in the product labeling in
such a way as to imply that a specific ingredient can treat or prevent
disease, the product, as a whole, will be considered to be intended to
treat or prevent disease.
(63.) A few comments requested FDA to clarify how proposed
Sec. 101.93(g)(2)(iv)(C) would operate. The comments questioned whether
they would have to delete a citation from a list or redact the
reference to a disease from the title of the article. One comment asked
whether an article that contains a reference to a disease can be cited
if the title is not used in the citation. The comments further
questioned whether they can provide the entire article, with the title
on it, if requested by a consumer. Some comments asked FDA to clarify
that a label may cite a title that appears in a publication whose name
includes a disease (such as the publication titled Cancer) or to
clarify how scientific studies may be cited. One comment requested that
the agency issue further guidance to clarify what is and is not covered
by Sec. 101.93(g)(2)(iv)(C).
FDA does not expect a manufacturer to redact portions of the
citation or delete a citation from a list of references or bibliography
if it is appropriate to include the reference to substantiate a claim.
As described above, if the citation to a scientific reference refers to
a disease, the agency will consider the
[[Page 1025]]
context in which the citation is presented, including its prominence in
the labeling and whether there is a reasonable relationship between the
reference and the express claim. In most cases, the unredacted
reference title can be included in the product labeling without
subjecting the product to regulation as a drug, as long as the
prominence of the reference does not suggest that it is being used to
imply disease treatment or prevention. Under revised
Sec. 101.93(g)(2)(iv)(C), the only reason a publication title would be
considered a disease claim regardless of prominence would be if the
reference is not reasonably related to substantiating the product's
express claim. In that case, FDA believes that the reference would be a
disease claim, even if the name of the disease is redacted, because the
only purpose of including the reference would be to suggest use of the
product for treatment or prevention of the disease discussed in the
reference.
With regard to citation of titles from journals whose official
names include the name of a disease, the same considerations of
appropriate prominence and reasonable relationship to the product's
express claims apply. FDA expects that accepted conventions of
scientific citation will be used for all citations that appear in
labeling.
Finally, if specific information about an unlabeled use of a
product is requested by a consumer, and the request is not solicited by
the manufacturer, providing articles that are responsive to the request
will not be considered a disease claim.
FDA will issue further guidance on Sec. 101.93(g)(2)(iv)(C), if
necessary.
(64.) Several comments sought modifications to proposed
Sec. 101.93(g)(2)(iv)(C). One comment suggested revising the provision
to permit companies to cite articles or references that use
``intermediate terms'' (which the comment said were terms or phrases
that have disease-related endpoints) on the label or labeling.
Whether a citation that refers to a disease-related endpoint will
be considered a disease claim under the rule will depend on the context
in which the disease-related endpoint is referred to and whether the
reference implies that the product has an effect on disease. For
example, the title of an article that states that a product was shown
to maintain cholesterol levels that were already within the normal
range, with no reference to a disease, would be considered a structure/
function statement about maintenance rather than a disease claim.
However, if the title of the article states that the product was shown
to lower elevated cholesterol levels, this implies that the product can
be used to have an effect on the disease states hypercholesterolemia
and heart disease, because heart disease is associated with high
cholesterol levels.
(65.) A trade association suggested that the title should not be
considered to be a disease claim unless it uses the terms ``treat,''
``cure,'' ``mitigate,'' ``prevent,'' or ``diagnose.''
As stated elsewhere in this document, FDA believes that a disease
claim can be made explicitly or implicitly using terms other than those
listed in the comment. For example, depending on how it was used in a
product's labeling, a scientific reference entitled ``Using Ingredient
X For Diabetes'' could constitute a claim that the product can
diagnose, mitigate, treat, cure, or prevent diabetes, without using any
of these specific terms.
(66.) A few comments argued that citation of articles that refer to
a disease use should be permitted because consumers have access to
these articles in connection with the sale of dietary supplements under
section 403B(a) of the act.
As stated above, FDA has revised the proposed rule's treatment of
citations to scientific articles. Under the final rule, such citations
will not always be considered disease claims. FDA does not agree,
however, that section 403B of the act applies to the citation of titles
in product labeling. Although section 403B of the act exempts certain
publications from the labeling provisions of the act, section
403B(a)(2) states that the exemption applies only when, among other
requirements, the publication is ``used in connection with the sale of
a dietary supplement to consumers when it * * * does not promote a
particular manufacturer or brand of a dietary supplement.'' If the
reference or the title of the reference was disseminated by a
particular manufacturer of the dietary supplement discussed in the
reference, the agency would conclude that it was being used to promote
that manufacturer's brand of the dietary supplement. Therefore, the
exemption in section 403B of the act would not apply.
Furthermore, to qualify for the exemption in section 403B of the
act, a publication must be ``an article, a chapter in a book, or an
official abstract * * * reprinted in its entirety'' and must be
``displayed or presented, or * * * displayed or presented with other
such items on the same subject matter, so as to present a balanced view
of the available scientific information of a dietary supplement.'' A
citation to an article alone could not meet these requirements.
L. Use of Disease or Diseased (Sec. 101.93(g)(2)(iv)(D))
(67.) Many comments agreed with proposed Sec. 101.93(g)(2)(iv)(D),
stating that the terms ``disease'' or ``diseased'' should classify a
statement as a disease claim. Several comments urged that a statement
referring in a general way to the concept of ``health promotion and
disease prevention'' not cause the statement to be considered a disease
claim, as long as no specific disease was mentioned. One comment asked
that the agency permit general discussions of the concept of disease
prevention, citing the following example from the U.S. Public Health
Service Healthy People 2000 initiative: ``Better dietary and exercise
patterns can contribute significantly to reducing conditions like heart
disease, stroke, diabetes, and cancer, and could prevent 300,000
deaths.''
FDA agrees that general statements about health promotion and
disease prevention may be acceptable, as long as the statements do not
imply that a specific product can diagnose, mitigate, cure, treat or
prevent disease. Accordingly, FDA has revised Sec. 101.93(g)(2)(iv)(D)
to permit general statements about disease prevention that do not refer
explicitly or implicitly to a specific disease or class of diseases or
to the specific product or ingredient. For example, the statement ``a
good diet promotes good health and prevents the onset of disease''
would not be considered a disease claim. On the other hand, the claim
``Promotes good health and prevents the onset of disease'' would refer
implicitly to the product and would constitute a disease prevention
claim. FDA also believes that the particular statement offered by one
of the commenters would constitute a disease claim. The example cites
four specific diseases. If that statement were included in the labeling
for a dietary supplement, a consumer would reasonably assume that the
statement applies to the product and that taking that dietary
supplement contributes to preventing the diseases listed. If, however,
the statement said ``better dietary and exercise patterns can
contribute to disease prevention and better health,'' FDA would not
consider it a disease claim.
M. Pictures, Vignettes, and Symbols (Sec. 101.93(g)(2)(iv)(E))
(68.) Many comments agreed that certain pictures, vignettes, and
symbols can explicitly or implicitly convey that the product has an
effect on disease. A few comments agreed that a diseased
[[Page 1026]]
organ should be considered a disease claim. They argued, however, that
a picture of a healthy heart, healthy artery, or other healthy organ
should be permitted because such pictures do not in and of themselves
depict a disease. A few comments stated that a healthy
electrocardiogram (EKG) tracing should not be considered a disease
claim. One comment requested that the agency clarify whether a picture
of an organ is permitted if the claims are appropriate and within the
scope of permitted structure/function claims. The comment offered as an
example a statement that a product maintains cardiovascular health
accompanied by a picture of a heart and circulatory system.
FDA agrees that in most cases, a picture of a healthy organ would
not be considered a disease claim, if, in the context of the labeling
as a whole, it did not imply treatment or prevention of disease. As
described in response to comment 51 of section II.I of this document,
however, there may be symbols for organs, like the heart symbol, that
have become so widely recognized as symbols for disease treatment or
prevention, their use in labeling would constitute an implied disease
claim. FDA also believes that a picture of a healthy EKG tracing is an
implied disease claim. Because most consumers cannot distinguish a
healthy EKG tracing from an unhealthy one, both types may be viewed as
references to diagnosis or treatment of unhealthy heart conditions.
N. Membership in Product Class (Sec. 101.93(g)(2)(v))
Some product class names are so strongly associated with use to
treat or prevent a specific disease or class of diseases that claiming
membership in the product class implies disease treatment or
prevention. Under proposed Sec. 101.93(g)(2)(v), a statement would have
been considered a disease claim if it claimed that the product belonged
in a class of products recognizable to health care professionals or
consumers as intended for use to diagnose, mitigate, treat, cure, or
prevent a disease. The preamble provided the following examples of
class names that would imply disease treatment or prevention: Claims
that the product was an ``antibiotic,'' a ``laxative,'' an
``analgesic,'' an ``antiviral,'' a ``diuretic,'' an ``antimicrobial,''
an ``antiseptic,'' an ``antidepressant,'' or a ``vaccine.'' These
examples were not intended to constitute an exclusive list of product
class names that convey disease claims. Under the proposed rule,
claiming that a product was in a class that is not recognizable to
health care professionals or consumers as intended for use to diagnose,
mitigate, treat, cure or prevent disease would not have constituted a
disease claim under this criterion. The preamble provided as examples
of acceptable structure/function claims: Claims that the product was an
``energizer,'' a ``rejuvenative,'' a ``revitalizer,'' or an
``adaptogen.'' In light of the agency's decision that claims for relief
of ``occasional constipation'' should not be considered disease claims,
the term ``laxative'' will not be considered a disease claim under the
final rule, as long as the remainder of the labeling makes clear that
the product is not intended to treat chronic constipation.
(69.) Most of the comments on proposed Sec. 101.93(g)(2)(v) were
generally supportive, but some wanted to ensure that the provision
would be applied in specific ways. One comment urged that ``appetite
suppressant'' be treated as a disease claim, while another comment
urged that ``tonic'' be treated as a structure/function claim.
FDA does not agree that ``appetite suppressant'' should be
considered a disease claim. As discussed elsewhere in this document,
although obesity is a disease, overweight is not. An appetite
suppressant may be intended for ordinary weight loss, rather than as a
treatment for obesity. Therefore, ``appetite suppressant'' would only
be considered a disease claim in a context where it implies use for
obesity. FDA agrees that ``tonic'' is not a disease claim. ``Tonic'' is
commonly understood as a general term for anything that refreshes, and,
by itself, would not be considered to constitute a disease claim.
(70.) Some comments stated that various class names should be
allowed when they describe the mechanism by which a supplement has its
effect, or when they are present in a product and it is truthful and
not misleading to name them. One comment offered as examples of class
names that might be used to describe a product's mechanism of action: A
statement that a product that is soothing to the stomach achieves its
effects as a result of its ``carminative (antispasmodic) properties''
or as a result of its ``anti-inflammatory effect on the
gastrointestinal tract.'' This comment stated that it is not membership
in a given class of compounds that should make a product a drug, but
rather the intended use of the product. One comment asked whether this
criterion precludes a statement that daily consumption of vitamins and
minerals may prevent the onset of disease or other physical ailments.
Nothing in this provision would preclude a manufacturer from
truthfully declaring the ingredients contained in a product. In fact,
FDA regulations require the ingredients in a dietary supplement to be
listed on its label. (See Sec. 101.4(a)(1) and (g) (21 CFR 101.4(a)(1)
and (g)), and Sec. 101.36). The rationale for Sec. 101.93(g)(2)(v) is
that certain product class names (not particular ingredients) are so
strongly associated with use to diagnose, treat, mitigate, cure, or
prevent disease that claiming membership in the class would constitute
a disease claim. FDA does not believe that claiming membership in a
product class is necessary in order to provide an accurate list of the
ingredients present in a product.
FDA agrees that dietary supplements may carry statements that
characterize ``the documented mechanism of action by which a nutrient
or dietary ingredient acts to maintain * * * structure or function,''
but only to the extent that such a statement does ``not claim to
diagnose, mitigate, treat, cure, or prevent a specific disease or class
of diseases'' (section 403(r)(6) of the act). In the examples provided
in the comment, FDA is unaware of evidence establishing that the claims
actually describe ``documented'' mechanisms by which the products
``maintain'' a calm stomach. Nevertheless, assuming that these
statements met the other requirements of section 403(r)(6)(A) of the
act, FDA would not consider the term ``antispasmodic'' to constitute a
disease claim because the agency does not believe that it is closely
associated with treatment or prevention of gastrointestinal disease.
The term ``anti-inflammatory'' is, however, strongly associated with
treatment of certain serious gastrointestinal diseases, and would
constitute a disease claim.
FDA agrees with the statement that it is not membership in a given
class of compounds that makes a product a drug, but rather the intended
use of the product. This criterion sets forth FDA's conclusion that
claiming membership in certain product classes that are strongly
associated with use to treat or prevent disease is evidence that the
product is intended to treat or prevent disease.
Although this provision does not itself treat as a disease claim a
statement by a vitamin manufacturer that the product prevents the onset
of a disease, such a statement would be considered a disease claim
under Sec. 101.93(g)(2)(I), which covers statements that a product has
an effect on a specific disease or class of diseases. In addition, a
general statement that a product prevents the onset of disease would be
considered a disease claim under
[[Page 1027]]
Sec. 101.93(g)(2)(iv)(D), as noted in the discussion of that provision.
Claiming membership in the class of vitamins or minerals would not
constitute a disease claim under this criterion.
(71.) A food manufacturers' trade association and an individual
manufacturer opposed the provision, arguing that it goes beyond the
intent of DSHEA and would prohibit the use of any term associated with
a drug product.
FDA does not agree that this provision goes beyond the intent of
DSHEA nor that it would prohibit the use of any term associated with a
drug product. DSHEA precludes statements under section 403(r)(6) of the
act from claiming to treat or prevent disease. This provision
constitutes FDA's conclusion that some drug class names (but not all
terms associated with drug products) are so strongly associated with
disease prevention or treatment that claiming membership in the class
constitutes a claim that the product, like other members of the class,
treats or prevents disease.
(72.) One pharmaceutical company argued that proposed
Sec. 101.93(g)(2)(v) would violate DSHEA, because DSHEA specifically
defines as a dietary supplement an article that is approved as a new
drug under section 505 of the act, if it was, prior to approval,
marketed as a dietary supplement.
FDA agrees that the dietary supplement definition includes the
provision cited by the comment (section 201(ff)(3)(A) of the act), but
believes that the definition and Sec. 101.93(g)(2)(v) are not
inconsistent. Section 101.93(g)(2)(v) would treat as a disease claim a
labeling statement that the supplement is a member of a product class
when that class is so recognizable for its disease treatment or
prevention use that the labeling statement would be understood as a
disease claim for the supplement. The criterion would not treat
inclusion of an ingredient in a dietary supplement as a disease claim
merely because the ingredient had been approved under section 505 of
the act nor would it preclude listing the ingredient in the Supplement
Facts panel or ingredient list.
O. Substitute for Disease Therapy (Sec. 101.93(g)(2)(vi))
Under proposed Sec. 101.93(g)(2)(vi), a statement would have been
considered a disease claim if it explicitly or implicitly claimed that
the product was a substitute for another product that is a therapy for
a disease. FDA offered ``Herbal Prozac'' as an example of such a claim.
A claim that did not identify a specific drug, drug action, or therapy
(e.g., ``use as part of your weight loss plan'') would not constitute a
disease claim under this criterion.
(73.) There was general support for the provision, particularly
for considering terms that make a direct connection with an approved
drug, like ``Herbal Prozac'' and ``Herbal Phen-fen,'' disease claims.
Several organizations noted that associating dietary supplements with
regulated drug products is deceptive and dangerous because it can
signal to consumers that because the product is ``herbal'' it is safer.
Several medical associations, however, objected to the interpretation
that ``use as part of your weight loss plan,'' is nonspecific and would
be acceptable. They maintained that the term implies treatment of a
disease, obesity. A comment from a manufacturer also strongly objected
to the statement in the proposal that ``Use as part of your weight loss
plan'' would be an acceptable structure/function claim. The comment
contended that the legislative history of the act shows that Congress
intended weight loss claims to be treated as disease claims. Finally,
the comment argued that even if FDA decides to permit weight loss
claims as structure/function claims, the legislative history of the act
and case law require that FDA classify products containing
``antinutrients'' as drugs.
FDA agrees with these comments that obesity is a disease, and that
obesity claims are not acceptable structure/function claims. Being
overweight, i.e., being more than one's ideal weight but less than
obese, however, is not a disease. FDA believes that it is commonly
understood that ``weight loss plans'' relate to a broad range of
overweight statuses. Therefore, weight loss plans are not so narrowly
associated with disease treatment that a reference to use as part of a
weight loss plan should be considered a disease claim.
FDA does not agree that either the legislative history of the act
or the case law interpreting section 201(g) of the act or DSHEA require
a determination that FDA classify as drugs products making weight loss
claims. The legislative history of section 201(g)(1)(C) of the act
shows that Congress added the structure/function definition of ``drug''
in part to capture obesity claims that were not covered by section
201(g)(1)(B) because obesity was not, at that time, considered a
disease. FDA believes that the legislative history in fact supports
FDA's view that weight loss claims are properly considered structure/
function claims. Although obesity claims are now covered by section
201(g)(1)(B) of the act because obesity is now considered a disease,
section 201(g)(1)(C) was added to cover conditions, like overweight,
that are not considered diseases, but that affect the structure or
function of the body. Structure/function claims under section 403(r)(6)
of the act are closely related to structure/function claims under
section 201(g)(1)(C) of the act and therefore should encompass weight
loss claims.
FDA also does not agree that cases cited by the comment compel the
conclusion that weight loss products must be regulated as drugs. In
Nutrilab v. Schweiker, 713 F.2d 335 (7th Cir. 1983), American Health
Products Co. v. Hayes, 574 F. Supp. 1498 (S.D.N.Y. 1982), aff'd, 744
F.2d 912 (2d Cir. 1984), and United States of America v. Undetermined
Quantities Of ``CAL-BAN 3000'', 776 F. Supp. 249 (E.D.N.C. 1991), the
courts held that certain weight loss products were drugs under section
201(g)(1)(C) of the act because they were labeled to affect the
structure or function of the body, and did not qualify for the ``food''
exception to section 201(g)(1)(C). At the time these cases were
decided, the only issue was whether these products were ``foods'' or
``drugs.'' Since then, however, DSHEA created a new statutory category
of products, dietary supplements. Section 403(r)(6) of the act, which
was added by DSHEA, permits structure/function claims to be made for
dietary supplements without subjecting them to regulation as drugs,
even if they could not qualify for the ``food'' exception in section
201(g)(1)(C) of the act. Therefore, these cases do not establish that
dietary supplements making weight loss claims must be regulated as
drugs. To the contrary, because the products were held to be drugs
under section 201(g)(1)(C) of the act rather than section 201(g)(1)(B),
these cases support treatment of weight loss claims for dietary
supplements as structure/function claims authorized under section
403(r)(6) of the act.
Finally, FDA does not agree that, under United States v. Ten
Cartons, More or Less, of an Article * * * Ener-B Vitamin B-12, 72 F.3d
285 (2d Cir. 1995), dietary supplements making weight loss claims must
necessarily be regulated as drugs. The court in Ener-B held that a
dietary supplement that makes a structure/function claim may
nevertheless be regulated as a drug, under certain circumstances. In
that case, the court found that FDA could regulate a product as a drug,
based on its method of intake (nasal administration). Nothing in that
case suggests that FDA must regulate dietary supplements making weight
loss claims as drugs.
[[Page 1028]]
(74.) Several comments reiterated that general statements about
the nature of a product or its mechanism of action should not be
disease claims, or should be structure/function claims as long as they
are truthful and not misleading. One comment objected to the provision
as duplicative of proposed Sec. 101.93(g)(2)(v). Another comment sought
to delete the provision, arguing that dietary supplement manufacturers
have the right to communicate to consumers that their products have
fewer side effects than drugs.
FDA does not believe that this provision precludes general
statements about the function or mechanism of action of a dietary
supplement. It is not necessary to claim that the product is a
substitute for a drug or therapy to describe its function or its
mechanism of action. Nor is Sec. 101.93(g)(2)(vi) duplicative of
Sec. 101.93(g)(2)(v). Claiming that a product is a substitute for a
specific drug or therapy, e.g., ``Herbal Prozac,'' is a different means
of communicating that a dietary supplement is intended to treat a
disease than claiming that the product belongs to a class of drugs
associated with treatment or prevention of that disease, e.g.,
``antidepressant.''
FDA does not agree that section 403(r)(6) of the act permits a
dietary supplement manufacturer to claim that its product has fewer
side effects than a drug, if the drug is intended to treat or prevent
disease, because the clear implication is that the dietary supplement
is intended for treatment or prevention of the same disease. If,
however, the drug is not intended to treat or prevent disease, a
dietary supplement manufacturer is free to make truthful, non-
misleading comparisons between the drug and the dietary supplement.
P. Augmentation of Therapy or Drug for Disease
(Sec. 101.93(g)(2)(vii)))
Under proposed Sec. 101.93(g)(2)(vii), a statement would have been
considered a disease claim if it explicitly or implicitly claimed that
the product augmented a particular therapy or drug action. The preamble
offered the following example of a disease claim under this criterion:
``Use as part of your diet when taking insulin to help maintain a
healthy blood sugar level.'' A claim that did not identify a specific
drug, drug action, or therapy would not constitute a disease claim
under this criterion. The preamble gave the following example of an
acceptable structure/function claim: ``use as a part of your weight
loss plan.''
(75.) Several comments supported this provision. A few comments
requested that FDA withdraw the provision, arguing that dietary
supplements are often useful in providing nutritional support to
complement drug therapy or medical treatment and that the agency should
encourage such information to be communicated to consumers. One comment
stated that as long as the statement makes it clear that the product is
being recommended for its nutritional impact on structure or function
``as part of the therapy and not as the therapy itself,'' FDA should
permit the statement. According to the comment, ``use as part of your
diet when taking insulin to help maintain a healthy blood sugar level''
should be acceptable because the product is being recommended for its
nutritional impact on structure or function as part of the therapy and
not as the therapy itself. Another comment asked whether removing the
words ``when taking insulin'' from the statement would make it an
acceptable structure/function claim.
The agency agrees that dietary supplements may be useful in
providing nutritional support. Associating such a statement with an
express or implied claim that the dietary supplement augments a therapy
or drug action, however, implies that the dietary supplement has a role
in treating or preventing the disease for which the drug or other
therapy is used.
The agency does not agree that the proposed claim involving
insulin is an acceptable structure/function claim. Persons who take
insulin have a disease, namely, diabetes. By referring to the use of
the dietary supplement in conjunction with and for the same purpose
(``to maintain a healthy blood sugar level'') as a drug (insulin),
which is used to for a disease (diabetes), the statement implies that
the dietary supplement will help treat diabetes.
A general statement that a dietary supplement provides nutritional
support would be an acceptable structure/function claim, provided that
the statement does not suggest that the supplement is intended to
augment or have the same purpose as a specific drug, drug action, or
therapy for a disease. In the example, if the statement were changed to
``use as part of your diet to help maintain a healthy blood sugar
level,'' the claim would be considered acceptable. Deleting the
reference to the drug, insulin, would remove the implication that the
dietary supplement is used to augment the insulin to treat, mitigate,
prevent, or cure diabetes.
On its own initiative, FDA is modifying Sec. 101.93(g)(2)(vii) to
limit its applicability to claims for augmentation of drugs or
therapies that are intended to diagnose, mitigate, treat, cure, or
prevent disease.
(76.) Another comment noted that the agency did not address the
use of synonyms for ``augment,'' such as ``strengthen,'' ``reduce,''
``improve,'' ``modify,'' ``inhibit,'' ``protect,'' or ``defend.''
Use of these terms may be appropriate in some contexts, i.e., when
the statements do not suggest disease prevention or treatment use. If,
however, the use of these terms implies that the dietary supplement
augments a particular therapy or drug action or otherwise suggests an
effect on disease, the agency will consider the statement a disease
claim.
(77.) A trade association maintained that under the proposal,
bread, crackers, and other baked goods used in conjunction with
prescription drugs and/or other therapy would not be considered a food,
but a drug, under certain circumstances.
Section 101.93 is intended to provide regulatory criteria for
statements made for dietary supplements. Under section 201(ff)(2)(B) of
the act, a dietary supplement does not include a product represented
for use as a conventional food or as a sole item of a meal or the diet.
If statements made for breads, crackers, and other baked goods
characterize the relationship between a substance in the food and a
disease or health-related condition, they must comply with the health
claims provisions for foods under section 403(r)(1)(B) and (r)(3)
through (r)(4) of the act.
Q. Role in Body's Response to Disease or Disease Vector
(Sec. 101.93(g)(2)(viii))
Under proposed Sec. 101.93(g)(2)(viii), a statement would have
been considered a disease claim if it explicitly or implicitly claimed
a role in the body's response to a disease or to a vector of disease.
The preamble to the proposal defined a vector of disease as an organism
or object that is able to transport or transmit to humans an agent,
such as a virus or bacterium, that is capable of causing disease in
man. The preamble offered as examples of disease claims under this
criterion claims that a product ``supports the body's antiviral
capabilities'' or ``supports the body's ability to resist infection.''
A more general reference to an effect on a body system that did not
imply prevention or treatment of a disease state would not have
constituted a disease claim under this criterion. FDA provided as an
example of an acceptable structure/function claim
[[Page 1029]]
under this criterion ``supports the immune system.''
(78.) Two comments from health associations supported this
provision. One comment from a manufacturer argued that it should be
deleted because a number of nutrients and dietary supplements ``have a
role in the body's response to disease.'' One comment argued that the
body has natural defenses to disease, that these are normal functions
of the body, and that therefore, statements such as ``enhances disease
resistance'' should be allowable as structure/function claims. Comments
from a consumer organization and a member of the President's Commission
on Dietary Supplement Labels asserted that the provision made too many
claims allowable. These comments stated that as long as a claim
includes a disease-fighting function of the body, e.g., ``supports the
immune system,'' it should be considered a disease claim, regardless of
other functions that might be involved.
FDA agrees that nutrients and dietary supplements may play a role
in the body's response to disease. This does not mean, however, that
disease prevention claims are acceptable structure/function claims. The
act requires dietary supplement manufacturers who wish to make disease
prevention claims to do so by obtaining authorization for a health
claim or by obtaining new drug approval. Although FDA agrees that
claims that a product fights disease, or enhances disease-fighting
functions of the body, are disease claims, FDA does not agree that
claims such as ``supports the immune system'' are specific enough to
imply prevention of disease.
(79.) Several comments argued that there was no significant
difference between ``supports the immune system'' (identified as a
structure/function claim in the proposal) and ``supports the body's
antiviral capabilities'' (identified as a disease claim in the
proposal). One view was that both should be considered structure/
function claims. Conversely, other comments contended that ``supports
the immune system'' is a disease claim, because it could be interpreted
as a claim for treatment or prevention of human immunodeficiency virus
(HIV) disease. Another comment recommended that ``supports the body's
antiviral capabilities'' be allowable as a structure/function claim,
stating that the broader ``supports the immune system'' statement was
vague and useless to consumers because the immune system has many
functions.
The distinction between the two claims is one of specificity. An
intact immune system has several functions. In addition to their role
in the defense against pathogens, certain components of the immune
system, namely white blood cells, have other important functions. For
example, white blood cells play an essential role in the phagocytosis
and disposal of aging red blood cells or otherwise damaged cells. A
statement of support for the immune system, by itself, conveys no
specific reference to disease treatment or prevention. The claim that
vitamin A is necessary to maintaining a healthy immune response does
not imply that a specific disease or class of diseases will be
prevented. In contrast, a claim that a product ``supports the body's
antiviral capabilities'' represents a claim of treatment or prevention
of a specific class of diseases, those caused by viruses (e.g., colds,
hepatitis, or HIV infection).
R. Treatment/Prevention of Adverse Events (Sec. 101.93(g)(2)(ix))
Under proposed Sec. 101.93(g)(2)(ix), a statement would have been
considered a disease claim if it explicitly or implicitly claimed to
treat, prevent, or mitigate adverse events associated with a therapy
for a disease (e.g., ``reduces nausea associated with chemotherapy,''
``helps avoid diarrhea associated with antibiotic use,'' and ``to aid
patients with reduced or compromised immune function, such as patients
undergoing chemotherapy''). A claim that did not mention a therapy for
disease (e.g., ``helps maintain healthy intestinal flora'') would not
have constituted a disease claim under this criterion.
(80.) Comments from two large health organizations supported this
provision, while two large business organizations and several other
comments criticized it. Those opposing the provision argued that the
proposal incorrectly categorized adverse reactions as diseases.
Opposing comments also contended that dietary supplements may be useful
as an adjunct to therapy by counterbalancing the effects of a drug in
depleting a nutrient or interfering with the metabolism of a nutrient,
and that this should be considered a structure/function role.
FDA believes that some of these comments may have misconstrued the
provision. The criterion is not intended to capture every adverse event
claim, but only claims about adverse events that satisfy the definition
of disease. In the proposed rule, this limitation was conveyed by the
phrase ``and manifested by a characteristic set of signs or symptoms.''
Because the final rule uses a different definition of disease,
Sec. 101.93(g)(2)(ix) has been revised to state that claims about
adverse events are disease claims only ``if the adverse events
constitute diseases.'' FDA believes that a claim that a product is
useful because it counterbalances the effects of a drug in depleting a
nutrient or interfering with the metabolism of a nutrient would be
acceptable as a structure/function statement. Such a claim would not
suggest treatment of an adverse reaction that meets the definition of
disease. However, as discussed above, if the claim expressly or
impliedly suggests that the supplement is intended to augment a
specific drug, drug action, or therapy for a disease, or serve the same
purpose as a specific drug or therapy for a disease, then the statement
may be considered a disease claim.
(81.) A dietary supplement manufacturer requested that FDA clarify
why a statement that refers to a drug but not a disease, such as
``helps individuals using antibiotics to maintain normal intestinal
flora'' is a disease claim, but a general statement, such as ``helps
maintain intestinal flora'' is a permissible structure/function claim.
Although the statement ``helps individuals using antibiotics to
maintain normal intestinal flora'' does not explicitly refer to a
disease, there is an implicit claim that use of the dietary supplement
while taking antibiotics will prevent or mitigate a disease. Persons
using certain antibiotics are at risk of developing overgrowth in the
gut of a pathogenic organism because along with fighting the target
organisms in the body the antibiotic can suppress normal intestinal
flora that are used to prevent infection in the intestinal tract. A
firm that markets its product to address this concern, with claims that
the product can be used to maintain normal intestinal flora while
taking antibiotics, is making an implied disease prevention claim.
Conversely, the statement ``helps maintain intestinal flora'' alone,
without any reference to a disease, drug, drug action, or therapy, does
not imply an effect on disease and would be considered a structure/
function claim about general health maintenance.
S. Otherwise Affects Disease (Sec. 101.93(g)(2)(x))
Under proposed Sec. 101.93(g)(2)(x), a statement would have been
considered a disease claim if it suggested an effect on a disease or
class of diseases in a manner other than those specifically enumerated
in the first nine criteria.
(82.) A food manufacturers' trade association commented that this
provision is of no regulatory importance, whereas a dietary supplement
trade association and
[[Page 1030]]
several other comments considered it an over-reaching ``catch-all''
provision that would allow FDA to treat any claim as a disease claim.
These comments provided examples of a number of claims that they
believed would be disease claims under this provision, e.g. ``provides
nutritional support for women during premenstruation by promoting
proper fluid balances and breast health,'' and ``ginger supports the
cardiovascular system by inhibiting leukotriene and thromboxane
synthesis, substances associated with platelet aggregation.''
FDA believes that this provision is necessary to allow for implied
disease claims that may not fit into the nine enumerated criteria. The
nine criteria are examples, and not an exhaustive list, of types of
claims that the agency believes would constitute disease claims, based
on past experience. Rather than attempting to evaluate or categorize
statements that have not yet been presented to FDA,
Sec. 101.93(g)(2)(x) recognizes the possibility that other types of
statements may also imply disease treatment or prevention. FDA does not
believe that the provision will cause the agency to classify any
structure/function statement as a disease claim. To regulate a
statement as a disease claim under this provision, the agency would
have to show that the statement implied an effect on disease. The two
examples quoted in the comments do not appear to the agency to
constitute disease claims.
T. Specific Claims Not Mentioned in the Proposed Rule
(83.) One comment contended that a dietary supplement called
``pain free'' or ``pain product,'' that is labeled ``to support and
maintain joints,'' should not be regulated as an internal analgesic
drug product under the OTC drug review because it is intended to
maintain or support ``normal well-being and pain levels.'' According to
this comment, however, products sold as ``pain relief'' or ``otherwise
indicated to relieve temporary occurrences of arthritis pain'' could be
regulated as drug products under the OTC review, because the tentative
final monograph for internal analgesics requires that such products be
labeled for the ``temporary relief of minor aches and pains'' (53 FR
46204). At the same time, this comment argued that pain, in and of
itself, is not a disease and therefore that pain claims should not be
regulated as disease claims unless accompanied by an explicit reference
to a specific disease.
FDA agrees in part and disagrees in part with this comment. FDA
agrees that some minor pain relief claims may be appropriate structure/
function claims for dietary supplements. A claim that a product is
intended to treat minor pain, without reference of any other
conditions, symptoms, or parts of the body that would imply disease
treatment or prevention, would be an appropriate structure/function
claims, because minor pain, by itself, can be caused by a variety of
conditions, not all of them disease-related.
FDA does not agree, however that general well-being or health
maintenance claims would encompass such pain claims. Pain is not a
normal state, nor are there ``normal pain levels.'' The claim is thus
clearly one of pain treatment or prevention. FDA also does not agree
that section 403(r)(6) of the act authorizes a product whose name
promises freedom from or relief of pain (``pain-free'' or ``pain
product'') and whose labeling includes claims related to maintenance or
support of joints. While the latter claims alone are appropriate
structure/function statements, in conjunction with a name that includes
the term ``pain,'' the product is clearly making a claim related to
treatment or prevention of joint pain. As explained elsewhere in this
document, joint pain is a characteristic symptom of arthritis, and
joint pain claims are therefore disease claims. Acceptable structure/
function claims could be made, however, for pain associated with
nondisease states, e.g., muscle pain following exercise.
(84.) One comment listed several claims and sought concurrence
that they were acceptable structure/function claims: ``Boosts stamina,
helps increase muscle size, and helps enhance muscle tone''; ``deters
bacteria from adhering to the wall of the bladder and urinary tract'';
and ``dietary support during the cold and flu season.'' Another comment
asked whether ``promotes general well-being during the cold and flu
season'' is a permissible claim.
FDA agrees that ``boosts stamina, helps increase muscle size, and
helps enhance muscle tone'' are acceptable structure/function claims,
because they do not refer to any disease. However, the agency notes
that a claim to increase muscle size implies an effect that may subject
the product regulation as an anabolic steroid under the Controlled
Substances Act (see 21 U.S.C. 802(41)). ``Deters bacteria from adhering
to the wall of the bladder and urinary tract'' is not an acceptable
structure/function claim because it implies prevention of bacterial
infections of the bladder and urinary tract. The claims ``dietary
support during the cold and flu season'' and ``promotes general well-
being during the cold and flu season'' are disease claims because they
imply that the product will prevent colds and flu or will mitigate the
symptoms of those diseases.
(85.) One comment asked that the FDA clarify that dietary
supplements can bear ``smoking-alternative'' claims if they avoid
references to nicotine, nicotine withdrawal symptoms, and tobacco-
related disease. The comment sought concurrence that the following
types of claims were permitted: ``Smoking alternative,'' ``temporarily
reduces your desire to smoke,'' ``to be used as a dietary adjunct in
conjunction with your smoking cessation plan;'' and ``mimics the oral
sensations of cigarette smoke.''
FDA agrees that certain smoking alternative claims may be
acceptable structure/function claims, if they do not imply treatment of
nicotine addiction, relief of nicotine withdrawal symptoms, or
prevention or mitigation of tobacco-related illnesses. ``Smoking
alternative,'' ``temporarily reduces your desire to smoke'' and
``mimics the oral sensations of cigarette smoke'' may be acceptable
(for products that otherwise meet the definition of a dietary
supplement), if the context does not imply treatment of nicotine
addiction, e.g., by suggesting that the product can be used in smoking
cessation, or prevention or mitigation of tobacco-related diseases. For
example, such claims would not be disease claims if the context made
clear that they were for short-term use in situations where smoke is
prohibited or socially unacceptable. ``To be used as a dietary adjunct
in conjunction with your smoking cessation plan,'' however, is a
disease claim because it is a claim that the product aids in smoking
cessation, thereby implying that the product is useful in treating
nicotine addiction. As noted earlier, a claim that the product is
useful in counterbalancing the effects of a drug in depleting a
nutrient or interfering with the metabolism of a nutrient would be
acceptable as a structure/function statement.
(86.) One comment offered as acceptable structure/function claims a
long list of OTC drug claims provided for in the monographs for
antacids, antiflatulents (antigas), antiemetics, nighttime sleep-aids,
stimulants (alertness aids), daytime sedatives, aphrodisiacs, products
for relief of symptoms of benign prostatic hypertrophy,
anticholinergics (products that, at low doses, depress salivary and
bronchial secretions), and products for certain uses. Two comments
sought clarification that inclusion of a claim in an OTC monograph does
not preclude its use as a structure/function claim.
[[Page 1031]]
FDA agrees that some of the claims on the comment's list of OTC
drug claims may be acceptable structure/function claims, but believes
that others on the list are disease claims. Of the claims listed in the
comment from the ``Antacids'' monograph, ``relief of sour stomach'' and
``upset stomach'' are acceptable structure/function claims, because
they refer to a nonspecific group of conditions that have a variety of
causes, many of which are not disease-related. Thus, they are not
characteristic of a specific disease or class of diseases. Although
``relief of heartburn'' and ``relief of acid indigestion'' without
further qualification are not appropriate structure/function claims,
the agency has concluded that ``occasional heartburn'' and ``occasional
acid indigestion'' can also be considered nonspecific symptoms, arising
as they do in overindulgence and other sporadic situations. These
claims could be appropriate structure/function claims. In contrast,
``recurrent'' or ``persistent'' heartburn and acid indigestion can be
hallmarks of significant illness, and are therefore disease claims.
All of the claims listed in the comment from the
``Antiflatulents'' (antigas) monograph are acceptable structure/
function claims, because the symptoms in the claims are not
sufficiently characteristic of specific diseases: ``Alleviates the
symptoms referred to as gas,'' ``alleviates bloating,'' ``alleviates
pressure,'' ``alleviates fullness,'' and ``alleviates stuffed
feeling.'' The claim listed in the comment from the ``Antiemetics''
monograph, ``for the prevention and treatment of the nausea, vomiting,
or dizziness associated with motion,'' is also a permitted structure/
function claim.
Of the claims listed in the comment from the ``Nighttime'' sleep-
aids monograph, ``for the relief of occasional sleeplessness'' is an
acceptable structure/function claim, because occasional sleeplessness
is not a characteristic symptom of a disease. ``Helps you fall asleep
if you have difficulty falling asleep,'' and ``helps to reduce
difficulty falling asleep'' are disease claims because, unless the
context makes clear that the product is only for occasional
sleeplessness, they imply treatment of insomnia, a disease. The claim
listed in the comment from the ``Stimulants'' (alertness aids)
monograph, ``helps restore mental alertness or wakefulness when
experiencing fatigue or drowsiness,'' is an acceptable structure/
function claim because occasional fatigue and drowsiness are not
characteristic symptoms of a specific disease or class of diseases. FDA
notes, however, that chronic fatigue or daytime drowsiness can be
symptoms of chronic fatigue syndrome and narcolepsy, respectively.
Products labeled ``to help restore mental alertness or wakefulness when
experiencing fatigue or drowsiness'' should not imply treatment of
either of these diseases.
Of the claims listed in the comment from the ``Daytime'' sedatives
monograph, almost all are acceptable structure/function claims.
``Occasional simple nervous tension,'' ``nervousness due to common
every day overwork and fatigue,'' ``a relaxed feeling,'' ``calming down
and relaxing,'' ``gently soothe away the tension,'' ``calmative,''
``resolving that irritability that ruins your day,'' ``helps you
relax,'' ``restlessness,'' ``nervous irritability,'' and ``when you're
under occasional stress, helps you work relaxed'' are all acceptable
structure/function claims, because all suggest occasional rather than
long-term or chronic mood changes. Although occasional or acute
symptoms can be characteristic of diseases in other settings, none of
the occasional symptoms referred to here is characteristic of a
specific disease. ``Nervous tension headache'' is a disease claim
because tension headache meets the definition of a disease.
Of the claims listed in the comment from the ``Aphrodisiacs''
monograph, ``arouses or increases sexual desire and improves sexual
performance'' is an acceptable structure/function claim because it does
not imply treatment of a disease. ``Helps restore sexual vigor,
potency, and performance,'' ``improves performance, staying power, and
sexual potency,'' and ``builds virility and sexual potency'' are
disease claims because they use the term ``potency,'' which implies
treatment of impotence, a disease. If, however, these claims made clear
that they were intended solely for decreased sexual function associated
with aging, they could be acceptable structure/function claims. The
claim from the ``Products for relief of symptoms of benign prostatic
hypertrophy'' monograph (``To relieve the symptoms of benign prostatic
hypertrophy, e.g., urinary urgency and frequency, excessive urinating
at night, and delayed urination'') is a disease claim, because benign
prostatic hypertrophy meets the definition of a disease.
The claim listed in the comment from the ``Anticholinergics''
monograph is a disease claim. ``Relieve excessive secretions of the
nose and eyes'' refers to the characteristic signs or symptoms of hay
fever. Of the claims listed in the comment from the ``Products for
certain uses'' monograph, ``digestive aid,'' ``stool softener,''
``weight control,'' and ``menstrual'' are, by themselves, acceptable
structure/function claims if the labeling does not otherwise imply
treatment or prevention of a disease. None mentions a characteristic
symptom of a disease. ``Laxative'' is a not a disease claim, if the
labeling makes clear that the intended use is for treatment of
occasional rather than chronic constipation. ``Nasal decongestant,''
``expectorant,'' and ``bronchodilator'' are disease claims. ``Nasal
decongestant'' is a treatment for a characteristic symptom of colds,
flu, and hay fever. ``Expectorant'' is a treatment for a characteristic
symptom of colds, flu, and bronchitis. ``Bronchodilator'' is a
treatment for bronchospasm, a characteristic symptom of asthma.
The claim from the ``Products for the treatment and/or prevention
of nocturnal leg muscle cramps'' monograph (``treatment and/or
prevention of nocturnal leg muscle cramps, i.e., a condition of
localized pain in the lower extremities usually occurring in middle
life and beyond with no regular pattern concerning time or severity'')
is an appropriate structure function claim. Nocturnal leg cramps do not
meet the definition of disease.
As is clear from this response, FDA agrees that inclusion of a
claim in an OTC monograph does not preclude its use as a structure/
function claim. FDA notes, however, that in light of the statutory
requirement that dietary supplements bear all information that is
material in light of consequences that may result from use of the
product or representations made about it, dietary supplements that
contain or are labeled as containing ingredients covered by an OTC
monograph and that are being sold for the claims covered by the
monograph may be misbranded to the extent that they omit material
information required under the monograph. For example, if the OTC
monograph required a label statement that products containing a
particular ingredient should not be used by persons taking a
prescription monoamine oxidase inhibitor, a dietary supplement
containing that ingredient would be misbranded if its label did not
include such statement.
U. Substantiation of Claims
(87.) Several comments requested that the final rule explicitly
state that structure/function statements must be adequately
substantiated and that FDA provide guidance on what constitutes
adequate substantiation. One comment
[[Page 1032]]
maintained that adequate substantiation is critical to ensuring that
consumers receive truthful and accurate information about the benefits
of dietary supplements. Another comment argued that this final rule
should focus on adequate substantiation of claims rather than on
delineating the boundaries between structure/function claims and
disease claims. Other comments maintained that substantiation is not as
effective in preventing consumer fraud as preapproval of the claims
because consumers will be using the products long before the label
claims are investigated.
FDA agrees that the statutory requirement to substantiate claims
is important. FDA does not agree, however, that it is necessary to
state in the regulatory text of the final rule that structure/function
claims must be adequately substantiated. Section 101.93(a)(3) requires
a firm notifying FDA of a claim under section 403(r)(6) of the act to
certify that the firm has substantiation that the claim is truthful and
not misleading. FDA also does not agree that substantiation is an
appropriate alternative to distinguishing structure/function claims
from disease claims. The requirement that structure/function statements
and other statements for dietary supplements under section 403(r)(6) of
the act be adequately substantiated is distinct from the requirement
that such statements not claim to diagnose, treat, mitigate, cure, or
prevent disease. Both of these requirements are imposed by the statute
and must be complied with.
(88.) Several comments offered advice on what types of evidence
should constitute adequate substantiation. A consumer health
organization suggested that health claims and structure/function claims
for dietary supplements be based on the totality of the publicly
available scientific evidence, including results from well-designed
studies conducted in a manner consistent with generally recognized
scientific principles and procedures. The comment added that consumers
would be better served if standards for support applied to both health
claims and structure/function claims. Another consumer health
organization suggested that substantiation be based on ``significant
scientific agreement.''
Many of the comments suggested that the agency adopt FTC standards
for substantiation. A comment from FTC explained that FTC typically
applies a substantiation standard known as ``competent and reliable
scientific evidence'' to claims about the safety and effectiveness of
dietary supplements, after first looking at the overall context to
determine what the claim is. The comment further stated that FTC's
approach to substantiation is consistent with the guidance provided by
the President's Commission on Dietary Supplement Labels, and, because
FDA concurred with the Commission's guidance on substantiation, the
comment suggested that FDA refer to the Commission guidance in the
final rule.
As stated above, the agency does not believe that this final rule
is the appropriate venue to address the substantiation requirement. FDA
does, however, agree that claims under section 403(r)(6) of the act
should be supported by adequate scientific evidence and may provide
additional guidance regarding substantiation for 403(r)(6) statements
at a future date.
The Commission report included guidance on what quantity and
quality of evidence should be used to substantiate claims made under
403(r)(6) of the act. It also contained guidance on the content of the
substantiation files for such statements, including the 30-day
notification letter to FDA, identification of the product's
ingredients, evidence to substantiate the statements, evidence to
substantiate safety, assurances that good manufacturing practices were
followed, and the qualifications of the person(s) who reviewed the data
on safety and efficacy. In a notice published in the Federal Register
(63 FR 23624 at 23633), FDA stated that it agreed with the guidance of
the Commission. FDA encourages manufacturers of dietary supplements
making a 403(r)(6) of the act statement for a dietary supplement to
follow this guidance.
(89.) A food manufacturer suggested that the agency require
dietary supplement manufacturers making structure/function claims to
disclose in labeling any and all scientific studies supporting the
claim. In addition, the comment advocated requiring that these studies
be performed using the marketed formulation. The comment also urged FDA
to determine how contrary studies should be addressed.
DSHEA does not require dietary supplement labeling that carries a
statement under section 403(r)(6) of the act to include in the labeling
``any and all scientific studies supporting the claim.'' Section
403(r)(6)(B) of the act requires only that the ``manufacturer have
substantiation that such statement is truthful and not misleading.''
Contrary studies should be considered when deciding whether to make and
how to word a 403(r)(6) of the act statement to ensure that any
statements made are truthful and not misleading. Additionally, in
response to a request for substantiation for the statement, the agency
would expect manufacturers to provide a requester with contrary as well
as supporting studies.
There is no specific statutory requirement that the studies
substantiating the statement be performed using the actual marketed
formulation. However, many ingredients and factors influencing the
formulation can affect the safety and effectiveness of the dietary
supplement. These variations from the marketed product should be
considered before using a study to substantiate a statement made for a
particular product.
V. Enforcement Issues
(90.) One comment said that the proposal shifts the burden of
proof to manufacturers to show that their files match and support the
claims made for their products.
The regulations issued by this final rule do not address or affect
the burden of proof during enforcement actions. However, section
403(r)(6)(B) of the act clearly states that manufacturers must have
substantiation to show that the statements that they make under section
403(r)(6) of the act are truthful and not misleading. This indicates
that manufacturers must be prepared to demonstrate to the court that
they have support for each claim.
(91.) One comment predicted widespread noncompliance with the rule
because of its complexity and limited FDA resources.
FDA disagrees with the comment. FDA believes that most of the rule
is straightforward, and the comments received on the proposed rule
indicate that dietary supplement manufacturers understood the
provisions of the rule. Moreover, as noted in the Analysis of Impact in
section VI.E of this document, most of the claims of which FDA has been
notified are consistent with the final rule. Thus, based on what has
been provided to FDA, most manufacturers would appear to be already in
compliance with this final rule. If it becomes apparent that there are
provisions that are being violated because of true confusion about
their applicability, FDA will issue clarifying guidance. FDA agrees
that its enforcement resources are limited, and is issuing this rule in
part to avoid inefficient use of those resources on case-by-case
enforcement. FDA believes that the dietary supplement industry will
make good faith efforts to comply with this rule, once it becomes
effective.
[[Page 1033]]
W. Other Comments
(92.) One comment said FDA should conduct an educational campaign
to enhance public awareness of the differences between structure/
function claims and disease claims and the meaning of individual
claims.
FDA intends to conduct various outreach activities on dietary
supplement matters.
(93.) One comment said FDA should amend the tentative final
monograph on OTC laxatives to be consistent with the rule. The comment
explained that the tentative final monograph should permit the words
``help maintain regularity'' on OTC labeling.
The agency disagrees with the comment. The fact that ``helps
maintain regularity'' is an acceptable structure/function claim does
not mean that it satisfies the requirements for inclusion in an OTC
monograph, including the requirement of a finding of general
recognition of safety and effectiveness.
(94.) Several comments addressed manufacturing or related issues.
One comment said FDA should investigate effects of dissolution on
product potency and efficacy, while other comments advocated using
United States Pharmacopeia standards for all dietary supplements on
matters pertaining to dissolution, disintegration, purity, and potency.
One comment added that poor product quality would present a health
threat to consumers and result in economic fraud.
Another comment said FDA should concentrate on standardization and
quality control instead of regulating labeling statements, but offered
no specific suggestions. Some comments, however, made specific
recommendations. One comment said that product labels should contain
lot numbers and expiration dates and that manufacturers should conduct
stability tests to determine accurate expiration dates. Another comment
said the public should be protected against poor manufacturing
standards for herbal products. Other comments simply stated that there
is substantial potential for public harm because there are: Multiple
sources of dietary supplement ingredients; multiple suppliers; a lack
of regulatory production standards, or questions concerning product
safety, efficacy, and manufacturing quality; vigorous product
promotion; and a sizeable market. One comment simply asked for good
manufacturing practice regulations for dietary supplements.
Manufacturing issues are outside the scope of this rule. FDA
intends to issue a separate proposed rule on current good manufacturing
practice (CGMP) for dietary supplements, and that proposed CGMP rule
may address some of the issues raised by the comments.
III. Legal Authority
A. Scope of Section 403(r)(6) of the Act
1. Relationship Between Sections 403(r)(6) and 201(g)(1)(C) of the Act
(95.) Several comments stated that the proposal mistakenly
suggests that there is only one type of structure/function claim that
may be used for dietary supplements. Some of these comments said that
if a structure/function claim does not trigger drug status for the
product and is not a health claim, then such a claim may be made in
labeling for a dietary supplement so long as it is truthful and not
misleading. These comments asserted that such a claim is not subject to
the notice, labeling, or disclaimer requirements in section 403(r)(6)
of the act. As an example, the comments said the claim that ``calcium
helps build strong bones'' is not a health claim because it does not
characterize a relationship between the substance and a disease,
damage, or dysfunction of the body. The comments added that FDA
recognized this in the final rule that it published in the Federal
Register on September 23, 1997 (62 FR 49859, 49860, 49863, and 49864),
when it stated in the preamble that claims that cranberry juice
cocktail helps maintain urinary tract health or that calcium builds
strong bones and teeth are not health claims because no disease is
mentioned explicitly or implicitly. Some comments added that FDA cannot
say that only those claims falling under section 406(r)(6) of the act
are structure/function claims because such a result would be contrary
to the act and would mean that the proposed rule must be withdrawn.
FDA agrees with these comments in part and disagrees in part. The
agency agrees that statements such as ``calcium helps build strong
bones'' are not health claims because they do not characterize the
relationship between a substance and a disease or health-related
condition. Rather, such statements are structure/function claims
authorized by section 403(r)(6) of the act.
FDA does not agree with the comment's statement that dietary
supplements may bear structure/function claims without complying with
the notice, disclaimer, and other requirements of section 403(r)(6) of
the act. Section 403(r)(6) of the act, by its terms, applies to dietary
supplements. The other possible source of authority to make structure/
function claims on dietary supplements is section 201(g)(1)(C) of the
act, which provides that ``articles (other than food) intended to
affect the structure or any function of the body of man or other
animals'' are drugs. Under this provision, foods may make claims to
affect the structure or function of the body without being regulated as
drugs. By its terms, however, section 201(g)(1)(C) of the act exempts a
dietary supplement that bears a structure/function claim from drug
regulation only if it is also a food. The last sentence of section
201(ff) of the act provides, ``Except for purposes of section 201(g), a
dietary supplement shall be deemed to be a food within the meaning of
this Act.'' The clear import of this language is that dietary
supplements are not foods under section 201(g) of the act and therefore
cannot qualify for the ``(other than food)'' exception to the drug
definition in section 201(g)(1)(C). As a result, dietary supplements
that use structure/function claims may do so only under section
403(r)(6) of the act and are therefore subject to the disclaimer,
notification, and other requirements in that section and in FDA's
implementing regulation.
The agency acknowledges that it took a contrary position in the
September 1997 final rule preamble referred to in the comment. In that
preamble, FDA said that a dietary supplement could bear a structure/
function claim under the ``(other than food)'' exception to the
definition of ``drug'' in section 201(g)(1)(C) of the act, provided
that the claim was truthful, non-misleading, and derived from nutritive
value (see 62 FR 49859 at 49860, 49863, and 49864). However, the agency
has now reconsidered in light of the plain language of section 201(ff)
of the act and is revoking its statements on this subject in the
September 1997 preamble (i.e., the statements at 62 FR 49859 at 49860,
49863, and 49864 concerning structure/function claims for dietary
supplements under section 201(g)(1)(C)). It should be noted, however,
that the agency is not revoking its statements in that preamble
concerning structure/function claims for conventional foods under
section 201(g)(1)(C) of the act. As explained in the September 1997
preamble (62 FR 49859 at 49860), conventional foods may make structure/
function claims under section 201(g)(1)(C) of the act as long as such
claims are truthful, non-misleading, and derive from the nutritive
value of the food.
For a limited transition period, FDA does not intend to take
enforcement action against firms who have relied on the agency's
September 1997 final rule preamble statements to make a structure/
function claim for a dietary supplement under section 201(g)(1)(C) of
the act. To allow a reasonable time for
[[Page 1034]]
the necessary label changes, the transition period will last until the
applicable compliance date for the rest of the rule; i.e., small
businesses will have 18 months from publication to comply, and other
firms will have 12 months. As of the applicable compliance date, firms
that have been making structure/function claims under section
201(g)(1)(C) of the act must either remove the claim or comply with the
requirements of section 403(r)(6) of the act and Sec. 101.93, including
notifying FDA of the claim and relabeling to add the required
disclaimer. New structure/function claims are not subject to this
transition period; any firm that makes a structure/function claim in
the labeling of a dietary supplement after the effective date of this
rule must comply with section 403(r)(6) of the act and Sec. 101.93.
(96.) One comment objected to a sentence in the introductory
paragraph in the preamble to the proposed rule. The sentence stated
that, before DSHEA, certain claims could have rendered a product a
``drug'' under the act. The comment argued that even before DSHEA,
dietary supplements could make structure/function claims and not be
considered drugs. The comment said that section 201(g)(1)(C) of the act
expressly excluded food from the definition of drug and that dietary
supplements fell within the ``food'' exception. The comment
characterized DSHEA as limiting and restricting ``what had been the
unconditional right of dietary supplement marketers to make structure/
function claims.''
The agency agrees that before DSHEA, dietary supplements that were
also foods could make structure/function claims under section
201(g)(1)(C) of the act without being considered drugs. However, the
passage of DSHEA changed the regulatory framework for structure/
function claims on dietary supplements by adding sections 201(ff) and
403(r)(6) to the act. As explained in the response to the preceding set
of comments, section 201(ff) of the act provides that dietary
supplements are not considered food for purposes of section 201(g).
Therefore, dietary supplements may no longer make structure/function
claims under the ``food'' exception to the drug definition in section
201(g)(1)(C) of the act. FDA therefore agrees with the comment that in
one respect, DSHEA limited the ability of dietary supplement marketers
to make structure/function claims.
The sentence in the introductory paragraph of the preamble to the
proposed rule correctly stated that ``certain claims''--structure/
function claims for dietary supplements that were not also foods--could
have rendered the product a drug before the passage of DSHEA (63 FR
23624). Post-DSHEA, however, dietary supplements may make structure/
function claims under section 403(r)(6) of the act regardless of
whether they are also foods. Thus, although in one way DSHEA did limit
the ability of dietary supplement marketers to make structure/function
claims, it also significantly expanded the opportunity to make
structure/function claims in another way by removing the limitation
that dietary supplements must be foods to make structure/function
claims. Under section 403(r)(6) of the act, claims may be made for
nondisease effects of a dietary supplement on the structure or function
of the body, regardless of whether those effects are nutritive, as long
as the product is intended to supplement the diet as provided in
section 201(ff)(1) of the act.
2. Structure/Function Claims for Conventional Foods
(97.) Several comments sought consistency in the treatment of
conventional foods and dietary supplements with respect to structure/
function claims and health claims. Some of these comments contended
that this rule would permit dietary supplements to carry claims that
would be health claims if made for a conventional food. One comment
stated that differential treatment of foods and dietary supplements was
inconsistent with the Commission's recommendations. This comment
suggested that differential treatment would cause consumers to perceive
dietary supplements as better sources for safeguarding health than
conventional foods. One comment expressed the view that the rule should
apply to claims for conventional foods as well as dietary supplements
and requested FDA to clarify the rule's scope. Other comments said that
any structure/function claims that may be made for dietary supplements
may also be made for conventional foods. The comments explained that
the history of the act shows that claims that food affect the structure
or function of the body do not result in the food being classified as a
drug, citing the district court and appellate decisions in American
Health Products Co. v. Hayes, 574 F. Supp. 1498, 1501 (S.D.N.Y. 1983),
aff'd, 744 F.2d 912 (2d Cir. 1984). Another comment stated that
established case law shows that an article may be a food if it is used
primarily for taste, aroma, or nutritional value, but that nutritional
value is not required in all instances. One comment further noted that
FDA, when it implemented the labeling requirements for DSHEA (62 FR
49859, 49860, and 49861) said that it was committed to ``as much parity
between dietary supplements and conventional foods as is possible
within the statute'' and that FDA has recognized that a dietary
supplement may lawfully be in conventional food form, but must be
represented as a dietary supplement (citing 62 FR 49826 at 49837,
September 23, 1997).
Given this background, the comments argued that FDA cannot take
the position that a structure/function claim may be made for a
conventional food only if the effect derives from the food's
nutritional value. One comment added that the act does not distinguish
foods based on their nutritional value and that DSHEA considers
structure/function claims for all dietary ingredients to be
``statements of nutritional support.'' The comment said FDA, therefore,
should recognize that structure/function claims that can be made for
dietary ingredients when those ingredients are in dietary supplements
can also be made when those ingredients are in conventional food, but
added that the disclaimer statement and notification to FDA, as
required by section 403(r)(6)(C) of the act, apply only to dietary
supplements and not to conventional food. One comment said that
requiring structure/function claims for conventional foods to be
derived from the food's nutritional value would create a marketing
disparity and put conventional foods at a competitive disadvantage.
This rule applies to claims for dietary supplements only. Its
purpose is to implement section 403(r)(6) of the act, which applies to
dietary supplements only. Therefore, a detailed discussion of the
regulatory framework applicable to structure/function claims for
conventional foods, which are made under section 201(g)(1)(C) of the
act, is beyond the scope of the rule. FDA advises, however, that for
consistency, the agency is likely to interpret the dividing line
between structure/function claims and disease claims in a similar
manner for conventional foods as for dietary supplements. The agency
also notes that as discussed in the response to comment 1 in section
II.A of this document, FDA reaffirms the statements about structure/
function claims for conventional foods in the September 23, 1997 (62 FR
49859), final rule entitled ``Food Labeling: Nutrient Content Claims,
Health Claims, and Statements of Nutritional Support for Dietary
Supplements.'' As explained in that rule (62 FR 49859 at 49860, 49861,
and 49864), the fact that structure/function claims for conventional
foods
[[Page 1035]]
are limited to effects derived from nutritional value, while structure/
function claims for dietary supplements are not, is a result of
differences in the language of the exemption for foods in section
201(g)(1)(C) of the act, as interpreted by the courts (see Nutrilab,
Inc. v. Schweiker, 713 F.2d 335, 338 (7th Cir. 1983)), and the language
of section 403(r)(6) of the act.
(98.) One comment suggested revising the definition of ``disease
or health-related condition'' in proposed Sec. 101.14(a)(6) to include
a reference to Sec. 101.93, and also recommended revising the
definition of ``health claim'' at Sec. 101.14(a)(1) to be consistent
with Sec. 101.93. Currently, Sec. 101.14(a)(1) reads as follows:
Health claim means any claim made on the label or in labeling
of a food, including a dietary supplement, that expressly or by
implication, including ``third party'' references, written
statements (e.g., a brand name including a term such as ``heart''),
symbols (e.g., a heart symbol), or vignettes, characterizes the
relationship of any substance to a disease or health-related
condition. Implied health claims include those statements, symbols,
vignettes, or other forms of communication that suggest, within the
context in which they are presented, that a relationship exists
between the presence or level of a substance in the food and a
disease or health-related condition.
The comment would revise the definition to read as follows:
Health claim means any claim made on the label or in labeling
of a food, including a dietary supplement, that expressly or by
implication, including ``third party'' references, written
statements (e.g., a brand name that includes or implies a disease,
such as ``Raynaudin''), symbols, or vignettes, characterizes the
relationship of any substance to a disease or health-related
condition (e.g., disease-indicating electrocardiogram tracings,
pictures of organs that suggest prevention or treatment of a disease
state, the prescription symbol, or any reference to prescription
use). Implied health claims include those statements, symbols,
vignettes, or other forms of communication that suggest, within the
context in which they are presented, that a relationship exists
between the presence or level of a substance in the food and a
disease or health-related condition.
As stated in response to comment 51 of section II.I of this
document, FDA does not believe that Secs. 101.14(a)(1) and 101.93(g)
are inconsistent. As a result of the special regime for dietary
supplements under DSHEA, there may be some differences in the treatment
of dietary supplements and conventional foods under Sec. 101.14(a)(1).
3. Relationship Between Structure/Function Claims and Health Claims
(99.) One comment stated that the proposed rule ``improperly
distinguishes between other health-related claims and structure/
function claims.'' Relying in part on the introduction to section
403(r)(6) of the act (``For purposes of paragraph (r)(1)(B) * * *''),
the comment asserted that structure/function claims are a subset of the
claims authorized by section 403(r)(1)(B) of the act (health claims).
Consequently, because claims under section 403(r)(1)(B) of the act may
characterize the relationship of a nutrient to a disease, the comment
stated that FDA cannot preclude structure/function claims from making
any contextual references to diseases.
FDA disagrees with this comment. Structure/function claims are not
a subset of health claims because, clearly, there are claims about the
effect of a product on the structure or function of the body that are
not also health claims. To be a health claim, a claim must refer to the
relationship between a food substance and a disease or health-related
condition. FDA interprets ``health-related condition'' to mean a state
of health leading to disease. Claims such as ``calcium builds strong
bones'' are not health claims because they do not refer explicitly or
implicitly to any disease or health-related condition. Therefore, the
comment is based on an invalid premise.
(100.) One comment requested that FDA revise Sec. 101.93(f) to
state that the requirements of section 403(r)(6) of the act, e.g., use
of the disclaimer and substantiation, apply only to structure/function
claims that fall within the definition of a ``health claim'' in
Sec. 101.14(a)(1) and (a)(5). According to this comment, the
introduction to section 403(r)(6) of the act (``For purposes of
paragraph (r)(1)(B) * * *'') establishes that structure/function claims
that do not fall within the definition of health claims are not subject
to section 403(r)(6), and may be made without complying with any of its
requirements.
FDA does not agree and, in fact, believes that the opposite is
true. As explained elsewhere in this document and in the proposed rule,
structure/function claims that fall within the definition of health
claims, or that otherwise constitute disease claims, do not fall within
the scope of claims authorized under section 403(r)(6) of the act, but
other structure/function claims do fall within the scope of section
403(r)(6) and are subject to its requirements. Adopting the
interpretation advocated by the comment would bring about illogical
results for dietary supplement labeling claims in two ways. First,
structure/function claims that are also health claims would not be
subject to the health claims prior authorization requirements, but
instead could be made simply by meeting the requirements of section
403(r)(6) of the act and FDA's implementing regulations. The language
in section 403(r)(6) of the act excluding claims to affect disease from
the coverage of that section demonstrates that Congress made a public
health judgment that claims promoting dietary supplements for disease
uses should continue to require premarket authorization. It would not
make sense for Congress to exclude labeling claims pertaining to
disease uses in one part of section 403(r)(6) of the act, while
permitting such claims in another paragraph of the same section.
Moreover, the interpretation advocated by the comment would lead to
confusing and contradictory labeling. A dietary supplement that bears a
health claim--a claim that, by definition, is a claim that a substance
in the supplement in some way has an effect on a disease--would also
have to bear a contradictory disclaimer that it is not intended to
treat, mitigate, or prevent any disease. Second, structure/function
claims that are not also health claims would not be authorized under
section 403(r)(6) of the act at all. In fact, a structure/function
claim on a dietary supplement would subject it to drug regulation
because, as explained in the response to comment 1 in section II.A of
this document, section 403(r)(6) of the act is the only provision that
authorizes the use of structure/function claims on dietary supplements.
The introductory language in section 403(r)(6) (``For purposes of
[section 403](r)(1)(B) * * *'') does not support the interpretation
advocated in the comment. If Congress had wanted to subject only
structure/function claims that are also health claims to section
403(r)(6) of the act, it could have done so much more directly by using
language such as ``A statement for a dietary supplement may be made if
* * * and the statement is a statement of the type governed by
paragraph (r)(1)(B).'' The ambiguity of the ``For purposes of
(r)(1)(B)'' language is well demonstrated by the diametrically opposed
interpretations adopted by this comment and the preceding comment. FDA
interprets this language as a caution that the category of claims
covered by section 403(r)(6) of the act is not to be interpreted as
coextensive with health claims, the category covered by section
403(r)(1)(B) of the act. Congress may have been concerned that the
health claims category would swallow the category of claims under
section 403(r)(6) of the act because all claims
[[Page 1036]]
under section 403(r)(6) could be characterized as referring to a
``health-related condition'' if that term were defined broadly as ``a
state of health.'' The result would have been that all structure/
function claims, as claims about the relationship between a substance
and a health-related condition, would also have been health claims and
would have required premarket authorization. By including the
introductory language, Congress effectively forestalled such an
interpretation.
(101.) Another comment said the proposed rule does not distinguish
between structure/function statements that assert health claims and
those that do not, and said the failure to make this distinction would
mean that more products would be subject to the rule than necessary.
FDA does not agree that the rule fails to distinguish between
structure/function claims that do and do not assert health claims. On
the contrary, the rule makes clear that only structure/function claims
that do not assert health claims may be made under section 403(r)(6) of
the act. To the extent that the comment may be suggesting that
structure/function claims that are also health claims should be exempt
from the health claims authorization requirements, the agency disagrees
for the reasons given in the response to the previous comment.
B. Miscellaneous Legal Issues
(102.) Two comments said the proposed rule violated the
Administrative Procedure Act because it was arbitrary and capricious,
on two grounds. One comment asserted that FDA failed to consider an
important aspect of the problem of distinguishing between drug claims
and dietary supplement claims: The application of the ``general well-
being'' provision of section 403(r)(6) of the act. The comment argued
that FDA should have considered whether claims relating to normal body
functions might qualify as ``general well-being'' claims under section
403(r)(6) of the act before deciding to regulate them as disease
claims. The comment also argued that FDA's explanation of the need for
the proposed rule ran counter to the evidence before the agency, in
that the agency's actions on notifications of claims under section
403(r)(6) of the act did not support a need for further regulation.
The ``general well-being'' provision of section 403(r)(6) of the
act authorizes statements in dietary supplement labeling that describe
``general well-being from consumption of a nutrient or dietary
ingredient'' (section 403(r)(6)(A) of the act). FDA did not consider
whether statements were authorized under this provision in developing
the proposed rule because the purpose of the rule was to implement the
structure/function provisions of section 403(r)(6)(A) of the act, not
other provisions. However, consideration of this provision as applied
to normal body functions would not have led to a different result. The
criteria in the rule were developed to identify claims that refer
directly or indirectly to an effect on disease and do not encompass
claims that refer only to general well-being. Claims relating to normal
body functions are authorized under the rule.
The comment's argument about the use of FDA's actions on
notifications of claims under section 403(r)(6) of the act to justify
the rule is addressed in comment 4 of section II.A of this document.
(103.) One comment claimed that the proposal does not require FDA
to show any evidence of a manufacturer's intent to find that a dietary
supplement claim constitutes an illegal drug claim. The comment argued
that proposed Sec. 101.93(g)(2)(ii), (g)(2)(iii), (g)(2)(viii), and
(g)(2)(x) run afoul of the recent appellate decision in Brown &
Williamson Tobacco Corp. v. FDA, 153 F.3d 155 (4th Cir. 1998),
contending that ``a product is not a drug merely because a consumer
uses it as one'' and that ``there must be proof as to the
manufacturer's intent.'' The comment also cited National Nutritional
Foods Ass'n v. Mathews, 557 F.2d 325 (2d Cir. 1977), to support its
position that a manufacturer's intent, as determined from labeling or
advertising, is the primary factor in determining whether a product is
intended to treat a disease.
Although FDA disagrees with the Brown & Williamson decision and is
awaiting the outcome of Supreme Court review, this rule does not depend
on the resolution of the legal issues in that case. The focus of the
rule is on express and implied claims made by the vendor in labeling.
None of the provisions of the rule, including those mentioned in the
comment, rely on consumer use as a standard for determining whether the
product is intended to treat or prevent disease.
The rule is consistent with the decision in National Nutritional
Foods Ass'n v. Mathews, in which the court said, ``FDA is not bound by
the manufacturer's subjective claims of intent but can find actual
therapeutic intent on the basis of objective evidence. Such intent also
may be derived or inferred from labeling, promotional material,
advertising, and `any other relevant source''' (557 F.2d at 334
(citations omitted)). See also Sec. 201.128 (listing evidence FDA will
consider in determining the intended use of a drug).
(104.) One comment said that the proposal must be withdrawn
because, contrary to section 403(r)(6) of the act, it gives
manufacturers the burden to prove that a claim is not a drug claim
when, in fact, FDA has the burden, by a preponderance of relevant
evidence, to establish that a dietary supplement is misbranded. The
comment cited two court opinions, United States v. 29 Cartons * * * an
Article of Food (Oakmont), 987 F.2d 33 (1st Cir. 1993) and United
States v. An Article of Food * * * Viponte Ltd. Black Currant Oil, 984
F.2d 814 (7th Cir. 1993), for the proposition that, before DSHEA was
enacted, courts had invalidated an FDA enforcement theory that shifted
the burden of proof to manufacturers.
FDA disagrees with this comment. Although the comment is correct
that FDA has the burden of proving that a dietary supplement--or, in
fact, any food--is misbranded, the rule does not give manufacturers the
burden of proving that a claim is not a drug claim. The rule does not
shift the burden of proof in an enforcement action but rather sets
forth criteria for what claims are disease claims that may subject a
product marketed as a dietary supplement to regulation as a drug.
The two cases cited in the comment are inapposite. They concern
FDA's efforts to regulate certain dietary ingredients as food additives
and do not have any relevance to claims issues.
(105.) One comment said that the proposed rule is inconsistent
with the act and congressional intent, arguing that, by enacting DSHEA,
Congress had taken steps to reverse FDA's ``overly restrictive''
approach towards claims and had commanded the agency to expand, rather
than restrict, the amount of health information permitted on dietary
supplement labels and labeling. According to the comment, the proposal
``directly and substantially violates the overall statutory scheme and
the expressed legislative intent'' and FDA ``has no authority to
proceed with the rulemaking without a grant of authority from Congress
in light of the Act's language and Congressional intent.''
The agency disagrees with this comment and believes that the rule
is consistent with the act and congressional intent. Although Congress,
in enacting DSHEA, did expand the scope of information in dietary
supplement labeling by providing for claims to affect the structure or
function of the body and the other types of claims authorized by
[[Page 1037]]
section 403(r)(6) of the act, Congress also explicitly limited
statements under section 403(r)(6) to those that do not claim to
``diagnose, mitigate, treat, cure, or prevent a specific disease or
class of diseases.'' This rule does not create new restrictions but
merely implements the provisions of section 403(r)(6) of the act. FDA
has authority to issue implementing regulations under section 701(a) of
the act, which authorizes the agency to issue regulations for the
efficient enforcement of the act.
(106.) One comment declared that FDA has no legal basis to include
a broad variety of implied claims.
FDA disagrees with this comment. The agency has regulated implied
claims in labeling for many years, in many contexts. (See, e.g., 21 CFR
104.5(b) and (d) (prohibiting certain implied claims relating to
compliance with nutritional quality guidelines); 21 CFR 101.13(a)
(classifying implied claims to characterize the level of a nutrient in
food as nutrient content claims subject to the same requirements as
express claims); 21 CFR 101.95 (prescribing conditions under which
implied claims of freshness may be made for foods); 21 CFR 201.10(c)(3)
(prohibiting use in ingredient statement of fanciful drug or ingredient
names that falsely imply that the drug or ingredient has some unique
effectiveness or composition); 21 CFR 201.302(c) (prohibiting implied
claims that drugs for internal use that contain mineral oil are for
administration to infants). The agency has also regulated implied
claims in prescription drug advertising. (See, e.g., Sec. 202.1(a)(3)
(21 CFR 202.1(a)(3)) (prohibiting use in advertising of fanciful
product or ingredient names that falsely imply that the drug or
ingredient has some unique effectiveness or composition);
Sec. 202.1(e)(6)(v) (prohibiting implied claims that a study represents
more widespread experience with the drug than it actually does).) More
specifically, the agency has repeatedly taken the position that implied
disease claims in labeling subject a product to regulation as a drug.
In the animal drug context, Sec. 500.52 (21 CFR 500.52) provides that
the use of certain terms in the labeling of products intended for use
in or on animals implies that the product is capable of a therapeutic
effect and causes the product to be a drug within the meaning of
section 201(g) of the act. In the human drug context, Sec. 201.56(c)
(21 CFR 201.56(c)) prohibits ``implied claims or suggestions of drug
use'' in prescription drug labeling unless the product has been shown
to be safe and effective for the implied or suggested use. (See also
Sec. 310.530 (21 CFR 310.530) (use of the word ``hormone'' in labeling
is an implied drug claim).) Moreover, courts have upheld FDA's
authority to regulate implied drug claims. (See, e.g., United States v.
Storage Spaces Designated Nos. ``8'' and ``49'', 777 F.2d 1363, 1366 &
n. 5 (9th Cir. 1985), cert. denied, 479 U.S. 1086 (1987); Pasadena
Research Labs., Inc. v. United States, 169 F.2d 375, 383 (9th Cir.),
cert. denied, 335 U.S. 853 (1948); United States v. Six Dozen Bottles *
* * ``Dr. Peter's Kuriko'', 158 F.2d 667, 669 (7th Cir. 1947); United
States v. John J. Fulton Co., 33 F.2d 506, 507 (9th Cir. 1929); Bradley
v. United States, 264 F. 79, 81-82 (5th Cir. 1920); 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. 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).)
(107.) Many comments argued that the proposed rule ignored the
Supreme Court decision in Daubert v. Merrell Dow Pharmaceuticals, Inc.,
509 U.S. 579 (1993).
FDA disagrees with these comments. The comments did not explain
how the rule was contrary to or even affected by the decision. Daubert
involved the admissibility of scientific evidence in a judicial
proceeding under the Federal Rules of Evidence. This rulemaking does
not present issues regarding the admissibility of evidence in any
proceeding, judicial or administrative, nor does it address expert
testimony (which was at issue in Daubert). Thus, FDA does not agree
that the rule ``ignores'' or is contrary to the Daubert decision.
C. Constitutional Issues
1. First Amendment
(108.) Several comments focused on the First Amendment. One
comment argued that the rule violates the First Amendment because it is
more restrictive than is necessary to advance FDA's interests. The
comment conceded that the government may regulate or prohibit
commercial speech if the speech is inherently false, deceptive, or
misleading, but argued that the government can only restrict commercial
speech that is not false, deceptive, or misleading if the government
shows that the restriction directly and materially advances a
substantial state interest in a manner that is no more extensive than
necessary to serve that interest (citing Ibanez v. Florida Dept. Of
Bus. & Prof'l Regulation, 512 U.S. 136, 142 (1994); Central Hudson Gas
& Elec. Corp. v. Pub. Serv. Comm'n, 447 U.S. 557, 566 (1980)). The
comment argued that not all structure/function claims prohibited under
the proposed rule are inherently false or misleading and that if FDA
does not review the evidence for a claim, the claim does not become
false or misleading. Although the comment admitted that FDA has a
substantial interest in regulating the safety, efficacy, and labeling
of dietary supplements in order to protect the public health, the
comment claimed that the regulation was more extensive than necessary.
The comment argued that a disclaimer is ``the constitutionally mandated
method of regulating commercial speech.''
Other comments said the proposed rule violates the First Amendment
because, using the analysis in Central Hudson Gas & Electric Corp. v.
Public Service Commission, 447 U.S. 557 (1980), it is not narrowly
tailored to meet FDA's interests and does not directly and materially
advance the agency's interests. In general, these comments offered
various reasons why the proposed rule did not survive scrutiny under
Central Hudson. For example, under Central Hudson, the government may
regulate commercial speech that concerns unlawful activity or is
misleading if, among other things, the government asserts a substantial
interest in support of its regulation. In brief, the comments said FDA
failed to assert a substantial interest or construed the government's
interest to be Congress' interest in increasing the amount of
information to consumers. Others said that, contrary to Central Hudson,
the proposed rule was not narrowly tailored and suppressed more speech
than necessary to protect a possible government interest in protecting
consumers from fraud and protecting public health and either suggested
alternatives or said FDA should consider less restrictive alternatives.
Some comments said the proposal also did not advance the asserted
government interest because it blurred, instead of clarified, the line
between drug and dietary supplement claims.
One comment also asserted that there is no substantial government
interest involved, because FDA has not shown a concern for consumer
safety or a danger to public health; according to this comment, the
proposed rule was a response to confusion by manufacturers and
consumers about what claims are permitted.
Some comments also argued that FDA has not shown that the claims
are misleading or that the commercial speech covered by the proposed
rule is
[[Page 1038]]
inherently misleading. One comment asserted that, if statements were
untruthful or misleading, DSHEA would have prohibited them.
Another comment said the proposal ``trenches on'' the First
Amendment because consumers have the right to receive, and
manufacturers have the right to express, non-misleading information.
The comment cited Washington Legal Foundation v. Friedman, 13 F. Supp.
2d 51 (D.D.C. 1998) for this proposition. Another comment cited the
Washington Legal Foundation decision to argue that the proposed rule
would ``impermissibly curtail'' the flow of information to consumers.
The comment suggested that less restrictive alternatives, such as
``allowing implicit, but not explicit, claims,'' establishing
``categories of diseases that clearly denoted drug claims'' or
identifying terms that connote ``treatment,'' ``cure,'' or
``mitigation'' exist.
A few comments simply claimed that the proposal violates the First
Amendment because it would decrease the amount of scientific
information on labels and labeling or because it represents a ``prior
restraint'' on health claims. Other comments objected to particular
provisions of the proposed rule on First Amendment grounds, notably
proposed Sec. 101.93(g)(2)(iv)(C), which provided that citation of the
title of a scientific reference in dietary supplement labeling would be
a disease claim if the title referred to a disease use of the product.
Several comments said that this provision of the proposed rule would
violate the First Amendment as an unlawful restraint on commercial
speech. Others characterized the proposed provision as simply a
restriction on freedom of speech, whether the restriction was on the
right of companies to provide the information or on the right of
consumers to receive the information. One comment said that references
to publication titles could be prohibited if they were misleading, but
that the rule should not contain a blanket prohibition. Some comments
added that the agency should reconsider its position on this provision
in light of Washington Legal Foundation v. Friedman.
Finally, a comment said that the proposal was contrary to the
decision of the U.S. Court of Appeals for the District of Columbia
Circuit in Pearson v. Shalala, 164 F.3d 650 (D.C. Cir. 1999). According
to the comment, the court of appeals' First Amendment ruling in Pearson
requires the agency to permit health claims that do not satisfy the
``significant scientific agreement'' standard as long as the claim can
be rendered non-misleading by requiring a disclaimer. According to the
comment, the court's decision also requires FDA to further define the
``significant scientific agreement'' standard for authorizing dietary
supplement health claims. The comment said that the proposed rule was
premature in light of the need to amend the health claims regulations
to conform to the Pearson decision. The comment also argued that, in
light of Pearson, FDA may not issue a final rule that prohibits disease
claims but rather must choose the less restrictive alternative of
permitting such claims provided that they are accompanied with
disclaimers.
FDA does not believe that the rule violates the First Amendment.
The rule does not prohibit any speech; rather, it clarifies the
circumstances under which FDA will consider a certain type of speech--
labeling claims--to be evidence of intended use as a drug, absent
health claim authorization. Thus, the rule does not regulate speech as
such, but rather as evidence of intended use. The use of speech as
evidence of a company's intended use for its products is constitutional
because ``[t]he First Amendment * * * does not prohibit the evidentiary
use of speech * * * to prove motive or intent'' (Wisconsin v. Mitchell,
508 U.S. 476, 489 (1993).) (See also Village of Hoffman Estates v.
Flipside, 455 U.S. 489, 495-96 (1982) (upholding village ordinance
treating the proximity of drug-oriented literature as evidence that
items were marketed for use with illegal drugs). Because it is the
intent and not the speech that triggers a regulatory burden on the
speaker, there is no First Amendment violation. (See Wisconsin v.
Mitchell, 508 U.S. at 489; United States v. Articles of Drug * * * B-
Complex Cholinos Capsules, 362 F.2d 923, 927 (3d Cir. 1966) (no
impingement on free speech for FDA to use statements made by a lecturer
employed by a manufacturer as evidence of the manufacturer's intent
that its products be used for therapeutic purposes).)
Even if the rule were viewed as a direct restriction on speech, it
would not violate the First Amendment. The marketing in interstate
commerce of a drug that has not been determined by FDA to be safe and
effective is illegal (see section 301(a) and (d) of the act (21 U.S.C.
331(a) and (d)) and 505 of the act. Thus, labeling claims that promote
a dietary supplement for disease uses promote the product for use as an
unapproved new drug, which is illegal. Speech promoting an illegal
activity may be restricted without violating the First Amendment
(Central Hudson, 447 U.S. at 563-564). In Pittsburgh Press Co. v.
Pittsburgh Comm'n on Human Relations, 413 U.S. 376 (1973), the Supreme
Court held that an advertisement could be prohibited where it indicated
that the advertiser was likely to have an illegal intent while engaging
in the proposed transaction (id. at 389). There, as here, ``the
restriction * * * is incidental to a valid limitation on economic
activity'' (id.).
Nor does the rule create an unconstitutional prior restraint. FDA
does not believe that the regulations in Sec. 101.93(f) and (g) are
properly analyzed as a prior restraint at all. As explained previously,
the regulations do not restrict speech but rather treat it as evidence
of a product's intended use. Using speech to infer intent does not
violate the First Amendment (Wisconsin v. Mitchell, 508 U.S. 476, 489
(1993)). Thus, the regulations do not prevent speech from happening,
but, as evidence of intended use, they determine the consequences that
result from certain types of speech. (See Village of Hoffman Estates v.
Flipside, 455 U.S. at 495-96 (rejecting head shop's ``exorbitant''
claim that village ordinance treating the proximity of drug-oriented
literature as evidence of intended use was a prior restraint).)
Although the regulations cannot themselves be considered as a
direct prior restraint, it is true that claims classified as disease
claims under the regulations are subject to prior authorization
requirements that could be considered prior restraints--namely, the
prior authorization requirement for dietary supplement health claims
and the new drug approval requirements that are triggered in the
absence of health claim authorization. In both cases, a disease claim
cannot be made until FDA has evaluated the safety of the product and
the evidence supporting the claim. However, labeling claims are
commercial speech, and the Supreme Court has indicated that the prior
restraint doctrine may not apply to commercial speech. (See Central
Hudson, 447 U.S. at 571 n.13 (``[C]ommercial speech is such a sturdy
brand of expression that traditional prior restraint doctrine may not
apply to it.''; Virginia State Bd. of Pharmacy v. Va. Citizens Consumer
Council, 425 U.S. 748, 771-72 n.24 (1976) (greater objectivity and
hardiness of commercial speech may make prior restraint doctrine
inapplicable). Commercial speech is ``sturdy'' because of its profit
motive. ``[S]ince advertising is the sine qua non of commercial
profits, there is little likelihood of its being chilled by proper
regulation and forgone entirely'' (Virginia State Bd. of Pharmacy, 425
U.S. at 771-72 n.24). The same is true
[[Page 1039]]
of labeling. The Supreme Court has expressed approval of prior review
requirements in commercial speech cases. (See Shapero v. Kentucky Bar
Ass'n, 486 U.S. 466, 476 (1988) (lawyer may be required to file
solicitation letter with State in advance, to give it ``ample
opportunity to supervise mailings and penalize actual abuses'');Central
Hudson, 447 U.S. at 571 n.13 (State may require ``a system of
previewing advertising campaigns'').)
If the prior authorization requirement for dietary supplement
health claims and the approval requirement for new drugs were to be
considered prior restraints, they would be constitutional prior
restraints. The only court of appeals to address the issue in the
health claims context ruled that the health claims authorization
process is not an unconstitutional prior restraint. In a recent case
challenging the NLEA and FDA's health claim regulations for dietary
supplements, the U.S. Court of Appeals for the Second Circuit held that
the prior restraint doctrine did apply, but it went on to uphold the
statute and regulations based on consideration of the Central Hudson
factors. Nutritional Health Alliance v. Shalala, 144 F.3d 220, 227-28
(2d Cir.), cert. denied, 119 S. Ct. 589 (1998). In Nutritional Health
Alliance, the Second Circuit held that the health claims authorization
process is ``sufficiently narrowly tailored'' and has adequate
procedural safeguards--including a deadline for final agency action, a
decision making standard to constrain the agency's discretion, and
provision for development of a record for judicial review--to render it
constitutionally valid (144 F.3d at 228; see Sec. 101.70 (procedures
for petitioning for a health claim)). In upholding the regulatory
scheme, the court also stressed that matters of public health and
safety were involved (144 F.3d at 228). The same considerations that
the court in Nutritional Health Alliance relied on also operate in the
new drug approval context: Matters of public health and safety are
involved, and the act and implementing regulations provide many
procedural safeguards, including a deadline, a decision making
standard, and the development of an record for judicial review (see
section 505(c)(1), (d), and (h) of the act and; 21 CFR 314.200.)
Moreover, as far as FDA is aware, the constitutionality of the new drug
approval process has never been challenged on First Amendment grounds.
Therefore, FDA does not believe that the prior restraint argument in
the comments has merit.
Many of the comments assumed that the test for restrictions on
commercial speech set forth by the Supreme Court in Central Hudson
applies. FDA believes that it is not necessary to reach the Central
Hudson test because the rule is constitutional under Wisconsin v.
Mitchell, Pittsburgh Press, and Village of Hoffman Estates; however,
the rule also easily passes muster under the four-part test in Central
Hudson. Under that test, the first question is whether the commercial
speech at issue is false, misleading, or concerns unlawful activity,
because such speech is beyond the First Amendment's protection and may
be prohibited. If the speech is truthful, non-misleading, and concerns
lawful activity, the government may nonetheless regulate it if the
government interest asserted to justify the regulation is substantial;
the regulation directly advances the asserted governmental interest;
and the regulation is no more extensive than necessary to serve the
government interest (Central Hudson, 447 U.S. at 566). The Supreme
Court has explained that the last element of the test is not a ``least
restrictive means'' requirement, but rather requires narrow tailoring--
``a fit that is not necessarily perfect, but reasonable'' between means
and ends (Board of Trustees of the State Univ. of N.Y. v.Fox, 109 S.
Ct. 3028, 3032-35 (1989)). In subsequent decisions, the Court has also
clarified that ``misleading'' in the first element of the test refers
to speech that is inherently or actually misleading. Thus, if the
speech to be regulated is not inherently or actually misleading, the
remainder of the test applies. (See In re R.M.J., 455 U.S. 191, 203
(1982).)
As previously discussed, FDA believes that claims for disease uses
that have not been found to be safe and effective are speech related to
an unlawful activity, and therefore there is no need to reach the
remaining elements of the Central Hudson test. The agency also
considers such claims inherently misleading because, when accompanied
by a disclaimer that directly contradicts the claim by stating that the
product is not intended to have an effect on disease, they are
inherently likely to confuse consumers rather than provide them with
useable information. Speech that is ``more likely to deceive the public
than to inform it'' is not protected by the First Amendment (Central
Hudson, 447 U.S. at 563). If not inherently misleading, claims for
disease uses that have not been found to be safe and effective are at
least potentially misleading because of the confusion caused by the
disclaimer. Such claims also may lead consumers to believe that the
product has benefits in treating or preventing disease, even if that is
not the case.
Even if the remaining elements of the Central Hudson test are
reached, the rule and the statutory provisions that it implements are
constitutional. As previously noted, this rule restricts no speech
directly. Rather, it determines what types of speech in dietary
supplement labeling will trigger other statutory provisions and
regulations that may be considered restrictions on speech. To the
extent that this rule, the statute, and the drug and health claim
regulations restrict speech by requiring either health claim
authorization or new drug approval before a business may make a disease
claim for a dietary supplement, that restriction directly advances the
substantial government interest in protecting and promoting the public
health by helping to ensure that products intended to have an effect on
a disease are safe and effective for that intended use. That interest
is an interest both in preventing direct harm from such products--i.e.,
protecting the public from adverse events that such products might
cause--and in preventing the indirect harm to health that is caused
when an ill person foregoes medical care in favor of ineffective self-
treatment.
Requiring prior FDA review and authorization of disease claims
ensures that such claims will be evaluated by a public health agency
that has scientific and medical expertise so that only products that
are safe and effective will be permitted to be sold for therapeutic
purposes. As a government agency with no financial stake in either
permitting or denying claims, FDA is in a position to evaluate the
strength of the safety and efficacy evidence objectively.
The rule and the other components of the regulatory framework for
drugs and health claims also advance the related substantial government
interest in protecting consumers from fraud. If products are marketed
for disease uses only after they have been demonstrated to be safe and
effective for such uses, consumers will not suffer economic harm from
spending money on worthless remedies.
Moreover, the rule is not more extensive than necessary. The
agency does not believe that the alternatives mentioned in the
comments, or any other alternative, would adequately further its
substantial interest in protecting and promoting public health by
ensuring the safety and efficacy of products intended to have an effect
on disease. For example, allowing implicit disease claims, but not
explicit ones, would merely allow companies to do indirectly what they
cannot do
[[Page 1040]]
directly--to market products for disease uses without demonstrating
their safety and efficacy. Likewise, identifying specific terms that
connote treatment, cure, or mitigation would not accomplish the goal of
requiring proof of the safety and effectiveness of products marketed
for disease uses. Merely regulating synonyms for those terms would
leave unregulated those claims that achieve the same effect without
using such a synonym, such as the claims ``herbal Prozac'' and ``for
cancer.'' The suggestion in one comment that FDA establish ``categories
of diseases that clearly denote drug claims'' is not a workable
alternative either. Section 403(r)(6) of the act provides that the
category of structure/function claims excludes claims to affect any
category of disease, not just certain categories.
Permitting disease claims under section 403(r)(6) of the act as
long as they are accompanied with a disclaimer, as suggested by the
comment that cited the Pearson decision, would be an untenable
alternative. If companies could avoid the time and expense of complying
with the new drug provisions of the act merely by attaching a
disclaimer to a disease treatment or prevention claim, the longstanding
system of drug regulation in this country would be eviscerated, with
serious public health consequences. Nothing in Pearson requires such a
result. Indeed, the Pearson court recognized that its ruling did not
apply to drugs (164 F.3d at 656 n. 6). Because the act classifies
products on the basis of intended use, dietary supplements that make
disease claims are drugs, unless the disease claim is also an
authorized health claim for which the product qualifies (see section
201(g)(1) of the act).
The Washington Legal Foundation decision is not to the contrary.
That case involved the dissemination of information on ``off-label''
(unapproved) uses for approved drugs and devices to physicians by means
of scientific and educational symposia, reprints, and textbooks. The
U.S. District Court for the District of Columbia held certain FDA
guidance documents that described acceptable ways of disseminating such
information unconstitutional under the Central Hudson test. While
recognizing the substantial government interest in having off-label
uses for drugs and devices found to be safe and effective by FDA, the
court held that the guidance documents violated the First Amendment
because it believed that they ``restricted'' speech in a manner that
was more extensive than necessary to further that interest. (See 13 F.
Supp. 2d at 73.) (Subsequent to the 1998 decision cited by the
comments, the court rendered another decision adverse to FDA
(Washington Legal Foundation v. Henney, 1999 WL 557679 (D.D.C. July 28,
1999)). That decision concerned the constitutionality of certain
provisions of the FDA Modernization Act of 1997 involving the same
subject matter as the guidance documents, and the court's First
Amendment rationale was similar to its rationale in the 1998 decision
pertaining to the guidance documents.)
FDA disagrees with the district court decision in Washington Legal
Foundation and has appealed. In any event, however, the outcome in
Washington Legal Foundation does not determine the outcome here for
several reasons. First, in Washington Legal Foundation the court found
a less restrictive alternative that it concluded would more precisely
address the government's regulatory concerns: Requiring manufacturers
who disseminate information about off-label uses to physicians through
scientific reprints or educational symposia to disclose: (1) Their
interest in drugs or devices that are the subject of such activities,
and (2) the fact that the use discussed has not been approved by FDA.
Here, as explained previously, there are no less restrictive
alternatives to this rule that would further the government's
substantial public health interest. Second, in Washington Legal
Foundation physicians were the intended audience of the commercial
speech at issue. In contrast, consumers are the primary audience for
dietary supplement labeling. Although the marketplace includes
consumers of varying levels of sophistication, the average consumer
does not possess the medical and scientific expertise necessary to
evaluate claims about the effect of a product on disease. (See American
Home Products Corp. v. FTC, 695 F.2d 681, 698 (3d Cir. 1983);
Association of Nat'l Advertisers, Inc. v. Lungren, 44 F.3d 726, 733-34
(9th Cir. 1994), cert. denied, 516 U.S. 812 (1995).) Finally, in
Washington Legal Foundation, it was undisputed that the products
involved were drugs (or, in some cases, devices) to be used in treating
or preventing disease. In contrast, the purpose of this rule is to
distinguish between products that are intended to affect disease and
products that are not.
The agency does not believe this rule is premature in light of the
need to reassess the regulatory regime for health claims under Pearson.
Since health claims and structure/function claims are regulated
separately, there is no need to wait for any post-Pearson changes for
health claims to be complete before proceeding with this rulemaking on
structure/function claims. Moreover, since the agency has decided not
to amend the health claims regulations as part of this rulemaking,
there is no potential conflict between the two.
The First Amendment issues raised in comments on
Sec. 101.93(g)(4)(iii) (proposed Sec. 101.93(g)(2)(iv)(C)), concerning
citations to scientific references in labeling, are not different from
those raised by comments on the rule as a whole and are addressed in
the preceding analysis. FDA also notes that, as discussed elsewhere in
this document, Sec. 101.93(g)(4)(iii) has been revised to narrow the
circumstances under which the agency will consider citations to
scientific references in labeling to be disease claims.
(109.) Another comment further asserted that the prohibition
against implied disease claims violates the First Amendment because it
does not advance the safety of dietary supplements. The comment
acknowledged that some dietary supplements ``may present serious safety
risks,'' but said ``these risks will not be lessened by prohibiting
truthful, non-misleading structure/function claims * * *.'' The comment
suggested that other provisions in DSHEA address the safety of dietary
supplements and that FDA can bring an enforcement action if it has
safety concerns.
FDA agrees with this comment in part and disagrees in part. The
agency agrees that prohibiting truthful, non-misleading structure/
function claims would not lessen the safety risks posed by some dietary
supplements. The rule is aimed at the safety risks posed by unapproved
drug claims and unauthorized health claims on dietary supplements.
Unproven disease claims on a product marketed as a dietary supplement
may induce consumers to treat themselves with the supplement instead of
seeking treatments that are known to be effective. Such claims may also
dissuade consumers from seeing a doctor. These are very real safety
risks. To the extent that safety risks are caused by the composition of
a dietary supplement rather than by claims made for it, the agency
agrees that other provisions in DSHEA and the act are the appropriate
remedy.
2. Equal Protection
(110.) One comment claimed the rule violates the equal protection
clause of the Fourteenth Amendment because it supposedly gives more
protection to the ``labeling rights and speech'' of pharmaceutical
manufacturers than to dietary supplement manufacturers.
[[Page 1041]]
First, it should be noted that the equal protection clause of the
Fourteenth Amendment applies only to the States, not to the Federal
Government. However, the due process clause of the Fifth Amendment
contains an equal protection component that is equivalent to the equal
protection clause of the Fourteenth Amendment (Schweiker v. Wilson, 450
U.S. 221, 226 & n. 6 (1981)). Even if the comment is interpreted to
refer to equal protection under the Fifth Amendment, FDA disagrees with
it. First, the comment does not explain in what manner the rule gives
more protection to the labeling rights and speech of pharmaceutical
manufacturers than to those of dietary supplement manufacturers.
Second, even if the rule does treat these two classes of manufacturers
differently, treating different regulated groups differently does not
in itself violate the equal protection clause. Unless a regulatory
classification jeopardizes the exercise of a fundamental right or
classifies upon inherently suspect grounds such as race or religion, it
is subject to the least exacting form of equal protection review:
Whether the classification it draws bears a rational relationship to a
legitimate government interest. (See Nordlinger v. Hahn, 505 U.S. 1, 10
(1992).)
This rule neither jeopardizes the exercise of a fundamental right
nor creates a suspect classification. The purpose of the rule is to
clarify the statutory distinction between products that are intended
for use in treating or preventing disease and products that are
intended for use in affecting the structure or function of the body.
Products intended to treat or prevent disease are subject to regulation
as drugs, unless they qualify for an authorized health claim. Products
intended to affect the structure or function of the body may be
regulated as dietary supplements, subject to certain conditions.
Products regulated as drugs must meet strict requirements for a
premarket demonstration of safety and efficacy (see sections 201(p) and
505 of the act); these requirements do not apply to dietary
supplements. The distinction that the statute and this rule draw
between products that are intended to have an effect on disease and
those that are intended only to affect the structure or function of the
body is clearly rationally related to the legitimate government
interest of ensuring that products intended to have an effect on a
disease are safe and effective for that intended use.
3. Takings Under the Fifth Amendment
(111.) Several comments claimed that the proposal violates the
Takings Clause of the Fifth Amendment because it would prohibit the use
of specific terms that now appear in product names, trademarks, trade
names, symbols, and company logos, or would harm companies that use
such terms in their corporate names. One comment said FDA must provide
compensation for each taking, but that the proposal failed to do so.
FDA disagrees with these comments. The Takings Clause forbids the
government from taking private property for public use without just
compensation. However, FDA believes that no taking will occur as a
result of this rule.
The first issue to be considered is whether the categories of
names, words, and symbols identified in the comments on this issue are
property within the meaning of the Takings Clause. The Constitution
itself does not define what qualifies as property. Rather, ``existing
rules or understandings derived from an independent source,'' such as
State or Federal law, define the interests that qualify for protection
as property under the Fifth Amendment (Lucas v. South Carolina Coastal
Council, 505 U.S. 1003, 1030 (1992)).
The categories of names, words, and symbols mentioned by the
comments are intangible property interests. As discussed below,
trademarks and trade names are property to the extent that they are
associated with business goodwill. A trademark is a word, name, symbol,
device, or combination thereof that a person uses, or intends to use
and has applied to register, to identify and distinguish his or her
goods from others on the market and to indicate their source (15 U.S.C.
1127). A trade name is the name a person uses to identify his or her
business (15 U.S.C. 1127) and may include corporate, partnership, and
other names. Symbols and logos, when used to identify a product or
company, may be property insofar as they are trademarks or trade names.
Likewise, product names may be property if they are protected by a
trademark or trade name. For brevity, in the remainder of this
discussion the categories of names, words, and symbols mentioned by the
comments on the takings issue will be referred to collectively as
``trademarks and trade names.''
Trademarks and trade names are property, but only insofar as they
are associated with the goodwill of an ongoing business. (See American
Steel Foundries v. Robertson, 269 U.S. 372, 380 (1926).) They have no
intrinsic value. The purpose of a trademark or trade name is to prevent
confusion with the products of another manufacturer. (See United Drug
Co. v. Theodore Rectanus Co., 248 U.S. 90, 97 (1918).) Trademarks and
trade names are given legal protection to prevent one manufacturer from
passing off its goods as the goods of another and thus taking advantage
of the latter's goodwill (American Steel Foundries, 269 U.S. at 380;
United Drug, 248 U.S. at 97).
The Supreme Court has declined to prescribe a ``set formula'' for
identifying takings and instead has characterized takings analysis as
an ``essentially ad hoc, factual'' inquiry (Penn Central Transp. Co. v.
City of New York, 438 U.S. 104, 124 (1978)). Nonetheless, the Court has
identified three factors for consideration in assessing whether a
regulatory taking has occurred: The character of the governmental
action; the regulation's economic impact; and the extent to which the
regulation interferes with reasonable investment-backed expectations
(Ruckelshaus v. Monsanto Co., 467 U.S. 986, 1005 (1984)). The force of
any one of these factors may be ``so overwhelming * * * that it
disposes of the taking question'' (Monsanto, 467 U.S. at 1005). When
examined in light of these three factors, the rule does not effect a
compensable taking under the Fifth Amendment.
a. The character of the government action. With respect to the
first factor, the character of the government action, courts are more
likely to find a taking when the interference with property can be
characterized as a physical invasion by government than when the
interference is caused by a regulatory program that ``adjust[s] the
benefits and burdens of economic life to promote the common good''
(Penn Central, 438 U.S. at 124). The Supreme Court has held that, when
a governmental action is taken in order to protect the public interest
in health, safety, and welfare, this factor weighs heavily against
finding a taking. (See Keystone Bituminous Coal Ass'n v. DeBenedictis,
480 U.S. 470, 488 (1987).) Regulatory actions taken to protect the
public health are rarely, if ever, held to constitute takings. (See
Porter v. DiBlasio, 93 F.3d 301, 310 (7th Cir. 1996) (action taken to
protect public health falls within class of property deprivations for
which Fifth Amendment does not require compensation); Jarboe-Lackey
Feedlots, Inc. v. United States, 7 Cl. Ct. 329 (1985) (seizure of
adulterated meat not a taking).)
Although these regulations will restrict the use of certain terms,
including terms that appear in some trademarks and trade names, this
restriction does not rise to the level of a taking. Governmental
restrictions on the uses individuals can make of their
[[Page 1042]]
property are ``properly treated as part of the burden of common
citizenship'' (Keystone, 480 U.S. at 491 (citation omitted)). These
burdens are ``borne to secure `the advantage of living and doing
business in a civilized community''' (Andrus v. Allard, 444 U.S. 51, 67
(1979) (quoting Pennsylvania Coal Co. v. Mahon, 260 U.S. 393, 422
(1922) (Brandeis, J., dissenting)). Moreover, these regulations are not
without benefit to manufacturers. (See Keystone, 480 U.S. at 491
(``While each of us is burdened somewhat by such restrictions, we, in
turn, benefit greatly from the restrictions that are placed on
others.'').) The regulations will help ensure a level playing field in
the dietary supplement market because no manufacturer will be able to
make an implied disease claim without prior FDA review under the health
claim or new drug standard. Previously, unreviewed implied disease
claims on dietary supplements proliferated, in part because of
uncertainty about the line between structure/function claims and
disease claims.
These regulations are rationally related to, and substantially
advance, FDA's legitimate interest in promoting and protecting the
public health by ensuring the safety and efficacy of products promoted
for use in treating or preventing disease. (See Keystone, 480 U.S. 470
at 485; Monsanto, 467 U.S. at 1007.) By clarifying that such products
may not be marketed under the structure/function claim regime, FDA is
seeking to ensure that they are regulated through the drug approval or
health claims authorization process, as appropriate.
The effect of the regulations cannot be characterized as a taking
of property. Dietary supplement companies will not be precluded from
using terms that imply a disease claim in their trademarks and trade
names. If they wish to continue using trademarks and trade names that
imply a disease claim, they may do so, provided that they first meet
the safety and efficacy standards and other regulatory requirements
applicable to drugs or, in appropriate cases, provided that they obtain
authorization to make a health claim. (As discussed below, only non-
misleading trademarks and trade names may be used.)
Even if these regulations could be said to prevent a business from
using a trademark or trade name on its dietary supplements, such a
result still would not constitute a taking of the trademark or trade
name. The purpose of giving trademarks and trade names legal protection
is to prevent one manufacturer from passing off its goods as the goods
of another (American Steel Foundries, 269 U.S. at 380). This regulation
will not allow one manufacturer to use another's trademark or trade
name; rather, all manufacturers will be precluded from using trademarks
and trade names that contain an implied disease claim unless they have
obtained new drug approval or health claim authorization. Thus,
manufacturers will not suffer any competitive injury.
Moreover, deprivation of a trademark alone is not a deprivation of
property. Because the trademark is ``merely a protection for the good
will'' (Hanover Star Milling Co. v. Metcalf, 240 U.S. 403, 414 (1916)),
only if a regulation takes the owner's goodwill as well would the
regulation be a taking. It is not apparent, however, that these
regulations will deprive manufacturers of any goodwill. Manufacturers
will be faced with a choice as to whether to change their trademark or
trade name or to seek approval for their products as drugs. In some
cases, they will also have a third option: Seeking authorization to
make a health claim. If they are able to obtain drug approval for the
intended use suggested by the trademark or trade name, they will not
have to change the trademark or trade name, provided that the name is
not confusingly similar to the name of another drug or otherwise
misleading (see section 502(a)(1) of the act (21 U.S.C. 352(a)(1)); and
Sec. 201.10(c)(3) and (c)(5).) Similarly, if they are able to obtain
authorization to make a health claim for the intended use suggested by
the trademark or trade name, they will not have to change the trademark
or trade name unless it is misleading. (See section 403(a)(1) of the
act.) Even if a manufacturer chooses to change its trade name or
trademark, it will not be deprived of the goodwill underlying them but
only of that particular symbol of the goodwill. The manufacturer will
still be able to transfer the goodwill associated with its products to
another trade name or trademark.
Case law on the treatment of goodwill under the Takings Clause
supports the view that no taking will occur as a result of these
regulations. The general rule is that the owner of a place of business
to which the government takes title is not entitled to compensation for
loss of goodwill (United States v. General Motors Corp., 323 U.S. 373,
379 (1945)). The reason for the rule is that the business may reopen at
another location to which the goodwill may be transferred (Kimball
Laundry Co. v. United States, 338 U.S. 1, 11-12 (1949)). Only where the
government operates the business, thereby depriving the owner of its
``going-concern value,'' is there a compensable taking of goodwill. In
Kimball, the Supreme Court held that the government owed compensation
for the loss of goodwill associated with the temporary taking of a
laundry during World War II. This action was held to be a taking of
goodwill because the government not only physically took but also
operated the laundry during the war (Kimball, 338 U.S. at 12-13). Thus,
during the period that the government operated the laundry, there was
no business to whose benefit the goodwill associated with the private
laundry business could inure. Here, the government is not taking any
trademark or trade name for its own use, nor is it shutting down the
businesses that own them. Therefore, the goodwill symbolized by the
trademark or trade name will remain with these businesses.
Finally, although trademarks and trade names can be property when
they symbolize and protect the goodwill associated with a business,
there can be no property interest in an illegal product. Dietary
supplements that bear claims to treat or prevent disease are misbranded
and are also unapproved new drugs (unless the claim is an authorized
health claim). As such, they may not legally be sold in interstate
commerce (see section 301 (a) and (d) of the act. There can be no
taking of an illegal article. (See Meserey v. United States, 447 F.
Supp. 548, 554 (D. Nev. 1977) (``Plaintiff has not been denied his
property. He is denied the right to introduce his goods into commerce
unless they are in compliance with the [Federal Food, Drug, and
Cosmetic] Act.'').) Moreover, it has always been illegal to market
dietary supplements or other foods with disease claims, except that
since 1990 the act has permitted authorized health claims. These
regulations merely clarify the line between acceptable structure/
function claims and prohibited disease claims. (See Lucas, 505 U.S. at
1030 (``The use of [property] for what are now expressly prohibited
purposes was always unlawful, and * * * it was open to the State at any
point to make the implication of those background principles of * * *
law explicit'' without paying compensation) (emphasis in original).)
For this reason and the other reasons previously discussed, the first
factor of the takings analysis indicates that these regulations effect
no takings.
b. The economic impact of the government action. The second factor
to consider is the economic impact of the government action. This
impact is not to be considered piecemeal by dividing a property
interest ``into discrete
[[Page 1043]]
segments and attempt[ing] to determine whether rights in a particular
segment have been entirely abrogated'' (Penn Central, 438 U.S. at 130).
The analysis involves looking not just at what has been lost, but at
the nature and extent of the interference with rights in the property
as a whole. (See Penn Central, 438 U.S. at 130-31; Andrus v. Allard,
444 U.S. at 65-66.) Thus, here the total impact of the regulations on
property rights should be considered, rather than only whether a
business can or cannot continue to use a particular trademark or trade
name. It is clear that a regulation's economic impact may be great
without rising to the level of a taking. (See Pace Resources, Inc. v.
Shrewsbury Township, 808 F.2d 1023, 1031 (3d Cir.), cert. denied, 482
U.S. 906 (1987) (citing Hadacheck v. Sebastian, 239 U.S. 394 (1915)
(reduction in value from $800,000 to $60,000); Euclid v. Ambler Realty
Co., 272 U.S. 365 (1926) (75 percent diminution in value)).)
In assessing whether a regulation effects a taking, the Supreme
Court has considered whether the regulation denies an owner the
``economically viable'' use of its property. (See, e.g., Keystone, 480
U.S. at 499.) Although it is undeniable that compliance with these
regulations will cost money and may mean that certain trademarks and
trade names must be altered, companies will not be denied the
economically viable use of their property. As previously discussed,
some firms may be able to obtain new drug approval or health claim
authorization for those products that bear trademarks or trade names
that include disease claims. If approved as new drugs or authorized to
bear a health claim, in many cases these products could continue to
bear the original trademark or trade name. This approach would,
however, require the company involved to make significant expenditures
of time and money to submit a new drug application (NDA) or health
claim petition to FDA. The financial burden required to comply with
such requirements is not a taking under these circumstances, however,
just as it is not a taking to require other companies to comply with
applicable requirements before marketing a new drug or a food bearing a
health claim. Obtaining new drug approval or authorization to make a
health claim may be costly, but it is not the kind of economic impact
that leads to a taking. ``Requiring money to be spent is not a taking
of property'' (Atlas Corp.) v. United States, 895 F.2d 745, 756 (Fed.
Cir.), cert. denied, 498 U.S. 811 (1990)).
As previously noted in the discussion of the first factor of the
takings analysis, case law indicates that the regulations will cause no
loss of goodwill even in cases where a trademark or trade name must be
changed because new drug approval or health claim authorization cannot
be obtained. Even if the regulations do cause a loss of goodwill,
however, FDA believes that the economic impact of that loss of goodwill
is outweighed in the takings analysis by lack of reasonable investment-
backed expectations in being able to make disease claims in trademarks
and trade names.
c. Interference with reasonable investment-backed expectations.
The final factor to consider is whether a company has a reasonable
investment-backed expectation in continuing to use a trademark or trade
name. To be reasonable, expectations must take into account the power
of the state to regulate in the public interest (Pace Resources, 808
F.2d at 1033). Reasonable expectations must also take into account the
regulatory environment, including the foreseeability of changes in the
regulatory scheme. ``In an industry that long has been the focus of
great public concern and significant government regulation,'' Monsanto,
467 U.S. at 1008, the possibility is substantial that there will be
modifications of the regulatory requirements. ``Those who do business
in the regulated field cannot object'' if the regulatory scheme is
``buttressed * * * to achieve the legislative end'' (Connolly v.
Pension Benefit Guar. Corp., 475 U.S. 211, 227 (1986) (citation
omitted)). The lack of a reasonable investment-backed expectation can
outweigh the other takings factors and be determinative in whether a
taking has occurred (Monsanto, 467 U.S. at 1005).
Companies that use trademarks or trade names that include disease
claims lack a reasonable investment-backed expectation that they will
be able to continue to use those trademarks and trade names. First, the
Supreme Court has said that it is unreasonable to have high
expectations in personal property (i.e., property other than land):
``[I]n the case of personal property, by reason of the State's
traditionally high degree of control over commercial dealings, [the
property owner] ought to be aware of the possibility that new
regulation might even render his property economically worthless * *
*.'' (Lucas v. South Carolina Coastal Council, 505 U.S. at 1027-28).
Second, the dietary supplement and drug industries are a ``focus of
great public concern and significant government regulation'' (Monsanto,
467 U.S. at 1008). A product that bears a disease claim, whether that
claim appears in a trademark, trade name, or elsewhere, has been
subject to regulation as a drug since 1906, except that since 1990 the
act has permitted conventional foods and dietary supplements to bear
authorized health claims without drug approval. Since 1938, drugs (with
certain narrow exceptions) have been subject to a premarket approval
requirement. Given this longstanding history of close regulation, it
cannot be reasonable for a manufacturer or distributor to expect to be
able to make disease claims without prior authorization from FDA.
Moreover, it has always been illegal to market dietary supplements
or other foods with disease claims, except that since 1990 authorized
health claims have been permitted. These regulations merely clarify the
line between acceptable structure/function claims and prohibited
disease claims. (See Lucas, 505 U.S. at 1030 (``The use of [property]
for what are now expressly prohibited purposes was always unlawful, and
* * * it was open to the State at any point to make the implication of
those background principles of * * * law explicit.'').) Companies in
the dietary supplement industry should have been aware that FDA was
likely to issue such a clarification, not only because of the
regulatory environment generally but also for several specific reasons.
First, the passage of DSHEA, which added section 403(r)(6) to the act,
created a likelihood that FDA would issue regulations ``to achieve the
legislative end'' of permitting structure/function claims without
premarket review, while continuing to prohibit disease claims lacking
FDA authorization (see Connolly, 475 U.S. at 227 (citation omitted)).
Second, the Commission on Dietary Supplement Labels specifically
encouraged FDA to clarify the appropriate scope of structure/function
statements (Ref. to Commission report, p. 38). Third, the rapidly
expanding dietary supplement market and the proliferation of implied
disease claims in labeling should have put the industry on notice that
FDA might take action.
For all these reasons, there can be no reasonable investment-
backed expectations with respect to trademarks and trade names that
include disease claims. Thus, the third factor of the takings analysis
weighs strongly against finding a taking of property that requires
compensation under the Fifth Amendment. Moreover, the three factors,
taken together, show that these regulations do not effect such a
taking. Therefore, FDA concludes that the comments arguing the contrary
are unpersuasive.
[[Page 1044]]
IV. Implementation Plan
The preamble to the proposed rule discussed FDA's tentative
conclusions regarding the effective date of a final rule and the
agency's implementation plan. In general, the preamble to the proposed
rule stated that a final rule would become effective 30 days after the
date of the final rule's publication in the Federal Register. Any
product that is marketed for the first time after publication of the
final rule, and any new claims made for an existing product for the
first time after the publication of the final rule, will be expected to
be in compliance beginning 30 days after publication of the final rule.
However, small businesses that marketed a product as of the date of
publication of a final rule would have had an additional 17 months to
bring existing claims (i.e., claims already in the products's labeling
on January 6, 2000 for those products into compliance, provided that
the small business had notified FDA of the claim as required by section
403(r)(6) of the act and Sec. 101.93(a) and that FDA had not objected
to the claim. For all other products that were on the market as of the
date of publication of a final rule, FDA would have allowed an
additional 11 months beyond the effective date to bring existing claims
for those products into compliance, provided that the firm had notified
FDA of the claim as required by section 403(r)(6) of the act and
Sec. 101.93(a) and that FDA had not objected to the claim. Any product
marketed for the first time after the date of publication of the final
rule, and any new claim made for an existing product for the first time
after publication of the final rule, would have been expected to be in
compliance beginning 30 days after the date of publication of a final
rule.
(112.) Two comments suggested extending the compliance period to 6
months after the date of publication of a final rule. The comments also
advocated that there be no distinction between large and small
businesses for compliance dates. The comments further suggested that
FDA give businesses whose products were on the market as of the date of
publication of a final rule 15 months (instead of 11 or 17 months) to
comply. Another comment suggested that the final rule become effective
12 months, rather than 30 days, after its publication date.
FDA believes that the proposed compliance periods of 11 and 17
months following the effective date of the final rule are reasonable
and fair, and that the distinction between large and small businesses
is appropriate. FDA has decided, however, that it will not treat
manufacturers who have not notified the agency of their claims
differently from other manufacturers. At least some of those
manufacturers who did not submit 30-day notifications to the agency may
have failed to do so believing that notification was not necessary
under section 201(g)(1)(C) of the act. Therefore, all manufacturers
will have 11 months after the effective date of the final rule to come
into compliance, and small businesses will have 17 months after the
effective date of the final rule. The agency believes that these
compliance periods, uniformly applied, are sufficiently long that it is
not necessary to extend the effective date to 6 months after
publication in the Federal Register.
For a limited transition period, FDA does not intend to take
enforcement action against firms who have relied on the agency's
September 1997 preamble statements to make a structure/function claim
for a dietary supplement under section 201(g)(1)(C) of the act. To
allow a reasonable time for the necessary label changes, the transition
period will last until the applicable compliance date for the rest of
the rule; i.e., small businesses will have 18 months from publication
to comply, and other firms will have 12 months. As of the applicable
compliance date, firms that have been making structure/function claims
under section 201(g)(1)(C) must either remove the claim or comply with
the requirements of section 403(r)(6) of the act and Sec. 101.93,
including notifying FDA of the claim and relabeling to add the required
disclaimer. New structure/function claims are not subject to this
transition period; any firm that makes a structure/function claim in
the labeling of a dietary supplement after the effective date of this
rule must comply with section 403(r)(6) of the act and Sec. 101.93.
V. Environmental Impact
The agency has determined under 21 CFR 25.30(h) and (k), that this
action is of a type that does not individually or cumulatively have a
significant effect on the human environment. Therefore, neither an
environmental assessment nor an environmental impact statement is
required.
VI. Analysis of Impacts
A. Background
FDA has examined the impacts of the final rule under Executive
Order 12866, the Regulatory Flexibility Act (5 U.S.C. 601-612), and the
Unfunded Mandates Reform Act of 1995 (Public Law 104-4). Executive
Order 12866 directs agencies to assess all costs and benefits of
available regulatory alternatives and, when regulation is necessary, to
select regulatory approaches that maximize net benefits (including
potential economic, environmental, public health and safety, and other
advantages; distributive impacts; and equity). The Regulatory
Flexibility Act requires agencies to examine the economic impact of a
rule on small entities. The Unfunded Mandates Reform Act requires
agencies to prepare an assessment of anticipated costs and benefits
before enacting any rule that may result in an expenditure in any one
year by State, local and tribal governments, in the aggregate, or by
the private sector, of $100 million (adjusted annually for inflation).
FDA concludes that this final rule is consistent with the
principles set forth in the Executive Order and in these two statutes.
The agency has determined that the rule is a significant regulatory
action as defined by the Executive Order, because it raises novel
policy issues. FDA has further determined that the final rule may have
a significant economic impact on a substantial number of small
entities. This section constitutes the agency's final regulatory
flexibility analysis as required under the Regulatory Flexibility Act.
Because this rule imposes no mandates on government entities and will
not result in private expenditures of $100 million in any one year, the
Unfunded Mandates Reform Act does not require the agency to prepare a
cost-benefit analysis.
B. Benefits of the Labeling Requirements
The primary purpose of the rule is to provide a consistent
standard for distinguishing between claims that may be made in labeling
without prior review by FDA and claims that require prior authorization
as health claims or prior review as drug claims. The larger goal is to
ensure that information about non-disease-related effects of a dietary
supplement on the body may be freely disseminated in labeling, while at
the same time guaranteeing that claims for use of a dietary supplement
to treat or prevent disease are not made without prior review to ensure
that the supplement is safe and effective for that use.
Although dietary supplements can play a valuable role in consumer
health, the agency recognizes that, when inappropriately labeled, they
can pose unnecessary risks. Such risks arise when the product labeling:
(1) Encourages consumers to self-treat for a serious disease without
the benefit of a medical diagnosis, or to self-treat for a
[[Page 1045]]
serious disease by substituting a dietary product of uncertain value
for a medical therapy that has been shown to be safe and effective; (2)
encourages consumers to feel sufficiently protected from a serious
disease (e.g., cancer) that they delay, or possibly forego, regular
screening or early medical attention that may be critical to improved
odds of patient survival; or (3) increases the risk of adverse
reactions due to interactions with other chemical compounds (e.g.,
prescription medications) taken by the patient. As consumer spending on
dietary supplements continues to rise, the need for an information
standard that minimizes these risks becomes more acute.
The rule may also benefit consumers by encouraging manufacturers of
dietary supplements to develop the safety and effectiveness data needed
to support a health or drug claim. Where disease claims can be made
without this demonstration of safety and effectiveness, product
manufacturers have less incentive to develop the substantial
documentation needed to receive this agency authorization. The
availability of additional products with authorized health or drug
claims would be extremely useful to the many consumers who have
difficulty distinguishing among the variety of products now marketed
for particular health concerns.
The dietary supplement industry has grown rapidly, with estimated
sales in 1996 of $10.4 billion for all dietary supplements, including
$4.9 billion for vitamins and $3.0 billion for nonprescription herbal
products (Ref. 8). FDA has limited information on the number of
products and quantities sold, or on the age, gender, and disease status
of persons currently using dietary supplements. However, a 1997 survey
of 43,000 households, conducted by the Hartman and New Hope research
organization, indicates that approximately 70 percent of all households
reported using vitamins, minerals, or herbal supplements in the past 6
months (Ref. 9). Among survey respondents, those under age 30 accounted
for only 8 percent of all households with a member using dietary
supplements; ages 30 to 39 accounted for 21 percent, ages 40 to 49
accounted for 22 percent, ages 50 to 59 accounted for 18 percent, and
ages 60 or older accounted for 30 percent (Ref. 10). Although the
oldest group of survey respondents were, on the whole, less
knowledgeable about individual products, they reported more regular
product use and more use for specific conditions than younger
respondents.
FDA anticipates, therefore, that the final rule will clarify the
dividing line between acceptable structure/function claims and disease
claims, and thereby reduce the number of inappropriate disease claims
in dietary supplement labeling. The defined standard for structure/
function claims under section 403(r)(6) of the act will help to avoid
instances of inappropriate substitution of dietary products for timely
disease screening or medical treatment, and of adverse interactions or
contraindications of drug-supplement combinations. In addition, the
rule may promote the development of data and information for the
support of new health or drug claims. Although FDA cannot quantify
these regulatory benefits, the agency expects that this standard will
positively support the effective integration of dietary supplements
into consumers' overall programs of wellness and self-care.
C. Costs of Compliance
The costs to industry are the direct costs of compliance, which are
primarily the costs of the needed product relabeling; and the indirect
costs of compliance, which include the potential loss of product sales
due to the elimination of disease claims. The following section details
the agency's calculation of the direct costs of compliance. FDA has
been unable, however, to estimate the extent of the indirect costs of
this rule. As explained below, the agency estimates that over 800
dietary supplement products will need to be relabeled due to this rule.
The substitution of a valid structure/function claim for a disease
claim may, in fact, lead to a decrease in the sale of certain products.
The magnitude of this impact, however, is unknown, as most firms will
replace the disease claim with a structure/function claim that appeals
to many of the same consumers. It is also possible that some firms will
avoid a potential drop in sales by developing the safety and
effectiveness data needed to obtain either a new drug approval or
authorization from FDA to make a health claim. The agency cannot
quantify the probability of these occurrences, however, and no industry
comment includes such data.
1. Proposed Rule
In the preamble to the proposed rule (63 FR 23624), FDA had
projected that the direct costs of compliance would range from $0.1
million to $8.5 million. This figure largely reflected agency estimates
of the average cost of relabeling a typical dietary supplement product
multiplied by the number of dietary supplement products that would need
to be relabeled to conform with the proposed criteria for structure/
function claims. The cost categories included administrative,
analytical, and inventory disposal activities.
FDA acknowledged that estimates of the number of dietary
supplement products were approximate, but projected that the proposed
rule would cover about 29,000 products, with about 75,000 distinct
labels, or stock keeping units (SKU's). The agency also explained that
the rule would directly affect from 500 to 850 manufacturers of dietary
supplement products.
To estimate the lower-bound costs of the proposed rule, FDA assumed
that the 2,300 notifications initially received from dietary supplement
manufacturers adequately represented the number of products with
structure/function claims. The agency had already objected to 150
notifications because they contained obvious disease claims, but
identified an additional 60 notifications containing one or more claims
that might not have met the newly proposed criteria for structure/
function claims. Consequently, FDA's lower-bound direct cost estimate
included label changes for 60 dietary supplement products. The
estimated administrative, redesign, and inventory losses associated
with these 60 label changes totaled between $91,400 and $123,400.
FDA also presented an upper-bound $8.5 million estimate of the
direct costs of the proposed rule, based on the likelihood that many
additional dietary supplements are marketed with structure/function
claims. For this estimate, the agency concluded that about 30 percent,
or 22,500, of the estimated universe of 75,000 dietary supplement
labels contain structure-function claims. Assuming that the proportion
of disease claims on all labels containing structure/function claims
equals the proportion of disease claims in the 2,300 notifications
containing structure/function claims, the agency calculated that up to
585 labels (60/2,300 x 22,500) could need to be changed if the proposed
rule became final. The higher costs of the upper-bound estimate
resulted both from the substantially increased assumed number of
affected labels and from the impact of the significantly shorter
compliance period (30 days) for manufacturers that had not notified FDA
of their structure/function claim by the publication date of the final
rule.
2. Final Rule
A number of the comments submitted in response to the proposed
rule specifically addressed FDA's analysis of compliance costs. As a
result, the
[[Page 1046]]
agency has altered several of its cost assumptions. In addition, FDA
has adjusted its analysis to reflect the modified provisions of the
final rule. As described below, the agency estimates the total direct
costs of the final rule to be about $3.73 million, but presents
sensitivity analysis to indicate that the costs could rise to as much
as $10.35 million under certain worst-case assumptions.
Although several industry comments suggested that FDA had
underestimated the costs of relabeling, no comments objected to the
specific elements that were considered, i.e., administrative, redesign,
and inventory disposal activities. In response, FDA has retained this
format for its analysis of the final rule. One comment claimed that FDA
had underestimated the number of products that would be affected, but
provided no evidence or basis for determining a more accurate count.
Another comment stated that the agency's cost estimates were not well
explained and that all assumptions were not disclosed. Consequently,
FDA has revised its analysis to; (1) Simplify the cost-estimating
methodology, (2) clearly present and describe each assumption, (3)
fully explain the derivation of the estimated direct costs of
compliance, and (4) conduct sensitivity analysis for the remaining
areas of significant uncertainty.
a. Cost of designing new labels. Dietary supplements will no
longer be able to make claims whose status was previously unclear, but
which now have been defined as disease claims. Firms may comply either
by obtaining new drug approval, by receiving authorization from FDA to
make a health claim, or by revising their product labeling to eliminate
disease claims. Because the cost of submitting adequate documentation
to obtain new drug approval or health claim authorization far exceeds
the cost of modifying a label, this analysis assumes that the direct
costs of the rule will be the costs of modifying labels with disease
claims. As explained above, FDA recognizes that some firms may choose
to obtain health claim authorization or new drug approval as an
alternative means of compliance, or to improve the marketability of
their products. The agency believes, however, that it is unlikely that
the rule would be the determining factor in a large number of
instances.
No public comments provided alternative estimates of the number of
affected dietary supplement products. As noted above, FDA had estimated
that the industry markets approximately 29,000 covered products with
about 75,000 distinct labels. The agency has used this estimate for its
analyses of dietary supplement rules over the past several years (e.g.,
60 FR 67211 December 28, 1995) and has received no indication from
industry that better estimates were available. Although the agency's
preliminary analysis reported that an estimated 30 percent of the
products (8,700) carry structure/function claims, more recent data from
a random survey conducted for FDA by RTI of about 3,000 dietary
supplement products indicates that this percentage may have been too
low (Ref. 11). Although RTI notes that the surveyed sample is too small
to support quantitative inferences for the population of dietary
supplements, FDA finds the data to be the best available. The RTI
report actually shows that 69 percent of the products in its sample
have claims, but this percentage includes ``diet supplementation''
claims. When adjusted to exclude ``diet supplementation'' only 62
percent of the products in the RTI data base include relevant claims.
Even this 62 percent figure is too high, however, because RTI over-
sampled herbal products, which have a higher probablity of claims and
would not exceed 60 percent and has used this figure as its final
estimate.
Of the first 2,300 notifications of structure/function claims
reviewed by FDA, no more than 60, or 2.6 percent of the products with
claims, would have needed labeling changes due to the criteria
described in the proposed rule. Since that time, the total number of
notifications with structure/function claims submitted to the agency
has increased to about 5,200. A subsequent review of all of the
submitted claims indicates that the final rule could require about 1.9
times as many label modifications as the proposed rule, owing largely
to the revised criteria for cholesterol claims in the final rule. FDA
estimates that the final rule may require revised labels for about 4.81
percent of the 17,400 dietary supplement products (29,000 x 60 percent
currently estimated as marketed with structure/function claims (Refs.
15 and 16). (Excluding cholesterol claims would reduce this figure to
1.74 percent of the products with claims.)
The resulting label cost calculations are straightforward. First,
the agency found that revised labels (for all claims including
cholesterol) may be needed for approximately 837 products (17,400
products with claims x 4.81 percent). Because each product may contain
roughly 2.6 distinct SKU's (75,000 SKU's 29,000 products),
labels for an estimated 2,164 SKU's may need to be modified (837
products x 2.6 SKU's/product). As described in its earlier analysis,
based on an average of the estimates provided in comments to earlier
rules, FDA determined that the average label redesign cost is about
$1,700 per dietary supplement SKU for a 12-month compliance period, and
$1,300 for an 18-month compliance period. No industry comment
questioned the reasonableness of these unit cost estimates.
The final rule sets compliance periods of 1 year for large firms
(revenues above $20 million) and 18 months for small firms (revenues
below $20 million), except that new claims (i.e., claims not made
before the publication of the final rule) must be in compliance as of
the effective date. Such claims will not necessitate relabeling,
however. FDA does not know the size of the firms that will need to make
label changes. RTI (Ref. 12) reports that 95 percent of the firms in
the industry are small, but that the 5 percent that are large account
for 80 percent of industry sales. The RTI product data base also
indicates that approximately 25 percent of the sample products were
manufactured by just 5 percent of the companies. Thus, FDA has assumed
that approximately one-quarter of the affected products will come from
large firms and three-quarters from small firms. Consequently, the
total estimated label redesign costs equal about $3.03 million (i.e.,
$1,700 x 0.25 x 2,164 SKU's + $1,300 x 0.75 x 2,164 SKU's).
b. Administrative costs. One industry comment contended that FDA
had not adequately explained the basis for its company-specific
administrative costs, estimated at $425 and $320 respectively, for 12-
month and 18-month compliance periods. These figures were derived from
data presented in a 1991 RTI report on the cost of FDA's food labeling
regulations (Ref. 13). They included costs associated with interpreting
a regulation, determining the manner of compliance and managing the
compliance method. RTI had estimated that, on average, small firms
would bear administrative costs of $850 to comply with the new food
labeling rules for a 1-year compliance period, and $650 for a 2-year
compliance period. For its analysis of the proposed rule, FDA reduced
this figure by fifty percent, based on the smaller administrative
effort that would be needed to comply with the proposed rule, compared
to the conventional food labeling regulations evaluated by RTI in 1991.
The regulations that were the subject of the 1991 RTI evaluation
involved a broader range of administrative options and tasks, such as
nutritional testing and
[[Page 1047]]
product reformulation. (The $320 estimate for the 18-month compliance
period was determined by interpolating between the estimates for 12 and
24 months.) The agency has raised these costs by about 27 percent to
$540 and $407, respectively, to account for salary inflation since 1991
(Ref. 14).
FDA had initially estimated that 500 to 850 firms manufacture
dietary supplements. The recent RTI study, however, has identified
1,050 manufacturers (Ref. 12). This higher number probably
overestimates the size of the industry covered by this rule, because it
includes homeopathic products, which are drugs by statutory definition,
and ``functional foods'' and sports nutrition products, which may be
either conventional foods or dietary supplements depending on how they
are marketed and used. For this final analysis, FDA has assumed that
1,000 companies manufacture the dietary supplement products covered by
this rule. Although only a small fraction of these establishments will
need to implement changes in labeling due to this rule, the agency
anticipates most firms will review the final rule to assess whether
their labeling will be affected.
The administrative costs of the final rule would likely be higher
for those firms that will need to revise labels and lower for those
firms that do not. Nevertheless, FDA assumes that, on average, all
large dietary supplement manufacturers would incur costs of $540 and
all small dietary supplement manufacturers would incur costs of $407.
As noted above, RTI found that about 95 percent of the firms in this
industry are small. Thus, the agency calculated administrative costs to
equal about $413,000 (i.e., 950 small firms x $407 + 50 large firms x
$540). FDA notes that these estimates may overstate the incremental
administrative costs of this final rule, because dietary supplement
firms must already comply with DSHEA and this rule is meant to clarify
the meaning of that act, rather than to add new requirements.
Nevertheless, the agency's sensitivity analysis, presented below,
doubles the above cost estimates.
c. Costs of inventory losses. The final cost component involves
the value of lost inventory. FDA's preliminary analysis relied on
information from an earlier nutrition labeling rule that affected the
entire dietary supplement industry. That information indicated that
inventory disposal costs for the entire industry would be about $8
million for an 18-month compliance period and $15 million for a 12-
month compliance period. As explained above, FDA estimated that about
2.89 percent of the dietary supplement products will require new labels
as a result of this rule (837 29,000) and that about three
quarters of the affected products are manufactured by small firms.
Thus, total inventory disposal costs are calculated at $281,000 (i.e.,
$8 million x 2.89 percent x 0.75 + $15 million x 2.89 percent x 0.25).
d. Total direct compliance costs. As described above, FDA has
assumed the direct compliance costs of this rule to be the costs
associated with relabeling those dietary supplements whose labeling
claims are considered disease claims under the newly defined criteria.
Redesign costs are estimated at $3.03 million, administrative costs at
$413,000, and inventory disposal costs at $281,000. In sum, therefore,
the total estimated direct compliance costs equal almost $3.73 million.
In addition, there may be costs associated with the discussion in
the final rule concerning structure/function claims made under section
201(g)(1)(C) of the act. (See response to comment 95 in section III.A.1
of this document.) The agency believes that some firms have been making
structure/function claims for dietary supplements without including a
disclaimer statement or notifying FDA, based on FDA's statements in a
1997 preamble (62 FR 49859 at 49860, 49863, and 49864). Because the
agency has not repudiated these statements, any firm that has relied on
them to make a claim for a dietary supplement will need to add the
disclaimer to all applicable labels, as well as to notify FDA,
according to the requirements of this section 403(r)(6) of the act and
Sec. 101.93. Because firms making such claims have not identified
themselves to FDA, the agency does not have a reliable database on
which to base a cost estimate of the number of firms and products that
may incur costs to comply with this new provision.
The costs to industry of the final rule are substantially
different from the costs of the proposed rule, because of two important
changes to the proposed requirements. First, the final rule requires
more product labels to be changed, because it includes more specific
parameters for acceptable structure/function claims about cholesterol.
This change increases the direct compliance costs of the final rule.
Second, the proposed rule required needed label modifications to be
completed within 30 days after publication of the final rule, for those
products without a properly submitted claim notification. Roughly 70
percent of all products with claims may have fallen into this group (1-
5,200 products without notifications 17,400 products with
claims). Because relabeling costs are reported to double for each
halving of the compliance period, compliance costs would have been
eight times greater for those products. For the final rule, all large
firms will be expected to comply within 12 months, and all small firms
within 18 months, regardless of whether the firm has notified FDA of
the structure/function claims on its products. This change
significantly reduces the direct compliance costs of the final rule.
4 e. Sensitivity analysis. Due to uncertainty with respect to
several factors in the agency's direct cost model, FDA has prepared a
sensitivity analysis of other possible cost scenarios. First, FDA
tripled the percentage of product notifications assumed to be out of
compliance with the new criteria for structure/function claims. This
change results in almost tripling the total direct compliance costs of
the regulation, raising the estimate from about 3.73 million to about
10.35 to about $5.93 million. Second, FDA doubled its estimate of
administrative costs. This change raises the inital cost estimate to
about $4.14 million. Changing both assumptions simultaneously raises
the total estimated costs to about $11 million. Finally, under the
initial scenario, if all of the needed label changes were assumed to
affect only small businesses, the total cost estimate rises to about
$3.46 million. This sensitivity analysis indicates that the total
direct costs of this rule would not impose a major burden on this
industry even if the most uncertain cost factors are doubled or tripled
from FDA's best estimates.
D. Other Industry Comments
Several comments insisted that FDA had not conducted a
comprehensive cost-benefit analysis of the proposed rule, as required
under Executive Order 12866. These comments stated that FDA's economic
analysis ignored both the potential savings in consumer health care
expenditures that would be lost by restricting important labeling
information, as well as the likely negative effect of the proposal on
the growth of the dietary supplement industry. One industry comment,
for example, declared that a substantive cost-benefit analysis ``must
identify the potential health benefits that are lost as a consequence
of reduced consumer access to useful information about the health-
related properties of dietary supplements and ingredients.'' It noted
that FDA's analysis ``fails to consider the public health benefits
associated with ingesting dietary supplements as
[[Page 1048]]
well as the losses to public health that could result from consumers
failing to take appropriate dietary supplements due to uninformative
structure/function claims.'' That comment also maintains that ``FDA's
failure to assess and consider such benefits (and costs) stands in
contrast with the specific finding of DSHEA that `appropriate use of
safe nutritional supplements will limit the incidence of chronic
diseases, and reduce long-term health care expenditures'.'' The comment
also points out that FDA has performed such analyses in other
rulemakings, e.g., tobacco, nutrition labeling, and ephedra
regulations.
FDA disagrees. Although Executive Order 12866 directs agencies to
assess the costs and benefits of economically significant rules, the
quantification of these expected costs and benefits is required only
``to the extent feasible'' (58 FR 51735 at 51741, October 14, 1993). As
described above, FDA believes that its final rule strikes the
appropriate balance with respect to health-related claims in dietary
supplement labeling. The rule classifies certain claims as acceptable
structure/function claims that may be made without prior FDA review.
Although the provision of structure/function information to consumers
may reduce health care expenditures, no health organization, industry
association, or any other interested public or private group has
presented information or data that would allow the agency to develop a
quantifiable estimate of the health care benefits. The rule classifies
other claims as disease claims that are subject to existing
requirements for new drug approval or health claim authorization before
a product may be marketed with the claim. FDA believes that classifying
claims into a category that requires FDA review of safety and efficacy
evidence, where appropriate, will similarly reduce long-term health
care expenditures. Again, however, the agency has no means of
quantifying the probable health outcomes of this aspect of the rule and
therefore has no means of quantifying its impact on health care
expenditures. Because this analysis discusses the types of benefits and
costs reasonably expected, and quantifies those that can be
``feasibly'' quantified, the agency has, in fact, complied with the
direction of Executive Order 12866.
FDA has attempted to quantify the benefits of some of its previous
regulations. The agency's estimated benefits of the tobacco rule relied
on a widely established risk assessment published by the American
Cancer Society. Estimated benefits of the proposed ephedra rule were
based on incidents identified in the agency's adverse event database.
Estimated benefits of the nutrition labeling rule were derived from
epidemiological studies of the consequences of dietary fat. In each
case, the agency believed that it had a reasonably reliable data base
upon which to base conclusions, and each risk assessment dealt with the
risks of a single substance (tobacco, ephedra, and dietary fat). In
contrast, this structure/function rule governs structure/function
claims in the labeling for all dietary supplements. Although the agency
could conceivably analyze a few of the claims covered by the rule,
adequate data on the benefits and risks of most of these products are
not available. Consequently, the agency believes that this rule will
improve the nation's health, but concludes that it cannot feasibly
quantify the effects of the rule on the nation's health expenditures.
One industry comment suggested that the regulatory system could
impede firms from conducting research to substantiate structure/
function claims, if DSHEA is construed so narrowly that it excludes
meaningful health-related benefits. This comment noted, however, that
the absence of an enforceable legal standard for substantiation would
discriminate against companies that do research to support their claims
and would deter science-based companies from entering the market.
Similarly, a patient organization and several pharmaceutical companies
expressed concern that the rule would permit some products to escape
regulation as drugs and therefore diminish incentives for the costly
clinical research conducted by pharmaceutical companies and academic
scientists.
As stated previously in the document, FDA is not aware of any
evidence that would indicate that the establishment of criteria for
distinguishing structure/function claims from disease claims will
adversely affect the conduct of scientific research. In fact, FDA
believes that the final rule accords with the intent of DSHEA in
promoting the enhancements to consumer health expected from the broad
dissemination of structure/function information, while reducing the
risks to consumer health associated with the promotion of disease
treatment and/or prevention uses for products whose safety and efficacy
have not been demonstrated.
E. Regulatory Alternatives
FDA has considered several major alternatives to the proposed rule
as part of the rulemaking process. These include: (1) Taking no new
regulatory action; (2) treating a statement about a dietary supplement
as a disease claim only if the statement included an express reference
to a specific disease; and (3) treating a statement about a dietary
supplement as a disease claim if the statement mentions an abnormality
of the structure or function of the body, even if the abnormality was
not characterized by a set of signs or symptoms recognized as the
disease. These alternatives are fully discussed in the preamble to the
proposed rule (63 FR 23624 at 23630) and alternative (2) is also
discussed extensively in section II.E of this document. In brief, FDA
finds that the public comment does not include evidence or arguments
sufficient to persuade the agency to support these alternatives.
Within the broad framework of the final rule, FDA weighed other
policy changes that could affect the compliance costs. One option would
have set the compliance period for all firms at 6 months and another at
12 months from the publication date of the final rule. Other options
would have extended the compliance period beyond 18 months for small
businesses, or completely exempted small businesses from the rule.
Finally, the proposed rule would have permitted firms 12 or 18 months
to comply, depending on whether they were large or small firms; but
only if they had submitted timely notifications of their structure/
function claims to FDA and FDA had not objected to the claims. Other
firms had only a 30-day compliance period.
Based on its model of food labeling costs, FDA assumes that
compliance costs double for each halving of the compliance period (Ref.
13). Thus, the first option, which set a 6-month compliance date for
all firms, results in average relabeling costs twice as high as that of
the 12-month compliance period. FDA decided that this additional burden
was not warranted. The option of a 12-month compliance period for small
as well as large firms was rejected because of the additional burden to
small firms, which may find it more difficult to effect rapid shifts in
labeling procedures. The final rule provides small firms with an
additional 6 months to introduce these labeling changes. Extending the
compliance date for small firms beyond 18 months was rejected, because
the agency did not believe that the delayed consumer benefits would be
balanced by the relatively modest additional cost saving. Exempting all
small firms was not acceptable, because most firms covered by this rule
are small. The final option, which was to include the compliance
periods specified in the proposed rule, required label changes within
30 days for
[[Page 1049]]
products bearing claims of which FDA had not been notified or claims to
which FDA had already objected. This option was rejected because it
could have increased costs per label for many small firms by a factor
of eight.
F. Small Business Impacts
As stated above, the Regulatory Flexibility Act requires agencies
to analyze regulatory options that would minimize any significant
impact of a rule on small entities, unless the rule is not expected to
have a significant economic impact on a substantial number of small
entities. With this final rule, FDA is defining the types of statements
that can be made concerning the effect of a dietary supplement on the
structure or function of the body. It also establishes criteria for
determining when a statement represents a claim to diagnose, cure,
mitigate, treat, or prevent disease and thus is not acceptable as a
structure/function claim. The regulation was prepared in response to
the dietary supplement industry's request for clarification from FDA
with respect to the distinction between structure/function and disease
claims, and to guidance in the Commission report suggesting that FDA
provide such clarification to industry.
For its analysis of the proposed rule, FDA had estimated that
between 500 and 850 firms were involved in dietary supplement
manufacturing. A more recent industry survey reports that 1,050
companies manufacture dietary supplements; although as explained above,
some of these companies may manufacture products not covered by this
rule. FDA has projected the industry size for this rule at about 1,000
firms. The Small Business Administration (SBA) has determined that
dietary supplement manufacturers with fewer than 500 employees are
small businesses. Because most data sources characterize firms in this
industry by sales revenues rather than employment size, and because
company revenues of less than $20 million correlate reasonably well
with a 500 employee threshold, FDA has received approval from the SBA
to use a less-than-$20 million sales revenue standard to represent
small dietary supplement manufacturers. Table 1 displays the reported
size distribution of the dietary supplement manufacturing industry.
As described above, FDA assumes that all small manufacturers of
dietary supplements will incur administrative costs of about $407 per
firm. In addition, a number of small manufacturers of dietary
supplements will need to alter some product labels, at an average
redesign cost of about $1,300 per SKU, and an average inventory cost of
about $107 per SKU. FDA further analyzed the dietary supplement product
data base described in the October 1999 RTI report (Ref. 11) to
determine how these products may be distributed among small businesses.
As noted earlier, FDA estimates that about 628 of the 837 products (75
percent) needing revised labels due to this rule are manufactured by
small firms. If these 628 products were randomly distributed among the
950 small businesses, less than 0.1 percent of the small firms (1 firm)
would be likely to have more than 4 of these products and only about 3
percent (30 firms) to have more than 2 of these products.
A small firm that needs to redesign labels for three products
(about eight SKU's) due to the rule will incur estimated one-time
direct compliance costs of about $11,650. A small firm that needs to
redesign labels for 4 products (about 10 SKU's) would incur costs of
about $14,950, or roughly 1.2 percent of average company revenue. Thus,
the assumption that these products are randomly distributed among small
firms indicates that very few small businesses would be likely to incur
relabeling costs that are greater than 1 percent of average small
company revenue. It is possible, however, that some firms will have a
disproportionate number of labels to be revised. In the RTI database of
3,000 randomly selected products, only 3 companies (all large) have
more than 24 products. Although the data base sample show a number of
small companies with up to 24 products, it is very unlikely that all of
these product labels would need to be changed due to this rule. If a
small company needed to revise 10 products, however, its direct costs
of compliance would be about $37,000. Moreover, although FDA cannot
quantify the likelihood, some small firms could lose product sales due
to the necessary removal of a disease claim from a product label. Thus,
FDA finds that this rule may have a significant economic impact on a
substantial number of small companies.
Table 1.--Estimated Number of Dietary Supplement Manufacturers and
Revenues, by Size Category 1
------------------------------------------------------------------------
Number of Revenues ($ in Percentage of
Size Category Companies billions) Market
------------------------------------------------------------------------
>$100 million 16 3.32 55%
$20 to $100 38 1.54 25%
million
<$20 million="" 996="" 1.19="" 20%="" total="" 1,050="" 6.05="" 100%="" ------------------------------------------------------------------------="" \1\="" research="" triangle="" institute,="" ``economic="" characterization="" of="" the="" dietary="" supplement="" industry,''="" march="" 1999,="" pp.="" 5-15.="" vii.="" paperwork="" reduction="" act="" of="" 1995="" this="" final="" rule="" contains="" no="" collections="" of="" information.="" therefore,="" clearance="" by="" the="" office="" of="" management="" and="" budget="" under="" the="" paperwork="" reduction="" act="" of="" 1995="" is="" not="" required.="" viii.="" references="" the="" following="" references="" have="" been="" placed="" on="" display="" in="" the="" dockets="" management="" branch="" (address="" above)="" and="" may="" be="" seen="" by="" interested="" persons="" between="" 9="" a.m.="" and="" 4="" p.m.,="" monday="" through="" friday.="" 1.="" commission="" on="" dietary="" supplement="" labels,="" report="" to="" the="" president,="" congress,="" and="" the="" secretary="" of="" the="" department="" of="" health="" and="" human="" services,="" november="" 1997.="" 2.="" dorland's="" illustrated="" medical="" dictionary,="" 28th="" ed.,="" w.="" b.="" saunders="" co.,="" philadelphia,="" p.="" 478,="" 1994.="" 3.="" stedman's="" medical="" dictionary,="" 26th="" ed.,="" williams="" &="" wilkins,="" baltimore,="" p.="" 492,="" 1995.="" 4.="" the="" encyclopedia="" americana,="" international="" edition,="" grolier="" inc.,="" danbury,="" p.="" 168,="" 1985.="" 5.="" black's="" law="" dictionary,="" 6th="" ed.,="" west="" publishing="" co.,="" st.="" paul,="" p.="" 467,="" 1990.="" 6.="" the="" merck="" manual,="" 17th="" ed.,="" merck="" research="" laboratories,="" whitehouse="" station,="" nj,="" p.="" 416,="" 1999.="" 7.="" webster's="" encyclopedic="" unabridged="" dictionary,="" p.="" 1057,="" 1989.="" 8.="" economic="" characterization="" of="" the="" dietary="" supplement="" industry,="" prepared="" for="" dhhs/fda/cfsan="" by="" research="" triangle="" institute,="" center="" for="" economics="" research="" under="" contract="" no.="" 223-96-="" 2290:="" task="" order="" 3,="" final="" report,="" p.="" 5-2,="" march="" 1999.="" 9.="" herb="" and="" supplement="" usage="" nears="" 70="" percent,="" natural="" foods="" merchandiser,="">www.nfm-online.com/nfm--backs/
Feb--98/herbusage.html.
10. Wyngate, P., Consumers Not Supplement Brand Savvy, Natural
Foods Merchandiser, www.nfm-online.com/nfm--backs/
Mar--98/brandsavvy.html.
11. Dietary Supplement Sales Information, prepared for DHHS/
FDA/CFSAN by Research Triangle Institute, Center for Economics
Research Under Contract No. 223-96-2290:
[[Page 1050]]
Task Order 4, Final Report, pp. 5-8, October 1999.
12. Research Triangle Institute, Economic Characterization of
the Dietary Supplement Industry, p. 5-15.
13. Research Triangle Institute, ``Compliance Costs of Food
Labeling Regulations,'' prepared for CFSAN/FDA by RTI under Contract
No. 223-87-2097, final report, pp. 5-3, 5-4, January 1991.
14. U.S. Department of Labor, Bureau of Labor Statistics, BLS.
15. Memorandum from R. J. Moore, FDA, to file, review of
notifications made pursuant to 21 U.S.C. 343(r)(6).
16. Memorandum from J. Lienesch, FDA, to file, calculation of
relabeling cost estimate for final rule on statements made for
dietary supplements concerning the effect of the production on the
structure or function of the body, December 22, 1999.
List of Subjects in 21 CFR Part 101
Food labeling, Nutrition, Reporting and recordkeeping
requirements.
Therefore, under the Federal Food, Drug, and Cosmetic Act, the
Public Health Service Act, and under authority delegated to the
Commissioner of Food and Drugs, 21 CFR part 101 is amended as follows:
PART 101--FOOD LABELING
1. The authority citation for 21 CFR part 101 continues to read as
follows:
Authority: 15 U.S.C. 1453, 1454, 1455; 21 U.S.C. 321, 331, 342,
343, 348, 371.
2. Section 101.93 is amended by revising the section heading and
by adding paragraphs (f) and (g) to read as follows:
Sec. 101.93 Certain types of statements for dietary supplements.
* * * * *
(f) Permitted structure/function statements. Dietary supplement
labels or labeling may, subject to the requirements in paragraphs (a)
through (e) of this section, bear statements that describe the role of
a nutrient or dietary ingredient intended to affect the structure or
function in humans or that characterize the documented mechanism by
which a nutrient or dietary ingredient acts to maintain such structure
or function, provided that such statements are not disease claims under
paragraph (g) of this section. If the label or labeling of a product
marketed as a dietary supplement bears a disease claim as defined in
paragraph (g) of this section, the product will be subject to
regulation as a drug unless the claim is an authorized health claim for
which the product qualifies.
(g) Disease claims. (1) For purposes of 21 U.S.C. 343(r)(6), a
``disease'' is 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.
(2) FDA will find that a statement about a product claims to
diagnose, mitigate, treat, cure, or prevent disease (other than a
classical nutrient deficiency disease) under 21 U.S.C. 343(r)(6) if it
meets one or more of the criteria listed below. These criteria are not
intended to classify as disease claims statements that refer to the
ability of a product to maintain healthy structure or function, unless
the statement implies disease prevention or treatment. In determining
whether a statement is a disease claim under these criteria, FDA will
consider the context in which the claim is presented. A statement
claims to diagnose, mitigate, treat, cure, or prevent disease if it
claims, explicitly or implicitly, that the product:
(i) Has an effect on a specific disease or class of diseases;
(ii) Has an effect on the characteristic signs or symptoms of a
specific disease or class of diseases, using scientific or lay
terminology;
(iii) Has an effect on an abnormal condition associated with a
natural state or process, if the abnormal condition is uncommon or can
cause significant or permanent harm;
(iv) Has an effect on a disease or diseases 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 (other than an ingredient
that is an article included in the definition of ``dietary supplement''
under 21 U.S.C. 321(ff)(3)) that has been regulated by FDA as a drug
and is well known to consumers for its use or claimed use in preventing
or treating a disease;
(C) Citation of a publication or reference, if the citation refers
to a disease use, and if, in the context of the labeling as a whole,
the citation implies treatment or prevention of a disease, e.g.,
through placement on the immediate product label or packaging,
inappropriate prominence, or lack of relationship to the product's
express claims;
(D) Use of the term ``disease'' or ``diseased,'' except in general
statements about disease prevention that do not refer explicitly or
implicitly to a specific disease or class of diseases or to a specific
product or ingredient; or
(E) Use of pictures, vignettes, symbols, or other means;
(v) Belongs to a class of products that is intended to diagnose,
mitigate, treat, cure, or prevent a disease;
(vi) Is a substitute for a product that is a therapy for a
disease;
(vii) Augments a particular therapy or drug action that is
intended to diagnose, mitigate, treat, cure, or prevent a disease or
class of diseases;
(viii) Has a role in the body's response to a disease or to a
vector of disease;
(ix) Treats, prevents, or mitigates adverse events associated with
a therapy for a disease, if the adverse events constitute diseases; or
(x) Otherwise suggests an effect on a disease or diseases.
Dated: October 26, 1999.
Jane E. Henney,
Commissioner of Food and Drugs.
Donna E. Shalala,
Secretary of Health and Human Services.
[FR Doc. 00-53 Filed 01-5-00; 8:45 am]
BILLING CODE 4160-01-F
