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DEPARTMENT OF HEALTH AND restricted the structure/function claims disease, FDA will use the preexisting HUMAN SERVICES that could be made for dietary definition of ‘‘disease or health-related supplements. Most of the comments condition’’ in § 101.14(a)(5) (21 CFR Food and Drug Administration from health professional groups and 101.14(a)(5)) (formerly § 101.14(a)(6)), groups devoted to particular diseases which was issued as part of the 21 CFR Part 101 supported the proposed rule, or implementation of the health claims [Docket No. 98N±0044] believed it did not go far enough in provisions of the Nutrition Labeling and limiting structure/function claims for Education Act (NLEA). This change has RIN 0910±AB97 dietary supplements. been made in response to the large After reviewing the comments, FDA Regulations on Statements Made for number of comments that objected to concluded that the comments had raised Dietary Supplements Concerning the the proposed definition and urged that significant questions about some of the FDA retain the NLEA definition. Effect of the Product on the Structure key provisions of the proposal such that Second, FDA has revised the criterion or Function of the Body a public meeting was warranted. In the that applies to conditions associated AGENCY: Food and Drug Administration, Federal Register of July 8, 1999 (64 FR with such natural states or processes as HHS. 36824), FDA announced a public menopause, aging, adolescence, and ACTION: Final rule. meeting to be held on August 4, 1999, pregnancy. The proposed rule stated at which representatives of the dietary that menopause, aging, and pregnancy SUMMARY: The Food and Drug supplement industry, consumer groups, are not themselves diseases but that Administration (FDA) is issuing final and health professionals were asked to certain conditions associated with them regulations defining the types of address three major issues raised by the are diseases if they are recognizable to statements that can be made concerning comments. The three issues, described consumers or health professionals as the effect of a dietary supplement on the in the Federal Register notice, were: (1) abnormal. Many comments objected to structure or function of the body. The Whether to finalize the proposed classifying as diseases such common regulations also establish criteria for definition of ‘‘disease’’ or retain a 1993 conditions as hot flashes, premenstrual determining when a statement about a definition of ‘‘disease or health-related syndrome (PMS), and decreased sexual dietary supplement is a claim to condition’’ that was in effect at the time function associated with aging. In diagnose, cure, mitigate, treat, or the Dietary Supplement Health and response to these comments, FDA has prevent disease. This action is intended Education Act (DSHEA) was enacted; (2) revised proposed § 101.93(g)(2)(iii). to clarify the types of claims that may whether to modify one of the proposed Common conditions associated with be made for dietary supplements criteria for assessing disease claims to natural states or processes that do not without prior review by FDA and the permit structure/function claims related cause significant or permanent harm types of claims that require prior to certain conditions associated with will not be treated as diseases under the authorization as health claims or prior natural states, such as hot flashes final rule. For example, hot flashes, approval as drug claims. associated with menopause and common symptoms associated with the decreased sexual function associated menstrual cycle, ordinary morning DATES: The final rule will become effective February 7, 2000. with aging; and (3) whether to permit sickness associated with pregnancy, implied disease claims structure/ mild memory problems associated with FOR FURTHER INFORMATION CONTACT: Ann function claims. The July 8, 1999, notice aging, hair loss associated with aging, Marlin Witt, Office of Policy, Planning, also reopened the comment period until and noncystic acne will not be treated and Legislation (HF–11), Food and Drug August 4, 1999, to receive written as diseases under this provision. Administration, 5600 Fishers Lane, comments on these three issues. Uncommon or serious conditions like Rockville, MD 20857, 301–827–0084. This document addresses the senile dementia, toxemia of pregnancy, SUPPLEMENTARY INFORMATION: comments received on the proposed severe depression associated with the I. Introduction rule, as well as comments received in menstrual cycle, and cystic acne will response to the July 8, 1999, Federal continue to be treated as diseases under In the Federal Register of April 29, Register notice. A few comments raised the final rule. 1998 (63 FR 23624), FDA proposed issues that are beyond the scope of this Third, FDA has revised the criterion regulations to identify the types of rule and generally will not be addressed that relates to the use in labeling of the statements that may be made without in this document. titles of publications that refer to prior FDA review about the effects of diseases. In response to comments dietary supplements on the structure or A. Highlights of the Final Rule objecting that, as proposed, this function of the body (‘‘structure/ Like the proposed rule, the final rule criterion would hamper manufacturers function claims’’), and to distinguish contains criteria to determine when a from providing consumers with these claims from claims that a product labeling statement made about a dietary information substantiating their claims, diagnoses, treats, prevents, cures, or supplement constitutes a structure/ FDA has revised this criterion. Under mitigates disease (disease claims). FDA function claim for which no prior FDA the revised criterion, the use in labeling received over 235,000 submissions in review is required and when it of a publication title that refers to a response to the proposed rule. Many of constitutes a disease-related claim that disease will be considered a disease these were form letters, but over 22,000 requires either authorization of a health claim only if, in context, it implies that were individual letters from the dietary claim or review under the drug the product may be used to diagnose, supplement industry, trade associations, provisions of Federal Food, Drug, and treat, mitigate, cure, or prevent disease. health professional groups, and Cosmetic Act (the act). FDA has, Highlighting, bolding, using large type consumers. Almost all the comments however, made several important size, or prominent placement of a from the dietary supplement industry changes in the final rule in response to citation that refers to a disease use in and from individuals, which made up comments. the title could suggest that the product the vast majority of the comments, First, the agency has deleted the has an effect on disease. Placing a objected to all or part of the proposed proposed definition of ‘‘disease.’’ Rather citation to a scientific reference that rule, arguing that it inappropriately than creating a new definition of refers to a disease in the title on the

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The agency will also dietary ingredient intended to affect the also maintained the requirement of prior consider whether the cited article structure or function in humans’’ or that authorization of a claim that provides legitimate support for the ‘‘characterizes the documented characterizes the relationship of a express structure/function statement mechanism by which a nutrient or nutrient in a dietary supplement to a made for that dietary supplement. dietary ingredient acts to maintain such disease (section 403(r)(1)(B) and Enhancing the bibliography with structure or function.’’ Such statements (r)(5)(D) of the act). An interested person citations to scientific references that are generally referred to as ‘‘structure/ may submit a petition to FDA requesting refer to a disease in the title and that function claims.’’ Because many of these the agency to issue a regulation have no reasonable relation to the claims would previously have been authorizing the health claim (see statement made will be considered a covered by the drug definition in § 101.70 (21 CFR 101.70)). The disease claim. Similarly, the agency will section 201(g)(1)(C) of the act, section petitioner must demonstrate, among consider whether citations are to bona 201(g)(1) was amended by DSHEA to other things, that the use of the fide research. provide that a dietary supplement ‘‘for substance at levels necessary to justify which a truthful and not misleading B. Background the claim is safe and that there is statement is made in accordance with ‘‘significant scientific agreement’’ DSHEA created a new regime for the section 403(r)(6) is not a drug under among qualified experts that the claim regulation of dietary supplements. clause (C) solely because the label or the is supported by the totality of publicly These products were previously labeling contains such a statement.’’ available scientific evidence regulated either as foods or as drugs, Although a dietary supplement (§ 101.14(b)(3)(ii) and (c)). The agency depending upon whether they had the manufacturer who wishes to make a notes that for health claims to be used attributes of food and upon their statement permitted under section on conventional foods, an interested intended uses. Before the passage of 403(r)(6) of the act need not obtain prior person may submit to FDA a DSHEA, a dietary supplement for which review of the statement, the notification of an authoritative a health-related claim was made was manufacturer must possess statement by one of certain designated regulated either as a drug, which had to substantiation that the statement is scientific bodies concerning the be shown to be safe and effective before truthful and not misleading, and must substance-disease relationship to which marketing, or as a food, for which prior include in the statement the following the claim refers (see section 403(r)(3)(C) authorization to make a health claim disclaimer: ‘‘This statement has not of the act). Unless FDA issues a was required if the claim concerned a been evaluated by the Food and Drug regulation modifying or prohibiting the disease or health-related condition. If Administration. This product is not claim, or a Federal district court finds the claim concerned a non-disease- intended to diagnose, treat, cure, or that applicable statutory requirements related effect on the structure or prevent any disease.’’ DSHEA also have not been met, the claim may be function of the body and the claimed requires the manufacturer of a dietary used 120 days after the notification has effect derived from a food attribute, supplement bearing a statement under been submitted (see section such as nutritive value, the claim was section 403(r)(6) of the act to notify 403(r)(3)(C)(ii) and (r)(3)(D) of the act). considered a food claim, and prior FDA, no later than 30 days after the first This alternative authorization procedure authorization was not required. Under marketing of the dietary supplement does not apply to dietary supplements section 201(g)(1)(B) and (g)(1)(C) of the with the statement, that such a by statute, but FDA has proposed to act (21 U.S.C. 321(g)(1)(B) and (g)(1)(C)), statement is being made for the product. extend it to dietary supplements by a drug is defined as ‘‘an article intended Regulations implementing these regulation (see 64 FR 3250, January 21, for use in the diagnosis, cure, requirements were published in the 1999). mitigation, treatment, or prevention of Federal Register of September 23, 1997, disease,’’ or ‘‘an article (other than food) and are codified at § 101.93 (21 CFR Although FDA believes that dietary intended to affect the structure or any 101.93) (62 FR 49883 at 49886, supplements have potential benefits for function of the body.’’ Section 505 of September 23, 1997). consumers, dietary supplements labeled the act (21 U.S.C. 355) requires that new DSHEA did not alter the statutory with unproven disease claims, i.e., those drugs (see section 201(p) of the act) be treatment of dietary supplement claims that have not met the requirements for shown to be safe and effective for their related to disease (‘‘disease claims’’). health claim authorization or new drug intended uses before marketing. Under Section 403(r)(6) of the act, specifically approval, can pose serious risks. Such sections 403(r)(1)(B) and (r)(5)(D) of the provides that statements permitted claims may encourage consumers to act (21 U.S.C. 343(r)(1)(B) and (r)(5)(D)) under that section ‘‘may not claim to self-treat for a serious disease without and § 101.14, prior authorization is diagnose, mitigate, treat, cure, or benefit of a medical diagnosis or required to make a health claim for a prevent a specific disease or class of treatment. They may also cause dietary supplement. A health claim is a diseases,’’ except that such statements consumers to substitute potentially claim that ‘‘characterizes the may claim a benefit related to a classical ineffective products for proven ones, relationship of any nutrient * * * in the nutrient deficiency disease, provided foregoing or delaying effective treatment food to a disease or health-related that they also disclose the prevalence of for serious and life-threatening illnesses. condition’’ (section 403(r)(1)(B) of the the disease in the United States. Reliance on disease prevention claims act; see § 101.14(a)(1)). Consistent with the quoted provision, may encourage consumers to feel DSHEA specifically authorized Congress did not modify section sufficiently protected from developing certain types of claims about the uses of 201(g)(1)(B) of the act to exclude disease serious diseases (e.g., cancer or human dietary supplements, including some claims for dietary supplements from use immunodeficiency virus (HIV) claims that formerly would have as evidence of intended use as a drug, infection) that they delay or forego required review by FDA before the as it had done for section 201(g)(1)(C) of regular screening, and forfeit the claim is made. Section 403(r)(6) of the the act. Thus, dietary supplements opportunity for early medical treatment act, added by DSHEA, allows dietary ‘‘intended for use in the diagnosis, cure, that may be critical to survival. Finally, supplement labeling to bear, among mitigation, treatment, or prevention of use of dietary supplements to treat

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This final rule is intended to apply factors: (a) The name of the product; (b) Other comments suggested that FDA only to structure/function claims and a statement about the formulation of the simply adopt a ‘‘truthful and non- disease claims within the meaning of product, including a claim that the misleading’’ standard. Some comments section 403(r)(6) of the act. DSHEA, product contains an ingredient that has added that full disclosure of all generally, and section 403(r)(6) of the been regulated by FDA as a drug and is pertinent information (such as the act, specifically, apply only to dietary well known to consumers for its use in preliminary status of scientific studies supplements for human consumption preventing or treating a disease; (c) substantiating the claim) would be and were enacted to provide a unique citation of a publication or reference, if sufficient. Another comment questioned regulatory regime for these products. the citation refers to a disease use; (d) whether consumers would, as the Thus, this rule is neither intended to use of the term ‘‘disease’’ or ‘‘diseased;’’ preamble to the proposed rule stated, apply to products other than dietary or (e) use of pictures, vignettes, symbols, benefit from not having to search for supplements for human consumption or other means; (5) belongs to a class of information and from getting nor to interpret other provisions of the products that is intended to diagnose, appropriate information. The comment act. mitigate, treat, cure, or prevent a argued that consumers would receive The final rule establishes criteria for disease; (6) is a substitute for a product less information under the rule and determining whether a statement made that is a therapy for a disease; (7) would have to search more extensively about a dietary supplement is augments a particular therapy or drug for information. acceptable as a structure/function claim action; (8) has a role in the body’s Many comments supporting the under section 403(r)(6) of the act. The response to a disease or to a vector of proposed rule, including comments rule is neither intended to establish disease; (9) treats, prevents, or mitigates from nutrition counselors and health whether any particular structure/ adverse events associated with a therapy professionals, said that the proposal function claim is appropriate for any for a disease and manifested by a would reduce confusion among specific product, nor whether the claim characteristic set of signs or symptoms; patients, prevent consumers from being would be permitted under other or (10) otherwise suggests an effect on misled, diminish the number of provisions of the act. Like the labeling a disease or diseases. inappropriate disease claims, and help of any other FDA-regulated product, the Claims that did not fall within the consumers decide when to seek medical labeling of dietary supplements must proposed criteria for disease claims and attention. One comment added that, comply with all applicable requirements that otherwise complied with the while it supported the need for of the act and regulations. For example, notification and disclaimer provisions consumers to have choice regarding an otherwise acceptable structure/ of § 101.93(a) through (e) were to be dietary supplements, the choice should function claim might nevertheless be eligible for use as structure/function be made based on accurate information false or misleading for other reasons, claims. The proposed rule also provided that is supported by appropriate causing the product to be misbranded examples of claims that would be scientific investigations. One comment under section 403(a)(1) of the act. permitted as structure/function claims argued that in the absence of valid C. The Proposed Rule and those that would require prior effectiveness data, which does not exist review as disease claims under each of for most dietary supplements, it is not The proposed rule defined criteria for possible to provide ‘‘truthful’’ determining when a statement about a the 10 criteria. The basis for the proposed rule was information about the effects of these dietary supplement is a claim to products. Some comments said that the diagnose, cure, mitigate, treat, or the agency’s experience in implementing section 403(r)(6) of the proposal would protect consumers from prevent disease (‘‘disease claim’’), and harmful or potentially harmful products thus requires prior approval as a drug or act, and the final report (the report) of the President’s Commission on Dietary and save consumers from needless prior authorization as a health claim. suffering and financial loss; others The proposed rule included a definition Supplement Labels (Ref. 1), which included a number of recommendations expressed concern that inappropriate of ‘‘disease,’’ which was to replace a statements would expose consumers to definition of ‘‘disease or health-related for distinguishing structure/function and disease claims and suggested that potentially harmful drug-supplement condition’’ issued for implementation of interactions, create ‘‘false hopes,’’ and FDA issue further guidance on the health claims regulations, and 10 lead consumers to stop complying with acceptable structure/function claims. criteria for identifying express or advice from health care professionals or implied disease claims. FDA proposed II. Comments to avoid proven treatments. to treat a statement about a dietary FDA agrees that DSHEA encourages supplement as a disease claim if the A. General Comments the dissemination of truthful and non- statement claimed, explicitly or (1.) Many comments focused on the misleading information about the uses implicitly, that the product: (1) Has an impact of the rule on consumers. Many of dietary supplements to affect the effect on a specific disease or class of comments opposing the proposed rule structure or function of the body, and diseases; (2) has an effect, using said that consumers should be able to encourages full disclosure of scientific or lay terminology, on one or receive truthful and non-misleading information about claims authorized by more signs or symptoms that are information and that the proposed rule the statute. To the extent that truthful recognizable to health care professionals would curtail or restrict such and non-misleading information is or consumers as being characteristic of information or restrict the focus of being withheld from consumers in the a specific disease or of a number of dietary supplements to preventive care context of structure/function claims for different specific diseases; (3) has an and wellness. Some comments added dietary supplements, it is the statute effect on a consequence of a natural that DSHEA, through the dissemination that, in the first instance, precludes

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Contrary to the meeting the requirements for drug because of the unknown or unregulated suggestion in the comment, few dietary approval or health claim authorization, source materials for many dietary supplements have been the subjects of but precludes them from carrying supplements, the variety of suppliers, adequately designed clinical trials. unreviewed claims that the product and the lack of regulatory production This does not mean that dietary diagnoses, treats, mitigates, cures, or standards and quality control. supplements are unsafe or that they do prevents disease. (The statute does not Although this final rule may not not have benefits. Some have already ultimately prevent dissemination of appear to be a safety measure because it been shown to be safe and to have information about disease uses to the addresses the labeling of dietary benefits, and the safety and consumer in labeling claims or supplements rather than their effectiveness of others are likely to be otherwise. Instead, it requires that composition, protecting consumer shown in the future. At this time, claims about disease uses meet certain health and safety is one of its major however, many marketed supplements standards of substantiation and undergo purposes. Because structure/function have not been the subjects of adequate agency review.) This final rule claims are not subject to the new drug studies to establish whether or not they differentiates between structure/ approval standard or the health claim are safe or effective, or the nature of the function claims authorized by section authorization standard and do not benefits they may provide. 403(r)(6) of the act and disease claims undergo FDA review before marketing, (3.) Many comments asserted that that may not be made in dietary FDA believes it is important to ensure FDA had no authority to issue the supplement labeling under the authority that such claims do not promote proposed rule because it was of section 403(r)(6). The agency notes products for disease treatment or inconsistent with DSHEA and that, in response to comments, the final prevention claims. Disease treatment or congressional intent, in that it restricted rule classifies many more claims as prevention claims can pose serious risks rather than increased the amount of structure/function claims than would to consumers if they induce consumers information given to consumers. Some have been so classified under the to substitute ineffective or less effective comments said that Congress enacted proposed rule, thus increasing the treatments for proven ones, especially if DSHEA to reverse FDA’s ‘‘overly amount of information available to the the disease involved is serious or life- restrictive’’ approach towards health consumer without prior FDA review. threatening. Therefore, the agency claims and to increase the The agency also declines to adopt a believes that ensuring that such claims dissemination of truthful and non- ‘‘truthful and non-misleading’’ standard cannot be made without a misleading health information and that instead of the final rule. Section demonstration of safety and Congress repeatedly expressed its 403(a)(1) of the act already subjects all effectiveness will protect and promote displeasure with FDA’s regulatory food claims, including structure/ public health. approach. One comment said FDA must function claims on dietary supplements, FDA also believes that the safety and determine whether a proposed action is to the ‘‘truthful and non-misleading’’ the effectiveness of products intended to consistent with its statutory authority standard, so promulgating the same promote health, including both dietary before it takes any regulatory action. standard through regulations is supplements and drugs, cannot be The comment cited excerpts from unnecessary. In addition, section viewed independently of each other. congressional documents ‘‘condemning 403(r)(6)(B) of the act already requires FDA agrees that prescription drugs can the agency’s repeated penchant’’ for dietary supplement manufacturers to and do cause adverse reactions. It is restricting statements on dietary have substantiation that their statements important to remember, however, that supplement labels and labeling, and are truthful and non-misleading. Finally ‘‘safety’’ is relative. Products that are said that, given congressional intent and a fundamental problem with this capable of treating diseases have the act’s language, FDA has no authority approach is that a ‘‘truthful and non- powerful effects on the body and to proceed with rulemaking without a misleading’’ standard, unlike the final frequently carry risks. Before grant of authority from Congress. One rule, would not provide any criteria for prescription drugs are marketed, both comment cited section 403B of the act differentiating between structure/ their risks and their benefits must be (21 U.S.C. 343–2) as evidence that function claims and disease claims. carefully investigated and documented Congress, by exempting certain (2.) Some comments focused on in adequately designed clinical trials. publications from the definition of product safety. One comment said that Prescription drugs are permitted to be labeling, barred FDA from restricting in regulation of claims is unnecessary marketed only when the agency ‘‘any way whatsoever’’ the because dietary supplements are safe. concludes that their documented dissemination of such publications and Similarly, another comment claimed benefits outweigh their known and information. that ‘‘one million peer-reviewed potential risks. Those with significant FDA agrees that DSHEA was intended studies’’ showed that dietary risks are approved for marketing only if to authorize the dissemination of more supplements provide benefits, whereas the benefits warrant those risks. And truthful and non-misleading a recent medical journal reported deaths they are marketed as ‘‘prescription’’ information in dietary supplement and other injuries to patients who use drugs to ensure that health professionals labeling without the need for prior prescription drugs. Other comments manage their risks. Even over-the- agency review. In response to comments declared that dietary supplements are counter (OTC) drugs are evaluated for that the proposed rule was too safer than most regularly-used drug both benefits and risks and are restrictive, FDA has modified the final products. In contrast, other comments permitted to be marketed only when rule to incorporate many of the changes argued that the safety of many dietary their established benefits outweigh their requested by the comments, including a supplements is unknown, and that risks risks. There is no comparable testing return to the preexisting definition of have been documented with some and approval process for dietary ‘‘disease or health-related condition,’’ supplements. Some comments claimed supplements marketed with structure/ and a less restrictive interpretation of that dietary supplements pose risks function claims. The manufacturer must the types of structure/function claims

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Other comments contended that the FDA also does not agree that the The agency does not agree, however, Commission report did not support the Commission report was necessary to that section 403(r)(6) of the act proposed rule. These comments were provide support for this rule. The authorizes dissemination of any and all divided in their reasons. Some proposal was based not only on the information about dietary supplements comments argued that the Commission Commission report, but also on the without prior review. That section exceeded its statutory mandate under agency’s experience in reviewing 30-day authorizes statements about the effects section 12 of DSHEA or failed to notification letters submitted under of dietary supplements on the structure perform its statutory obligations. Thus, section 403(r)(6) of the act (63 FR 23624 or function of the body, but not the comments stated, FDA cannot base at 23625). Although FDA believes the statements that claim to diagnose, any regulation on the Commission’s rule is consistent with the views mitigate, treat, cure, or prevent a findings, guidance, or recommendations expressed in the Commission report, the specific disease or class of diseases. and has no authority to proceed with Commission report was not a necessary Section 403B of the act exempts from the rulemaking. Other comments stated prerequisite for the agency to issue the being considered labeling certain that FDA relied on statements from rule. FDA issued the proposal under balanced, third-party publications that individual Commission members rather section 403(r)(6) of the act (section 6 of are physically separate from product than the report itself, that the report did DSHEA) and the rulemaking authority labeling and do not promote a particular not suggest that FDA issue regulations, of section 701(a) of the act, not under brand or product. This provision does and that the report did not suggest that section 12 of DSHEA. FDA takes no not authorize dietary supplement FDA issue a new definition of disease. view on whether the Commission met manufacturers to ignore the restrictions One comment said that the Commission its statutory obligations in issuing its in section 403(r)(6) of the act on what did not support a need for regulations. report. To the extent that the report is structure/function claims may be made Another comment noted that the beyond the Commission’s authority, by a manufacturer about its product on Commission did not recommend FDA’s experience and section 701(a) of the product label and in materials that regulations and asserted that FDA had the act provide adequate support for the are indisputably part of the product’s publicly said that DSHEA is self- rule. Thus, whether or not the labeling. implementing. Commission exceeded its mandate is The agency also disagrees with the irrelevant to the validity of the rule. assertion that separate congressional FDA does not agree that there is With regard to the issues raised about authority is needed for this rulemaking. insufficient support for this rule. FDA’s the consistency of the agency’s FDA issued the proposed rule, and this experience, the Commission report, and approach with the Commission report, it final rule, to implement section FDA’s authority under section 701(a) of is true that the Commission did not 403(r)(6) of the act. No independent the act to issue regulations specifically recommend regulations, but authority to issue these regulations is implementing statutory requirements the Commission did express the view necessary because section 701(a) of the provide more than adequate support for that FDA guidance on claims under act (21 U.S.C 371(a)) expressly gives the rule. The preamble to the proposed section 403(r)(6) of the act would be FDA ‘‘the authority to promulgate rule referred to substantial confusion ‘‘appropriate and helpful in clarifying regulations for the efficient enforcement among manufacturers and consumers, the appropriate scope’’ of such claims of this Act, except as otherwise rather than manufacturers alone. (the report, p. 38). provided in (section 701 of the act) * * Comments received from other sources, As to the agency’s public statements *.’’ The proposed rule identified section particularly physicians, dieticians, and that DSHEA is self-implementing, the 701(a) of the act as being part of the health professional organizations, comment took those statements out of agency’s legal authority (see 63 FR agreed that consumers are confused and context. When DSHEA was passed, 23624 at 23628 and 23631), and there is misled by claims. In addition, the there was confusion in the industry no exception in the act that restricts or number of objection letters is not the about whether the types of statements limits, either expressly or impliedly, the sole indicator of manufacturer permitted by section 403(r)(6) of the act agency’s ability to issue regulations to confusion, for three reasons. First, could be made under the authority of implement section 403(r)(6) of the act. manufacturers and consumers have the statute alone, in the absence of Therefore, the rule is authorized by law asked FDA to provide clarification on implementing regulations. To clear up and consistent with FDA’s statutory structure/function and disease claims, this confusion, at least one agency authority. and such requests for clarification official publicly said that DSHEA was (4.) Some comments contended that would not necessarily have resulted in ‘‘self-implementing.’’ Agency statements FDA did not provide a sufficient an objection letter from FDA. Second, to this effect were intended to clarify justification for issuing the rule. Two the agency has repeatedly said that the that manufacturers were not required to comments challenged FDA’s assertion absence of an objection letter does not wait for FDA to issue implementing that the rule would reduce substantial necessarily indicate acceptance of the regulations before making claims under confusion among manufacturers. The claim. Third, there are apparently a section 403(r)(6) of the act; however, comments referred to statements in the large number of marketed dietary they were in no way intended to imply preamble to the proposed rule which supplement products making claims for that the agency lacked authority to issue said FDA received approximately 2,300 which FDA has not received 30-day implementing regulations. notifications of structure/function notification letters under section Contrary to the suggestion in one of claims and sent objection letters to 403(r)(6) of the act. (In the proposed the comments, FDA did not rely on the approximately 150 notifications. One rule, FDA estimated that approximately views of individual Commission comment said the low objection rate did 22,500 dietary supplement labels members, but on the official 7-point

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‘‘guidance’’ developed by the structure or function of humans may be made of the act authorizes such Commission ‘‘as to what constitutes an when the statements do not suggest disease dissemination. FDA strongly believes acceptable statement of nutritional prevention or treatment. that the dissemination of such support of the structure function type’’ (The report, p. 38) information on dietary supplement Accordingly, FDA believes that it is (the report at pp. 38 and 39). The labels increases the likelihood that appropriate to define the universe of criteria developed by FDA are highly consumers will believe that the permitted structure/function claims by consistent with the Commission’s supplements are intended to treat or first identifying those claims that should guidance. FDA also agrees that the prevent the diseases described in the be considered disease claims. Commission did not make any findings labeling. Therefore, it is important that Remaining claims about the effect of a or recommendations on the definition of any disease claims in dietary dietary supplement on the structure or disease. As described elsewhere in this supplement labeling continue to be function of the body may be acceptable rule, the final rule does not modify the subject to prior FDA review to evaluate structure/function claims under section existing definition of disease found in the safety and effectiveness of the 403(r)(6) of the act, provided that they FDA’s health claims regulations. product for the use described or are consistent with the requirement in (5.) One comment said that FDA suggested by the claim. should have admitted that there is and section 201(ff)(1) of the act that a dietary The agency also notes that there may will be some overlap between disease supplement be ‘‘intended to supplement be important health-related and structure/function claims and that the diet.’’ consequences associated with taking a (6.) Some comments, particularly the agency should have drafted a rule to dietary supplement, even if the product those received at the public hearing or prevent extreme overlap between does not bear disease claims. For the during the reopened comment period, structure/function claims and drug or labeling of a dietary supplement to be health claims. argued that it is difficult or impossible considered truthful and non-misleading FDA disagrees with this comment. In to draw principled distinctions between (see sections 403(a) and (r)(6) and the proposed rule, FDA recognized that structure/function claims and disease 201(g)(1) of the act), it must include all section 403(r)(6) of the act leaves open claims. Some of these comments said information that is material in light of questions concerning the distinction that section 403(r)(6) of the act, which the claims made for the product and the between structure/function claims and is premised on such a distinction, is not consequences that may result from its disease claims. Diseases cause, and can scientifically based. Other comments use (see section 201(m)) of the act. be characterized as, abnormalities in the argued that it is not necessary or (7.) Many comments discussed the structure or function of the body. It practical to draw clear lines between rule’s effect on scientific research. Some would therefore be possible to describe disease claims and structure/function comments argued that the proposal almost all products intended to treat or claims, and that dietary supplement would discourage scientific research on prevent disease in terms of their effects labeling should instead focus on dietary supplements. One comment on the structure or function of the body, educating consumers about the contended that such research might without mentioning the disease itself. conditions for which a product may be prompt FDA to consider a dietary The language of DSHEA, however, used. According to these comments, if supplement to be a drug. Another does not support treating those there are disease conditions that might comment said the proposal would structure/function claims that are also be implied by a particular claim, the ‘‘chill’’ the availability of third-party disease claims as statements permitted labeling should, for example, inform information on dietary supplements. under section 403(r)(6) of the act. As consumers of the symptoms of such The agency disagrees with the noted above, section 403(r)(6) of the act conditions, the importance of seeking comments. The comments provided no contains two passages that indicate medical attention for them, and their evidence, and the agency is aware of Congress’ intent to exclude from the health-related consequences. Other none, that establishing criteria for scope of structure/function claims any comments argued that consumers distinguishing structure/function claims claim that is also a disease claim. reading the labels of dietary and disease claims will adversely affect Section 403(r)(6) of the act provides that supplements will incorrectly assume the conduct or use of scientific research. structure/function statements ‘‘may not that the information provided therein In the agency’s experience, establishing claim to diagnose, mitigate, treat, cure, has been reviewed by the government regulatory standards has generated more or prevent a specific disease or class of and that the claims, express or implied, research rather than less. As described diseases.’’ It also requires structure/ are supported by the kind of scientific below, some comments from function claims to be accompanied by a evidence that supports drugs with pharmaceutical companies and from disclaimer stating that the product ‘‘is similar claims. patient organizations expressed the not intended to diagnose, treat, cure, or FDA agrees that it may be very contrary concern that allowing dietary prevent any disease.’’ difficult to draw clear lines between supplements to make disease claims In light of the statutory framework, structure/function claims and disease without FDA review would undermine FDA concluded in the preamble to the claims. Despite the difficulty, incentives for rigorous scientific proposed rule that section 403(r)(6) of implementing section 403(r)(6) of the research. The agency also notes that the act authorizes claims related to the act requires the agency to draw these nothing in this rule would treat effect of a product on the structure or lines. FDA would not be carrying out its scientific research or the publication of function of the body only if they are not statutory obligations if it abdicated research results in a scientific journal as also disease claims. FDA’s conclusion responsibility for distinguishing evidence that a product is marketed as was consistent with the policy guidance between the two types of claims, and a dietary supplement or is a drug. offered by the President’s Commission instead permitted dietary supplements (8.) Several comments addressed the on Dietary Supplement Labels. In the to disseminate information about relationship between dietary report the Commission offered general specific disease states. FDA agrees that supplements and drug products, and the guidance on structure/function claims, scientifically valid information about effects of this regulation on drug including the following: diseases is helpful to consumers, if it is products and drug development. Some 3. Statements indicating the role of a delivered consistently and accurately, comments suggested that the proposal nutrient or dietary ingredient in affecting the but does not agree that section 403(r)(6) represented an attempt by FDA to

VerDate 04-JAN-2000 16:16 Jan 05, 2000 Jkt 190000 PO 00000 Frm 00007 Fmt 4701 Sfmt 4700 E:\FR\FM\06JAR4.XXX pfrm11 PsN: 06JAR4 1006 Federal Register / Vol. 65, No. 4 / Thursday, January 6, 2000 / Rules and Regulations regulate dietary supplements in a FDA recognizes the importance of do not suggest disease prevention or manner that benefits pharmaceutical maintaining incentives for research and treatment or use for a serious health interests or to regulate dietary product innovation. By establishing condition that consumers cannot supplements in a manner that is similar criteria for determining when a evaluate (see 63 FR 23624 at 23626). to European regulatory systems that statement may be a disease claim, the (9.) A few comments objected to the apply drug requirements to such final rule indirectly contributes towards statement that a dietary supplement products. preserving the incentives for bearing an appropriate structure/ In contrast, other comments expressed pharmaceutical research and function claim may be subject to concern over the negative effects of development by ensuring that products regulation as a drug if there is other DSHEA and the proposed rule on marketed for treatment or prevention of evidence that it is intended for the incentives for pharmaceutical drug diseases must all meet the same diagnosis, cure, mitigation, treatment, or development. One comment asked FDA regulatory standards. As stated below, prevention of disease. One comment to provide an ‘‘unambiguous FDA believes that if the rule were to argued that many dietary supplements demarcation’’ that would preserve permit dietary supplements to carry are used for medicinal purposes and it research and development incentives for implied disease claims, the incentives would be ‘‘easy’’ for FDA to find drug products and permit evaluation of for new drug development could be evidence that they were intended for opportunities in the dietary supplement significantly undermined. this purpose based on consumer use of marketplace. According to this FDA agrees with the comment that the the product. comment, section 403(r)(6) of the act, structure/function provisions of sections Although FDA’s longstanding and DSHEA generally, were intended to 403(r)(6) and 201(g)(1)(C) of the act are interpretation of section 201(g)(1)(B) of create ‘‘parity’’ between the dietary similar in scope. FDA also agrees that to the act authorizes the agency to rely on supplement and food industries without make a statement about the mechanism evidence outside the labeling and undermining research and development by which a dietary supplement advertising of a product to establish its incentives for the pharmaceutical maintains structure or function, the intended use, FDA does not rely on industry and to address a perceived mechanism of action must be such evidence alone except in unusual failure by FDA to implement the health ‘‘documented.’’ FDA does not agree, circumstances. For example, the courts claims provision for dietary however, that this is the only provision have suggested that if the agency seeks supplements in section 403(r)(5)(D) of under which a dietary supplement may to rely solely on evidence that the act. The comment contended that claim to maintain healthy structure or consumers use a product for a particular section 403(r)(6) of the act is intended function. Maintenance claims also can purpose to support a finding of intended to provide a limited statutory safe be made under the provision that use for that purpose, consumers must harbor for certain dietary supplements authorizes statements that ‘‘describe the use the product predominantly or nearly that might otherwise be subject to role’’ of a supplement ‘‘intended to exclusively for that purpose. (See, e.g., regulation under the health claim rules affect the structure or function’’ of the Action on Smoking and Health (ASH) v. for food or as unapproved new drugs, body (section 403(r)(6)(A) of the act). Harris, 655 F.2d 236, 239–240 (D.C. Cir. but it does not permit any and all In response to the comment asking 1980); National Nutritional Foods structure/function statements for dietary FDA to limit claims to ‘‘maintaining,’’ (NNFA) v. Weinberger, 512 F.2d 688, supplements. Thus, the comment said rather than ‘‘promoting’’ or 702 (2d Cir. 1975), cert. denied, 423 U.S. FDA should have ‘‘parallel ‘‘improving,’’ structure/function, the 827 (1975).) The fact that some interpretations’’ of sections 201(g)(1)(C) agency agrees that ‘‘improving’’ often consumers used a dietary supplement and 403(r)(6) of the act. The comment suggests some abnormality or deficiency for medicinal purposes would not by suggested that FDA enforce the that can be treated, so a claim to itself be sufficient to establish intended requirement of a ‘‘documented ‘‘improve’’ a structure or function of the use as a drug, if use for medicinal mechanism’’ imposed in section body would be more likely to be a purposes was not the predominant use. 403(r)(6)(A) of the act, which permits disease claim. On the other hand, a FDA reiterates, however, that in claims that ‘‘characterize the claim to improve memory or strength appropriate circumstances, FDA may documented mechanism by which a would be a permitted structure/function find that a dietary supplement for which nutrient or dietary supplement acts to claim, unless disease treatment were only structure/function claims are made maintain’’ structure or function and that implied. Use of the term ‘‘promote’’ may in labeling may nevertheless be a drug FDA limit claims to ‘‘maintaining,’’ be acceptable under the portion of if there is other evidence of intended rather than ‘‘promoting’’ or ‘‘improving’’ section 403(r)(6)(A) of the act which use to prevent or treat disease. structure or function. authorizes claims that ‘‘describe[] the (10.) Some comments discussed the FDA does not agree that this rule was role of a * * * dietary ingredient ‘‘disclaimer’’ statement required by designed to benefit the pharmaceutical intended to affect the structure or section 403(r)(6)(C) of the act. The industry or to establish rules that are function.’’ Whether a claim for disclaimer reads as follows: ‘‘This consistent with European regulation of ‘‘promoting’’ structure or function is a statement has not been evaluated by the dietary supplements. As noted above, disease claim will depend on the Food and Drug Administration. This some pharmaceutical companies believe context and nature of the claim. For product is not intended to diagnose, that the rule will harm them by example, a claim that a product ‘‘helps treat, cure, or prevent any disease.’’ One permitting competition by products that promote digestion’’ would be a comment said the disclaimer resolves have not had to undergo rigorous testing structure/function claim because it does any consumer confusion between or review. Other pharmaceutical not refer explicitly or implicitly to an dietary supplement claims and drug companies already produce dietary effect on a disease state, but a claim that claims. Another comment said the supplements and expressed the same a product promotes low blood pressure proposed rule showed that FDA was reservations about the rule as other would be considered a disease claim. implicitly rejecting the disclaimer’s dietary supplement manufacturers. Both the preamble to the proposed rule meaning because the proposed rule There was also no attempt to model this and the Commission recognized that would restrict the amount of rule after European regulation of dietary statements using the word ‘‘promote’’ information flowing to consumers. One supplements. can be appropriate when the statements comment said the disclaimer reflects

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Congress’ understanding of a tension misbranded. The act forbids false and therapeutic benefit as well as harm, and between structure/function and disease misleading labeling and advertising suggested that existing and new dietary claims, while another comment asserted claims and requires businesses to have supplements that are marketed with that the disclaimers required on a label substantiation for any structure/function health-related claims be required to are an attempt to decrease the amount claims they make for dietary provide scientific evidence of their of space on a label for a structure/ supplements in labeling (see section safety and efficacy as a condition of function claim. 403(a) and (r)(6)(B)) of the act). The their being marketed as a drug or Section 403(r)(6) of the act requires presence of a disclaimer indicating that biologic. dietary supplement manufacturers who effectiveness has not been established FDA declines to adopt the comment’s wish to make a structure/function cannot vitiate these statutory suggestion. Section 403(r)(6) of the act statement to include the disclaimer, obligations. Therefore, it would be expressly authorizes certain structure/ and, since 1997, FDA regulations inappropriate for FDA to sanction the function claims for dietary supplements. regarding the disclaimer have been use of effectiveness disclaimers. Many of these claims may be said to be codified at § 101.93. However, the Although the act does not prescribe ‘‘health-related.’’ (The agency is disclaimer’s role does not eliminate the any specific statements concerning uncertain what is meant by need for this final rule to establish adverse reactions or contraindications ‘‘pharmacologic intent.’’) Thus, the act criteria for determining whether a that dietary supplements must carry, the does not require all substances with statement is a disease claim. Section agency notes that dietary supplement health-related claims to be classified as 403(r)(6) of the act provides that a labeling, like the labeling of all other a drug or biologic. statement for a dietary supplement that FDA-regulated products, is required to Regarding safety and effectiveness is made under section 403(r)(6) ‘‘may include all information that is material evidence for dietary supplements that not claim to diagnose, mitigate, treat, in light of consequences that may result bear health-related claims, FDA agrees cure, or prevent a specific disease or from the use of the product or that such evidence should continue to class of diseases.’’ Had Congress thought representations made about it (see be required where the claim is a health the disclaimer, alone, was sufficient to sections 403(a)(1) and 201(n) of the act). claim within the meaning of distinguish between structure/function As for requiring information on the § 101.14(a)(1) or a claim that subjects claims and disease claims, it would not percentage of RDI and actual units for the product to regulation as a drug have enacted the restriction against dietary ingredients in dietary under section 201(g)(1)(B) of the act. disease claims in section 403(r)(6) of the supplements, FDA agrees that such With regard to health-related claims that act. information is useful. In fact, FDA’s are authorized by section 403(r)(6) of the FDA does not agree with the assertion nutrition labeling regulations for dietary act, section 403(r)(6)(B) does require that the disclaimer, which is expressly supplements generally require the manufacturers to have substantiation for required by the act, is a scheme to percentage of the RDI or daily reference their claims. However, the act does not decrease the space for structure/ value (DRV) that a dietary supplement generally require dietary supplement function claims on a label. FDA believes contains to be given for dietary manufacturers that make claims for their that the disclaimer is intended to make ingredients that have an RDI or DRV products under section 403(r)(6) of the sure that consumers understand that (see § 101.36(b)(2)(iii) (21 CFR act to provide a premarket structure/function claims, unlike health 101.36(b)(2)(iii))). In addition, the demonstration of safety and claims and claims that appear on the amount in units must be given, effectiveness to FDA. labels of drugs, are not reviewed by FDA regardless of whether an RDI or DRV has (14.) One comment recommended that prior to marketing, and to caution been established (see § 101.36(b)(2) and FDA not finalize the proposed rule consumers that dietary supplements (b)(3) (21 CFR 101.36(b)(2) and (b)(3)). because it claimed that the proposal’s bearing such claims are not for This information can be found on the criteria were based on a subjective therapeutic uses. Supplement Facts panel of dietary evaluation of claims and not on (11.) Several comments sought supplements. objective information from market additional statements or language on (12.) One comment objected to research studies to determine whether product labels. One comment supported referring to structure/function consumers are confused by the claim. the marketing of dietary supplements statements as ‘‘claims.’’ The comment The comment also argued that FDA did and other substances whose said that, under section 403(r)(6) of the not provide data and information effectiveness has not been established act, such statements must be truthful regarding consumer confusion, and that and that have no appreciable toxicity as and non-misleading, so they should be all interested parties should be able to long as the product’s label stated that called ‘‘statements’’ instead of ‘‘claims.’’ evaluate and comment on any data effectiveness had not been proven. FDA has traditionally used the term before FDA finalizes the proposal. The Another comment said precautions, ‘‘claim’’ to refer to any statement made comment asserted that a significantly such as adverse reactions and by a manufacturer that recommends or revised and limited final rule could contraindications to certain diseases suggests a particular use of a product. provide a basic regulatory definition of and medications, are important This term is used for all products disease and a ‘‘construct’’ for structure/ information for labels. The comment regulated by FDA, including drugs, function claims so that detailed also sought a description of a dietary foods, devices, and dietary regulatory criteria would be supplement product’s contents as a supplements. Use of the term ‘‘claim’’ is unnecessary. percentage of a person’s recommended not intended to suggest that a statement The act does not require market daily intake (RDI) and in actual units. is untrue or misleading in any way. research studies to determine whether a FDA declines to revise the rule as (13.) One comment said that any particular statement is a structure/ suggested by the comments. With regard substance used with ‘‘pharmacologic function claim or disease claim, and it to the marketing of dietary supplements intent’’ should be classified as a drug or would be both impractical and with a label statement that the product’s biologic in order to ensure the efficacy, inefficient to require such studies to effectiveness has not been proven, the potency, and purity of medicines. The decide the status of every possible claim agency advises that dietary supplements comment explained that such that could be made under section that do not do what they claim to do are substances have a potential for 403(r)(6) of the act. FDA also does not

VerDate 04-JAN-2000 16:16 Jan 05, 2000 Jkt 190000 PO 00000 Frm 00009 Fmt 4701 Sfmt 4700 E:\FR\FM\06JAR4.XXX pfrm11 PsN: 06JAR4 1008 Federal Register / Vol. 65, No. 4 / Thursday, January 6, 2000 / Rules and Regulations believe that market research studies are guidance documents for specific claims FDA disagrees with the comments. necessary to provide a reasonable basis or recommended that FDA create or use Regulations offer several important for the agency’s determinations advisory committees to help draft advantages that case-by-case concerning the meaning of labeling guidance documents. Two comments clarification, individual enforcement claims. The agency has extensive said that the Commission report only actions, and educational activities experience in interpreting such claims. provided guidance and suggestions, so generally cannot. For example, when The agency has, however, modified the FDA did not have to issue the proposed FDA develops a regulation, it provides second criterion in § 101.93(g)(2)(ii) to rule. Another comment said that notice, obtains public comment, eliminate reference to recognition of publishing a guidance document would considers alternatives, and evaluates the signs and symptoms by consumers or consume fewer agency resources and rule’s potential impacts, costs, and health professionals because many that a rule is unnecessary because the benefits. Individual enforcement actions comments objected that this standard industry already knows the permissible and educational activities are not would appear to require consumer scope of statements for dietary subject to these considerations. testing. FDA has replaced the supplements. Regulations also establish uniform, recognition standard with an objective FDA disagrees with the comments. industry-wide requirements in a single standard. The final rule creates uniform, administrative proceeding (rulemaking). (15.) One comment said that it would enforceable requirements for structure/ In contrast, individual enforcement be inappropriate for FDA to issue any function claims. By doing so, the final actions focus on distinct facts that may regulation that restricted the scope of rule establishes a ‘‘level playing field’’ not lend themselves to uniform statements of nutritional support related for all members of the dietary application to an entire industry. to a nutrient content claim or claims supplement industry, and permits Moreover, enforcement actions are pertaining to a classical nutrient rational use of FDA’s limited resource-intensive and require multiple deficiency-related disease. The enforcement resources. In contrast, steps, such as inspections, warning comment said that claims such as guidance documents, although they letters, and sometimes litigation, before ‘‘calcium builds strong bones’’ are represent FDA’s best advice on a they are completed. Educational acceptable and that FDA should clarify particular matter, are not binding on any activities may deal with general topics this fact in the final rule. party. Relying solely on guidance and provide valuable opportunities for FDA agrees that dietary supplements documents would not be as effective in discussing issues with FDA, but they do may carry structure/function statements achieving consistency in the regulation not create uniform requirements. concerning the relationship of nutrients Regulations are also easier to locate of structure/function claims on dietary and the structure or function of the because they are published in the supplements and would lead to case-by- body, such as ‘‘calcium builds strong Federal Register when they are issued, case enforcement. bones.’’ The preamble to the proposed are codified and published in the Code rule also specifically acknowledged that FDA does, however, intend to issue a of Federal Regulations (CFR) and can be although statements under section guidance document to provide found in libraries and on government 403(r)(6) of the act generally may not additional information regarding Internet sites (such as the Government claim to diagnose, mitigate, treat, cure, structure/function and disease claims. Printing Office’s website at or prevent a specific disease or class of The guidance document would www.gpo.gov). In contrast, agency diseases, ‘‘such statements may claim a complement, rather than substitute for, correspondence and results of benefit related to a classical nutrient the final rule. individual enforcement actions are not deficiency disease, provided that they As for those comments stating that a as widely available and may be difficult also disclose the prevalence of the guidance document would permit new for some regulated entities and disease in the United States’’ (63 FR information to support new structure/ consumers to obtain. 23624). The final rule codifies this function claims or that outreach Thus, when it comes to establishing exception at § 101.93(g)(2), which states programs are necessary, FDA notes that uniform, industry-wide requirements, that ‘‘FDA will find that a statement interested persons may generate such conserving agency resources, and about a product claims to diagnose, information regardless of the rule. FDA providing public notice and an mitigate, treat, cure, or otherwise may also conduct research or other opportunity to comment, regulations are prevent disease (other than a classical programs or consult advisory preferable to individual enforcement nutrient deficiency disease) * * *’’ committees or other persons if such actions and educational activities. (emphasis added). Classical nutrient actions would be helpful. In short, (18.) A comment suggested that FDA diseases are also specifically excluded gathering more information or adopt an approach like hazard analysis from the definition of disease in conducting research and other programs critical control point (HACCP) instead § 101.93(g)(1). Thus, because the final is not dependent on whether FDA issues of issuing the rule. rule already contains the exception, no a guidance document instead of a rule. FDA disagrees with the comment. change to the rule is necessary. (17.) A few comments stated that FDA HACCP is best suited for issues relating (16.) Many comments suggested that should enforce existing laws and to how a product is manufactured. Here, FDA issue a guidance document instead regulations, remove unsafe products the principal issue is the claims made of regulations. Some of the comments from the market, take action against for a product rather than how the stated that regulations are neither dietary supplements that make product is made. desirable nor necessary. Others stated ‘‘extravagant, unsubstantiated’’ claims, (19.) A comment stated that FDA that a guidance document would be or promote educational activities lacks the expertise to determine whether appropriate because it would permit instead of issuing regulations. One a botanical is a drug or a dietary new information to support new comment suggested that FDA resources supplement. The comment explained structure/function claims or because it would be better spent reviewing notices that botanicals can be used for would enable FDA to conduct consumer sent to the agency instead of issuing medicinal purposes, but that they can research and industry outreach regulations. Another comment also be used for promoting general well programs before imposing new rules. suggested that FDA continue to clarify being and supporting the structure or Some comments also requested separate issues on a case-by-case basis. function of the body. According to the

VerDate 04-JAN-2000 16:16 Jan 05, 2000 Jkt 190000 PO 00000 Frm 00010 Fmt 4701 Sfmt 4700 E:\FR\FM\06JAR4.XXX pfrm11 PsN: 06JAR4 Federal Register / Vol. 65, No. 4 / Thursday, January 6, 2000 / Rules and Regulations 1009 comment, FDA declared Yellowdock, an proposed rule contained a definition of it does not exclude any such conditions, herb, to have medicinal purposes only, ‘‘disease.’’ The proposed definition was is the 1993 definition otherwise when the herb also had a long history based on standard medical and legal consistent with current medical of use as a food source. definitions of the term (Refs. 2, 3, 4, and definitions of disease? (4) If it does The comment may have 5). Proposed § 101.93(g)(1) defined exclude conditions that are medically misinterpreted the rule. The focus of ‘‘disease’’ as: understood to be diseases, could it be this rule is not on whether a substance any deviation from, impairment of, or revised in a way that would include has a history of use as a food but on interruption of the normal structure or such conditions? claims made in the product’s labeling. function of any part, organ, or system (or (22.) Almost all of the comments from The rule defines the types of statements combination thereof) of the body that is the dietary supplement industry and that may be made concerning a dietary manifested by a characteristic set of one or from individuals objected to the new more signs or symptoms, including definition of disease. Most of these supplement’s effect on the structure or laboratory or clinical measurements that are function of the body. FDA has many characteristic of a disease. comments argued that the new years of experience in regulating and The proposed definition would have definition is too broad, sweeping in interpreting health-related product replaced an earlier definition issued in many minor deviations or abnormalities claims. 1993 as part of the regulations that are not diseases. (Many of these (20.) One comment said other implementing the health claims comments did not appear to have countries (naming several European provisions of NLEA. The implementing understood that the definition required nations) and the World Health regulations require dietary supplement not only a deviation, but one that ‘‘is Organization have established lists of manufacturers to obtain prior manifested by a characteristic set of one ingredients and botanical products that authorization of any labeling statement or more signs or symptoms.’’) One are safe and permitted for therapeutic that characterizes the relationship comment said that under the new purposes. The comment suggested that between a substance in the supplement definition wrinkles and gray hair would qualify as diseases. Some comments FDA consider assembling a committee to a ‘‘disease or a health-related objected to the fact that the proposed to establish a similar list for the United condition’’ (section 403(r)(1)(B) of the definition was not limited to adverse States. act; § 101.14(a)(1)). The phrase ‘‘disease deviations from normal structure or A list of dietary ingredients and or health-related condition’’ was function. Other comments argued that botanical products and their therapeutic defined in those regulations as: uses might provide valuable damage to an organ, part, structure, or the breadth of the proposed definition is information. Nevertheless, section system of the body such that it does not inconsistent with the intent of DSHEA. 403(r)(6) of the act permits only function properly (e.g., cardiovascular Some comments objected to the structure/function claims for dietary disease), or a state of health leading to such distinction between normal and supplements that are not also disease dysfunctioning (e.g., hypertension); except abnormal functions, and argued that claims, and so such a list would not be that diseases resulting from essential nutrient Congress did not intend to limit relevant to this rulemaking. deficiencies (e.g., scurvy, pellagra) are not structure/function claims to normal (21.) Two comments suggested that included in this definition * * *. structure or function. Some comments FDA list examples of structure/function Section 101.14(a)(5) (formerly contended that the definition of disease claims in order to reduce confusion. § 101.14(a)(6)). The definition was should not include the phrase Another comment would have FDA redesignated as § 101.14(a)(5) effective ‘‘structure or function.’’ Other describe both disease claims and March 23, 1999 (see 62 FR 49859, comments said that Congress should be structure/function claims. 49867). presumed to have been aware of the FDA intends to issue a guidance FDA tentatively concluded that it did 1993 definition of ‘‘disease or health- document that will provide examples of not want to retain the older health related condition’’ and to have intended claims that would and would not be claims definition because its use of the FDA to use that definition. Several considered disease claims. This final term ‘‘damage’’ could be interpreted to comments argued that the new rule also includes many examples of limit the definition to serious or long- definition of ‘‘disease or health-related structure/function and disease claims. term diseases, and could imply that condition’’ for health claims would there needed to be pathological inappropriately broaden the scope of B. Permitted Structure/Function evidence of damage, which is not health claims for conventional foods Statements (§ 101.93(f)) always present. For example, most and concomitantly narrow the scope of Proposed § 101.93(f) stated that mental illnesses have no evidence of acceptable structure/function claims for dietary supplement labels and labeling anatomic damage, yet are clearly foods. One comment said that may bear structure/function statements diseases. redefining ‘‘disease or health-related that are not disease claims within the In the July 8, 1999, Federal Register condition’’ in § 101.14(a)(5) would meaning of proposed § 101.93(g) and notice announcing a public meeting and undermine the existing definition of that otherwise comply with the reopening the comment period, FDA ‘‘statement of nutritional support,’’ and notification and disclaimer provisions requested additional comment on the would violate DSHEA and the First of § 101.93(a) through (e). FDA is definition of disease. The notice listed Amendment. Most of the comments revising § 101.93(f) on its own initiative four questions on which it sought from the dietary supplement industry to make it clear that a dietary specific comment: (1) What are the and from individuals recommended that supplement may bear a disease claim if consequences, with respect to the range FDA return to the 1993 definition. it is the subject of an authorized health of acceptable structure/function claims, Most of the comments from health claim, but that otherwise disease claims of adopting: (a) The 1993 definition in professional groups and groups devoted will subject the product to regulation as § 101.14(a)(5), or (b) the definition in the to specific diseases, including those a drug. proposed rule? (2) If FDA were to retain who participated in the August 4, 1999, the 1993 definition, does the reference public meeting, supported the new C. Definition of Disease (§ 101.93(g)(1)) to ‘‘damage’’ exclude any conditions definition of disease as more consistent To assist in describing what that are medically understood to be with a medical understanding of disease constitutes a disease claim, the diseases? Please provide examples. (3) If than the NLEA definition. Some of these

VerDate 04-JAN-2000 16:16 Jan 05, 2000 Jkt 190000 PO 00000 Frm 00011 Fmt 4701 Sfmt 4700 E:\FR\FM\06JAR4.XXX pfrm11 PsN: 06JAR4 1010 Federal Register / Vol. 65, No. 4 / Thursday, January 6, 2000 / Rules and Regulations comments criticized the 1993 definition the number of claims that could be to a specific disease (e.g., ‘helps prevent because of its reliance on ‘‘damage’’ and made for dietary supplements without tumors’).’’ dysfunction and because of its failure to subjecting them to drug regulation, FDA FDA does not agree that a definition refer to signs and symptoms. While is persuaded that it is therefore of disease is unnecessary. The comment many comments from the dietary appropriate to retain a narrower that made this argument went on to use supplement industry said that no definition of disease at this time. the term disease in its ‘‘common sense’’ recognized diseases would be excluded FDA has concluded that the older principle, apparently assuming that by requiring evidence of ‘‘damage,’’ health claims definition, read as a there is some common sense comments from health professionals whole, will not exclude any significant understanding of the term. FDA is not pointed out a number of recognized conditions that are medically aware of any common sense disease conditions for which it is not understood to be diseases. For example, understanding of ‘‘disease,’’ and the currently possible to identify physical the requirement of ‘‘damage to an organ, diversity of comments received in this damage to an organ, part, or system of part, structure, or system of the body rulemaking on the appropriate the body, including most psychiatric such that it does not function properly’’ definition of disease supports FDA’s diseases (depression, bipolar disorder, indicates that a condition may be view that a definition is needed if FDA schizophrenia, and obsessive considered a disease if there is direct is to enforce section 403(r)(6) of the act compulsive disorder, among others), evidence of structural damage to an fairly and consistently. and the early stages of certain metabolic organ, part, structure, or system of the (24.) One comment argued that any diseases, including diabetes, genetic body, or indirect evidence of damage, definition of disease should exclude diseases, and nutritional deficiency indicated by the failure of the organ, symptoms or diseases that do not diseases. part, structure, or system of the body to normally require a drug or doctor’s care A few comments offered alternative function properly. This interpretation is because these states could be considered definitions of disease. A major medical appropriate because otherwise well- part of ‘‘normal’’ living. FDA does not agree that DSHEA was association contended that the proposed recognized psychiatric diseases, intended to permit structure/function definition would be improved by the migraine headaches, hypertension, claims about diseases that can normally addition of the phrase ‘‘or a state of blood lipid disorders, and many other be treated without a physician’s care. health leading to such deviation, well-accepted diseases, could be Nothing in the statute or its legislative impairment, or interruption.’’ An OTC excluded from coverage due to the lack history suggests that Congress intended drug and dietary supplement trade of direct evidence of physical damage. to accord different treatment to this association offered the following The reference to ‘‘a state of health subset of diseases. Diseases that do not alternative definition of disease, which leading to such dysfunctioning’’ also ordinarily require a physician’s care are would modify the proposed definition: permits the agency to look at evidence generally those for which drugs may be A disease is any adverse deviation from, or other than actual damage to an organ, impairment of, or interruption of the normal sold over OTC. (OTC drug claims part, structure, or system of the body. include both disease claims and structure or function of any part, organ, or FDA does not believe that it would be system (or combination thereof) of the body structure/function claims.) Drugs that is manifested by a characteristic set of constructive to defer a decision on the carrying OTC claims are already one or more signs or symptoms that are not definition of disease and seek a regulated under rules different from characteristic of a natural state or process. ‘‘consensus’’ of stakeholders. The those applicable to prescription drugs. According to this comment, the addition agency believes that it is unlikely that FDA has undertaken a comprehensive of the word ‘‘adverse’’ appropriately diverse, strongly-held views expressed review of OTC drug claims and narrows the nature of the deviation, in written comments and at the public published monographs on these claims. ‘‘laboratory or clinical measurements’’ hearing could be forged into a Had Congress intended to permit dietary are appropriately deleted because they consensus on this issue. FDA also supplements to make all OTC claims are already included under the concept believes that it is important to reach a (both disease claims and structure/ of ‘‘signs,’’ and the exclusion of natural decision as soon as possible to permit function claims) without prior review, it states ‘‘encompasses Congress’ intent to the issuance of clear, uniform rules that could easily have so indicated. Because allow health promotion/maintenance will apply to all dietary supplement Congress did not do so, FDA does not claims.’’ One comment suggested that, if labeling. believe that there is support for treating FDA were to retain the 1993 definition, Accordingly, the final rule does not this subset of diseases differently from it add the word ‘‘impairment’’ after include a new definition of disease, but other diseases. As discussed elsewhere ‘‘damage’’ to cover those recognized incorporates the definition of ‘‘disease in this document, the structure/function disease conditions for which evidence or health-related condition’’ in claims made for OTC drugs also may be of damage is missing. A pharmaceutical § 101.14(a)(5). If experience shows a made, in appropriate circumstances, for trade association urged FDA to convene public health need for a different or dietary supplements under section a small workshop of physicians, broader definition, however, FDA will 403(r)(6) of the act. patients, and other stakeholders to consider initiating a rulemaking to (25.) One comment argued that it was develop a consensus on the distinction amend that definition. irrelevant whether the 1993 definition between disease claims and structure/ (23.) One comment argued that it is excluded conditions that were function claims. unnecessary for FDA to define disease at medically understood to be diseases. In response to the comments, FDA has all, but that the agency should use a According to this comment, the reconsidered the proposed definition of ‘‘common sense’’ approach to definition of disease should be based on disease in § 101.93(g)(1), and has distinguishing structure/function claims consumer understanding rather than concluded that it is not necessary to from disease claims. According to this medical understanding, because DSHEA change the 1993 health claims comment, dietary supplements should was intended to educate consumers. definition, because it can be construed be allowed to make any claim that does FDA does not agree that its in a manner that covers conditions that not contain express references ‘‘to interpretation of a medical term like are medically understood to be diseases. specific diseases * * * or which can ‘‘disease’’ should ignore medical In light of Congress’ desire to increase only be reasonably interpreted to refer definitions of the term, unless there is

VerDate 04-JAN-2000 16:16 Jan 05, 2000 Jkt 190000 PO 00000 Frm 00012 Fmt 4701 Sfmt 4700 E:\FR\FM\06JAR4.XXX pfrm11 PsN: 06JAR4 Federal Register / Vol. 65, No. 4 / Thursday, January 6, 2000 / Rules and Regulations 1011 clear guidance from Congress that it the proposal in fact imply disease cup of tea.’’ While the preamble to the intended a nonmedical definition of the prevention. For example, some of these proposed rule considered the claim of term. In any case, the comment comments argued that health ‘‘improves absentmindedness’’ to be a provided no argument or evidence that maintenance claims imply disease structure/function claim, the comment the 1993 definition was based on, or prevention. On the other hand, a viewed the same claim as a disease reflects, consumer understanding of the comment from a major dietary claim ‘‘because of the association of term ‘‘disease.’’ supplement trade association argued absentmindedness with Alzheimer’s that the overall impact of the criteria disease.’’ The comment continued, D. Disease Claims (§ 101.93(g)(2)) restricts the value of structure/function ‘‘That claim should not be permissible (26.) Many comments agreed with the claims in providing consumers with for the same reason that a claim that a statement in proposed § 101.93(g)(2) useful information about dietary dietary supplement is an ‘oral that, in determining whether a supplements. contraceptive’ is not permissible—the statement is a disease claim, it is FDA agrees that consumers should claim is simply not one for the effects appropriate to consider the context in have access to, and be allowed to of a dietary ingredient.’’ which the claim is presented. One evaluate for themselves, as much FDA agrees that dietary supplements comment argued, however, that truthful information about dietary must be ‘‘intended to supplement the language of the regulation and preamble supplements as is possible, consistent diet’’ (section 201(ff) of the act). In showed that FDA was biased because with the statutory restrictions on disease interpreting section 403(r)(6) of the act, the agency would only consider the treatment and prevention claims. FDA however, FDA believes that it is context of a claim to convert a dietary believes that the criteria in this rule appropriate to focus on the claims made supplement to a drug. strike a reasonable balance between for the product. Unlike section FDA does not agree that it will these competing goals. Undoubtedly, 201(g)(1)(C) of the act, section 403(r)(6) consider context only to convert an the criteria will not satisfy everyone. For of the act does not limit authorization to otherwise acceptable structure/function example, some of the claims considered make structure/function claims (without claim to a disease claim. The context in to be structure/function claims may triggering drug approval requirements) which a claim appears can provide imply specific disease prevention to to substances that are ‘‘food.’’ FDA notes evidence in either direction. some consumers. Because of the that it is developing an overall dietary (27.) One comment argued that the importance of the context in which a supplement strategy and will, when a rule should have only the following claim is presented, it will not always be document incorporating the strategy is three criteria: (1) The words ‘‘diagnose,’’ possible to draw a line between released, state how the agency plans to ‘‘prevent,’’ ‘‘treat,’’ ‘‘cure,’’ and structure/function and disease claims in address the requirement that dietary ‘‘mitigate’’ should not be used in a this rule with great specificity. FDA supplements be ‘‘intended to structure/function claim; (2) the words believes that, within these constraints, supplement the diet.’’ ‘‘stimulate,’’ ‘‘maintain,’’ ‘‘support,’’ the criteria, as finalized, adequately (30.) One comment said FDA should ‘‘regulate,’’ and ‘‘promote’’—or other distinguish between structure/function develop a list of ‘‘acceptable subclinical, similar words—may be used in a claims and disease claims. In pre-disease, and normal states’’ that may structure/function claim to distinguish developing final criteria, the agency has be used in structure/function claims. the claim from a specific disease claim; tried to pay particularly close attention FDA declines to adopt the comment’s and (3) clinical endpoints that are to claims that might relate to serious suggestion. However, this rule contains recognizable to health professionals or health conditions that patients cannot many examples of acceptable structure/ consumers as being related to a disease safely evaluate on their own. The function claims and FDA intends to may be used in a structure/function question of whether health maintenance issue further guidance listing acceptable claim. claims necessarily imply disease claims. FDA does not believe that the three prevention is discussed in more detail (31.) One comment argued that all suggested criteria provide a sufficient below. statements about effects on structure or basis to distinguish between structure/ (29.) One comment, from a function should be deemed permissible function claims and disease claims. Commission member, said the ‘‘dietary unless they are already approved drug Nothing in these criteria would prevent relationship’’ of a structure/function claims. The comment noted that a structure/function claim from claim is relevant in considering whether ‘‘reduces joint pain’’ and ‘‘relieves discussing a specific disease, explicitly such a claim is appropriate. The headache’’ would not be structure/ or implicitly, as long as the claim did comment said that statements for function claims because they are OTC not contain the specific verbs dietary ingredients should ‘‘relate to the monograph claims. ‘‘diagnose,’’ ‘‘prevent,’’ ‘‘treat,’’ ‘‘cure,’’ role of the dietary ingredient in the diet FDA does not agree that such a or ‘‘mitigate.’’ in achieving effects like those associated criterion would appropriately (28.) Several comments from medical with the effects of foods.’’ The comment discriminate between structure/function and consumer groups supported the added that the claim ‘‘should be for an claims and disease claims. One kind of establishment of criteria for structure/ effect that is similar to the non-disease valid drug claim is a claim related to the function claims, but were concerned effects of a food on the body’’ and effect of the product on the structure or that the criteria in the proposed rule ‘‘phrased to indicate the role of the function of the body (section were too vague and would fail to protect dietary ingredient in the diet in 201(g)(1)(C) of the act) but not related to consumers from misleading claims. A maintaining or supporting the ordinary disease prevention or treatment. In other major medical association contended functioning of the body in a manner words, not all drug claims are disease that some of the structure/function similar to that achieved through foods.’’ claims. Congress specifically provided claims listed as acceptable in the Thus, the comment would consider a that structure/function claims proposal were debatable and expressed claim such as ‘‘promotes relaxation’’ to authorized by section 403(r)(6) of the act doubt that the public health would be be appropriate ‘‘only if it is indicated to do not, in themselves, subject a dietary adequately protected. Some of these be similar to the effects achieved from supplement to regulation as a drug comments expressed the view that some foods, such as by indicating that it under 201(g)(1)(C) of the act. It thus of the structure/function claims listed in provides a relaxing calming effect like a would not be appropriate to exclude

VerDate 04-JAN-2000 16:16 Jan 05, 2000 Jkt 190000 PO 00000 Frm 00013 Fmt 4701 Sfmt 4700 E:\FR\FM\06JAR4.XXX pfrm11 PsN: 06JAR4 1012 Federal Register / Vol. 65, No. 4 / Thursday, January 6, 2000 / Rules and Regulations from the scope of acceptable structure/ methods of substantiation may be more epilepsy’’ would be the corresponding function claims OTC monograph claims straightforward. Such an approach express claim); (3) ‘‘relief of sneezing, or other approved claims for products would turn section 403(r)(6) of the act runny nose, and itchy watery eyes classified as drugs under section on its head. caused by exposure to pollen or other 201(g)(1)(C) of the act. FDA also does not agree that it is allergens’’ (‘‘treatment of hayfever’’ (32.) A national pharmacy group impossible to substantiate the claims would be the corresponding express stated that the examples of structure/ described in the comments. For claim). The notice listed four questions function and disease claims in the example, to substantiate the claim related to implied disease claims on proposal were reasonable and based on ‘‘supports mood,’’ it is not necessary to which the agency sought specific good science and logic, but should be study the effects of a substance on comments: (1) If implied disease claims evaluated and revised as necessary over clinical depression. Instead, it is quite should be permitted, has FDA correctly time. possible to assess the effects of a drawn the line between what constitutes FDA agrees that it will be necessary substance on mood changes that do not an express disease claim and what to evaluate the examples over time and constitute clinical depression. constitutes a permitted implied claim? to revise them as experience dictates. (2) If such claims should be permitted, (33.) Some comments argued that the E. Effect on Disease or Class of Diseases (§ 101.93(g)(2)(i)) what are representative examples of the types of claims permitted under the types of implied disease claims that proposal may discourage serious Under proposed § 101.93(g)(2)(i), a should be permitted without prior approaches to substantiation because statement would be considered a review? (3) Are the examples of implied the terms used are not scientifically disease claim if it explicitly or claims mentioned in the July 8 notice verifiable. Stating that the preferred implicitly claimed an effect on a appropriate structure/function claims? method of substantiation is an adequate specific disease or class of diseases. (4) Is a claim that a product ‘‘maintains and well-controlled trial, one comment FDA included the following examples of healthy function’’ an implied disease contended that the claims permitted such disease claims: ‘‘Protective against claim in all cases? If not, under what under the rule are not amenable to such the development of cancer,’’ ‘‘reduces circumstances is such a claim not an proof. According to this comment, this the pain and stiffness associated with implied disease claim? rule may preclude companies from arthritis,’’ ‘‘decreases the effects of (34.) Many comments agreed with meeting the substantiation rules of the alcohol intoxication,’’ or ‘‘alleviates proposed § 101.93(g)(2)(I) that structure/ Federal Trade Commission (FTC). A few constipation.’’ FDA included the function statements should not comments said that manufacturers following examples of claims that do explicitly or implicitly mention specific cannot substantiate claims that a not refer explicitly or implicitly to an diseases or class of diseases. These product maintains healthy status. One effect on a specific disease state: ‘‘Helps comments contended that consumers of these comments stated that it was promote urinary tract health,’’ ‘‘helps cannot distinguish between implied and impossible to show by adequate studies maintain cardiovascular function and a express disease claims and that that ‘‘cranberry extract supports healthy healthy circulatory system,’’ ‘‘helps permitting implied disease claims poses urinary tract functioning,’’ and that maintain intestinal flora,’’ and significant dangers to consumers with companies should instead be able to ‘‘promotes relaxation.’’ FDA proposed to diseases. According to these comments, show that cranberry extract reduces treat both express and implied disease permitting implied disease claims on frequency of urinary tract infections in claims as disease claims that could not dietary supplements may cause susceptible people. Similarly, because it be made for dietary supplements consumers to delay or forego effective is ‘‘impossible’’ to test whether St. without prior review either as health treatment for serious diseases without John’s Wort ‘‘supports mood’’ in the claims or as drug claims. Implied assurance that the dietary supplement general population, companies need to disease claims do not mention the name that has been substituted is safe or be able to test its effect on depressed of a specific disease, but refer to effective for the disease. Some people. identifiable characteristics of a disease comments also argued that permitting FDA agrees that some structure/ from which the disease itself may be implied disease claims on dietary function claims that are acceptable inferred. There are many possible ways supplements will undermine the drug under DSHEA may be difficult to to imply treatment or prevention of approval process by permitting dietary substantiate. For example, some disease, from listing the characteristic supplement manufacturers to market structure/function claims currently in signs and symptoms of the disease to products for essentially the same the marketplace use terms that do not providing images of people suffering indications for which pharmaceutical have clear scientific meaning. Other from the disease. Nine of the 10 criteria companies have spent millions of claims concern health maintenance in proposed by FDA for identifying disease dollars obtaining approval. the general population and therefore claims could be considered methods of Many other comments objected to could require studies in a large implying disease treatment or treating implied disease claims as population for substantiation. FDA prevention. disease claims, arguing that dietary believes, however, that such claims are In the July 8, 1999, Federal Register supplements should be allowed to carry within the intended scope of section notice announcing a public meeting and any truthful claim that does not 403(r)(6) of the act. Difficulty in reopening the comment period, FDA explicitly refer to a specific disease. substantiating them does not alter the sought additional comment on the Some comments argued that Congress terms of the statute. Manufacturers are applicability of the rule to implied intended consumers to have access to as responsible for determining whether disease claims. The discussion in the much information about supplements as claims for their products can be notice offered three examples of possible. Other comments contended appropriately substantiated, and to use possible implied disease claims: (1) that barring implied disease claims only those claims for which they have ‘‘shrinks tumors of the lung’’ or eliminates any meaningful claims for substantiation. FDA does not agree that ‘‘prevents development of malignant dietary supplements. Other comments difficulty in substantiating a particular tumors’’ (‘‘treats cancer’’ would be the argued that treating implied claims as claim justifies the use of express or corresponding express claim); (2) disease claims gives FDA ‘‘unlimited implied disease claims for which ‘‘prevention of seizures’’ (‘‘treatment of discretion’’ to treat structure/function

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One comment agreed statement in context to determine Pharmaceutical manufacturers, faced with the proposal’s statement that while whether it conveys a disease claim. with this competition, might be less DSHEA authorizes structure/function FDA continues to believe that likely to undertake future research and claims that are not also disease claims, structure/function claims should not development, compromising one of the but nevertheless asserted that the statute imply disease treatment or prevention. nation’s most important sources of authorizes structure/function claims Most disease treatment or prevention therapeutic advances. Had Congress that imply ‘‘some protection against claims, including claims about serious intended to allow implied disease disease.’’ This comment reasoned that and life-threatening diseases, can be claims when it authorized dietary the act, as amended by DSHEA, allows described in a manner that will be easily supplement manufacturers to make dietary supplements to be ‘‘intended’’ to understood by consumers without structure/function claims without prior affect the structure or function of the express reference to a specific disease. review, it could easily have made clear body, provided that the product does The following examples of implied its intention through express statutory not ‘‘expressly claim to prevent, etc. disease claims demonstrate that it is not language or legislative history. As disease’’ (emphasis in original) and the difficult to convey prevention or discussed below, Congress did not do product bears ‘‘an express, formal treatment of a specific disease or class so. disclaimer of an intent to prevent, etc. of diseases without actually mentioning FDA does not agree that the final rule disease.’’ The comment also said that the name of the disease, which are given eliminates all meaningful claims for the Commission report only referred to in parentheses: ‘‘Relieves crushing chest dietary supplements. FDA believes that express claims. pain’’ (angina or heart attack), ‘‘prevents there are many meaningful structure/ Third, DSHEA requires structure/ bone fragility in post-menopausal function claims that can be made function claims to be accompanied by a women’’ (osteoporosis), ‘‘improves joint without implying disease treatment or disclaimer that reads, in part: ‘‘[T]his mobility and reduces joint inflammation prevention, and has listed a number of product is not intended to diagnose, and pain’’ (rheumatoid arthritis), ‘‘heals such claims in this preamble. treat, cure, or prevent any disease.’’ stomach or duodenal lesions and FDA does not agree that treating According to some comments, Congress bleeding’’ (ulcers), ‘‘anticonvulsant’’ implied claims as disease claims gives understood that specific disease (epilepsy), ‘‘relief of bronchospasm’’ the agency unfettered discretion to treat treatment or prevention effects can also (asthma), ‘‘prevents wasting in persons all structure/function claims as disease be described as effects on the structure with weakened immune systems’’ claims. The purpose of this rule is to or function of the body, and resolved (AIDS) (acquired immune deficiency clarify which claims are structure/ the tension by requiring the disclaimer. syndrome), ‘‘prevents irregular function claims permitted under section In contrast, however, another comment heartbeat’’ (arrhythmias), ‘‘controls 403(r)(6) of the act and which are argued that the drug definition in blood sugar in persons with insufficient disease claims. Both in the proposed section 201(g)(1)(B) of the act still insulin’’ (diabetes), ‘‘prevents the spread rule and in this final rule, FDA has applies to dietary supplements because of neoplastic cells’’ (prevention of provided many examples of specific the exemption for dietary supplements cancer metastases); ‘‘antibiotic’’ claims that would be acceptable added to section 201(g)(1) applies only (infections), ‘‘herbal Prozac’’ structure/function claims. to the structure/function definition in (depression). The distinction between (35.) Many comments pointed to three section 201(g)(1)(C). Many comments implied and express disease claims is provisions of DSHEA as evidence that argued generally that DSHEA was thus, in many cases, a semantic one that Congress intended to include implied intended to promote the free flow of has little, if any, practical meaning to disease claims among structure/function truthful information about dietary consumers. The argument that Congress claims permitted under section 403(r)(6) supplements, and that prohibiting intended to encourage the free flow of of the act. First, the ‘‘Findings’’ section implied disease claims is contrary to information about dietary supplements of DSHEA refers to the relationship this legislative goal. and therefore intended to permit between dietary supplements and FDA does not agree that DSHEA implied disease claims is illogical. If disease prevention. Many comments authorizes dietary supplement Congress wanted to ensure that argued that Congress would not have manufacturers to make implied disease consumers receive information about made statutory findings linking dietary claims without prior review of the how these products can treat or prevent supplements to disease prevention if it claims. There is no express provision of diseases, it is difficult to imagine why intended that FDA could prohibit such DSHEA that authorizes implied disease it would have specifically denied the references. claims, and a construction of DSHEA right to make such claims expressly, and Second, section 403(r)(6) of the act that permitted such claims would be allowed manufacturers to make the states that structure/function statements fundamentally incompatible with claims only by implication. may not ‘‘claim’’ to treat or prevent important provisions of the act that There are also serious public health disease, and, according to the were squarely before Congress when it questions raised by implied disease comments, this term should be read to passed DSHEA, including the claims. Treatment and prevention of refer only to express claims. Some definitions of ‘‘drug’’ and ‘‘new drug’’ disease are serious matters, and the comments noted that section 403(r)(6) of and the health claims provisions of statute reflects a congressional judgment the act does not use the word ‘‘implied’’ NLEA. that consumers deserve to have claims to qualify the term ‘‘claims,’’ and As described above, Congress created for such uses reviewed by experts for contrasted the language of the drug a partial exemption for dietary proof of safety and effectiveness. In definition in section 201(g)(1)(B) of the supplements from the definition of drug addition, permitting dietary supplement act (‘‘articles intended for use in the in section 201(g)(1)(C) of the act by manufacturers to make implied disease diagnosis, cure, mitigation, treatment, or providing that truthful and non- claims without prior review would prevention of disease’’) with the misleading claims under section

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403(r)(6) of the act do not in themselves Permitting implied disease claims as prevention of disease.’’ FDA has trigger drug regulation. Congress did structure/function claims would also interpreted section 201(g)(1)(B) of the not, however, create any exemption conflict with the health claims scheme act to cover both express and implied from section 201(g)(1)(B) of the act for established in section 403(r)(1) through claims for more than 50 years. Had dietary supplements. Thus, dietary (r)(1)(5) of the act, which requires food Congress intended 403(r)(6) of the act to supplements that are ‘‘intended for use and dietary supplement manufacturers permit any claims covered by section in the diagnosis, cure, mitigation, to obtain health claim authorization 201(g)(1)(B) of the act, it would have treatment, or prevention of disease’’ are before making a claim ‘‘which expressly had to provide an exemption from the subject to regulation as drugs under the or by implication’’ characterizes the latter section. act. It has been FDA’s longstanding relationship of a nutrient to a disease or Further, FDA does not agree that the interpretation of section 201(g)(1)(B) of health-related condition. Under this Commission report referred only to the act that the phrase ‘‘intended for provision, a claim that characterized, by express claims. In its guidance on use’’ refers to the objective intent of the implication, the relationship between a statements under section 403(r)(6) of the manufacturer, which is not limited to a dietary supplement ingredient and a act, the Commission specifically said manufacturer’s express representations. disease would require authorization as a that such statements ‘‘should be distinct See § 201.128 (21 CFR 201.128); NNFA health claim. Interpreting section from NLEA health claims in that they do v. Weinberger, 557 F.2d 325, 334 (2d 403(r)(6) of the act as permitting the not state or imply a link between a Cir. 1977) (‘‘the FDA is not bound by the same implied claim without supplement and prevention of a specific manufacturer’s subjective claims of authorization of a health claim directly disease or health-related condition’’ (the intent,’’ but may establish intent ‘‘on the conflicts with 403(r)(1) through (r)(1)(5) report, p. 38) (emphasis added). In basis of objective evidence’’). Evidence of the act. addition, the Commission cautioned of objective intent can come from a None of the statutory provisions that claims using terms such as, e.g., variety of sources, and may include both relied on by the comments provides ‘‘support,’’ ‘‘maintain,’’ or ‘‘promote’’ implied and express claims (United persuasive support for the conclusion are appropriate only if they do not States v. Undetermined Quantities * * * that structure/function claims can imply ‘‘suggest disease prevention or treatment Pets Smellfree, 22 F.3d 235 (10th Cir. disease treatment or prevention. or use for a serious health condition that 1994); United States v. Storage Spaces FDA agrees that the Findings section is beyond the ability of the consumer to Designated Nos. ‘‘8’’ and ‘‘49’’, 777 F.2d of DSHEA includes statements linking evaluate’’ (the report, p. 38) (emphasis 1363, 1366 (9th Cir. 1985) (‘‘intent may dietary supplements and disease added). Clearly, the Commission was be derived or inferred from labeling, prevention. However, in addition to the concerned about implied claims as well promotional material, advertising, or types of claims authorized for dietary as express claims. supplements in section 403(r)(6) of the FDA also does not agree that the any other relevant source’’), cert. act, the act specifically authorizes required disclaimer demonstrates an denied, 479 U.S. 1086 (1987); United dietary supplements to bear health intention to permit implied claims. To States v. Kasz Enterprises, Inc. 855 F. claims. Health claims are expressly the contrary, FDA believes that the Supp. 534, 539, 543–44 (D.R.I. 1994), described in the statute as claims that disclaimer language (‘‘This product is modified on other grounds, 862 F. Supp. characterize the link between a nutrient not intended to diagnose, treat, cure, or 717 (D.R.I. 1994); United States v. and a disease or health-related prevent any disease’’), which is virtually Articles of Drug * * * Neptone, 568 F. condition (section 403(r)(1)(B) of the identical to the language of section Supp. 1182 (N.D. Ca. 1983); United act). The statements in the ‘‘Findings’’ 201(g)(1)(B) of the act, provides further States v. * * * Vitasafe, 226 F. Supp. 266 section of the DSHEA are entirely evidence that Congress did not intend (D.N.J. 1964); United States v. 14 105 consistent with this scheme and do not section 403(r)(6) of the act claims to Pound Bags * * * Mineral Compound, compel the conclusion that claims overlap section 201(g)(1)(B) claims. As a 118 F. Supp. 837 (D.C. Idaho 1953); linking dietary supplements and disease practical matter, it is unreasonable to United States v. 43 1/2 Gross Rubber prevention may be made as structure/ interpret section 403(r)(6) of the act as Prophylactics, 65 F. Supp. 534, 535 (D. function claims. inviting a communication to consumers Minn. 1946), aff’d sub nom. Gellman v. The use of the word ‘‘claim’’ rather like the following: ‘‘This product United States, 159 F.2d 881 (8th Cir. than ‘‘intended for use’’ in section prevents bone fractures in post- 1947); 59 FR 6084, 6088 (February 9, 403(r)(6) of the act also does not show menopausal women due to bone loss. 1994) (terms ‘‘antibacterial,’’ that Congress intended to permit This product is not intended to ‘‘antimicrobial,’’ ‘‘antiseptic,’’ or ‘‘kills implied disease claims. First, the diagnose, treat, cure, or prevent any germs’’ constitute implied drug claims comment cites no authority, and FDA is disease.’’ The comments suggested that that cause products carrying them to be aware of none, for the proposition that the addition of the disclaimer would drugs); 58 FR 47611, 47612 (September the meaning of the word ‘‘claim’’ is somehow clarify the product’s purpose 9, 1993) (labeling indicating that limited to ‘‘express claim.’’ More to consumers. The comments provided ‘‘hormones’’ are present in a product importantly, section 403(r)(6) of the act no support, however, for their view that constitutes implied drug claim); 58 FR does not stand by itself. As Congress consumers reading the disclaimer 28194, 28204 (May 12, 1993) (products recognized when it provided that would interpret it as eliminating carrying term ‘‘sunscreen’’ are drugs dietary supplements making appropriate implications in the remainder of the because ‘‘sunscreen’’ implies disease claims under section 403(r)(6) of the act labeling that the product treats or prevention, even if not expressly do not thereby become drugs under prevents disease. FDA believes that the promoted for prevention of skin section 201(g)(1)(C) of the act, section two statements simply contradict one cancer)). 403(r)(6) must be read in conjunction another and could confuse consumers. Thus, interpreting section 403(r)(6) of with section 201(g)(1). As described Indeed, FDA is concerned that the act as permitting implied disease above, section 201(g)(1)(B) of the act juxtaposing two such contradictory claims would be irreconcilable with continues to apply to dietary statements is likely to cause consumers FDA’s longstanding interpretation of supplements and treats them as drugs if to ignore the disclaimer required by section 201(g)(1)(B) of the act, which they are ‘‘intended for use in the section 403(r)(6) of the act, undermining treats such claims as drug claims. diagnosis, cure, mitigation, treatment, or its effectiveness.

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(36.) A few comments addressed the FDA does not agree that every to the National Cancer Institute’’ would examples of implied claims listed in the structure/function claim implies disease be a disease claim because it used the July 8, 1999, Federal Register notice. prevention or treatment. In the proposed word ‘‘cancer.’’ Some comments said that all of the rule, FDA provided examples of many Although the National Cancer examples were appropriate structure/ types of claims that the agency would Institute (NCI) is associated with the function claims. Two comments not consider implied disease claims, treatment and prevention of cancer, suggested that ‘‘shrinks tumors,’’ and has expanded that list in the final such a statement will be considered a ‘‘prevents development of malignant rule. disease claim only if, within the context tumors,’’ and ‘‘prevents seizures’’ are (38.) Some comments disagreed with of the total labeling, the statement can express disease claims because they FDA’s examples of disease claims in the be reasonably understood to relate the employ ‘‘synonyms’’ for specific proposed rule. These comments stated product to the disease listed in the diseases. According to these comments, that intoxication and constipation are organization’s name, e.g., cancer. For ‘‘tumor’’ is a synonym for cancer, and not in and of themselves diseases, and example, FDA would regard as a disease ‘‘seizure’’ is a synonym for epilepsy. that these conditions are not readily claim ‘‘According to the National Another comment said that FDA should understood by consumers as diseases. A Cancer Institute, ingredient X protects treat as implied disease claims only few comments argued that alcohol smokers’ lungs.’’ intoxication is a ‘‘self-induced those claims ‘‘where there is a direct F. Signs or Symptoms of Disease condition’’ and not a disease. causal relationship between the (§ 101.93(g)(2)(ii)) structure/function parameter identified FDA continues to believe that alcohol in the claim and a specific known intoxication, like all poisonings Under proposed § 101.93(g)(2)(ii), a disease.’’ According to this comment, a (mushroom, digitalis, or any drug statement would be considered a tumor is a ‘‘direct manifestation of overdose), meets the definition of disease claim if it explicitly or cancer’’ and therefore reference to a disease, albeit a transient disease. The implicitly claimed an effect (using tumor is a disease claim. In contrast, definition in § 101.14(a)(5), which FDA scientific or lay terminology) on one or risk factors for disease, in which the is incorporating in this rule, states, in more signs or symptoms that are comment includes elevated cholesterol, part, that a disease is ‘‘damage to an recognizable to health care professionals are not direct manifestations of a organ, part or structure, or system of the or consumers as being characteristic of disease, and therefore may be the body such that it does not function a specific disease or of a number of subject of structure/function claims. properly * * *’’ All poisonings, like diseases. FDA provided as examples of Another comment contended that alcohol intoxication, cause dose-related such disease claims: ‘‘Improves urine disease claims should be limited to dysfunctioning and damage, ranging flow in men over 50 years old,’’ ‘‘lowers express claims and to terms or from mild impairments to death. cholesterol,’’ ‘‘reduces joint pain,’’ and measurements that are ‘‘surrogates for Alcohol intoxication causes temporary ‘‘relieves headache.’’ Stating that claims the disease itself.’’ According to this damage to brain function, causing of an effect on symptoms that are not comment, tumors are a surrogate for impairments of judgment, attention, recognizable as characteristic of a cancer, but elevated cholesterol is not a reflexes, and coordination. The fact that specific disease or diseases would not surrogate for heart disease. One it is ‘‘self-induced’’ does not remove it constitute disease claims, FDA provided comment argued that ‘‘relief of sneezing, from the definition of disease. the following examples of acceptable runny nose, and itchy watery eyes Deliberate barbiturate overdoses are also structure/function claims: ‘‘Reduces caused by exposure to pollen or other self-induced, but clearly meet the stress and frustration,’’ ‘‘inhibits platelet allergens’’ is an acceptable structure/ definition of disease. aggregation,’’ and ‘‘improves function claim, but did not explain why. FDA has considered the comments on absentmindedness.’’ The agency also FDA has considered these comments, constipation and agrees that certain stated that if the context did not suggest but does not believe that any of them constipation claims should not be treatment or prevention of a disease, a have provided a principle that treated as disease claims. Constipation claim that a substance helps maintain distinguishes between claims that has a variety of causes, many of them normal function would not ordinarily be consumers will understand as disease unrelated to disease. For example, a disease claim. Examples included: claims and those that will not be constipation can be caused by changes ‘‘Helps maintain a healthy cholesterol understood as disease claims. According in diet and schedule, and by travel. level,’’ or ‘‘helps maintain regularity.’’ to the comments, some of the claims Constipation can also, however, be a FDA specifically requested comment that FDA offered as examples of implied symptom of such serious diseases as on the distinction between maintaining disease claims should not be allowed as bowel obstruction and irritable bowel normal function, which is potentially structure/function claims. FDA agrees syndrome. FDA is aware that there may the basis for an acceptable structure/ that claims that refer to synonyms for be differences of opinion about whether function claim, and preventing or disease, direct manifestations of disease, occasional constipation, alone, treating abnormal function, which is and surrogates for disease are disease constitutes a disease, but believes that potentially a disease claim. FDA noted claims. Each of these principles, treating it as a disease would not be that the members of the Commission however, would permit many types of consistent with the intent of DSHEA. were divided on this issue, but that the implied disease claims that would be ‘‘For relief of occasional constipation’’ final report concluded that ‘‘statements clearly understood by consumers as would therefore not be considered a that mention a body system, organ, or disease claims, e.g., ‘‘Herbal Prozac’’ disease claim under the rule. The function affected by the supplement and ‘‘antibiotic.’’ labeling of a product that claimed to using terms such as ‘stimulate,’ (37.) Some comments argued that it is treat occasional constipation should ‘maintain,’ ‘support,’ ‘regulate,’ or impossible to construct a structure/ make clear, however, that the product is ‘promote’ can be appropriate when the function claim that does not imply not intended to be used to treat chronic statements do not suggest disease disease prevention or treatment. Several constipation, which may be a symptom prevention or treatment or use for a of these comments claimed that health of a serious disease. serious health condition that is beyond promotion claims inevitably imply (39.) One comment questioned the ability of the consumer to evaluate’’ disease prevention. whether a claim that begins, ‘‘According (the report, p. 38). Recognizing that

VerDate 04-JAN-2000 16:16 Jan 05, 2000 Jkt 190000 PO 00000 Frm 00017 Fmt 4701 Sfmt 4700 E:\FR\FM\06JAR4.XXX pfrm11 PsN: 06JAR4 1016 Federal Register / Vol. 65, No. 4 / Thursday, January 6, 2000 / Rules and Regulations claims relating to maintaining healthy FDA does not agree with the comment ‘‘improves absentmindedness’’ could be cholesterol levels raise particularly that objected to the recognition standard interpreted as a treatment for difficult issues, FDA sought specific because it would prohibit a claim ‘‘as Alzheimer’s disease. comment on these claims. soon as consumers understood that FDA believes that removing the (40.) Many comments from certain signs and symptoms are reference to recognition by consumers manufacturers and individuals objected characteristic of a disease—that is, as or health professionals from to proposed § 101.93(g)(2)(ii). Some of soon as consumers understood why they § 101.93(g)(2)(ii) will permit a clearer these comments argued that basing the should take a particular supplement * * distinction between those signs and criterion on which signs and symptoms *.’’ This comment assumes that the only symptoms that imply a disease and were ‘‘recognizable’’ to health care reason people take dietary supplements those that do not. The focus will be on professionals or consumers was too is to treat or prevent disease and that it whether specific signs or symptoms are vague, and that it was unclear what is appropriate to market supplements by characteristic of a disease, based on proportion of health care professionals implying that they can do so. Many objective sources. FDA does not believe or consumers would be necessary to people take dietary supplements for that ‘‘improves absentmindedness’’ or establish recognition. Some comments health-related reasons that do not ‘‘relieves stress and frustration’’ are asked whether FDA expected involve treatment or prevention of characteristic of the specific diseases manufacturers to conduct consumer specific diseases. As discussed mentioned in the comments. FDA agrees surveys. Other comments urged that elsewhere in this document, FDA does that some signs and symptoms are FDA itself conduct consumer surveys to not believe that the act permits associated with such a wide variety of determine which signs and symptoms structure/function claims to imply diseases and nondisease states that they were recognizable to consumers as treatment or prevention of specific may not imply a specific disease or class implied disease claims. Other comments diseases. of diseases. For example, FDA would not interpret ‘‘improves argued that the proposed provision (41.) Several comments contended absentmindedness’’ as implying would create a moving target because that the recognition standard was too treatment of Alzheimer’s disease ‘‘as soon as consumers understood that restrictive because all signs or because absentmindedness is not as certain signs and symptoms are symptoms relating to the structure or serious as the type of memory loss characteristic of a disease—that is, as function of the body are potentially characteristically suffered by soon as consumers understood why they recognizable to health care professionals should take a particular supplement— Alzheimer’s patients; absentmindedness and educated consumers as is, in fact, suffered predominantly by FDA could * * * prohibit a product label characteristic of some specific disease. from bearing the substantive claims people who do not have Alzheimer’s Another comment argued that the disease or any other disease. Stress and information.’’ proposal to treat references to signs and frustration, while associated with some FDA agrees with these comments that symptoms as disease claims was anxiety disorders, are not the the proposal’s focus on recognition of arbitrary and artificial. The comment characteristic symptoms of those signs and symptoms by consumers or said that specific examples of disease disorders; in addition, these symptoms health professionals might have made claims used in the proposal could as are equally associated with many other the provision difficult to apply, both for easily refer to nondisease states, e.g., nondisease states. manufacturers and for the agency. ‘‘reduces joint pain’’ could refer to over- The agency does agree, however, with Accordingly, the agency has substituted exercise. Conversely, ‘‘stress and the comment that ‘‘inhibits platelet a more objective criterion. The final rule frustration’’ could refer to anxiety and aggregation’’ is an implied disease eliminates the reference to recognition, depression. Another comment treatment or prevention claim. Although and focuses simply on whether the contended that ‘‘reduces joint pain’’ is platelet aggregation is a normal function labeling suggests that the product will an acceptable structure/function claim if needed to maintain homeostasis, produce a change in the characteristic other language or graphics in the inhibiting or decreasing platelet signs or symptoms of a specific disease labeling clearly communicated aggregation is a well-recognized therapy or class of diseases. FDA believes that treatment of conditions unrelated to for the prevention of stroke and it will be easier for manufacturers to arthritis. One comment asked whether recurrent heart attack (see, e.g., 63 FR verify whether symptoms are in fact ‘‘helps support cartilage and joint 56802, October 23, 1998 (final rule for characteristic of a disease. FDA and function’’ would constitute a professional labeling of aspirin for manufacturers may look to medical texts permissible structure/function claim. cardiovascular, cerebrovascular, and and other objective sources of Some comments said that references to rheumatologic uses); 53 FR 46204, information about disease to determine signs and symptoms should not be November 16, 1988, (internal analgesic whether a label implies treatment or evidence of a disease claim because tentative final monograph)). Inhibiting prevention of disease by listing the signs and symptoms can be associated or decreasing platelet aggregation is the characteristic signs and symptoms of a with a number of varying conditions. mechanism of action of a number of disease or class of diseases. One comment claimed that ‘‘inhibits drug products approved for the FDA notes that the standard in the platelet aggregation’’ does not mean treatment or prevention of stroke and rule may be met if characteristic signs anything to most consumers. On the heart attack. Thus, the agency would and symptoms are referred to either in other hand, some medical groups, consider a claim to inhibit normal technical or lay language. It also would groups devoted to specific diseases, and platelet function to be an implied claim not be necessary to mention every others expressed concern that the to treat or prevent these disease possible sign or symptom of a disease to examples of structure/function claims conditions. meet this standard. Instead, the standard provided by FDA permitted references FDA also believes that ‘‘joint pain’’ is focuses on whether the labeling suggests to signs or symptoms that imply disease characteristic of arthritis. According to that the product will produce a change treatment or prevention. According to the Merck Manual, joint tenderness is in a set of one or more signs or one comment, ‘‘inhibits platelet the most sensitive physical sign of symptoms that are characteristic of the aggregation’’ could be interpreted to rheumatoid arthritis (Ref. 6). The claim disease. mean ‘‘prevents heart attack,’’ and ‘‘helps support cartilage and joint

VerDate 04-JAN-2000 16:16 Jan 05, 2000 Jkt 190000 PO 00000 Frm 00018 Fmt 4701 Sfmt 4700 E:\FR\FM\06JAR4.XXX pfrm11 PsN: 06JAR4 Federal Register / Vol. 65, No. 4 / Thursday, January 6, 2000 / Rules and Regulations 1017 function,’’ on the other hand, would be in dietary supplement labeling Comments from dietary supplement a permissible structure/function claim, constitutes a disease claim. Another manufacturers and some consumer because it relates to maintaining normal comment argued that because signs and groups argued that both types of claims function rather than treating joint pain. symptoms do not appear in the should be permitted either because they (42.) One comment suggested that definition of ‘‘drug,’’ FDA is not are not implied disease claims or claims about a physiologic marker or authorized to treat a reference to because implied disease claims are symptom should be regarded as disease characteristic signs and symptoms as a permissible. Conversely, most of the claims in two situations: (1) If the drug claim. comments from health professional physiologic marker or symptom of a The health claims definition of groups, groups devoted to specific disease is described as being ‘‘disease or health-related condition’’ in diseases, pharmaceutical companies, quantifiably linked to that disease in an § 101.14(a)(5), which is being adopted as and other consumer groups argued that official government health agency the definition of ‘‘disease’’ in this neither type of claim should be summary statement or consensus report, regulation, does not include reference to permitted, because permitting implied or (2) if most clinicians treating patients the signs and symptoms of disease. disease claims to be made without prior with the condition prescribe Nonetheless, dietary supplement review would jeopardize the public prescription drugs to modify the marker labeling that refers to the characteristic health by encouraging substitution of and historically do so without including signs or symptoms of a specific disease nutritional or dietary intervention as or class of diseases will still be unproven remedies for proven ones. part of the treatment. According to this considered to have made an implied One comment argued that analysis of comment, references to cholesterol disease claim. Labeling that claims a health maintenance claims is no lowering or blood pressure reduction product ‘‘prevents bone fragility in post- different than analysis of any other would be regarded as disease claims menopausal women,’’ clearly implies structure/function claim: They are under the first suggested criterion, and that the product prevents osteoporosis. disease claims if they imply disease white cell counts and fever would be Similarly, labeling that claims a product prevention or treatment. According to disease claims under the second. This ‘‘prevents shortness of breath, an this comment, health maintenance comment also suggested that FDA enlarged heart, inability to exercise, claims are permissible unless they relate develop a list of disease markers and generalized weakness, and edema’’ has to endpoints that are understood to be symptoms that fall under each of the made a congestive heart failure claim. disease markers, such as blood pressure proposed criteria. The basis for determining whether and cholesterol. Comments from a FDA agrees in part and disagrees in such a reference to signs or symptoms former Commission member and from a part with this comment. The agency constitutes an implied disease claim is consumer group argued that many agrees that references in dietary not whether the definition of disease health maintenance claims will be supplement labeling to physiologic includes mention of signs or symptoms. perceived as disease treatment or markers or symptoms of a disease that Rather, FDA looks at whether the prevention claims, and urged that FDA are quantifiably linked to that disease in objective evidence shows that the follow the Commission’s guidelines, an official government health agency product is ‘‘intended for use in the under which the seriousness of the summary statement or consensus report diagnosis, cure, mitigation, treatment, or condition and the ability of the would be appropriately treated as prevention of disease’’ within the consumer to evaluate it are key factors implied disease claims. Indeed, in the meaning of section 201(g)(1)(B) of the in deciding whether a disease claim has cases described, elevated blood pressure act and § 201.128, or the claim been made. One comment argued that (hypertension) and elevated cholesterol constitutes a health claim within the FDA may not prohibit a claim that a (hypercholesterolemia) are diseases meaning of section 403(r)(1)(B) of the dietary supplement ‘‘maintains normal themselves, with subsequent events act and § 101.14(a)(1). For example, function’’ even if it implies a disease (heart attack, stroke) the late § 201.128 provides that the objective claim because 403(r)(6)(A) of the act consequences of those diseases. intent of those responsible for the expressly authorizes such claims. Although FDA agrees that fever and labeling of drugs ‘‘is determined by such elevated white cell counts are almost persons’ expressions or may be shown One comment said that the proposed always evidence of a disease, FDA does by the circumstances surrounding the rule would frustrate the ‘‘orphan drug’’ not agree that the second criterion distribution of the article.’’ Section process. The comment contended that if appropriately describes the remaining 101.14(a)(1) provides that ‘‘[i]mplied dietary supplement labeling may claim circumstances in which references to health claims include those statements, to promote or maintain ‘‘healthy’’ signs or symptoms should be treated as symbols, vignettes, or other forms of endpoints that are related to signs and disease claims. The appropriate test is communication that suggest, within the symptoms of specific diseases, then whether: (1) The condition to be treated context in which they are presented, incentives to conduct research on or prevented is a disease and (2) the that a relationship exists between the orphan drugs would be undermined. signs and symptoms referred to in the presence or level of a substance in the The comment explained that dietary labeling, in context, are characteristic of food and a disease or health-related supplements do not require the same a disease and thus permit the inference condition.’’ Both of these provisions financial investment as drugs do that the product is intended to treat or permit FDA to look at whether a (because drugs must be approved as safe prevent the disease. The second reference to the characteristic signs or and effective for their intended uses and criterion offered by the comment does symptoms of a disease constitute an meet quality controls), and could not provide information on either of implied disease claim. undercut sales of a more heavily these elements. (44.) Many comments argued that the regulated and more expensive approved (43.) Some comments that objected to distinction between claims that a drug. The comment said that a dietary the proposed definition of disease product maintains healthy function and supplement manufacturer’s ability to argued that the inclusion of ‘‘signs or that it prevents or treats abnormal make a disease prevention claim by symptoms’’ as part of the definition of function is artificial, and that consumers characterizing the product as promoting disease should not mean that a reference understand both types of claims as good health ‘‘cannot become a license to to the signs and symptoms of a disease disease treatment or prevention claims. sell an active ingredient in a product

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Several comments argued that function is supported by the statute and suggest disease prevention or treatment or use for a serious health condition that is lowering cholesterol is inextricably the Commission report. FDA does not beyond the ability of the consumer to linked to cardiovascular disease. Some agree that health maintenance claims evaluate. comments argued that the distinction must always be treated as implied 5. Statements should not be made that between maintaining normal cholesterol disease claims. Section 403(r)(6)(A) of products ‘‘restore’’ normal or ‘‘correct’’ and lowering cholesterol is arbitrary the act demonstrates that Congress abnormal function when the abnormality because both have as their purpose intended to treat as structure/function implies the presence of disease. An example preventing heart disease, and consumers claims some claims concerning might be a claim to ‘‘restore’’ normal blood link cholesterol levels with disease pressure when the abnormality implies maintenance of normal structure or prevention. Other comments, however, function, because it expressly permits hypertension. (Report at pp. 38 and 39.) argued that cholesterol claims do not statements that ‘‘characterize the imply disease prevention. A comment documented mechanism by which a FDA agrees that if a health maintenance claim implies disease from an organization devoted to nutrient or dietary ingredient acts to prevention and treatment of heart maintain such structure or function.’’ treatment or prevention, it would not be acceptable. (In FDA’s view, a claim disease argued that if any cholesterol FDA also believes that many claims claims were to be permitted, a claim like concerning the maintenance of promoting ‘‘use for a serious health condition that is beyond the ability of ‘‘promotes cholesterol clearance’’ would ‘‘normal’’ or ‘‘healthy’’ structure or be a more accurate structure/function function do not imply disease the consumer to evaluate’’ is simply one form of implied disease claim.) FDA statement than ‘‘maintains healthy prevention in the context of dietary cholesterol’’ and less likely to imply supplement labeling, unless other believes that many health maintenance claims are acceptable. In some cases, a disease prevention. Two comments statements or pictures in the labeling contended that changing a claim from imply prevention of a specific disease or health maintenance claim could use terms that are so closely identified with ‘‘lowers cholesterol’’ to ‘‘maintains class of diseases. There may be cases, healthy cholesterol levels’’ does not however, in which a statement of health a specific disease or that so clearly refer to a particular at-risk population that change the effect of the product or its maintenance can be understood only as use. Some comments argued that a claim of prevention of a specific FDA would consider the claim to be an ‘‘lowers cholesterol’’ claims should be disease, in which case it will be implied disease prevention claim, e.g., permitted for cholesterol levels that are considered a disease claim. Thus, any ‘‘maintains healthy lungs in smokers’’ not ‘‘abnormal’’ or are below reference to ‘‘maintaining a tumor-free would imply prevention of tobacco- hypercholesterolemia. state’’ would be a disease claim. related lung cancer and chronic lung Similarly, a claim to ‘‘maintain normal disease. ‘‘Maintains healthy lung FDA does not agree that claims bone density in post-menopausal function,’’ alone, however, would be an concerning maintenance of normal women’’ is a disease claim because post- acceptable structure/function claim. cholesterol levels necessarily constitute menopausal women characteristically In response to the comment implied disease claims. Although an develop osteoporosis, a disease whose contending that dietary supplements elevated cholesterol level is a sign of principal sign is decreased bone mass. undercut sales of orphan drugs by hypercholesterolemia and an important FDA has added a sentence to making health promotion claims for risk factor for heart disease, a § 101.93(g)(2) clarifying that the criteria active ingredients already approved as cholesterol level within the normal in that paragraph are not intended to orphan drugs, FDA notes that section range is not a sign or risk factor for preclude structure/function claims that 201(ff)(3) of the act excludes from the disease. Moreover, maintaining refer to the maintenance of healthy definition of ‘‘dietary supplement’’ cholesterol levels within the normal structure or function, unless they imply articles that have been approved as range is essential to the structure and disease treatment or prevention. drugs or for which substantial clinical function of the body for reasons other For the reasons described elsewhere investigations conducted under an than prevention of heart disease. in this document, however, FDA does investigational new drug application Although many people think of not believe that DSHEA permits claims (IND) have been made public, before cholesterol solely in terms of the concerning treatment or prevention of they were marketed as dietary negative role of elevated cholesterol in abnormal function, where such supplements or foods. heart disease, normal cholesterol levels abnormal function implies a specific (45.) Many comments responded to play a positive role in maintaining a disease or class of diseases. FDA’s specific request for comment on healthy body. Cholesterol is a necessary Accordingly, FDA believes that the whether it is appropriate to treat constituent of cell membranes and of statutory scheme is consistent with ‘‘maintains healthy cholesterol levels’’ myelin, the sheath that coats nerves. treating many health maintenance as a permissible structure/function Cholesterol is also required for the statements as structure/function claims, claim, while treating ‘‘lowers synthesis of steroid hormones, which while treating as health claims or new cholesterol’’ as a disease claim. A few are essential for life. Finally, cholesterol drug claims statements that imply comments supported the distinction is required for the production of bile in disease treatment or prevention by drawn in the proposed rule. Many did the liver, making possible absorption of reference to an effect on abnormal not, however. One comment from a dietary fat and fat soluble vitamins. structure or function. major trade association claimed that the Thus, a claim that a dietary supplement The Commission report also supports distinction between lowering and helps maintain cholesterol levels that the distinction drawn by FDA between maintaining cholesterol levels is are already within the normal range maintaining healthy function and ambiguous, asking ‘‘What is a healthy does not necessarily imply disease

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Although DSHEA disease) but not others (e.g., hot flashes, that references to ‘‘healthy’’ cholesterol requires that manufacturers who make common symptoms associated with the may be misleading to consumers structure/function claims have menstrual cycle, and decreased sexual because the phrase ‘‘healthy substantiation, manufacturers are not function associated with aging), what cholesterol’’ is now frequently used to currently required to submit that would be an appropriate principle for refer to high density lipoproteins (HDL), substantiation to FDA for premarket distinguishing the two groups? (2) For a specific cholesterol fraction believed review, nor does FDA have the example, would it be appropriate to to be beneficial. To avoid this resources to inspect and review the consider the severity of the health confusion, FDA has concluded that an quality of the substantiation in most consequences if the condition were to appropriate structure/function claim for cases. For this reason, FDA does not go without effective treatment? (3) If so, maintaining cholesterol would be believe that permitting ‘‘lowers how should ‘‘severity’’ be defined? ‘‘helps to maintain cholesterol levels cholesterol’’ claims on dietary (48.) Although some comments from that are already within the normal supplements without prior review disease-specific organizations and range.’’ serves the public health. health professionals supported this FDA continues to believe that ‘‘lowers (47.) A few comments argued that provision, most of the comments cholesterol,’’ however qualified, is an FDA may not prohibit ‘‘lowers strongly objected to classifying common implied disease claim. As many cholesterol’’ claims because the agency conditions associated with natural states comments argued, lowering cholesterol had earlier issued an advisory letter as diseases. None of the objecting is inextricably linked in the public mind permitting such claims if the claim comments argued that toxemia of with treating elevated cholesterol and stated that the product was useful in the pregnancy or Alzheimer’s disease are preventing heart disease. The agency context of a healthy diet. One of these not diseases. Almost all of these also believes that ‘‘promotes cholesterol comments contended that the agency comments, however, contended that clearance’’ is an implied disease claim may not change its advice or guidance PMS, hot flashes, and various because it is directed at lowering because it has cited no studies in this conditions associated with aging, such cholesterol rather than maintaining rulemaking to support the view that as decreased sexual function, are so levels already determined to be within ‘‘lowers cholesterol’’ implies disease common that they should be considered a normal range. FDA will review all treatment. neither abnormal nor diseases. Some cholesterol claims to determine whether FDA does not agree that it may not comments argued that any condition the labeling as a whole implies that the change its position on whether suffered by more than 50 percent of the product is intended to lower elevated particular cholesterol claims imply population should be considered cholesterol levels. In such cases, FDA disease treatment. The record and normal and not a disease, and gave as would consider the labeling to create an analysis in this rulemaking, as well as an example benign prostatic implied disease claim. FDA’s experience in implementing hypertrophy. Other comments cited (46.) A comment from a former DSHEA, provide an ample basis for the prevalence rates for conditions such as Surgeon General of the United States conclusions that the agency has reached PMS and hot flashes, and contended argued that, given the importance of on cholesterol claims. that the cited rates were too high for preventing cardiovascular disease, these conditions to be considered dietary supplements should be G. Conditions Associated With Natural States (§ 101.93(g)(2)(iii)) abnormal. A large number of comments permitted to make claims for cholesterol asserted that the proposed rule would reduction, because ‘‘our citizens deserve The proposed rule stated that natural treat pregnancy, menopause, and aging the opportunity to know when safe and states such as aging, menopause, as diseases. A few comments argued effective dietary supplements are pregnancy, and the menstrual cycle, are that if menopause, aging, and pregnancy available to lower cholesterol.’’ A not themselves diseases, but can be are not diseases, then signs and comment from the Nutrition Committee associated with abnormal conditions symptoms associated with these states of the American Heart Association that are diseases. FDA proposed in cannot be diseases. One comment argued that current scientific evidence § 101.93(g)(2)(iii) to treat as a disease argued that conditions related to natural does not support added benefits of claim a statement that a product had an states are not diseases but ‘‘health- dietary supplementation with nutritive effect on a condition associated with a related conditions’’ and that DSHEA substances for prevention of natural state if the condition presented permits statements about health-related cardiovascular disease in the general ‘‘a characteristic set of signs or conditions. population, and expressed concern that symptoms recognizable to health care In response to the questions in the dietary supplements also carry risks. professionals or consumers’’ as an July 8, 1999, Federal Register notice, FDA agrees that prevention of heart ‘‘abnormality.’’ FDA provided as many comments argued that the severity disease is an extremely important public examples of such abnormal conditions of the condition associated with a health goal. Lowering cholesterol with the following: Toxemia of pregnancy; natural state was not an appropriate certain drugs has been conclusively premenstrual syndrome; hot flashes; principle for distinguishing diseases shown to be effective in reducing and presbyopia, decreased sexual from nondiseases. These comments mortality from coronary artery disease. function, and Alzheimer’s disease generally argued that the severity of the Indeed, the evidence linking the associated with aging. symptoms (rather than the severity of lowering of elevated cholesterol with In the July 8, 1999, Federal Register the consequences of going without preventing heart disease is so strong that notice announcing a public meeting and effective treatment) was not an adequate identifying and using effective therapies reopening the comment period, FDA basis to distinguish diseases from to lower cholesterol in patients with asked for additional comment on this nondiseases. One comment from a food elevated cholesterol levels has become provision of the proposed rule. The industry group argued that this was an of compelling importance. With this in agency sought specific comment on the inappropriate principle because ‘‘all

VerDate 04-JAN-2000 16:16 Jan 05, 2000 Jkt 190000 PO 00000 Frm 00021 Fmt 4701 Sfmt 4700 E:\FR\FM\06JAR4.XXX pfrm11 PsN: 06JAR4 1020 Federal Register / Vol. 65, No. 4 / Thursday, January 6, 2000 / Rules and Regulations natural states can have severe physical and psychological scars if not comments that conditions associated consequences if left unattended.’’ This effectively treated. with a stage of life or a normal comment suggested that conditions that Whether all of these conditions physiological process be considered were ‘‘universal’’ should not be treated represent diseases is, in part, a matter of common if they occur in more than one- as diseases. This comment and one definition and, in part, depends on the half of those experiencing that stage or other also suggested that the consequences of the conditions if not process. distinguishing principle was whether effectively treated, and on how The following are examples of the cause of the condition was commonly they occur, i.e., whether they conditions about which structure/ ‘‘pathological.’’ may be considered ‘‘normal.’’ Although function claims could be made under FDA has reconsidered proposed most people consider the more serious § 101.93(g)(2)(iii): (1) Morning sickness § 101.93(g)(2)(iii), and has concluded or infrequent conditions referred to associated with pregnancy; (2) leg that it is not appropriate, under DSHEA, above to be diseases, views vary with edema associated with pregnancy; (3) to treat certain common, nonserious respect to the common, milder mild mood changes, cramps, and edema conditions associated with natural states conditions. FDA has reconsidered the associated with the menstrual cycle; (4) as diseases. There are a wide variety of position it took in the proposed rule and hot flashes; (5) wrinkles; (6) other signs conditions representing impaired agrees with the comments that treating of aging on the skin, e.g., liver spots, function of an organ or system that are as diseases the common, mild spider veins; (7) presbyopia (inability to associated with particular stages of life symptoms associated with normal life change focus from near to far and vice or normal physiologic processes. These stages or processes would not be versa) associated with aging; (8) mild stages and processes include consistent with the intent of DSHEA. memory problems associated with adolescence, the menstrual cycle, FDA does not believe that the aging; (9) hair loss associated with pregnancy, menopause, and aging. (FDA frequency with which a condition aging; and (10) noncystic acne. The notes that, contrary to the comments, associated with a natural state occurs is, following are examples of conditions the proposed rule would not have by itself, sufficient to distinguish that would remain disease claims: (1) classified these stages or processes diseases from nondiseases. The severity Toxemia of pregnancy; (2) hyperemesis themselves as diseases; it classified only of the consequences of disease, as well gravidarum; (3) acute psychosis of certain abnormal conditions associated as the consequences of ineffective pregnancy; (4) osteoporosis; (5) with these stages or processes as treatment, must also be considered. As Alzheimer’s disease, and other senile diseases.) The conditions associated noted above, whether common, minor dementias; (6) glaucoma; (7) with these stages or processes can vary conditions associated with natural states arteriosclerotic diseases of coronary, from common, relatively mild are diseases is a matter of debate, but cerebral or peripheral blood vessels; (8) abnormalities, for which medical FDA has decided not to treat them as cystic acne; and (9) severe depression attention is not required, to serious diseases because the agency believes associated with the menstrual cycle. conditions that can cause significant or this approach is consistent with the FDA has not included benign permanent harm if not effectively intent of DSHEA. FDA does not, prostatic hypertrophy (BPH) on either of treated. however, believe that DSHEA was these lists, because the agency does not For example, pregnancy is associated intended to permit unreviewed claims believe that BPH should be considered with common and mild abnormalities about serious conditions that could a consequence of aging. Like many other such as morning sickness and leg edema cause significant or permanent harm, diseases, e.g., diabetes, prostate cancer, that cause no permanent harm if left particularly where effective treatment is and heart disease, the incidence of BPH untreated, as well as with such serious available. FDA also does not agree that is much higher among older men. This conditions as hyperemesis gravidarum, ‘‘all natural states can have severe does not mean that BPH or prostate toxemia of pregnancy, and acute consequences if left unattended.’’ FDA cancer is caused by the aging process. psychosis of pregnancy, which can be has listed a large number of conditions Even if BPH were considered a direct life-threatening if not effectively treated. associated with natural states that consequence of aging, however, claims The menstrual cycle is commonly commonly do not have serious to treat or prevent it would still be associated with mild mood changes, consequences even if not effectively treated as disease claims because failure edema, and cramping that do not cause treated. FDA also does not agree that it to obtain effective treatment can cause significant or permanent harm if left is helpful in this context to distinguish significant or permanent harm. untreated, but also, more rarely, with between diseases and nondiseases by FDA notes that it does not base the serious cyclical depression that can asking which have a ‘‘pathological’’ exclusion of the mild common result in significant harm if not basis. The term ‘‘pathological’’ is itself conditions associated with natural states effectively treated. Aging is almost defined by reference to disease, namely, from § 101.93(g)(2)(iii) on the argument invariably associated with characteristic ‘‘caused by or involving disease; advanced by one of the comments that skin and scalp changes, such as morbid’’ (Ref. 7). these are ‘‘health-related conditions’’ wrinkles and hair loss, which do not Accordingly, for purposes of this rule, and that DSHEA permits structure/ need medical attention. It is also, mild conditions commonly associated function claims about health-related however, associated with serious with particular stages of life or normal conditions. FDA believes that a ‘‘health- diseases that will result in significant, physiological processes will not be related condition’’ is a state of health often irreversible damage, many of considered diseases. Therefore, leading to disease. As FDA has said which can be effectively treated. These § 101.93(g)(2)(iii) now states that a previously, ‘‘diseases’’ and ‘‘health- diseases include osteoporosis, statement will be considered a disease related conditions’’ are ‘‘so closely glaucoma, and arteriosclerotic diseases claim if it claims that the product ‘‘has related that no bright-line distinction is of coronary, cerebral, and peripheral an effect on an abnormal condition practicable’’ (58 FR 2478, 2481 January vessels. Adolescence is commonly associated with a natural state or 6, 1993). There is nothing in DSHEA, its associated with mild acne, which does process, if the abnormal condition is legislative history, or in the definition of not cause significant or permanent harm uncommon or can cause significant or ‘‘disease or health-related condition’’ if not treated, and, rarely, with cystic permanent harm.’’ Ordinarily, FDA that would suggest that common acne, which can produce severe would follow the suggestion in the conditions associated with natural states

VerDate 04-JAN-2000 16:16 Jan 05, 2000 Jkt 190000 PO 00000 Frm 00022 Fmt 4701 Sfmt 4700 E:\FR\FM\06JAR4.XXX pfrm11 PsN: 06JAR4 Federal Register / Vol. 65, No. 4 / Thursday, January 6, 2000 / Rules and Regulations 1021 are ‘‘health-related conditions’’ within H. Generally (§ 101.93(g)(2)(iv)) I. Product Name (§ 101.93(g)(2)(iv)(A)) the meaning of section 403(r)(1)(B) of Under proposed § 101.93(g)(2)(iv), (51.) One comment observed that the act. Further, FDA does not agree that FDA stated that a statement would be there is an inconsistency between the section 403(r)(6) of the act authorizes considered a disease claim if it claimed statement in the proposed rule that structure/function claims about ‘‘health- explicitly or implicitly to have an effect ‘‘Heart Tabs’’ does not imply an effect related conditions.’’ Had Congress on disease through one or more of the on a disease and § 101.14(a)(1), which intended to authorize structure/function following factors: (1) The name of the states that: claims about ‘‘health-related product (e.g., ‘‘Carpaltum’’ (carpal Health claim means any claim made on the conditions’’ it could easily have used tunnel syndrome), ‘‘Raynaudin’’ label or in the labeling of a food, including that terminology, but did not. (Raynaud’s phenomenon), ‘‘Hepatacure’’ a dietary supplement, that expressly or by (49.) Some comments concerned (liver problems)). Names that did not implication, including ‘‘third party’’ references, written statements (e.g., a brand specific claims under proposed imply an effect on a disease, such as § 101.93(g)(2)(iii). One comment sought name including a term such as ‘‘heart’’), ‘‘Cardiohealth’’ and ‘‘Heart Tabs,’’ symbols (e.g., a heart symbol) characterizes concurrence that the following are would not constitute disease claims; (2) the relationship of any substance to a disease acceptable structure/function claims: statements about the formulation of the or health-related condition * * * ‘‘supports a normal, healthy attitude product, including a claim that the and requested clarification. during PMS’’ and ‘‘supportive for product contained an ingredient that FDA agrees, in part, and disagrees, in menopausal women.’’ Another comment has been regulated by FDA part, with the comment. FDA does not argued that a statement that a product predominantly as a drug and is well agree that § 101.93(g)(2)(iv)(A) and provides nutrients that diminish the known to consumers for its use in § 101.14(a)(1) are inconsistent. Section normal symptomatology of preventing or treating a disease (e.g., 101.14(a)(1) was issued in 1993 to premenstrual syndrome or menopause aspirin, digoxin, or laetrile); (3) citation implement the health claims provisions is a permissible structure/function of a publication or other reference, if the of NLEA. In § 101.14(a)(1), use of the claim. Another comment asked whether citation refers to a disease use. For term ‘‘heart’’ in a brand name and use ‘‘helps to maintain normal urine flow in example, labeling for a vitamin E of the heart symbol in labeling are men over 50 years old’’ is a permissible product that included a citation to an offered as examples of health claims, if structure/function claim. One comment article entitled ‘‘Serial Coronary in the context of the labeling as a whole, urged that only products proven safe Angiographic Evidence That the word or symbol suggests that there when used as directed should be Antioxidant Vitamin Intake Reduces is a relationship between the product permitted for sale for enlarged prostate Progression of Coronary Artery and a disease or health-related and that such products should Atherosclerosis,’’ would create a disease condition. Thus, according to the recommend that a man see his claim under this criterion; (4) use of the preamble to that final rule (58 FR 2478 physician. Another comment argued term ‘‘disease’’ or ‘‘diseased;’’ or (5) at 2486), the heart symbol might that the claim ‘‘for men over 50 years otherwise suggesting an effect on appropriately appear in the labeling of old,’’ which FDA had proposed as an disease by use of pictures, vignettes, a food product if, in context, it did not acceptable structure/function claim, is symbols, or other means (e.g., suggest a relationship to heart disease, vague and ambiguous and is of no use electrocardiogram tracings, pictures of e.g, in conjunction with ‘‘Hey, Fudge to consumers. organs that suggest prevention or Lovers.’’ If, however, the heart symbol FDA agrees that ‘‘supports a normal, treatment of a disease state, or the appeared alone on a food, without healthy attitude during PMS’’ and prescription symbol (Rx)). The proposed further explanation from context, ‘‘supportive for menopausal women’’ rule stated that a picture of a body consumers might conclude that the food are appropriate structure/function would not constitute a disease claim was beneficial for reducing the risk of claims. ‘‘Supports a normal, healthy under this criterion. developing cardiovascular disease (id.). attitude during PMS’’ is acceptable (50.) A few comments stated that the Following the issuance of because PMS is generally a common, phrase ‘‘has an effect on’’ in proposed § 101.14(a)(1), Congress enacted mild condition associated with a normal § 101.93(g)(2)(iv) is vague and could be DSHEA. DSHEA created a special physiologic process. ‘‘Supportive for interpreted by the agency to mean regulatory regime for dietary menopausal women’’ is acceptable almost anything. Some of these supplements. That regime, while closely because it is a general statement that comments argued that disease claims related to the regime for food, was not does not refer to symptoms of any should include only those that use the identical to the food regime. Section conditions at all. Claims about specific terms ‘‘diagnose,’’ ‘‘prevent,’’ 403(r)(6) of the act specifies certain diminishing the normal ‘‘treat,’’ ‘‘mitigate,’’ or ‘‘cure.’’ types of structure/function claims and symptomatology of premenstrual FDA does not agree that the phrase general well-being claims that may be syndrome or menopause would also be ‘‘has an effect on’’ is inappropriately made for dietary supplements without acceptable structure/function claims, if vague. FDA believes that it is necessary first obtaining new drug approval or they did not suggest, for example, to use a phrase that encompasses health claim authorization. The types of prevention or treatment of osteoporosis, synonyms for the terms ‘‘diagnose,’’ claims listed in section 403(r)(6) of the or another disease associated with these ‘‘prevent,’’ ‘‘treat,’’ ‘‘mitigate,’’ or act are similar, but not identical to the states. ‘‘Helps to maintain normal urine ‘‘cure.’’ If disease claims were limited to claims permitted for foods under section flow in men over 50 years old,’’ those that used the specific terms in the 201(g)(1)(C) of the act. Under Nutrilab v. however, is an implied disease claim statute, it would be possible to make Schweiker, 713 F.2d 335 (7th Cir. 1983), because, as many comments pointed obvious and explicit disease claims conventional food claims are limited to out, the average or ‘‘normal’’ state in simply by using terms that are similar structure/function effects that derive men over 50 years old is diminishing in meaning to the statutory terms, e.g., from the taste, aroma, or nutritive value urine flow, in most cases due to BPH, ‘‘relieves arthritis pain’’ rather than of the food. Dietary supplement claims so that the apparent ‘‘maintenance’’ ‘‘treats arthritis pain,’’ or ‘‘eliminates are not subject to that limitation. Had really represents a claim of the risk of cancer’’ rather than ‘‘prevents Congress intended the scope of the improvement (treatment). cancer.’’ permitted claims to be identical, it

VerDate 04-JAN-2000 16:16 Jan 05, 2000 Jkt 190000 PO 00000 Frm 00023 Fmt 4701 Sfmt 4700 E:\FR\FM\06JAR4.XXX pfrm11 PsN: 06JAR4 1022 Federal Register / Vol. 65, No. 4 / Thursday, January 6, 2000 / Rules and Regulations could simply have declared that dietary contain the name, or a recognizable The agency notes, however, that the use supplements are ‘‘foods.’’ In light of portion of the name, of a disease. of these terms on dietary supplement Congress’ intent to expand the types of Second, the name should not use terms products may deceive consumers into claims authorized for dietary such as ‘‘cure,’’ ‘‘treat,’’ ‘‘correct,’’ thinking that they are purchasing a supplements in DSHEA, FDA interprets ‘‘prevent’’ or other terms that suggest prescription drug without a § 101.14(a)(1) as permitting dietary treatment or prevention of a disease. prescription. Thus, use of the terms supplements to have brand names that Thus, ‘‘CarpalHealth’’ and ‘‘CircuCure’’ ‘‘prescription’’ or ‘‘Rx’’ is misleading include the word ‘‘heart’’ or other would be considered disease claims. In and will misbrand the product under organs, if, in the context of the labeling some cases, to determine whether a section 403(a)(1) of the act if, in the as a whole, the name does not imply product name implies an effect on context of the labeling as a whole, the disease treatment or prevention. disease, the agency will need to terms imply that the product is a FDA does agree, however, that under consider the context in which a term is prescription drug. .§ 101.14(a)(1), a dietary supplement presented in the labeling as a whole. (54.) A few comments cited in a name that included the word ‘‘heart’’ Thus, ‘‘Soothing Sleep’’ could be proposed rule published in the Federal could be a health claim, depending on considered a claim to treat insomnia, Register of March 27, 1974 (39 FR the context. Thus, a dietary supplement unless the labeling made clear that the 11298), in which FDA stated that it could be called ‘‘HeartTabs’’ if its claim product was intended only for would challenge brand names only in was ‘‘to maintain healthy circulation,’’ occasional sleeplessness. ‘‘HepataCare’’ situations where clarifying language is or some other role related to the and ‘‘HepataHealth’’ could also be incapable of rectifying FDA’s concern structure or function of the heart that considered disease claims because with the brand name and that excision did not imply treatment or prevention of ‘‘Hepata’’ could be read as a reference to of a brand name should be a last resort disease. If, however, the product name hepatitis, unless the labeling made clear and should be pursued only when all was not qualified by any further claim that the product was intended for other methods of qualifying the name in the labeling, the product could be general liver health and not intended to have failed. considered, under § 101.14(a)(1), to be treat or prevent hepatitis. The agency notes that the proposed intended for treatment or prevention of The agency notes that in the near rule cited in this comment was never cardiovascular disease. future, FDA will issue for public finalized and was withdrawn on FDA also believes that the heart comment a draft guidance to provide December 30, 1991 (56 FR 67440), as symbol has become so widely associated additional clarification and examples of part of an FDA initiative to reduce the with prevention of heart disease that its claims that would and would not be backlog of outstanding proposed rules use in the labeling of a dietary considered disease claims under the that have never been finalized. The supplement would be ordinarily final rule. FDA will include in the draft policies outlined in the March 27, 1974, considered an implied heart disease guidance examples of product names. Federal Register notice are not in effect. prevention claim. Consistent with the (53.) Another comment stated that (55.) Several comments sought a examples provided in the January 6, proposed § 101.93(g)(2)(iv)(A) would statement from FDA that if a product 1993, Federal Register document on prohibit the use of the name of the brand name becomes synonymous over health claims (58 FR 2486), however, ‘‘dispensing institution’’ if it had the time with use for prevention or there may be unusual cases in which, in word ‘‘Cancer’’ in it because the agency treatment of a disease, it will still be context, the use of a heart symbol does would interpret the labeling as implying permitted. As an example, the not imply heart disease prevention. an effect on disease, when in fact the comments claimed that Kleenex has (52.) Several comments agreed with product was listing the institution become synonymous with treatment of proposed § 101.93(g)(2)(iv)(A) that where the product was dispensed, e.g., nasal congestion, but did not provide product names that imply an effect on ABC Cancer Institute. Other comments support for this assertion. disease, including implying cure or were concerned that the proposed rule FDA does not believe that Kleenex is treatment of a disease, should not be would prohibit the use of their company synonymous with treatment of nasal allowed. The comments, however, trade name, which includes the use of congestion and, absent any supportive requested that the agency provide the word ‘‘prescription’’ and its data, has no reason to believe that further guidance as to what types of abbreviation ‘‘Rx.’’ consumers believe them to be product names are acceptable and what The agency reiterates that it will view synonymous. The agency would agree types are not. Some comments the name in the context of the entire that Kleenex has become synonymous questioned whether product names such labeling to determine whether a disease with ‘‘tissue,’’ and that both are used in as ‘‘CarpalHealth,’’ ‘‘HepatoHealth,’’ claim is being made. However, a conjunction with nasal congestion. ‘‘HepataCare,’’ ‘‘CircuCure,’’ or manufacturer may not circumvent the Neither tissue nor Kleenex, however, ‘‘Soothing Sleep’’ would be acceptable requirements of the act, DSHEA, or this treat, prevent, or otherwise affect nasal under proposed § 101.93(g)(2)(iv)(A). final rule by using the name of an congestion in any way. Because the Other comments disagreed with the institution or the manufacturer to imply agency was not presented with any agency’s examples and stated that it is a disease claim. specific examples of, nor is it aware of difficult to distinguish the reasoning The agency agrees that the use of the any, names of products that are not behind some of the examples cited. For word ‘‘prescription’’ or its abbreviation intended to treat disease but that have example, a few comments stated that ‘‘Rx’’ in the name of the product should become synonymous with disease both ‘‘Cardiohealth’’ and ‘‘Heart Tabs’’ not automatically be interpreted as a treatment or prevention, it does not imply that the product prevents heart disease claim. Although these terms have reason to believe that there is a real disease. imply that the product is a prescription basis for concern. Two principles formed the basis for drug, some prescription drugs are the distinctions in the proposed rule intended for nondisease conditions. J. Product Formulation between product names that were Therefore, if nothing else in the labeling (§ 101.93(g)(2)(iv)(B)) considered structure/function claims suggests a disease use, the agency will (56.) Several comments questioned and those that were considered disease not consider the use of ‘‘prescription’’ or whether the inclusion of a dietary claims. First, the name should not ‘‘Rx’’ to be an implied disease claim. ingredient in the ingredient list of a

VerDate 04-JAN-2000 16:16 Jan 05, 2000 Jkt 190000 PO 00000 Frm 00024 Fmt 4701 Sfmt 4700 E:\FR\FM\06JAR4.XXX pfrm11 PsN: 06JAR4 Federal Register / Vol. 65, No. 4 / Thursday, January 6, 2000 / Rules and Regulations 1023 dietary supplement would be exclude disease claims, Congress made supplement’’ under section 201(ff)(3) of interpreted as a disease claim under a judgment that the public health will the act. proposed § 101.93(g)(2)(iv)(B). They be served by requiring premarket review (58.) One comment misunderstood argued that to provide truthful labeling, of such claims. § 101.93(g)(2)(iv)(B) and believed that this information must be included. FDA agrees that it is important to this provision only applies to the listing Another comment stated that the inform consumers about potential of OTC drug ingredients recognized by proposal fails to distinguish between adverse effects or drug interactions for consumers. true claims and false claims. Several specific dietary supplement ingredients. This provision is not limited to the comments further argued that ingredient In fact, dietary supplement labeling, like listing of OTC drug ingredients. For information may be of value to the labeling of other FDA-regulated purposes of § 101.93(g)(2)(iv)(B), the consumers to alert them to potential products, is required to include all facts agency may consider as a disease claim adverse effects or drug interactions. One that are material in light of a claim that the product contains an comment urged that the presence of a consequences that may result from use ingredient that has been regulated by constituent that is naturally occurring in of the product or representations made FDA as a drug, whether marketed over- a plant and is also regulated as a drug about it (sections 403(a)(1) and 201(n) of the-counter or by prescription, and that does not automatically classify the the act). This provision is not intended is well known for its use in preventing substance as a drug. The comment in any way to preclude truthful adverse or treating a disease. asserted that 45 percent of drugs are event or drug interaction information K. Citation of Publication Titles derived from plants, which, according from appearing in a dietary (§ 101.93(g)(2)(iv)(C)) to the comment, would classify a supplement’s labeling. (59.) Many comments objected to this number of dietary ingredients as drugs. (57.) A dietary supplement proposed criterion or sought Listing a dietary ingredient in the manufacturer asked FDA to clarify the clarification. Many comments said that ingredient list of a dietary supplement effect of § 101.93(4)(ii) on a dietary the proposed criterion undermines will not be considered to imply an effect ingredient found in common food(s), DSHEA by prohibiting the use of most on disease unless the ingredient is one whose biological activity is first journals, is not required by DSHEA, or that has been regulated primarily by characterized in a food context, but is contrary to section 403B of the act (21 FDA as a drug and is well-known to which is subsequently approved as a U.S.C. 343–2), which, the comment consumers for its use or claimed use in drug. The comment asked whether, if said, exempts scientific publications preventing or treating a disease. (In the indole-3-carbinol, a compound from labeling rules and is intended to proposed rule, the agency gave as discovered in broccoli and other allow consumers to be more informed examples aspirin, digoxin, and laetrile.) vegetables, were to be approved as a by reading scientific studies. Other Very few dietary ingredients meet this breast cancer drug, claims to the effect comments said that Congress intended test. The agency agrees that a certain that a vegetable-based dietary to encourage the dissemination of percentage of drug products are derived supplement product contains indole-3- scientific research and truthful, non- from plants. However, only a handful of carbinol would be permitted as misleading information, so FDA should these drugs are well-known to structure/function claims under the not prohibit titles of scientific studies. consumers under the name of the plant proposed rule. The comment claimed Some comments stated that the issue or natural plant ingredient from which that the proposed rule would classify should not be whether a publication’s they were derived. Instead, they are such claims as disease claims even if the title refers to a disease use, but rather known to consumers under a brand biological activity of this dietary whether, on balance, the entire name or generic name, e.g., aspirin. ingredient were first identified in the presentation, including the product Thus, FDA does not believe that listing food context. label, package insert, and other labeling, dietary ingredients that happen to be Where an ingredient has been represents a disease claim. These related to well-known drugs will fall approved as a drug, section 201(ff)(3) of comments supported the use of under this provision, except in unusual the act prohibits marketing of the complete citations to scientific circumstances. In those cases where a ingredient as a dietary supplement literature, including the titles of manufacturer does add a drug unless the ingredient itself was scientific articles. Some comments ingredient that is well-known to treat or previously marketed as a food suggested that the proposal contradicted prevent disease to its product and label (including a dietary supplement), or earlier FDA positions. One comment its presence, however, FDA may unless a food containing the ingredient referred to the September-October 1998 consider it a disease claim. The fact that was previously marketed for the issue of FDA Consumer which, the the labeling is truthful does not presence of the ingredient. In the comment stated, suggested that necessarily mean that it falls within the example provided in the comment, the consumers contact companies to obtain scope of claims authorized by section isolated ingredient indole-3-carbinol scientific articles that the company 403(r)(6) of the act. For example, the could not be marketed as a dietary might have to substantiate a claim. agency believes that there are many supplement, unless a food containing Another comment said the proposal was dietary ingredients that could be shown the ingredient had been marketed for contrary to FDA policy to recognize and to treat or prevent diseases, and for the presence of the ingredient before the accept valid science. Several comments which it could thus be truthful to state drug was approved or was the subject of questioned how to provide that the product treats or prevents a substantial investigations that had been substantiation of labeling claims, in specific disease. Under the act, made public. However, to avoid a compliance with 403(r)(6)(B) of the act, however, if a manufacturer wants to conflict between this provision and if the supporting articles cannot be label its product to treat or prevent section 201(ff)(3) of the act in a situation cited. One comment stated that there disease, it must do so under the drug where the ingredient was marketed as a will be more fraud and deception in the approval provisions or the health claim food first, FDA has revised marketplace because companies will not provisions of the act. It may not do so § 101.93(g)(2)(iv)(B) to exclude claims cite scientific support for their under section 403(r)(6) of the act. In about an ingredient that is an article statements. Several comments stated drafting section 403(r)(6) of the act to included in the definition of ‘‘dietary that the proposed rule will restrict

VerDate 04-JAN-2000 16:16 Jan 05, 2000 Jkt 190000 PO 00000 Frm 00025 Fmt 4701 Sfmt 4700 E:\FR\FM\06JAR4.XXX pfrm11 PsN: 06JAR4 1024 Federal Register / Vol. 65, No. 4 / Thursday, January 6, 2000 / Rules and Regulations access by consumers and the medical labeling. If, for example, the citation is claims authorized under section community to important new research simply listed in the bibliography section 403(r)(6) of the act. results and discourage companies from of the labeling among other titles, it will (61.) A few comments stated that the investing in research. A dietary generally not suggest an implied disease agency did not provide any support for supplement manufacturer suggested claim. On the other hand, highlighting, the assumption that citations are disease revising the provision to permit bolding, using large type size, or claims rather than substantiation for a companies to cite ‘‘bonafide’’ textbooks prominent placement of a citation that claim. and peer-reviewed scientific journals refers to a disease use in the title could FDA believes that a citation of a title that mention a disease in the title. suggest that the product has an effect on that refers to a specific disease can serve Another dietary supplement disease. The agency will also consider both as a disease claim and as manufacturer suggested revising this whether the cited article provides substantiation for a claim. A citation of provision to permit citation of a legitimate support for a 403(r)(6) of the a publication title that links the product publication or reference if the citation act statement that appears in the to a particular disease could lead ‘‘is necessary to present a balanced labeling of the dietary supplement. consumers to believe that the product discussion of the documented Enhancing the bibliography with can be used to diagnose, prevent, mechanism by which a nutrient or citations to scientific references that mitigate, treat, or cure a disease, even if dietary ingredient acts to maintain the refer to a disease in the title and that the title also provides substantiation for structure or function of the body.’’ have no reasonable relation to the the product claims. FDA agrees that in enacting DSHEA, statement made will be considered a As stated above, citation of a scientific Congress intended to encourage the disease claim. Similarly, the agency will reference will not be treated as a disease dissemination of scientific research and consider whether citations are to bona claim if, in the context of the labeling truthful, non-misleading information. fide research. as a whole, the reference lacks FDA also agrees that consumers can FDA also agrees that it is important to prominence and if it is appropriate benefit from reviewing the scientific provide a balanced discussion of the support for the product claim. support used to substantiate a statement scientific literature regarding the claim. (62.) One comment sought made for a dietary supplement under FDA encourages manufacturers to cite clarification of the effect of this section 403(r)(6) of the act. In keeping references that provide a balanced provision on multi-ingredient products. with these goals, FDA has modified discussion of the evidence supporting a The comment asked whether a disease § 101.93(g)(2)(iv)(C) to narrow the structure/function claim. claim for the entire product would be circumstances under which citation to a The agency believes that the final rule created if the labeling cited an article scientific reference will be considered a strikes a reasonable balance between about only one ingredient of a multi- disease claim. Based on Congress’ encouraging the dietary supplement ingredient product. explicit prohibition in section 403(r)(6) industry to inform consumers about the Generally, if a citation is presented in of the act of claims to affect disease, substantiation for their claims and the product labeling in such a way as to however, FDA does not believe that preventing abuses of section 403(r)(6) of imply that a specific ingredient can treat Congress intended to permit scientific the act. or prevent disease, the product, as a references to be used in a way that (60.) Several comments challenged whole, will be considered to be constitutes an implied disease claim. the basis for the proposed restriction of intended to treat or prevent disease. Consequently, § 101.93(g)(2)(iv)(C) has scientific references. One comment from (63.) A few comments requested FDA been revised to state that citation of a industry said the proposed restriction to clarify how proposed title referring to a disease will be treated on titles is outside DSHEA because the § 101.93(g)(2)(iv)(C) would operate. The as a disease claim, if, in the context of act refers to statements. The comment comments questioned whether they the labeling as a whole, the citation said titles could be prohibited if they would have to delete a citation from a implies treatment or prevention of a were misleading, but said the rule list or redact the reference to a disease disease, e.g., through placement on the should not contain a blanket from the title of the article. One immediate product label or packaging, prohibition. comment asked whether an article that inappropriate prominence, or lack of The comment is apparently referring contains a reference to a disease can be relationship to the product’s express to section 403(r)(6) of the act, which cited if the title is not used in the claims. prescribes the terms under which a citation. The comments further The agency continues to believe that ‘‘statement’’ may be made for a dietary questioned whether they can provide placing a citation to a scientific supplement. FDA believes that the the entire article, with the title on it, if reference that mentions a disease in the comment’s reading is too literal, requested by a consumer. Some title on the immediate product label or however. A ‘‘statement’’ does not have comments asked FDA to clarify that a packaging should be considered a to be a declaratory sentence but rather label may cite a title that appears in a disease claim for that product, because is fairly read to include other kinds of publication whose name includes a of the unusual and unnecessary statements, such as citations of disease (such as the publication titled prominence of such placement. For scientific authority. In keeping with Cancer) or to clarify how scientific citations to scientific references that DSHEA’s purpose to broaden the scope studies may be cited. One comment refer to a disease use in the title and that of labeling claims that may be made for requested that the agency issue further are included in other types of labeling dietary supplements without subjecting guidance to clarify what is and is not (i.e., other than the product label or them to regulation as drugs, FDA covered by § 101.93(g)(2)(iv)(C). packaging) the agency will consider the believes that Congress intended FDA does not expect a manufacturer context in which the citation is ‘‘statement’’ to refer to any claim made to redact portions of the citation or presented. FDA agrees with the that recommends or suggests a delete a citation from a list of references comments that the totality of all particular use of a dietary supplement. or bibliography if it is appropriate to available labeling should be considered In addition to being under inclusive, a include the reference to substantiate a to determine the context. One element narrower interpretation would not claim. As described above, if the that the agency will look at is the benefit the dietary supplement industry citation to a scientific reference refers to prominence of the citation in the because it would limit the scope of a disease, the agency will consider the

VerDate 04-JAN-2000 16:16 Jan 05, 2000 Jkt 190000 PO 00000 Frm 00026 Fmt 4701 Sfmt 4700 E:\FR\FM\06JAR4.XXX pfrm11 PsN: 06JAR4 Federal Register / Vol. 65, No. 4 / Thursday, January 6, 2000 / Rules and Regulations 1025 context in which the citation is cholesterol levels, this implies that the article alone could not meet these presented, including its prominence in product can be used to have an effect on requirements. the labeling and whether there is a the disease states hypercholesterolemia L. Use of Disease or Diseased reasonable relationship between the and heart disease, because heart disease (§ 101.93(g)(2)(iv)(D)) reference and the express claim. In most is associated with high cholesterol cases, the unredacted reference title can levels. (67.) Many comments agreed with be included in the product labeling (65.) A trade association suggested proposed § 101.93(g)(2)(iv)(D), stating without subjecting the product to that the title should not be considered that the terms ‘‘disease’’ or ‘‘diseased’’ regulation as a drug, as long as the to be a disease claim unless it uses the should classify a statement as a disease prominence of the reference does not terms ‘‘treat,’’ ‘‘cure,’’ ‘‘mitigate,’’ claim. Several comments urged that a suggest that it is being used to imply ‘‘prevent,’’ or ‘‘diagnose.’’ statement referring in a general way to disease treatment or prevention. Under As stated elsewhere in this document, the concept of ‘‘health promotion and revised § 101.93(g)(2)(iv)(C), the only FDA believes that a disease claim can be disease prevention’’ not cause the reason a publication title would be made explicitly or implicitly using statement to be considered a disease considered a disease claim regardless of terms other than those listed in the claim, as long as no specific disease was prominence would be if the reference is comment. For example, depending on mentioned. One comment asked that the not reasonably related to substantiating how it was used in a product’s labeling, agency permit general discussions of the the product’s express claim. In that case, a scientific reference entitled ‘‘Using concept of disease prevention, citing the FDA believes that the reference would Ingredient X For Diabetes’’ could following example from the U.S. Public be a disease claim, even if the name of constitute a claim that the product can Health Service Healthy People 2000 initiative: ‘‘Better dietary and exercise the disease is redacted, because the only diagnose, mitigate, treat, cure, or patterns can contribute significantly to purpose of including the reference prevent diabetes, without using any of reducing conditions like heart disease, would be to suggest use of the product these specific terms. stroke, diabetes, and cancer, and could for treatment or prevention of the (66.) A few comments argued that prevent 300,000 deaths.’’ disease discussed in the reference. citation of articles that refer to a disease With regard to citation of titles from FDA agrees that general statements use should be permitted because about health promotion and disease journals whose official names include consumers have access to these articles the name of a disease, the same prevention may be acceptable, as long as in connection with the sale of dietary considerations of appropriate the statements do not imply that a supplements under section 403B(a) of prominence and reasonable relationship specific product can diagnose, mitigate, the act. to the product’s express claims apply. cure, treat or prevent disease. As stated above, FDA has revised the FDA expects that accepted conventions Accordingly, FDA has revised proposed rule’s treatment of citations to of scientific citation will be used for all § 101.93(g)(2)(iv)(D) to permit general citations that appear in labeling. scientific articles. Under the final rule, statements about disease prevention that Finally, if specific information about such citations will not always be do not refer explicitly or implicitly to a an unlabeled use of a product is considered disease claims. FDA does specific disease or class of diseases or to requested by a consumer, and the not agree, however, that section 403B of the specific product or ingredient. For request is not solicited by the the act applies to the citation of titles in example, the statement ‘‘a good diet manufacturer, providing articles that are product labeling. Although section 403B promotes good health and prevents the responsive to the request will not be of the act exempts certain publications onset of disease’’ would not be considered a disease claim. from the labeling provisions of the act, considered a disease claim. On the other FDA will issue further guidance on section 403B(a)(2) states that the hand, the claim ‘‘Promotes good health § 101.93(g)(2)(iv)(C), if necessary. exemption applies only when, among and prevents the onset of disease’’ (64.) Several comments sought other requirements, the publication is would refer implicitly to the product modifications to proposed ‘‘used in connection with the sale of a and would constitute a disease § 101.93(g)(2)(iv)(C). One comment dietary supplement to consumers when prevention claim. FDA also believes that suggested revising the provision to it * * * does not promote a particular the particular statement offered by one permit companies to cite articles or manufacturer or brand of a dietary of the commenters would constitute a references that use ‘‘intermediate terms’’ supplement.’’ If the reference or the title disease claim. The example cites four (which the comment said were terms or of the reference was disseminated by a specific diseases. If that statement were phrases that have disease-related particular manufacturer of the dietary included in the labeling for a dietary endpoints) on the label or labeling. supplement discussed in the reference, supplement, a consumer would Whether a citation that refers to a the agency would conclude that it was reasonably assume that the statement disease-related endpoint will be being used to promote that applies to the product and that taking considered a disease claim under the manufacturer’s brand of the dietary that dietary supplement contributes to rule will depend on the context in supplement. Therefore, the exemption preventing the diseases listed. If, which the disease-related endpoint is in section 403B of the act would not however, the statement said ‘‘better referred to and whether the reference apply. dietary and exercise patterns can implies that the product has an effect on Furthermore, to qualify for the contribute to disease prevention and disease. For example, the title of an exemption in section 403B of the act, a better health,’’ FDA would not consider article that states that a product was publication must be ‘‘an article, a it a disease claim. shown to maintain cholesterol levels chapter in a book, or an official abstract that were already within the normal * * * reprinted in its entirety’’ and must M. Pictures, Vignettes, and Symbols range, with no reference to a disease, be ‘‘displayed or presented, or * * * (§ 101.93(g)(2)(iv)(E)) would be considered a structure/ displayed or presented with other such (68.) Many comments agreed that function statement about maintenance items on the same subject matter, so as certain pictures, vignettes, and symbols rather than a disease claim. However, if to present a balanced view of the can explicitly or implicitly convey that the title of the article states that the available scientific information of a the product has an effect on disease. A product was shown to lower elevated dietary supplement.’’ A citation to an few comments agreed that a diseased

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(See few comments stated that a healthy acceptable structure/function claims: § 101.4(a)(1) and (g) (21 CFR 101.4(a)(1) electrocardiogram (EKG) tracing should Claims that the product was an and (g)), and § 101.36). The rationale for not be considered a disease claim. One ‘‘energizer,’’ a ‘‘rejuvenative,’’ a § 101.93(g)(2)(v) is that certain product comment requested that the agency ‘‘revitalizer,’’ or an ‘‘adaptogen.’’ In light class names (not particular ingredients) clarify whether a picture of an organ is of the agency’s decision that claims for are so strongly associated with use to permitted if the claims are appropriate relief of ‘‘occasional constipation’’ diagnose, treat, mitigate, cure, or and within the scope of permitted should not be considered disease prevent disease that claiming structure/function claims. The comment claims, the term ‘‘laxative’’ will not be membership in the class would offered as an example a statement that considered a disease claim under the constitute a disease claim. FDA does not a product maintains cardiovascular final rule, as long as the remainder of believe that claiming membership in a health accompanied by a picture of a the labeling makes clear that the product class is necessary in order to heart and circulatory system. product is not intended to treat chronic provide an accurate list of the FDA agrees that in most cases, a constipation. ingredients present in a product. picture of a healthy organ would not be (69.) Most of the comments on FDA agrees that dietary supplements considered a disease claim, if, in the proposed § 101.93(g)(2)(v) were may carry statements that characterize context of the labeling as a whole, it did generally supportive, but some wanted ‘‘the documented mechanism of action not imply treatment or prevention of to ensure that the provision would be by which a nutrient or dietary disease. As described in response to applied in specific ways. One comment ingredient acts to maintain * * * comment 51 of section II.I of this urged that ‘‘appetite suppressant’’ be structure or function,’’ but only to the document, however, there may be treated as a disease claim, while another extent that such a statement does ‘‘not symbols for organs, like the heart comment urged that ‘‘tonic’’ be treated claim to diagnose, mitigate, treat, cure, symbol, that have become so widely as a structure/function claim. or prevent a specific disease or class of recognized as symbols for disease FDA does not agree that ‘‘appetite diseases’’ (section 403(r)(6) of the act). treatment or prevention, their use in suppressant’’ should be considered a In the examples provided in the labeling would constitute an implied disease claim. As discussed elsewhere comment, FDA is unaware of evidence disease claim. FDA also believes that a in this document, although obesity is a establishing that the claims actually picture of a healthy EKG tracing is an disease, overweight is not. An appetite describe ‘‘documented’’ mechanisms by implied disease claim. Because most suppressant may be intended for which the products ‘‘maintain’’ a calm consumers cannot distinguish a healthy ordinary weight loss, rather than as a stomach. Nevertheless, assuming that EKG tracing from an unhealthy one, treatment for obesity. Therefore, these statements met the other both types may be viewed as references ‘‘appetite suppressant’’ would only be requirements of section 403(r)(6)(A) of to diagnosis or treatment of unhealthy considered a disease claim in a context the act, FDA would not consider the heart conditions. where it implies use for obesity. FDA term ‘‘antispasmodic’’ to constitute a agrees that ‘‘tonic’’ is not a disease disease claim because the agency does N. Membership in Product Class claim. ‘‘Tonic’’ is commonly understood not believe that it is closely associated (§ 101.93(g)(2)(v)) as a general term for anything that with treatment or prevention of Some product class names are so refreshes, and, by itself, would not be gastrointestinal disease. The term ‘‘anti- strongly associated with use to treat or considered to constitute a disease claim. inflammatory’’ is, however, strongly prevent a specific disease or class of (70.) Some comments stated that associated with treatment of certain diseases that claiming membership in various class names should be allowed serious gastrointestinal diseases, and the product class implies disease when they describe the mechanism by would constitute a disease claim. treatment or prevention. Under which a supplement has its effect, or FDA agrees with the statement that it proposed § 101.93(g)(2)(v), a statement when they are present in a product and is not membership in a given class of would have been considered a disease it is truthful and not misleading to name compounds that makes a product a claim if it claimed that the product them. One comment offered as examples drug, but rather the intended use of the belonged in a class of products of class names that might be used to product. This criterion sets forth FDA’s recognizable to health care professionals describe a product’s mechanism of conclusion that claiming membership in or consumers as intended for use to action: A statement that a product that certain product classes that are strongly diagnose, mitigate, treat, cure, or is soothing to the stomach achieves its associated with use to treat or prevent prevent a disease. The preamble effects as a result of its ‘‘carminative disease is evidence that the product is provided the following examples of (antispasmodic) properties’’ or as a intended to treat or prevent disease. class names that would imply disease result of its ‘‘anti-inflammatory effect on Although this provision does not treatment or prevention: Claims that the the gastrointestinal tract.’’ This itself treat as a disease claim a statement product was an ‘‘antibiotic,’’ a comment stated that it is not by a vitamin manufacturer that the ‘‘laxative,’’ an ‘‘analgesic,’’ an membership in a given class of product prevents the onset of a disease, ‘‘antiviral,’’ a ‘‘diuretic,’’ an compounds that should make a product such a statement would be considered a ‘‘antimicrobial,’’ an ‘‘antiseptic,’’ an a drug, but rather the intended use of disease claim under § 101.93(g)(2)(I), ‘‘antidepressant,’’ or a ‘‘vaccine.’’ These the product. One comment asked which covers statements that a product examples were not intended to whether this criterion precludes a has an effect on a specific disease or constitute an exclusive list of product statement that daily consumption of class of diseases. In addition, a general class names that convey disease claims. vitamins and minerals may prevent the statement that a product prevents the Under the proposed rule, claiming that onset of disease or other physical onset of disease would be considered a a product was in a class that is not ailments. disease claim under

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§ 101.93(g)(2)(iv)(D), as noted in the (e.g., ‘‘use as part of your weight loss disease, section 201(g)(1)(C) was added discussion of that provision. Claiming plan’’) would not constitute a disease to cover conditions, like overweight, membership in the class of vitamins or claim under this criterion. that are not considered diseases, but minerals would not constitute a disease (73.) There was general support for that affect the structure or function of claim under this criterion. the provision, particularly for the body. Structure/function claims (71.) A food manufacturers’ trade considering terms that make a direct under section 403(r)(6) of the act are association and an individual connection with an approved drug, like closely related to structure/function manufacturer opposed the provision, ‘‘Herbal Prozac’’ and ‘‘Herbal Phen-fen,’’ claims under section 201(g)(1)(C) of the arguing that it goes beyond the intent of disease claims. Several organizations act and therefore should encompass DSHEA and would prohibit the use of noted that associating dietary weight loss claims. any term associated with a drug supplements with regulated drug FDA also does not agree that cases product. products is deceptive and dangerous cited by the comment compel the FDA does not agree that this provision because it can signal to consumers that conclusion that weight loss products goes beyond the intent of DSHEA nor because the product is ‘‘herbal’’ it is must be regulated as drugs. In Nutrilab that it would prohibit the use of any safer. Several medical associations, v. Schweiker, 713 F.2d 335 (7th Cir. term associated with a drug product. however, objected to the interpretation 1983), American Health Products Co. v. DSHEA precludes statements under that ‘‘use as part of your weight loss Hayes, 574 F. Supp. 1498 (S.D.N.Y. section 403(r)(6) of the act from plan,’’ is nonspecific and would be 1982), aff’d, 744 F.2d 912 (2d Cir. 1984), claiming to treat or prevent disease. acceptable. They maintained that the and United States of America v. This provision constitutes FDA’s term implies treatment of a disease, Undetermined Quantities Of ‘‘CAL–BAN conclusion that some drug class names obesity. A comment from a 3000’’, 776 F. Supp. 249 (E.D.N.C. (but not all terms associated with drug manufacturer also strongly objected to 1991), the courts held that certain products) are so strongly associated the statement in the proposal that ‘‘Use weight loss products were drugs under with disease prevention or treatment as part of your weight loss plan’’ would section 201(g)(1)(C) of the act because that claiming membership in the class be an acceptable structure/function they were labeled to affect the structure constitutes a claim that the product, like claim. The comment contended that the or function of the body, and did not other members of the class, treats or legislative history of the act shows that qualify for the ‘‘food’’ exception to prevents disease. Congress intended weight loss claims to section 201(g)(1)(C). At the time these (72.) One pharmaceutical company be treated as disease claims. Finally, the cases were decided, the only issue was argued that proposed § 101.93(g)(2)(v) comment argued that even if FDA whether these products were ‘‘foods’’ or would violate DSHEA, because DSHEA decides to permit weight loss claims as ‘‘drugs.’’ Since then, however, DSHEA specifically defines as a dietary structure/function claims, the legislative created a new statutory category of supplement an article that is approved history of the act and case law require products, dietary supplements. Section as a new drug under section 505 of the that FDA classify products containing 403(r)(6) of the act, which was added by act, if it was, prior to approval, ‘‘antinutrients’’ as drugs. DSHEA, permits structure/function marketed as a dietary supplement. FDA agrees with these comments that claims to be made for dietary FDA agrees that the dietary obesity is a disease, and that obesity supplements without subjecting them to supplement definition includes the claims are not acceptable structure/ regulation as drugs, even if they could provision cited by the comment (section function claims. Being overweight, i.e., not qualify for the ‘‘food’’ exception in 201(ff)(3)(A) of the act), but believes that being more than one’s ideal weight but section 201(g)(1)(C) of the act. the definition and § 101.93(g)(2)(v) are less than obese, however, is not a Therefore, these cases do not establish not inconsistent. Section 101.93(g)(2)(v) disease. FDA believes that it is that dietary supplements making weight would treat as a disease claim a labeling commonly understood that ‘‘weight loss loss claims must be regulated as drugs. statement that the supplement is a plans’’ relate to a broad range of To the contrary, because the products member of a product class when that overweight statuses. Therefore, weight were held to be drugs under section class is so recognizable for its disease loss plans are not so narrowly 201(g)(1)(C) of the act rather than treatment or prevention use that the associated with disease treatment that a section 201(g)(1)(B), these cases support labeling statement would be understood reference to use as part of a weight loss treatment of weight loss claims for as a disease claim for the supplement. plan should be considered a disease dietary supplements as structure/ The criterion would not treat inclusion claim. function claims authorized under of an ingredient in a dietary supplement FDA does not agree that either the section 403(r)(6) of the act. as a disease claim merely because the legislative history of the act or the case Finally, FDA does not agree that, ingredient had been approved under law interpreting section 201(g) of the act under United States v. Ten Cartons, section 505 of the act nor would it or DSHEA require a determination that More or Less, of an Article * * * Ener- preclude listing the ingredient in the FDA classify as drugs products making B Vitamin B–12, 72 F.3d 285 (2d Cir. Supplement Facts panel or ingredient weight loss claims. The legislative 1995), dietary supplements making list. history of section 201(g)(1)(C) of the act weight loss claims must necessarily be shows that Congress added the regulated as drugs. The court in Ener-B O. Substitute for Disease Therapy structure/function definition of ‘‘drug’’ held that a dietary supplement that (§ 101.93(g)(2)(vi)) in part to capture obesity claims that makes a structure/function claim may Under proposed § 101.93(g)(2)(vi), a were not covered by section 201(g)(1)(B) nevertheless be regulated as a drug, statement would have been considered because obesity was not, at that time, under certain circumstances. In that a disease claim if it explicitly or considered a disease. FDA believes that case, the court found that FDA could implicitly claimed that the product was the legislative history in fact supports regulate a product as a drug, based on a substitute for another product that is FDA’s view that weight loss claims are its method of intake (nasal a therapy for a disease. FDA offered properly considered structure/function administration). Nothing in that case ‘‘Herbal Prozac’’ as an example of such claims. Although obesity claims are now suggests that FDA must regulate dietary a claim. A claim that did not identify a covered by section 201(g)(1)(B) of the supplements making weight loss claims specific drug, drug action, or therapy act because obesity is now considered a as drugs.

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(74.) Several comments reiterated that that FDA withdraw the provision, of drugs or therapies that are intended general statements about the nature of a arguing that dietary supplements are to diagnose, mitigate, treat, cure, or product or its mechanism of action often useful in providing nutritional prevent disease. should not be disease claims, or should support to complement drug therapy or (76.) Another comment noted that the be structure/function claims as long as medical treatment and that the agency agency did not address the use of they are truthful and not misleading. should encourage such information to synonyms for ‘‘augment,’’ such as One comment objected to the provision be communicated to consumers. One ‘‘strengthen,’’ ‘‘reduce,’’ ‘‘improve,’’ as duplicative of proposed comment stated that as long as the ‘‘modify,’’ ‘‘inhibit,’’ ‘‘protect,’’ or § 101.93(g)(2)(v). Another comment statement makes it clear that the ‘‘defend.’’ sought to delete the provision, arguing product is being recommended for its Use of these terms may be appropriate that dietary supplement manufacturers nutritional impact on structure or in some contexts, i.e., when the have the right to communicate to function ‘‘as part of the therapy and not statements do not suggest disease consumers that their products have as the therapy itself,’’ FDA should prevention or treatment use. If, fewer side effects than drugs. permit the statement. According to the however, the use of these terms implies FDA does not believe that this comment, ‘‘use as part of your diet that the dietary supplement augments a provision precludes general statements when taking insulin to help maintain a particular therapy or drug action or about the function or mechanism of healthy blood sugar level’’ should be otherwise suggests an effect on disease, action of a dietary supplement. It is not acceptable because the product is being the agency will consider the statement necessary to claim that the product is a recommended for its nutritional impact a disease claim. substitute for a drug or therapy to on structure or function as part of the (77.) A trade association maintained describe its function or its mechanism therapy and not as the therapy itself. that under the proposal, bread, crackers, of action. Nor is § 101.93(g)(2)(vi) Another comment asked whether and other baked goods used in duplicative of § 101.93(g)(2)(v). removing the words ‘‘when taking conjunction with prescription drugs Claiming that a product is a substitute insulin’’ from the statement would make and/or other therapy would not be for a specific drug or therapy, e.g., it an acceptable structure/function considered a food, but a drug, under ‘‘Herbal Prozac,’’ is a different means of claim. certain circumstances. communicating that a dietary The agency agrees that dietary supplement is intended to treat a supplements may be useful in providing Section 101.93 is intended to provide disease than claiming that the product nutritional support. Associating such a regulatory criteria for statements made belongs to a class of drugs associated statement with an express or implied for dietary supplements. Under section with treatment or prevention of that claim that the dietary supplement 201(ff)(2)(B) of the act, a dietary disease, e.g., ‘‘antidepressant.’’ augments a therapy or drug action, supplement does not include a product FDA does not agree that section however, implies that the dietary represented for use as a conventional 403(r)(6) of the act permits a dietary supplement has a role in treating or food or as a sole item of a meal or the supplement manufacturer to claim that preventing the disease for which the diet. If statements made for breads, its product has fewer side effects than drug or other therapy is used. crackers, and other baked goods a drug, if the drug is intended to treat The agency does not agree that the characterize the relationship between a or prevent disease, because the clear proposed claim involving insulin is an substance in the food and a disease or implication is that the dietary acceptable structure/function claim. health-related condition, they must supplement is intended for treatment or Persons who take insulin have a disease, comply with the health claims prevention of the same disease. If, namely, diabetes. By referring to the use provisions for foods under section however, the drug is not intended to of the dietary supplement in 403(r)(1)(B) and (r)(3) through (r)(4) of treat or prevent disease, a dietary conjunction with and for the same the act. supplement manufacturer is free to purpose (‘‘to maintain a healthy blood Q. Role in Body’s Response to Disease make truthful, non-misleading sugar level’’) as a drug (insulin), which or Disease Vector (§ 101.93(g)(2)(viii)) comparisons between the drug and the is used to for a disease (diabetes), the dietary supplement. statement implies that the dietary Under proposed § 101.93(g)(2)(viii), a supplement will help treat diabetes. statement would have been considered P. Augmentation of Therapy or Drug for A general statement that a dietary a disease claim if it explicitly or Disease (§ 101.93(g)(2)(vii))) supplement provides nutritional implicitly claimed a role in the body’s Under proposed § 101.93(g)(2)(vii), a support would be an acceptable response to a disease or to a vector of statement would have been considered structure/function claim, provided that disease. The preamble to the proposal a disease claim if it explicitly or the statement does not suggest that the defined a vector of disease as an implicitly claimed that the product supplement is intended to augment or organism or object that is able to augmented a particular therapy or drug have the same purpose as a specific transport or transmit to humans an action. The preamble offered the drug, drug action, or therapy for a agent, such as a virus or bacterium, that following example of a disease claim disease. In the example, if the statement is capable of causing disease in man. under this criterion: ‘‘Use as part of your were changed to ‘‘use as part of your The preamble offered as examples of diet when taking insulin to help diet to help maintain a healthy blood disease claims under this criterion maintain a healthy blood sugar level.’’ A sugar level,’’ the claim would be claims that a product ‘‘supports the claim that did not identify a specific considered acceptable. Deleting the body’s antiviral capabilities’’ or drug, drug action, or therapy would not reference to the drug, insulin, would ‘‘supports the body’s ability to resist constitute a disease claim under this remove the implication that the dietary infection.’’ A more general reference to criterion. The preamble gave the supplement is used to augment the an effect on a body system that did not following example of an acceptable insulin to treat, mitigate, prevent, or imply prevention or treatment of a structure/function claim: ‘‘use as a part cure diabetes. disease state would not have constituted of your weight loss plan.’’ On its own initiative, FDA is a disease claim under this criterion. (75.) Several comments supported this modifying § 101.93(g)(2)(vii) to limit its FDA provided as an example of an provision. A few comments requested applicability to claims for augmentation acceptable structure/function claim

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For example, white blood counterbalances the effects of a drug in argued that it should be deleted because cells play an essential role in the depleting a nutrient or interfering with a number of nutrients and dietary phagocytosis and disposal of aging red the metabolism of a nutrient would be supplements ‘‘have a role in the body’s blood cells or otherwise damaged cells. acceptable as a structure/function response to disease.’’ One comment A statement of support for the immune statement. Such a claim would not argued that the body has natural system, by itself, conveys no specific suggest treatment of an adverse reaction defenses to disease, that these are reference to disease treatment or that meets the definition of disease. normal functions of the body, and that prevention. The claim that vitamin A is However, as discussed above, if the therefore, statements such as ‘‘enhances necessary to maintaining a healthy claim expressly or impliedly suggests disease resistance’’ should be allowable immune response does not imply that a that the supplement is intended to as structure/function claims. Comments specific disease or class of diseases will augment a specific drug, drug action, or from a consumer organization and a be prevented. In contrast, a claim that a therapy for a disease, or serve the same member of the President’s Commission product ‘‘supports the body’s antiviral purpose as a specific drug or therapy for on Dietary Supplement Labels asserted capabilities’’ represents a claim of a disease, then the statement may be that the provision made too many treatment or prevention of a specific considered a disease claim. claims allowable. These comments class of diseases, those caused by (81.) A dietary supplement stated that as long as a claim includes viruses (e.g., colds, hepatitis, or HIV manufacturer requested that FDA clarify a disease-fighting function of the body, infection). why a statement that refers to a drug but e.g., ‘‘supports the immune system,’’ it not a disease, such as ‘‘helps should be considered a disease claim, R. Treatment/Prevention of Adverse individuals using antibiotics to regardless of other functions that might Events (§ 101.93(g)(2)(ix)) maintain normal intestinal flora’’ is a be involved. Under proposed § 101.93(g)(2)(ix), a disease claim, but a general statement, FDA agrees that nutrients and dietary statement would have been considered such as ‘‘helps maintain intestinal flora’’ supplements may play a role in the a disease claim if it explicitly or is a permissible structure/function body’s response to disease. This does implicitly claimed to treat, prevent, or claim. not mean, however, that disease mitigate adverse events associated with Although the statement ‘‘helps prevention claims are acceptable a therapy for a disease (e.g., ‘‘reduces individuals using antibiotics to structure/function claims. The act nausea associated with chemotherapy,’’ maintain normal intestinal flora’’ does requires dietary supplement ‘‘helps avoid diarrhea associated with not explicitly refer to a disease, there is manufacturers who wish to make antibiotic use,’’ and ‘‘to aid patients an implicit claim that use of the dietary disease prevention claims to do so by with reduced or compromised immune supplement while taking antibiotics will obtaining authorization for a health function, such as patients undergoing prevent or mitigate a disease. Persons claim or by obtaining new drug chemotherapy’’). A claim that did not using certain antibiotics are at risk of approval. Although FDA agrees that mention a therapy for disease (e.g., developing overgrowth in the gut of a claims that a product fights disease, or ‘‘helps maintain healthy intestinal pathogenic organism because along with enhances disease-fighting functions of flora’’) would not have constituted a fighting the target organisms in the body the body, are disease claims, FDA does disease claim under this criterion. the antibiotic can suppress normal not agree that claims such as ‘‘supports (80.) Comments from two large health intestinal flora that are used to prevent the immune system’’ are specific organizations supported this provision, infection in the intestinal tract. A firm enough to imply prevention of disease. while two large business organizations that markets its product to address this (79.) Several comments argued that and several other comments criticized concern, with claims that the product there was no significant difference it. Those opposing the provision argued can be used to maintain normal between ‘‘supports the immune system’’ that the proposal incorrectly categorized intestinal flora while taking antibiotics, (identified as a structure/function claim adverse reactions as diseases. Opposing is making an implied disease prevention in the proposal) and ‘‘supports the comments also contended that dietary claim. Conversely, the statement ‘‘helps body’s antiviral capabilities’’ (identified supplements may be useful as an maintain intestinal flora’’ alone, without as a disease claim in the proposal). One adjunct to therapy by counterbalancing any reference to a disease, drug, drug view was that both should be the effects of a drug in depleting a action, or therapy, does not imply an considered structure/function claims. nutrient or interfering with the effect on disease and would be Conversely, other comments contended metabolism of a nutrient, and that this considered a structure/function claim that ‘‘supports the immune system’’ is a should be considered a structure/ about general health maintenance. disease claim, because it could be function role. interpreted as a claim for treatment or FDA believes that some of these S. Otherwise Affects Disease prevention of human immunodeficiency comments may have misconstrued the (§ 101.93(g)(2)(x)) virus (HIV) disease. Another comment provision. The criterion is not intended Under proposed § 101.93(g)(2)(x), a recommended that ‘‘supports the body’s to capture every adverse event claim, statement would have been considered antiviral capabilities’’ be allowable as a but only claims about adverse events a disease claim if it suggested an effect structure/function claim, stating that the that satisfy the definition of disease. In on a disease or class of diseases in a broader ‘‘supports the immune system’’ the proposed rule, this limitation was manner other than those specifically statement was vague and useless to conveyed by the phrase ‘‘and enumerated in the first nine criteria. consumers because the immune system manifested by a characteristic set of (82.) A food manufacturers’ trade has many functions. signs or symptoms.’’ Because the final association commented that this The distinction between the two rule uses a different definition of provision is of no regulatory claims is one of specificity. An intact disease, § 101.93(g)(2)(ix) has been importance, whereas a dietary immune system has several functions. revised to state that claims about supplement trade association and

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One comment asked that the claims that they believed would be body that would imply disease FDA clarify that dietary supplements disease claims under this provision, e.g. treatment or prevention, would be an can bear ‘‘smoking-alternative’’ claims if ‘‘provides nutritional support for appropriate structure/function claims, they avoid references to nicotine, women during premenstruation by because minor pain, by itself, can be nicotine withdrawal symptoms, and promoting proper fluid balances and caused by a variety of conditions, not all tobacco-related disease. The comment breast health,’’ and ‘‘ginger supports the of them disease-related. sought concurrence that the following cardiovascular system by inhibiting FDA does not agree, however that types of claims were permitted: leukotriene and thromboxane synthesis, general well-being or health ‘‘Smoking alternative,’’ ‘‘temporarily substances associated with platelet maintenance claims would encompass reduces your desire to smoke,’’ ‘‘to be aggregation.’’ such pain claims. Pain is not a normal used as a dietary adjunct in conjunction FDA believes that this provision is state, nor are there ‘‘normal pain with your smoking cessation plan;’’ and necessary to allow for implied disease levels.’’ The claim is thus clearly one of ‘‘mimics the oral sensations of cigarette claims that may not fit into the nine pain treatment or prevention. FDA also smoke.’’ enumerated criteria. The nine criteria does not agree that section 403(r)(6) of FDA agrees that certain smoking are examples, and not an exhaustive list, the act authorizes a product whose alternative claims may be acceptable of types of claims that the agency name promises freedom from or relief of structure/function claims, if they do not believes would constitute disease pain (‘‘pain-free’’ or ‘‘pain product’’) imply treatment of nicotine addiction, claims, based on past experience. Rather and whose labeling includes claims relief of nicotine withdrawal symptoms, than attempting to evaluate or categorize related to maintenance or support of or prevention or mitigation of tobacco- statements that have not yet been joints. While the latter claims alone are related illnesses. ‘‘Smoking alternative,’’ presented to FDA, § 101.93(g)(2)(x) appropriate structure/function ‘‘temporarily reduces your desire to recognizes the possibility that other statements, in conjunction with a name smoke’’ and ‘‘mimics the oral sensations types of statements may also imply that includes the term ‘‘pain,’’ the of cigarette smoke’’ may be acceptable disease treatment or prevention. FDA product is clearly making a claim (for products that otherwise meet the does not believe that the provision will related to treatment or prevention of definition of a dietary supplement), if cause the agency to classify any joint pain. As explained elsewhere in the context does not imply treatment of structure/function statement as a this document, joint pain is a nicotine addiction, e.g., by suggesting disease claim. To regulate a statement as characteristic symptom of arthritis, and that the product can be used in smoking a disease claim under this provision, the joint pain claims are therefore disease cessation, or prevention or mitigation of agency would have to show that the claims. Acceptable structure/function statement implied an effect on disease. claims could be made, however, for pain tobacco-related diseases. For example, The two examples quoted in the associated with nondisease states, e.g., such claims would not be disease claims comments do not appear to the agency muscle pain following exercise. if the context made clear that they were to constitute disease claims. (84.) One comment listed several for short-term use in situations where claims and sought concurrence that they smoke is prohibited or socially T. Specific Claims Not Mentioned in the were acceptable structure/function unacceptable. ‘‘To be used as a dietary Proposed Rule claims: ‘‘Boosts stamina, helps increase adjunct in conjunction with your (83.) One comment contended that a muscle size, and helps enhance muscle smoking cessation plan,’’ however, is a dietary supplement called ‘‘pain free’’ or tone’’; ‘‘deters bacteria from adhering to disease claim because it is a claim that ‘‘pain product,’’ that is labeled ‘‘to the wall of the bladder and urinary the product aids in smoking cessation, support and maintain joints,’’ should tract’’; and ‘‘dietary support during the thereby implying that the product is not be regulated as an internal analgesic cold and flu season.’’ Another comment useful in treating nicotine addiction. As drug product under the OTC drug asked whether ‘‘promotes general well- noted earlier, a claim that the product review because it is intended to being during the cold and flu season’’ is is useful in counterbalancing the effects maintain or support ‘‘normal well-being a permissible claim. of a drug in depleting a nutrient or and pain levels.’’ According to this FDA agrees that ‘‘boosts stamina, interfering with the metabolism of a comment, however, products sold as helps increase muscle size, and helps nutrient would be acceptable as a ‘‘pain relief’’ or ‘‘otherwise indicated to enhance muscle tone’’ are acceptable structure/function statement. relieve temporary occurrences of structure/function claims, because they (86.) One comment offered as arthritis pain’’ could be regulated as do not refer to any disease. However, acceptable structure/function claims a drug products under the OTC review, the agency notes that a claim to increase long list of OTC drug claims provided because the tentative final monograph muscle size implies an effect that may for in the monographs for antacids, for internal analgesics requires that such subject the product regulation as an antiflatulents (antigas), antiemetics, products be labeled for the ‘‘temporary anabolic steroid under the Controlled nighttime sleep-aids, stimulants relief of minor aches and pains’’ (53 FR Substances Act (see 21 U.S.C. 802(41)). (alertness aids), daytime sedatives, 46204). At the same time, this comment ‘‘Deters bacteria from adhering to the aphrodisiacs, products for relief of argued that pain, in and of itself, is not wall of the bladder and urinary tract’’ is symptoms of benign prostatic a disease and therefore that pain claims not an acceptable structure/function hypertrophy, anticholinergics (products should not be regulated as disease claim because it implies prevention of that, at low doses, depress salivary and claims unless accompanied by an bacterial infections of the bladder and bronchial secretions), and products for explicit reference to a specific disease. urinary tract. The claims ‘‘dietary certain uses. Two comments sought FDA agrees in part and disagrees in support during the cold and flu season’’ clarification that inclusion of a claim in part with this comment. FDA agrees that and ‘‘promotes general well-being an OTC monograph does not preclude some minor pain relief claims may be during the cold and flu season’’ are its use as a structure/function claim.

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FDA agrees that some of the claims on symptoms of a specific disease or class comment from the ‘‘Products for certain the comment’s list of OTC drug claims of diseases. FDA notes, however, that uses’’ monograph, ‘‘digestive aid,’’ may be acceptable structure/function chronic fatigue or daytime drowsiness ‘‘stool softener,’’ ‘‘weight control,’’ and claims, but believes that others on the can be symptoms of chronic fatigue ‘‘menstrual’’ are, by themselves, list are disease claims. Of the claims syndrome and narcolepsy, respectively. acceptable structure/function claims if listed in the comment from the Products labeled ‘‘to help restore mental the labeling does not otherwise imply ‘‘Antacids’’ monograph, ‘‘relief of sour alertness or wakefulness when treatment or prevention of a disease. stomach’’ and ‘‘upset stomach’’ are experiencing fatigue or drowsiness’’ None mentions a characteristic acceptable structure/function claims, should not imply treatment of either of symptom of a disease. ‘‘Laxative’’ is a because they refer to a nonspecific these diseases. not a disease claim, if the labeling group of conditions that have a variety Of the claims listed in the comment makes clear that the intended use is for of causes, many of which are not from the ‘‘Daytime’’ sedatives treatment of occasional rather than disease-related. Thus, they are not monograph, almost all are acceptable chronic constipation. ‘‘Nasal characteristic of a specific disease or structure/function claims. ‘‘Occasional decongestant,’’ ‘‘expectorant,’’ and class of diseases. Although ‘‘relief of simple nervous tension,’’ ‘‘nervousness ‘‘bronchodilator’’ are disease claims. heartburn’’ and ‘‘relief of acid due to common every day overwork and ‘‘Nasal decongestant’’ is a treatment for indigestion’’ without further fatigue,’’ ‘‘a relaxed feeling,’’ ‘‘calming a characteristic symptom of colds, flu, qualification are not appropriate down and relaxing,’’ ‘‘gently soothe and hay fever. ‘‘Expectorant’’ is a structure/function claims, the agency away the tension,’’ ‘‘calmative,’’ treatment for a characteristic symptom has concluded that ‘‘occasional ‘‘resolving that irritability that ruins of colds, flu, and bronchitis. heartburn’’ and ‘‘occasional acid your day,’’ ‘‘helps you relax,’’ ‘‘Bronchodilator’’ is a treatment for indigestion’’ can also be considered ‘‘restlessness,’’ ‘‘nervous irritability,’’ bronchospasm, a characteristic nonspecific symptoms, arising as they and ‘‘when you’re under occasional symptom of asthma. do in overindulgence and other sporadic stress, helps you work relaxed’’ are all The claim from the ‘‘Products for the situations. These claims could be acceptable structure/function claims, treatment and/or prevention of appropriate structure/function claims. because all suggest occasional rather nocturnal leg muscle cramps’’ In contrast, ‘‘recurrent’’ or ‘‘persistent’’ than long-term or chronic mood monograph (‘‘treatment and/or heartburn and acid indigestion can be changes. Although occasional or acute prevention of nocturnal leg muscle hallmarks of significant illness, and are symptoms can be characteristic of cramps, i.e., a condition of localized therefore disease claims. diseases in other settings, none of the pain in the lower extremities usually All of the claims listed in the occasional symptoms referred to here is occurring in middle life and beyond comment from the ‘‘Antiflatulents’’ characteristic of a specific disease. with no regular pattern concerning time (antigas) monograph are acceptable ‘‘Nervous tension headache’’ is a disease or severity’’) is an appropriate structure structure/function claims, because the claim because tension headache meets function claim. Nocturnal leg cramps do symptoms in the claims are not the definition of a disease. not meet the definition of disease. sufficiently characteristic of specific Of the claims listed in the comment As is clear from this response, FDA diseases: ‘‘Alleviates the symptoms from the ‘‘Aphrodisiacs’’ monograph, agrees that inclusion of a claim in an referred to as gas,’’ ‘‘alleviates bloating,’’ ‘‘arouses or increases sexual desire and OTC monograph does not preclude its ‘‘alleviates pressure,’’ ‘‘alleviates improves sexual performance’’ is an use as a structure/function claim. FDA fullness,’’ and ‘‘alleviates stuffed acceptable structure/function claim notes, however, that in light of the feeling.’’ The claim listed in the because it does not imply treatment of statutory requirement that dietary comment from the ‘‘Antiemetics’’ a disease. ‘‘Helps restore sexual vigor, supplements bear all information that is monograph, ‘‘for the prevention and potency, and performance,’’ ‘‘improves material in light of consequences that treatment of the nausea, vomiting, or performance, staying power, and sexual may result from use of the product or dizziness associated with motion,’’ is potency,’’ and ‘‘builds virility and representations made about it, dietary also a permitted structure/function sexual potency’’ are disease claims supplements that contain or are labeled claim. because they use the term ‘‘potency,’’ as containing ingredients covered by an Of the claims listed in the comment which implies treatment of impotence, OTC monograph and that are being sold from the ‘‘Nighttime’’ sleep-aids a disease. If, however, these claims for the claims covered by the monograph, ‘‘for the relief of occasional made clear that they were intended monograph may be misbranded to the sleeplessness’’ is an acceptable solely for decreased sexual function extent that they omit material structure/function claim, because associated with aging, they could be information required under the occasional sleeplessness is not a acceptable structure/function claims. monograph. For example, if the OTC characteristic symptom of a disease. The claim from the ‘‘Products for relief monograph required a label statement ‘‘Helps you fall asleep if you have of symptoms of benign prostatic that products containing a particular difficulty falling asleep,’’ and ‘‘helps to hypertrophy’’ monograph (‘‘To relieve ingredient should not be used by reduce difficulty falling asleep’’ are the symptoms of benign prostatic persons taking a prescription disease claims because, unless the hypertrophy, e.g., urinary urgency and monoamine oxidase inhibitor, a dietary context makes clear that the product is frequency, excessive urinating at night, supplement containing that ingredient only for occasional sleeplessness, they and delayed urination’’) is a disease would be misbranded if its label did not imply treatment of insomnia, a disease. claim, because benign prostatic include such statement. The claim listed in the comment from hypertrophy meets the definition of a the ‘‘Stimulants’’ (alertness aids) disease. U. Substantiation of Claims monograph, ‘‘helps restore mental The claim listed in the comment from (87.) Several comments requested that alertness or wakefulness when the ‘‘Anticholinergics’’ monograph is a the final rule explicitly state that experiencing fatigue or drowsiness,’’ is disease claim. ‘‘Relieve excessive structure/function statements must be an acceptable structure/function claim secretions of the nose and eyes’’ refers adequately substantiated and that FDA because occasional fatigue and to the characteristic signs or symptoms provide guidance on what constitutes drowsiness are not characteristic of hay fever. Of the claims listed in the adequate substantiation. One comment

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Another comment argued President’s Commission on Dietary well as supporting studies. that this final rule should focus on Supplement Labels, and, because FDA There is no specific statutory adequate substantiation of claims rather concurred with the Commission’s requirement that the studies than on delineating the boundaries guidance on substantiation, the substantiating the statement be between structure/function claims and comment suggested that FDA refer to performed using the actual marketed disease claims. Other comments the Commission guidance in the final formulation. However, many ingredients maintained that substantiation is not as rule. effective in preventing consumer fraud As stated above, the agency does not and factors influencing the formulation as preapproval of the claims because believe that this final rule is the can affect the safety and effectiveness of consumers will be using the products appropriate venue to address the the dietary supplement. These long before the label claims are substantiation requirement. FDA does, variations from the marketed product investigated. however, agree that claims under should be considered before using a FDA agrees that the statutory section 403(r)(6) of the act should be study to substantiate a statement made requirement to substantiate claims is supported by adequate scientific for a particular product. important. FDA does not agree, evidence and may provide additional V. Enforcement Issues however, that it is necessary to state in guidance regarding substantiation for the regulatory text of the final rule that 403(r)(6) statements at a future date. (90.) One comment said that the structure/function claims must be The Commission report included proposal shifts the burden of proof to adequately substantiated. Section guidance on what quantity and quality manufacturers to show that their files 101.93(a)(3) requires a firm notifying of evidence should be used to match and support the claims made for FDA of a claim under section 403(r)(6) substantiate claims made under their products. of the act to certify that the firm has 403(r)(6) of the act. It also contained The regulations issued by this final substantiation that the claim is truthful guidance on the content of the rule do not address or affect the burden and not misleading. FDA also does not substantiation files for such statements, of proof during enforcement actions. agree that substantiation is an including the 30-day notification letter appropriate alternative to distinguishing to FDA, identification of the product’s However, section 403(r)(6)(B) of the act structure/function claims from disease ingredients, evidence to substantiate the clearly states that manufacturers must claims. The requirement that structure/ statements, evidence to substantiate have substantiation to show that the function statements and other safety, assurances that good statements that they make under section statements for dietary supplements manufacturing practices were followed, 403(r)(6) of the act are truthful and not under section 403(r)(6) of the act be and the qualifications of the person(s) misleading. This indicates that adequately substantiated is distinct from who reviewed the data on safety and manufacturers must be prepared to the requirement that such statements efficacy. In a notice published in the demonstrate to the court that they have not claim to diagnose, treat, mitigate, Federal Register (63 FR 23624 at support for each claim. cure, or prevent disease. Both of these 23633), FDA stated that it agreed with (91.) One comment predicted requirements are imposed by the statute the guidance of the Commission. FDA widespread noncompliance with the and must be complied with. encourages manufacturers of dietary rule because of its complexity and (88.) Several comments offered advice supplements making a 403(r)(6) of the limited FDA resources. on what types of evidence should act statement for a dietary supplement FDA disagrees with the comment. constitute adequate substantiation. A to follow this guidance. FDA believes that most of the rule is consumer health organization suggested (89.) A food manufacturer suggested that health claims and structure/ that the agency require dietary straightforward, and the comments function claims for dietary supplements supplement manufacturers making received on the proposed rule indicate be based on the totality of the publicly structure/function claims to disclose in that dietary supplement manufacturers available scientific evidence, including labeling any and all scientific studies understood the provisions of the rule. results from well-designed studies supporting the claim. In addition, the Moreover, as noted in the Analysis of conducted in a manner consistent with comment advocated requiring that these Impact in section VI.E of this document, generally recognized scientific studies be performed using the most of the claims of which FDA has principles and procedures. The marketed formulation. The comment been notified are consistent with the comment added that consumers would also urged FDA to determine how final rule. Thus, based on what has been be better served if standards for support contrary studies should be addressed. provided to FDA, most manufacturers applied to both health claims and DSHEA does not require dietary would appear to be already in structure/function claims. Another supplement labeling that carries a compliance with this final rule. If it consumer health organization suggested statement under section 403(r)(6) of the becomes apparent that there are that substantiation be based on act to include in the labeling ‘‘any and provisions that are being violated ‘‘significant scientific agreement.’’ all scientific studies supporting the because of true confusion about their Many of the comments suggested that claim.’’ Section 403(r)(6)(B) of the act applicability, FDA will issue clarifying the agency adopt FTC standards for requires only that the ‘‘manufacturer guidance. FDA agrees that its substantiation. A comment from FTC have substantiation that such statement enforcement resources are limited, and explained that FTC typically applies a is truthful and not misleading.’’ is issuing this rule in part to avoid substantiation standard known as Contrary studies should be considered inefficient use of those resources on ‘‘competent and reliable scientific when deciding whether to make and case-by-case enforcement. FDA believes evidence’’ to claims about the safety and how to word a 403(r)(6) of the act that the dietary supplement industry effectiveness of dietary supplements, statement to ensure that any statements will make good faith efforts to comply after first looking at the overall context made are truthful and not misleading. with this rule, once it becomes effective.

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W. Other Comments dietary supplements, and that proposed that ‘‘articles (other than food) intended (92.) One comment said FDA should CGMP rule may address some of the to affect the structure or any function of conduct an educational campaign to issues raised by the comments. the body of man or other animals’’ are drugs. Under this provision, foods may enhance public awareness of the III. Legal Authority differences between structure/function make claims to affect the structure or claims and disease claims and the A. Scope of Section 403(r)(6) of the Act function of the body without being meaning of individual claims. 1. Relationship Between Sections regulated as drugs. By its terms, FDA intends to conduct various 403(r)(6) and 201(g)(1)(C) of the Act however, section 201(g)(1)(C) of the act outreach activities on dietary (95.) Several comments stated that the exempts a dietary supplement that bears supplement matters. proposal mistakenly suggests that there a structure/function claim from drug (93.) One comment said FDA should is only one type of structure/function regulation only if it is also a food. The amend the tentative final monograph on claim that may be used for dietary last sentence of section 201(ff) of the act OTC laxatives to be consistent with the supplements. Some of these comments provides, ‘‘Except for purposes of rule. The comment explained that the said that if a structure/function claim section 201(g), a dietary supplement shall be deemed to be a food within the tentative final monograph should permit does not trigger drug status for the meaning of this Act.’’ The clear import the words ‘‘help maintain regularity’’ on product and is not a health claim, then of this language is that dietary OTC labeling. such a claim may be made in labeling supplements are not foods under section The agency disagrees with the for a dietary supplement so long as it is 201(g) of the act and therefore cannot comment. The fact that ‘‘helps maintain truthful and not misleading. These qualify for the ‘‘(other than food)’’ regularity’’ is an acceptable structure/ comments asserted that such a claim is exception to the drug definition in function claim does not mean that it not subject to the notice, labeling, or section 201(g)(1)(C). As a result, dietary satisfies the requirements for inclusion disclaimer requirements in section supplements that use structure/function in an OTC monograph, including the 403(r)(6) of the act. As an example, the claims may do so only under section requirement of a finding of general comments said the claim that ‘‘calcium 403(r)(6) of the act and are therefore recognition of safety and effectiveness. helps build strong bones’’ is not a health subject to the disclaimer, notification, (94.) Several comments addressed claim because it does not characterize a and other requirements in that section manufacturing or related issues. One relationship between the substance and and in FDA’s implementing regulation. comment said FDA should investigate a disease, damage, or dysfunction of the The agency acknowledges that it took effects of dissolution on product body. The comments added that FDA a contrary position in the September potency and efficacy, while other recognized this in the final rule that it 1997 final rule preamble referred to in comments advocated using United published in the Federal Register on the comment. In that preamble, FDA States Pharmacopeia standards for all September 23, 1997 (62 FR 49859, said that a dietary supplement could dietary supplements on matters 49860, 49863, and 49864), when it bear a structure/function claim under pertaining to dissolution, disintegration, stated in the preamble that claims that the ‘‘(other than food)’’ exception to the purity, and potency. One comment cranberry juice cocktail helps maintain definition of ‘‘drug’’ in section added that poor product quality would urinary tract health or that calcium 201(g)(1)(C) of the act, provided that the present a health threat to consumers and builds strong bones and teeth are not claim was truthful, non-misleading, and result in economic fraud. health claims because no disease is derived from nutritive value (see 62 FR Another comment said FDA should mentioned explicitly or implicitly. 49859 at 49860, 49863, and 49864). concentrate on standardization and Some comments added that FDA cannot However, the agency has now quality control instead of regulating say that only those claims falling under reconsidered in light of the plain labeling statements, but offered no section 406(r)(6) of the act are structure/ language of section 201(ff) of the act and specific suggestions. Some comments, function claims because such a result is revoking its statements on this subject however, made specific would be contrary to the act and would in the September 1997 preamble (i.e., recommendations. One comment said mean that the proposed rule must be the statements at 62 FR 49859 at 49860, that product labels should contain lot withdrawn. 49863, and 49864 concerning structure/ numbers and expiration dates and that FDA agrees with these comments in function claims for dietary supplements manufacturers should conduct stability part and disagrees in part. The agency under section 201(g)(1)(C)). It should be tests to determine accurate expiration agrees that statements such as ‘‘calcium noted, however, that the agency is not dates. Another comment said the public helps build strong bones’’ are not health revoking its statements in that preamble should be protected against poor claims because they do not characterize concerning structure/function claims for manufacturing standards for herbal the relationship between a substance conventional foods under section products. Other comments simply stated and a disease or health-related 201(g)(1)(C) of the act. As explained in that there is substantial potential for condition. Rather, such statements are the September 1997 preamble (62 FR public harm because there are: Multiple structure/function claims authorized by 49859 at 49860), conventional foods sources of dietary supplement section 403(r)(6) of the act. may make structure/function claims ingredients; multiple suppliers; a lack of FDA does not agree with the under section 201(g)(1)(C) of the act as regulatory production standards, or comment’s statement that dietary long as such claims are truthful, non- questions concerning product safety, supplements may bear structure/ misleading, and derive from the efficacy, and manufacturing quality; function claims without complying with nutritive value of the food. vigorous product promotion; and a the notice, disclaimer, and other For a limited transition period, FDA sizeable market. One comment simply requirements of section 403(r)(6) of the does not intend to take enforcement asked for good manufacturing practice act. Section 403(r)(6) of the act, by its action against firms who have relied on regulations for dietary supplements. terms, applies to dietary supplements. the agency’s September 1997 final rule Manufacturing issues are outside the The other possible source of authority to preamble statements to make a scope of this rule. FDA intends to issue make structure/function claims on structure/function claim for a dietary a separate proposed rule on current dietary supplements is section supplement under section 201(g)(1)(C) good manufacturing practice (CGMP) for 201(g)(1)(C) of the act, which provides of the act. To allow a reasonable time for

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As of the applicable regardless of whether they are also FDA has recognized that a dietary compliance date, firms that have been foods. Thus, although in one way supplement may lawfully be in making structure/function claims under DSHEA did limit the ability of dietary conventional food form, but must be section 201(g)(1)(C) of the act must supplement marketers to make represented as a dietary supplement either remove the claim or comply with structure/function claims, it also (citing 62 FR 49826 at 49837, September the requirements of section 403(r)(6) of significantly expanded the opportunity 23, 1997). the act and § 101.93, including notifying to make structure/function claims in Given this background, the comments FDA of the claim and relabeling to add another way by removing the limitation argued that FDA cannot take the the required disclaimer. New structure/ that dietary supplements must be foods position that a structure/function claim function claims are not subject to this to make structure/function claims. may be made for a conventional food transition period; any firm that makes a Under section 403(r)(6) of the act, only if the effect derives from the food’s structure/function claim in the labeling claims may be made for nondisease nutritional value. One comment added of a dietary supplement after the effects of a dietary supplement on the that the act does not distinguish foods effective date of this rule must comply structure or function of the body, based on their nutritional value and that with section 403(r)(6) of the act and regardless of whether those effects are DSHEA considers structure/function § 101.93. nutritive, as long as the product is claims for all dietary ingredients to be (96.) One comment objected to a intended to supplement the diet as ‘‘statements of nutritional support.’’ The sentence in the introductory paragraph provided in section 201(ff)(1) of the act. comment said FDA, therefore, should in the preamble to the proposed rule. 2. Structure/Function Claims for recognize that structure/function claims The sentence stated that, before DSHEA, Conventional Foods that can be made for dietary ingredients certain claims could have rendered a (97.) Several comments sought when those ingredients are in dietary product a ‘‘drug’’ under the act. The consistency in the treatment of supplements can also be made when comment argued that even before conventional foods and dietary those ingredients are in conventional DSHEA, dietary supplements could supplements with respect to structure/ food, but added that the disclaimer make structure/function claims and not function claims and health claims. statement and notification to FDA, as be considered drugs. The comment said Some of these comments contended that required by section 403(r)(6)(C) of the that section 201(g)(1)(C) of the act this rule would permit dietary act, apply only to dietary supplements expressly excluded food from the supplements to carry claims that would and not to conventional food. One definition of drug and that dietary be health claims if made for a comment said that requiring structure/ supplements fell within the ‘‘food’’ conventional food. One comment stated function claims for conventional foods exception. The comment characterized that differential treatment of foods and to be derived from the food’s nutritional DSHEA as limiting and restricting dietary supplements was inconsistent value would create a marketing ‘‘what had been the unconditional right with the Commission’s disparity and put conventional foods at of dietary supplement marketers to recommendations. This comment a competitive disadvantage. make structure/function claims.’’ suggested that differential treatment This rule applies to claims for dietary The agency agrees that before DSHEA, would cause consumers to perceive supplements only. Its purpose is to dietary supplements that were also dietary supplements as better sources implement section 403(r)(6) of the act, foods could make structure/function for safeguarding health than which applies to dietary supplements claims under section 201(g)(1)(C) of the conventional foods. One comment only. Therefore, a detailed discussion of act without being considered drugs. expressed the view that the rule should the regulatory framework applicable to However, the passage of DSHEA apply to claims for conventional foods structure/function claims for changed the regulatory framework for as well as dietary supplements and conventional foods, which are made structure/function claims on dietary requested FDA to clarify the rule’s under section 201(g)(1)(C) of the act, is supplements by adding sections 201(ff) scope. Other comments said that any beyond the scope of the rule. FDA and 403(r)(6) to the act. As explained in structure/function claims that may be advises, however, that for consistency, the response to the preceding set of made for dietary supplements may also the agency is likely to interpret the comments, section 201(ff) of the act be made for conventional foods. The dividing line between structure/ provides that dietary supplements are comments explained that the history of function claims and disease claims in a not considered food for purposes of the act shows that claims that food similar manner for conventional foods section 201(g). Therefore, dietary affect the structure or function of the as for dietary supplements. The agency supplements may no longer make body do not result in the food being also notes that as discussed in the structure/function claims under the classified as a drug, citing the district response to comment 1 in section II.A ‘‘food’’ exception to the drug definition court and appellate decisions in of this document, FDA reaffirms the in section 201(g)(1)(C) of the act. FDA American Health Products Co. v. Hayes, statements about structure/function therefore agrees with the comment that 574 F. Supp. 1498, 1501 (S.D.N.Y. claims for conventional foods in the in one respect, DSHEA limited the 1983), aff’d, 744 F.2d 912 (2d Cir. 1984). September 23, 1997 (62 FR 49859), final ability of dietary supplement marketers Another comment stated that rule entitled ‘‘Food Labeling: Nutrient to make structure/function claims. established case law shows that an Content Claims, Health Claims, and The sentence in the introductory article may be a food if it is used Statements of Nutritional Support for paragraph of the preamble to the primarily for taste, aroma, or nutritional Dietary Supplements.’’ As explained in proposed rule correctly stated that value, but that nutritional value is not that rule (62 FR 49859 at 49860, 49861, ‘‘certain claims’’—structure/function required in all instances. One comment and 49864), the fact that structure/ claims for dietary supplements that further noted that FDA, when it function claims for conventional foods

VerDate 04-JAN-2000 16:16 Jan 05, 2000 Jkt 190000 PO 00000 Frm 00036 Fmt 4701 Sfmt 4700 E:\FR\FM\06JAR4.XXX pfrm11 PsN: 06JAR4 Federal Register / Vol. 65, No. 4 / Thursday, January 6, 2000 / Rules and Regulations 1035 are limited to effects derived from related claims and structure/function health claims prior authorization nutritional value, while structure/ claims.’’ Relying in part on the requirements, but instead could be function claims for dietary supplements introduction to section 403(r)(6) of the made simply by meeting the are not, is a result of differences in the act (‘‘For purposes of paragraph (r)(1)(B) requirements of section 403(r)(6) of the language of the exemption for foods in * * *’’), the comment asserted that act and FDA’s implementing section 201(g)(1)(C) of the act, as structure/function claims are a subset of regulations. The language in section interpreted by the courts (see Nutrilab, the claims authorized by section 403(r)(6) of the act excluding claims to Inc. v. Schweiker, 713 F.2d 335, 338 (7th 403(r)(1)(B) of the act (health claims). affect disease from the coverage of that Cir. 1983)), and the language of section Consequently, because claims under section demonstrates that Congress 403(r)(6) of the act. section 403(r)(1)(B) of the act may made a public health judgment that (98.) One comment suggested revising characterize the relationship of a claims promoting dietary supplements the definition of ‘‘disease or health- nutrient to a disease, the comment for disease uses should continue to related condition’’ in proposed stated that FDA cannot preclude require premarket authorization. It § 101.14(a)(6) to include a reference to structure/function claims from making would not make sense for Congress to § 101.93, and also recommended any contextual references to diseases. exclude labeling claims pertaining to revising the definition of ‘‘health claim’’ FDA disagrees with this comment. disease uses in one part of section at § 101.14(a)(1) to be consistent with Structure/function claims are not a 403(r)(6) of the act, while permitting § 101.93. Currently, § 101.14(a)(1) reads subset of health claims because, clearly, such claims in another paragraph of the as follows: there are claims about the effect of a same section. Moreover, the Health claim means any claim made on the product on the structure or function of interpretation advocated by the label or in labeling of a food, including a the body that are not also health claims. comment would lead to confusing and dietary supplement, that expressly or by To be a health claim, a claim must refer contradictory labeling. A dietary implication, including ‘‘third party’’ to the relationship between a food supplement that bears a health claim— references, written statements (e.g., a brand substance and a disease or health- name including a term such as ‘‘heart’’), a claim that, by definition, is a claim related condition. FDA interprets that a substance in the supplement in symbols (e.g., a heart symbol), or vignettes, ‘‘health-related condition’’ to mean a characterizes the relationship of any some way has an effect on a disease— substance to a disease or health-related state of health leading to disease. Claims would also have to bear a contradictory condition. Implied health claims include such as ‘‘calcium builds strong bones’’ disclaimer that it is not intended to those statements, symbols, vignettes, or other are not health claims because they do treat, mitigate, or prevent any disease. forms of communication that suggest, within not refer explicitly or implicitly to any Second, structure/function claims that the context in which they are presented, that disease or health-related condition. are not also health claims would not be a relationship exists between the presence or Therefore, the comment is based on an authorized under section 403(r)(6) of the level of a substance in the food and a disease invalid premise. act at all. In fact, a structure/function or health-related condition. (100.) One comment requested that claim on a dietary supplement would The comment would revise the FDA revise § 101.93(f) to state that the subject it to drug regulation because, as definition to read as follows: requirements of section 403(r)(6) of the explained in the response to comment 1 Health claim means any claim made on the act, e.g., use of the disclaimer and in section II.A of this document, section label or in labeling of a food, including a substantiation, apply only to structure/ 403(r)(6) of the act is the only provision dietary supplement, that expressly or by function claims that fall within the implication, including ‘‘third party’’ that authorizes the use of structure/ definition of a ‘‘health claim’’ in references, written statements (e.g., a brand function claims on dietary supplements. § 101.14(a)(1) and (a)(5). According to name that includes or implies a disease, such The introductory language in section as ‘‘Raynaudin’’), symbols, or vignettes, this comment, the introduction to characterizes the relationship of any section 403(r)(6) of the act (‘‘For 403(r)(6) (‘‘For purposes of [section substance to a disease or health-related purposes of paragraph (r)(1)(B) * * *’’) 403](r)(1)(B) * * *’’) does not support condition (e.g., disease-indicating establishes that structure/function the interpretation advocated in the electrocardiogram tracings, pictures of organs claims that do not fall within the comment. If Congress had wanted to that suggest prevention or treatment of a definition of health claims are not subject only structure/function claims disease state, the prescription symbol, or any subject to section 403(r)(6), and may be that are also health claims to section reference to prescription use). Implied health made without complying with any of its 403(r)(6) of the act, it could have done claims include those statements, symbols, requirements. so much more directly by using vignettes, or other forms of communication language such as ‘‘A statement for a that suggest, within the context in which FDA does not agree and, in fact, they are presented, that a relationship exists believes that the opposite is true. As dietary supplement may be made if * * between the presence or level of a substance explained elsewhere in this document * and the statement is a statement of the in the food and a disease or health-related and in the proposed rule, structure/ type governed by paragraph (r)(1)(B).’’ condition. function claims that fall within the The ambiguity of the ‘‘For purposes of As stated in response to comment 51 definition of health claims, or that (r)(1)(B)’’ language is well demonstrated of section II.I of this document, FDA otherwise constitute disease claims, do by the diametrically opposed does not believe that §§ 101.14(a)(1) and not fall within the scope of claims interpretations adopted by this 101.93(g) are inconsistent. As a result of authorized under section 403(r)(6) of the comment and the preceding comment. the special regime for dietary act, but other structure/function claims FDA interprets this language as a supplements under DSHEA, there may do fall within the scope of section caution that the category of claims be some differences in the treatment of 403(r)(6) and are subject to its covered by section 403(r)(6) of the act is dietary supplements and conventional requirements. Adopting the not to be interpreted as coextensive with foods under § 101.14(a)(1). interpretation advocated by the health claims, the category covered by 3. Relationship Between Structure/ comment would bring about illogical section 403(r)(1)(B) of the act. Congress Function Claims and Health Claims results for dietary supplement labeling may have been concerned that the (99.) One comment stated that the claims in two ways. First, structure/ health claims category would swallow proposed rule ‘‘improperly function claims that are also health the category of claims under section distinguishes between other health- claims would not be subject to the 403(r)(6) of the act because all claims

VerDate 04-JAN-2000 16:16 Jan 05, 2000 Jkt 190000 PO 00000 Frm 00037 Fmt 4701 Sfmt 4700 E:\FR\FM\06JAR4.XXX pfrm11 PsN: 06JAR4 1036 Federal Register / Vol. 65, No. 4 / Thursday, January 6, 2000 / Rules and Regulations under section 403(r)(6) could be dietary ingredient’’ (section 403(r)(6)(A) relevant source’’’ (557 F.2d at 334 characterized as referring to a ‘‘health- of the act). FDA did not consider (citations omitted)). See also § 201.128 related condition’’ if that term were whether statements were authorized (listing evidence FDA will consider in defined broadly as ‘‘a state of health.’’ under this provision in developing the determining the intended use of a drug). The result would have been that all proposed rule because the purpose of (104.) One comment said that the structure/function claims, as claims the rule was to implement the structure/ proposal must be withdrawn because, about the relationship between a function provisions of section contrary to section 403(r)(6) of the act, substance and a health-related 403(r)(6)(A) of the act, not other it gives manufacturers the burden to condition, would also have been health provisions. However, consideration of prove that a claim is not a drug claim claims and would have required this provision as applied to normal body when, in fact, FDA has the burden, by premarket authorization. By including functions would not have led to a a preponderance of relevant evidence, to the introductory language, Congress different result. The criteria in the rule establish that a dietary supplement is effectively forestalled such an were developed to identify claims that misbranded. The comment cited two interpretation. refer directly or indirectly to an effect court opinions, United States v. 29 (101.) Another comment said the on disease and do not encompass claims Cartons * * * an Article of Food proposed rule does not distinguish that refer only to general well-being. (Oakmont), 987 F.2d 33 (1st Cir. 1993) between structure/function statements Claims relating to normal body and United States v. An Article of Food that assert health claims and those that functions are authorized under the rule. * * * Viponte Ltd. Black Currant Oil, 984 do not, and said the failure to make this The comment’s argument about the F.2d 814 (7th Cir. 1993), for the distinction would mean that more use of FDA’s actions on notifications of proposition that, before DSHEA was products would be subject to the rule claims under section 403(r)(6) of the act enacted, courts had invalidated an FDA than necessary. to justify the rule is addressed in enforcement theory that shifted the FDA does not agree that the rule fails comment 4 of section II.A of this burden of proof to manufacturers. to distinguish between structure/ document. FDA disagrees with this comment. function claims that do and do not (103.) One comment claimed that the Although the comment is correct that assert health claims. On the contrary, proposal does not require FDA to show FDA has the burden of proving that a the rule makes clear that only structure/ any evidence of a manufacturer’s intent dietary supplement—or, in fact, any function claims that do not assert health to find that a dietary supplement claim food—is misbranded, the rule does not claims may be made under section constitutes an illegal drug claim. The give manufacturers the burden of 403(r)(6) of the act. To the extent that comment argued that proposed proving that a claim is not a drug claim. the comment may be suggesting that § 101.93(g)(2)(ii), (g)(2)(iii), (g)(2)(viii), The rule does not shift the burden of structure/function claims that are also and (g)(2)(x) run afoul of the recent proof in an enforcement action but health claims should be exempt from appellate decision in Brown & rather sets forth criteria for what claims the health claims authorization Williamson Tobacco Corp. v. FDA, 153 are disease claims that may subject a requirements, the agency disagrees for F.3d 155 (4th Cir. 1998), contending that product marketed as a dietary the reasons given in the response to the ‘‘a product is not a drug merely because supplement to regulation as a drug. previous comment. a consumer uses it as one’’ and that The two cases cited in the comment ‘‘there must be proof as to the are inapposite. They concern FDA’s B. Miscellaneous Legal Issues manufacturer’s intent.’’ The comment efforts to regulate certain dietary (102.) Two comments said the also cited National Nutritional Foods ingredients as food additives and do not proposed rule violated the Ass’n v. Mathews, 557 F.2d 325 (2d Cir. have any relevance to claims issues. Administrative Procedure Act because it 1977), to support its position that a (105.) One comment said that the was arbitrary and capricious, on two manufacturer’s intent, as determined proposed rule is inconsistent with the grounds. One comment asserted that from labeling or advertising, is the act and congressional intent, arguing FDA failed to consider an important primary factor in determining whether a that, by enacting DSHEA, Congress had aspect of the problem of distinguishing product is intended to treat a disease. taken steps to reverse FDA’s ‘‘overly between drug claims and dietary Although FDA disagrees with the restrictive’’ approach towards claims supplement claims: The application of Brown & Williamson decision and is and had commanded the agency to the ‘‘general well-being’’ provision of awaiting the outcome of Supreme Court expand, rather than restrict, the amount section 403(r)(6) of the act. The review, this rule does not depend on the of health information permitted on comment argued that FDA should have resolution of the legal issues in that dietary supplement labels and labeling. considered whether claims relating to case. The focus of the rule is on express According to the comment, the proposal normal body functions might qualify as and implied claims made by the vendor ‘‘directly and substantially violates the ‘‘general well-being’’ claims under in labeling. None of the provisions of overall statutory scheme and the section 403(r)(6) of the act before the rule, including those mentioned in expressed legislative intent’’ and FDA deciding to regulate them as disease the comment, rely on consumer use as ‘‘has no authority to proceed with the claims. The comment also argued that a standard for determining whether the rulemaking without a grant of authority FDA’s explanation of the need for the product is intended to treat or prevent from Congress in light of the Act’s proposed rule ran counter to the disease. language and Congressional intent.’’ evidence before the agency, in that the The rule is consistent with the The agency disagrees with this agency’s actions on notifications of decision in National Nutritional Foods comment and believes that the rule is claims under section 403(r)(6) of the act Ass’n v. Mathews, in which the court consistent with the act and did not support a need for further said, ‘‘FDA is not bound by the congressional intent. Although regulation. manufacturer’s subjective claims of Congress, in enacting DSHEA, did The ‘‘general well-being’’ provision of intent but can find actual therapeutic expand the scope of information in section 403(r)(6) of the act authorizes intent on the basis of objective evidence. dietary supplement labeling by statements in dietary supplement Such intent also may be derived or providing for claims to affect the labeling that describe ‘‘general well- inferred from labeling, promotional structure or function of the body and the being from consumption of a nutrient or material, advertising, and ‘any other other types of claims authorized by

VerDate 04-JAN-2000 16:16 Jan 05, 2000 Jkt 190000 PO 00000 Frm 00038 Fmt 4701 Sfmt 4700 E:\FR\FM\06JAR4.XXX pfrm11 PsN: 06JAR4 Federal Register / Vol. 65, No. 4 / Thursday, January 6, 2000 / Rules and Regulations 1037 section 403(r)(6) of the act, Congress CFR 310.530) (use of the word Central Hudson Gas & Elec. Corp. v. also explicitly limited statements under ‘‘hormone’’ in labeling is an implied Pub. Serv. Comm’n, 447 U.S. 557, 566 section 403(r)(6) to those that do not drug claim).) Moreover, courts have (1980)). The comment argued that not claim to ‘‘diagnose, mitigate, treat, cure, upheld FDA’s authority to regulate all structure/function claims prohibited or prevent a specific disease or class of implied drug claims. (See, e.g., United under the proposed rule are inherently diseases.’’ This rule does not create new States v. Storage Spaces Designated false or misleading and that if FDA does restrictions but merely implements the Nos. ‘‘8’’ and ‘‘49’’, 777 F.2d 1363, 1366 not review the evidence for a claim, the provisions of section 403(r)(6) of the act. & n. 5 (9th Cir. 1985), cert. denied, 479 claim does not become false or FDA has authority to issue U.S. 1086 (1987); Pasadena Research misleading. Although the comment implementing regulations under section Labs., Inc. v. United States, 169 F.2d admitted that FDA has a substantial 701(a) of the act, which authorizes the 375, 383 (9th Cir.), cert. denied, 335 interest in regulating the safety, efficacy, agency to issue regulations for the U.S. 853 (1948); United States v. Six and labeling of dietary supplements in efficient enforcement of the act. Dozen Bottles * * * ‘‘Dr. Peter’s Kuriko’’, order to protect the public health, the (106.) One comment declared that 158 F.2d 667, 669 (7th Cir. 1947); comment claimed that the regulation FDA has no legal basis to include a United States v. John J. Fulton Co., 33 was more extensive than necessary. The broad variety of implied claims. F.2d 506, 507 (9th Cir. 1929); Bradley v. comment argued that a disclaimer is FDA disagrees with this comment. United States, 264 F. 79, 81–82 (5th Cir. ‘‘the constitutionally mandated method The agency has regulated implied 1920); United States v. Kasz Enterprises, of regulating commercial speech.’’ claims in labeling for many years, in Inc., 855 F. Supp. 534, 539, 543–44 Other comments said the proposed many contexts. (See, e.g., 21 CFR (D.R.I. 1994), modified on other rule violates the First Amendment 104.5(b) and (d) (prohibiting certain grounds, 862 F. Supp. 717 (D.R.I.1994); because, using the analysis in Central implied claims relating to compliance United States v. 43 1/2 Gross Rubber Hudson Gas & Electric Corp. v. Public with nutritional quality guidelines); 21 Prophylactics, 65 F. Supp. 534, 535 (D. Service Commission, 447 U.S. 557 CFR 101.13(a) (classifying implied Minn. 1946), aff’d sub nom. Gellman v. (1980), it is not narrowly tailored to claims to characterize the level of a United States, 159 F.2d 881 (8th Cir. meet FDA’s interests and does not nutrient in food as nutrient content 1947).) directly and materially advance the claims subject to the same requirements (107.) Many comments argued that the agency’s interests. In general, these as express claims); 21 CFR 101.95 proposed rule ignored the Supreme comments offered various reasons why (prescribing conditions under which Court decision in Daubert v. Merrell the proposed rule did not survive implied claims of freshness may be Dow Pharmaceuticals, Inc., 509 U.S. 579 scrutiny under Central Hudson. For made for foods); 21 CFR 201.10(c)(3) (1993). example, under Central Hudson, the (prohibiting use in ingredient statement FDA disagrees with these comments. government may regulate commercial of fanciful drug or ingredient names that The comments did not explain how the speech that concerns unlawful activity falsely imply that the drug or ingredient rule was contrary to or even affected by or is misleading if, among other things, has some unique effectiveness or the decision. Daubert involved the the government asserts a substantial composition); 21 CFR 201.302(c) admissibility of scientific evidence in a interest in support of its regulation. In (prohibiting implied claims that drugs judicial proceeding under the Federal brief, the comments said FDA failed to for internal use that contain mineral oil Rules of Evidence. This rulemaking assert a substantial interest or construed are for administration to infants). The does not present issues regarding the the government’s interest to be agency has also regulated implied admissibility of evidence in any Congress’ interest in increasing the claims in prescription drug advertising. proceeding, judicial or administrative, amount of information to consumers. (See, e.g., § 202.1(a)(3) (21 CFR nor does it address expert testimony Others said that, contrary to Central 202.1(a)(3)) (prohibiting use in (which was at issue in Daubert). Thus, Hudson, the proposed rule was not advertising of fanciful product or FDA does not agree that the rule narrowly tailored and suppressed more ingredient names that falsely imply that ‘‘ignores’’ or is contrary to the Daubert speech than necessary to protect a the drug or ingredient has some unique decision. possible government interest in effectiveness or composition); protecting consumers from fraud and C. Constitutional Issues § 202.1(e)(6)(v) (prohibiting implied protecting public health and either claims that a study represents more 1. First Amendment suggested alternatives or said FDA widespread experience with the drug (108.) Several comments focused on should consider less restrictive than it actually does).) More the First Amendment. One comment alternatives. Some comments said the specifically, the agency has repeatedly argued that the rule violates the First proposal also did not advance the taken the position that implied disease Amendment because it is more asserted government interest because it claims in labeling subject a product to restrictive than is necessary to advance blurred, instead of clarified, the line regulation as a drug. In the animal drug FDA’s interests. The comment conceded between drug and dietary supplement context, § 500.52 (21 CFR 500.52) that the government may regulate or claims. provides that the use of certain terms in prohibit commercial speech if the One comment also asserted that there the labeling of products intended for use speech is inherently false, deceptive, or is no substantial government interest in or on animals implies that the misleading, but argued that the involved, because FDA has not shown a product is capable of a therapeutic effect government can only restrict concern for consumer safety or a danger and causes the product to be a drug commercial speech that is not false, to public health; according to this within the meaning of section 201(g) of deceptive, or misleading if the comment, the proposed rule was a the act. In the human drug context, government shows that the restriction response to confusion by manufacturers § 201.56(c) (21 CFR 201.56(c)) prohibits directly and materially advances a and consumers about what claims are ‘‘implied claims or suggestions of drug substantial state interest in a manner permitted. use’’ in prescription drug labeling that is no more extensive than necessary Some comments also argued that FDA unless the product has been shown to be to serve that interest (citing Ibanez v. has not shown that the claims are safe and effective for the implied or Florida Dept. Of Bus. & Prof’l misleading or that the commercial suggested use. (See also § 310.530 (21 Regulation, 512 U.S. 136, 142 (1994); speech covered by the proposed rule is

VerDate 04-JAN-2000 16:16 Jan 05, 2000 Jkt 190000 PO 00000 Frm 00039 Fmt 4701 Sfmt 4700 E:\FR\FM\06JAR4.XXX pfrm11 PsN: 06JAR4 1038 Federal Register / Vol. 65, No. 4 / Thursday, January 6, 2000 / Rules and Regulations inherently misleading. One comment rendered non-misleading by requiring a v. Pittsburgh Comm’n on Human asserted that, if statements were disclaimer. According to the comment, Relations, 413 U.S. 376 (1973), the untruthful or misleading, DSHEA would the court’s decision also requires FDA to Supreme Court held that an have prohibited them. further define the ‘‘significant scientific advertisement could be prohibited Another comment said the proposal agreement’’ standard for authorizing where it indicated that the advertiser ‘‘trenches on’’ the First Amendment dietary supplement health claims. The was likely to have an illegal intent while because consumers have the right to comment said that the proposed rule engaging in the proposed transaction receive, and manufacturers have the was premature in light of the need to (id. at 389). There, as here, ‘‘the right to express, non-misleading amend the health claims regulations to restriction * * * is incidental to a valid information. The comment cited conform to the Pearson decision. The limitation on economic activity’’ (id.). Washington Legal Foundation v. comment also argued that, in light of Nor does the rule create an Friedman, 13 F. Supp. 2d 51 (D.D.C. Pearson, FDA may not issue a final rule unconstitutional prior restraint. FDA 1998) for this proposition. Another that prohibits disease claims but rather does not believe that the regulations in comment cited the Washington Legal must choose the less restrictive § 101.93(f) and (g) are properly analyzed Foundation decision to argue that the alternative of permitting such claims as a prior restraint at all. As explained proposed rule would ‘‘impermissibly provided that they are accompanied previously, the regulations do not curtail’’ the flow of information to with disclaimers. restrict speech but rather treat it as consumers. The comment suggested that FDA does not believe that the rule evidence of a product’s intended use. less restrictive alternatives, such as violates the First Amendment. The rule Using speech to infer intent does not ‘‘allowing implicit, but not explicit, does not prohibit any speech; rather, it violate the First Amendment (Wisconsin claims,’’ establishing ‘‘categories of clarifies the circumstances under which v. Mitchell, 508 U.S. 476, 489 (1993)). diseases that clearly denoted drug FDA will consider a certain type of Thus, the regulations do not prevent claims’’ or identifying terms that speech—labeling claims—to be speech from happening, but, as connote ‘‘treatment,’’ ‘‘cure,’’ or evidence of intended use as a drug, evidence of intended use, they ‘‘mitigation’’ exist. absent health claim authorization. Thus, determine the consequences that result A few comments simply claimed that the rule does not regulate speech as from certain types of speech. (See the proposal violates the First such, but rather as evidence of intended Village of Hoffman Estates v. Flipside, Amendment because it would decrease use. The use of speech as evidence of a 455 U.S. at 495–96 (rejecting head the amount of scientific information on company’s intended use for its products shop’s ‘‘exorbitant’’ claim that village labels and labeling or because it is constitutional because ‘‘[t]he First ordinance treating the proximity of represents a ‘‘prior restraint’’ on health Amendment * * * does not prohibit the drug-oriented literature as evidence of claims. Other comments objected to evidentiary use of speech * * * to prove intended use was a prior restraint).) particular provisions of the proposed motive or intent’’ (Wisconsin v. Although the regulations cannot rule on First Amendment grounds, Mitchell, 508 U.S. 476, 489 (1993).) (See themselves be considered as a direct notably proposed § 101.93(g)(2)(iv)(C), also Village of Hoffman Estates v. prior restraint, it is true that claims which provided that citation of the title Flipside, 455 U.S. 489, 495–96 (1982) classified as disease claims under the of a scientific reference in dietary (upholding village ordinance treating regulations are subject to prior supplement labeling would be a disease the proximity of drug-oriented literature authorization requirements that could claim if the title referred to a disease use as evidence that items were marketed be considered prior restraints—namely, of the product. Several comments said for use with illegal drugs). Because it is the prior authorization requirement for that this provision of the proposed rule the intent and not the speech that dietary supplement health claims and would violate the First Amendment as triggers a regulatory burden on the the new drug approval requirements an unlawful restraint on commercial speaker, there is no First Amendment that are triggered in the absence of speech. Others characterized the violation. (See Wisconsin v. Mitchell, health claim authorization. In both proposed provision as simply a 508 U.S. at 489; United States v. Articles cases, a disease claim cannot be made restriction on freedom of speech, of Drug * * * B–Complex Cholinos until FDA has evaluated the safety of whether the restriction was on the right Capsules, 362 F.2d 923, 927 (3d Cir. the product and the evidence of companies to provide the information 1966) (no impingement on free speech supporting the claim. However, labeling or on the right of consumers to receive for FDA to use statements made by a claims are commercial speech, and the the information. One comment said that lecturer employed by a manufacturer as Supreme Court has indicated that the references to publication titles could be evidence of the manufacturer’s intent prior restraint doctrine may not apply to prohibited if they were misleading, but that its products be used for therapeutic commercial speech. (See Central that the rule should not contain a purposes).) Hudson, 447 U.S. at 571 n.13 blanket prohibition. Some comments Even if the rule were viewed as a (‘‘[C]ommercial speech is such a sturdy added that the agency should reconsider direct restriction on speech, it would brand of expression that traditional its position on this provision in light of not violate the First Amendment. The prior restraint doctrine may not apply to Washington Legal Foundation v. marketing in interstate commerce of a it.’’; Virginia State Bd. of Pharmacy v. Friedman. drug that has not been determined by Va. Citizens Consumer Council, 425 Finally, a comment said that the FDA to be safe and effective is illegal U.S. 748, 771–72 n.24 (1976) (greater proposal was contrary to the decision of (see section 301(a) and (d) of the act (21 objectivity and hardiness of commercial the U.S. Court of Appeals for the District U.S.C. 331(a) and (d)) and 505 of the act. speech may make prior restraint of Columbia Circuit in Pearson v. Thus, labeling claims that promote a doctrine inapplicable). Commercial Shalala, 164 F.3d 650 (D.C. Cir. 1999). dietary supplement for disease uses speech is ‘‘sturdy’’ because of its profit According to the comment, the court of promote the product for use as an motive. ‘‘[S]ince advertising is the sine appeals’ First Amendment ruling in unapproved new drug, which is illegal. qua non of commercial profits, there is Pearson requires the agency to permit Speech promoting an illegal activity little likelihood of its being chilled by health claims that do not satisfy the may be restricted without violating the proper regulation and forgone entirely’’ ‘‘significant scientific agreement’’ First Amendment (Central Hudson, 447 (Virginia State Bd. of Pharmacy, 425 standard as long as the claim can be U.S. at 563–564). In Pittsburgh Press Co. U.S. at 771–72 n.24). The same is true

VerDate 04-JAN-2000 16:16 Jan 05, 2000 Jkt 190000 PO 00000 Frm 00040 Fmt 4701 Sfmt 4700 E:\FR\FM\06JAR4.XXX pfrm11 PsN: 06JAR4 Federal Register / Vol. 65, No. 4 / Thursday, January 6, 2000 / Rules and Regulations 1039 of labeling. The Supreme Court has in Central Hudson applies. FDA treating or preventing disease, even if expressed approval of prior review believes that it is not necessary to reach that is not the case. requirements in commercial speech the Central Hudson test because the rule Even if the remaining elements of the cases. (See Shapero v. Kentucky Bar is constitutional under Wisconsin v. Central Hudson test are reached, the Ass’n, 486 U.S. 466, 476 (1988) (lawyer Mitchell, Pittsburgh Press, and Village of rule and the statutory provisions that it may be required to file solicitation letter Hoffman Estates; however, the rule also implements are constitutional. As with State in advance, to give it ‘‘ample easily passes muster under the four-part previously noted, this rule restricts no opportunity to supervise mailings and test in Central Hudson. Under that test, speech directly. Rather, it determines penalize actual abuses’’);Central the first question is whether the what types of speech in dietary Hudson, 447 U.S. at 571 n.13 (State may commercial speech at issue is false, supplement labeling will trigger other require ‘‘a system of previewing misleading, or concerns unlawful statutory provisions and regulations that advertising campaigns’’).) activity, because such speech is beyond may be considered restrictions on If the prior authorization requirement the First Amendment’s protection and speech. To the extent that this rule, the for dietary supplement health claims statute, and the drug and health claim may be prohibited. If the speech is and the approval requirement for new regulations restrict speech by requiring truthful, non-misleading, and concerns drugs were to be considered prior either health claim authorization or new lawful activity, the government may restraints, they would be constitutional drug approval before a business may prior restraints. The only court of nonetheless regulate it if the make a disease claim for a dietary appeals to address the issue in the government interest asserted to justify supplement, that restriction directly health claims context ruled that the the regulation is substantial; the advances the substantial government health claims authorization process is regulation directly advances the interest in protecting and promoting the not an unconstitutional prior restraint. asserted governmental interest; and the public health by helping to ensure that In a recent case challenging the NLEA regulation is no more extensive than products intended to have an effect on and FDA’s health claim regulations for necessary to serve the government a disease are safe and effective for that dietary supplements, the U.S. Court of interest (Central Hudson, 447 U.S. at intended use. That interest is an interest Appeals for the Second Circuit held that 566). The Supreme Court has explained both in preventing direct harm from the prior restraint doctrine did apply, that the last element of the test is not a such products—i.e., protecting the but it went on to uphold the statute and ‘‘least restrictive means’’ requirement, public from adverse events that such regulations based on consideration of but rather requires narrow tailoring—‘‘a products might cause—and in the Central Hudson factors. Nutritional fit that is not necessarily perfect, but preventing the indirect harm to health Health Alliance v. Shalala, 144 F.3d reasonable’’ between means and ends that is caused when an ill person 220, 227–28 (2d Cir.), cert. denied, 119 (Board of Trustees of the State Univ. of foregoes medical care in favor of S. Ct. 589 (1998). In Nutritional Health N.Y. v.Fox, 109 S. Ct. 3028, 3032–35 ineffective self-treatment. Alliance, the Second Circuit held that (1989)). In subsequent decisions, the Requiring prior FDA review and the health claims authorization process Court has also clarified that authorization of disease claims ensures is ‘‘sufficiently narrowly tailored’’ and ‘‘misleading’’ in the first element of the that such claims will be evaluated by a has adequate procedural safeguards— test refers to speech that is inherently or public health agency that has scientific including a deadline for final agency actually misleading. Thus, if the speech and medical expertise so that only action, a decision making standard to to be regulated is not inherently or products that are safe and effective will constrain the agency’s discretion, and actually misleading, the remainder of be permitted to be sold for therapeutic provision for development of a record the test applies. (See In re R.M.J., 455 purposes. As a government agency with for judicial review—to render it U.S. 191, 203 (1982).) no financial stake in either permitting or denying claims, FDA is in a position to constitutionally valid (144 F.3d at 228; As previously discussed, FDA see § 101.70 (procedures for petitioning evaluate the strength of the safety and believes that claims for disease uses that for a health claim)). In upholding the efficacy evidence objectively. have not been found to be safe and regulatory scheme, the court also The rule and the other components of effective are speech related to an stressed that matters of public health the regulatory framework for drugs and unlawful activity, and therefore there is and safety were involved (144 F.3d at health claims also advance the related no need to reach the remaining elements 228). The same considerations that the substantial government interest in court in Nutritional Health Alliance of the Central Hudson test. The agency protecting consumers from fraud. If relied on also operate in the new drug also considers such claims inherently products are marketed for disease uses approval context: Matters of public misleading because, when accompanied only after they have been demonstrated health and safety are involved, and the by a disclaimer that directly contradicts to be safe and effective for such uses, act and implementing regulations the claim by stating that the product is consumers will not suffer economic provide many procedural safeguards, not intended to have an effect on harm from spending money on including a deadline, a decision making disease, they are inherently likely to worthless remedies. standard, and the development of an confuse consumers rather than provide Moreover, the rule is not more record for judicial review (see section them with useable information. Speech extensive than necessary. The agency 505(c)(1), (d), and (h) of the act and; 21 that is ‘‘more likely to deceive the does not believe that the alternatives CFR 314.200.) Moreover, as far as FDA public than to inform it’’ is not mentioned in the comments, or any is aware, the constitutionality of the protected by the First Amendment other alternative, would adequately new drug approval process has never (Central Hudson, 447 U.S. at 563). If not further its substantial interest in been challenged on First Amendment inherently misleading, claims for protecting and promoting public health grounds. Therefore, FDA does not disease uses that have not been found to by ensuring the safety and efficacy of believe that the prior restraint argument be safe and effective are at least products intended to have an effect on in the comments has merit. potentially misleading because of the disease. For example, allowing implicit Many of the comments assumed that confusion caused by the disclaimer. disease claims, but not explicit ones, the test for restrictions on commercial Such claims also may lead consumers to would merely allow companies to do speech set forth by the Supreme Court believe that the product has benefits in indirectly what they cannot do

VerDate 04-JAN-2000 16:16 Jan 05, 2000 Jkt 190000 PO 00000 Frm 00041 Fmt 4701 Sfmt 4700 E:\FR\FM\06JAR4.XXX pfrm11 PsN: 06JAR4 1040 Federal Register / Vol. 65, No. 4 / Thursday, January 6, 2000 / Rules and Regulations directly—to market products for disease 2d at 73.) (Subsequent to the 1998 health claims to be complete before uses without demonstrating their safety decision cited by the comments, the proceeding with this rulemaking on and efficacy. Likewise, identifying court rendered another decision adverse structure/function claims. Moreover, specific terms that connote treatment, to FDA (Washington Legal Foundation since the agency has decided not to cure, or mitigation would not v. Henney, 1999 WL 557679 (D.D.C. July amend the health claims regulations as accomplish the goal of requiring proof 28, 1999)). That decision concerned the part of this rulemaking, there is no of the safety and effectiveness of constitutionality of certain provisions of potential conflict between the two. products marketed for disease uses. the FDA Modernization Act of 1997 The First Amendment issues raised in Merely regulating synonyms for those involving the same subject matter as the comments on § 101.93(g)(4)(iii) terms would leave unregulated those guidance documents, and the court’s (proposed § 101.93(g)(2)(iv)(C)), claims that achieve the same effect First Amendment rationale was similar concerning citations to scientific without using such a synonym, such as to its rationale in the 1998 decision references in labeling, are not different the claims ‘‘herbal Prozac’’ and ‘‘for pertaining to the guidance documents.) from those raised by comments on the cancer.’’ The suggestion in one FDA disagrees with the district court rule as a whole and are addressed in the comment that FDA establish ‘‘categories decision in Washington Legal preceding analysis. FDA also notes that, of diseases that clearly denote drug Foundation and has appealed. In any as discussed elsewhere in this claims’’ is not a workable alternative event, however, the outcome in document, § 101.93(g)(4)(iii) has been either. Section 403(r)(6) of the act Washington Legal Foundation does not revised to narrow the circumstances provides that the category of structure/ determine the outcome here for several under which the agency will consider function claims excludes claims to reasons. First, in Washington Legal citations to scientific references in affect any category of disease, not just Foundation the court found a less labeling to be disease claims. certain categories. restrictive alternative that it concluded (109.) Another comment further Permitting disease claims under would more precisely address the asserted that the prohibition against section 403(r)(6) of the act as long as government’s regulatory concerns: implied disease claims violates the First they are accompanied with a disclaimer, Requiring manufacturers who Amendment because it does not as suggested by the comment that cited disseminate information about off-label advance the safety of dietary the Pearson decision, would be an uses to physicians through scientific supplements. The comment untenable alternative. If companies reprints or educational symposia to acknowledged that some dietary could avoid the time and expense of disclose: (1) Their interest in drugs or supplements ‘‘may present serious complying with the new drug devices that are the subject of such safety risks,’’ but said ‘‘these risks will provisions of the act merely by attaching activities, and (2) the fact that the use not be lessened by prohibiting truthful, a disclaimer to a disease treatment or discussed has not been approved by non-misleading structure/function prevention claim, the longstanding FDA. Here, as explained previously, claims * * *.’’ The comment suggested system of drug regulation in this there are no less restrictive alternatives that other provisions in DSHEA address country would be eviscerated, with to this rule that would further the the safety of dietary supplements and serious public health consequences. government’s substantial public health that FDA can bring an enforcement Nothing in Pearson requires such a interest. Second, in Washington Legal action if it has safety concerns. result. Indeed, the Pearson court Foundation physicians were the recognized that its ruling did not apply intended audience of the commercial FDA agrees with this comment in part to drugs (164 F.3d at 656 n. 6). Because speech at issue. In contrast, consumers and disagrees in part. The agency agrees the act classifies products on the basis are the primary audience for dietary that prohibiting truthful, non- of intended use, dietary supplements supplement labeling. Although the misleading structure/function claims that make disease claims are drugs, marketplace includes consumers of would not lessen the safety risks posed unless the disease claim is also an varying levels of sophistication, the by some dietary supplements. The rule authorized health claim for which the average consumer does not possess the is aimed at the safety risks posed by product qualifies (see section 201(g)(1) medical and scientific expertise unapproved drug claims and of the act). necessary to evaluate claims about the unauthorized health claims on dietary The Washington Legal Foundation effect of a product on disease. (See supplements. Unproven disease claims decision is not to the contrary. That case American Home Products Corp. v. FTC, on a product marketed as a dietary involved the dissemination of 695 F.2d 681, 698 (3d Cir. 1983); supplement may induce consumers to information on ‘‘off-label’’ (unapproved) Association of Nat’l Advertisers, Inc. v. treat themselves with the supplement uses for approved drugs and devices to Lungren, 44 F.3d 726, 733–34 (9th Cir. instead of seeking treatments that are physicians by means of scientific and 1994), cert. denied, 516 U.S. 812 known to be effective. Such claims may educational symposia, reprints, and (1995).) Finally, in Washington Legal also dissuade consumers from seeing a textbooks. The U.S. District Court for Foundation, it was undisputed that the doctor. These are very real safety risks. the District of Columbia held certain products involved were drugs (or, in To the extent that safety risks are caused FDA guidance documents that described some cases, devices) to be used in by the composition of a dietary acceptable ways of disseminating such treating or preventing disease. In supplement rather than by claims made information unconstitutional under the contrast, the purpose of this rule is to for it, the agency agrees that other Central Hudson test. While recognizing distinguish between products that are provisions in DSHEA and the act are the the substantial government interest in intended to affect disease and products appropriate remedy. having off-label uses for drugs and that are not. 2. Equal Protection devices found to be safe and effective by The agency does not believe this rule (110.) One comment claimed the rule FDA, the court held that the guidance is premature in light of the need to violates the equal protection clause of documents violated the First reassess the regulatory regime for health the Fourteenth Amendment because it Amendment because it believed that claims under Pearson. Since health supposedly gives more protection to the they ‘‘restricted’’ speech in a manner claims and structure/function claims are ‘‘labeling rights and speech’’ of that was more extensive than necessary regulated separately, there is no need to pharmaceutical manufacturers than to to further that interest. (See 13 F. Supp. wait for any post-Pearson changes for dietary supplement manufacturers.

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First, it should be noted that the equal of the Fifth Amendment because it Rectanus Co., 248 U.S. 90, 97 (1918).) protection clause of the Fourteenth would prohibit the use of specific terms Trademarks and trade names are given Amendment applies only to the States, that now appear in product names, legal protection to prevent one not to the Federal Government. trademarks, trade names, symbols, and manufacturer from passing off its goods However, the due process clause of the company logos, or would harm as the goods of another and thus taking Fifth Amendment contains an equal companies that use such terms in their advantage of the latter’s goodwill protection component that is equivalent corporate names. One comment said (American Steel Foundries, 269 U.S. at to the equal protection clause of the FDA must provide compensation for 380; United Drug, 248 U.S. at 97). Fourteenth Amendment (Schweiker v. each taking, but that the proposal failed The Supreme Court has declined to Wilson, 450 U.S. 221, 226 & n. 6 (1981)). to do so. prescribe a ‘‘set formula’’ for identifying Even if the comment is interpreted to FDA disagrees with these comments. takings and instead has characterized refer to equal protection under the Fifth The Takings Clause forbids the takings analysis as an ‘‘essentially ad Amendment, FDA disagrees with it. government from taking private hoc, factual’’ inquiry (Penn Central First, the comment does not explain in property for public use without just Transp. Co. v. City of New York, 438 what manner the rule gives more compensation. However, FDA believes U.S. 104, 124 (1978)). Nonetheless, the protection to the labeling rights and that no taking will occur as a result of Court has identified three factors for speech of pharmaceutical manufacturers this rule. consideration in assessing whether a than to those of dietary supplement The first issue to be considered is regulatory taking has occurred: The manufacturers. Second, even if the rule whether the categories of names, words, character of the governmental action; does treat these two classes of and symbols identified in the comments the regulation’s economic impact; and manufacturers differently, treating on this issue are property within the the extent to which the regulation different regulated groups differently meaning of the Takings Clause. The interferes with reasonable investment- does not in itself violate the equal Constitution itself does not define what backed expectations (Ruckelshaus v. protection clause. Unless a regulatory qualifies as property. Rather, ‘‘existing Monsanto Co., 467 U.S. 986, 1005 classification jeopardizes the exercise of rules or understandings derived from an (1984)). The force of any one of these a fundamental right or classifies upon independent source,’’ such as State or factors may be ‘‘so overwhelming * * * inherently suspect grounds such as race Federal law, define the interests that that it disposes of the taking question’’ or religion, it is subject to the least qualify for protection as property under (Monsanto, 467 U.S. at 1005). When exacting form of equal protection the Fifth Amendment (Lucas v. South examined in light of these three factors, review: Whether the classification it Carolina Coastal Council, 505 U.S. the rule does not effect a compensable draws bears a rational relationship to a 1003, 1030 (1992)). taking under the Fifth Amendment. legitimate government interest. (See The categories of names, words, and a. The character of the government Nordlinger v. Hahn, 505 U.S. 1, 10 symbols mentioned by the comments action. With respect to the first factor, (1992).) are intangible property interests. As the character of the government action, This rule neither jeopardizes the discussed below, trademarks and trade courts are more likely to find a taking exercise of a fundamental right nor names are property to the extent that when the interference with property can creates a suspect classification. The they are associated with business be characterized as a physical invasion purpose of the rule is to clarify the goodwill. A trademark is a word, name, by government than when the statutory distinction between products symbol, device, or combination thereof interference is caused by a regulatory that are intended for use in treating or that a person uses, or intends to use and program that ‘‘adjust[s] the benefits and preventing disease and products that are has applied to register, to identify and burdens of economic life to promote the intended for use in affecting the distinguish his or her goods from others common good’’ (Penn Central, 438 U.S. structure or function of the body. on the market and to indicate their at 124). The Supreme Court has held Products intended to treat or prevent source (15 U.S.C. 1127). A trade name that, when a governmental action is disease are subject to regulation as is the name a person uses to identify his taken in order to protect the public drugs, unless they qualify for an or her business (15 U.S.C. 1127) and interest in health, safety, and welfare, authorized health claim. Products may include corporate, partnership, and this factor weighs heavily against intended to affect the structure or other names. Symbols and logos, when finding a taking. (See Keystone function of the body may be regulated used to identify a product or company, Bituminous Coal Ass’n v. DeBenedictis, as dietary supplements, subject to may be property insofar as they are 480 U.S. 470, 488 (1987).) Regulatory certain conditions. Products regulated trademarks or trade names. Likewise, actions taken to protect the public as drugs must meet strict requirements product names may be property if they health are rarely, if ever, held to for a premarket demonstration of safety are protected by a trademark or trade constitute takings. (See Porter v. and efficacy (see sections 201(p) and name. For brevity, in the remainder of DiBlasio, 93 F.3d 301, 310 (7th Cir. 505 of the act); these requirements do this discussion the categories of names, 1996) (action taken to protect public not apply to dietary supplements. The words, and symbols mentioned by the health falls within class of property distinction that the statute and this rule comments on the takings issue will be deprivations for which Fifth draw between products that are referred to collectively as ‘‘trademarks Amendment does not require intended to have an effect on disease and trade names.’’ compensation); Jarboe-Lackey Feedlots, and those that are intended only to Trademarks and trade names are Inc. v. United States, 7 Cl. Ct. 329 (1985) affect the structure or function of the property, but only insofar as they are (seizure of adulterated meat not a body is clearly rationally related to the associated with the goodwill of an taking).) legitimate government interest of ongoing business. (See American Steel Although these regulations will ensuring that products intended to have Foundries v. Robertson, 269 U.S. 372, restrict the use of certain terms, an effect on a disease are safe and 380 (1926).) They have no intrinsic including terms that appear in some effective for that intended use. value. The purpose of a trademark or trademarks and trade names, this 3. Takings Under the Fifth Amendment trade name is to prevent confusion with restriction does not rise to the level of (111.) Several comments claimed that the products of another manufacturer. a taking. Governmental restrictions on the proposal violates the Takings Clause (See United Drug Co. v. Theodore the uses individuals can make of their

VerDate 04-JAN-2000 16:16 Jan 05, 2000 Jkt 190000 PO 00000 Frm 00043 Fmt 4701 Sfmt 4700 E:\FR\FM\06JAR4.XXX pfrm11 PsN: 06JAR4 1042 Federal Register / Vol. 65, No. 4 / Thursday, January 6, 2000 / Rules and Regulations property are ‘‘properly treated as part of manufacturer from passing off its goods business, thereby depriving the owner the burden of common citizenship’’ as the goods of another (American Steel of its ‘‘going-concern value,’’ is there a (Keystone, 480 U.S. at 491 (citation Foundries, 269 U.S. at 380). This compensable taking of goodwill. In omitted)). These burdens are ‘‘borne to regulation will not allow one Kimball, the Supreme Court held that secure ‘the advantage of living and manufacturer to use another’s trademark the government owed compensation for doing business in a civilized or trade name; rather, all manufacturers the loss of goodwill associated with the community’’’ (Andrus v. Allard, 444 will be precluded from using temporary taking of a laundry during U.S. 51, 67 (1979) (quoting trademarks and trade names that World War II. This action was held to Pennsylvania Coal Co. v. Mahon, 260 contain an implied disease claim unless be a taking of goodwill because the U.S. 393, 422 (1922) (Brandeis, J., they have obtained new drug approval government not only physically took but dissenting)). Moreover, these regulations or health claim authorization. Thus, also operated the laundry during the are not without benefit to manufacturers will not suffer any war (Kimball, 338 U.S. at 12–13). Thus, manufacturers. (See Keystone, 480 U.S. competitive injury. during the period that the government at 491 (‘‘While each of us is burdened Moreover, deprivation of a trademark operated the laundry, there was no somewhat by such restrictions, we, in alone is not a deprivation of property. business to whose benefit the goodwill turn, benefit greatly from the restrictions Because the trademark is ‘‘merely a associated with the private laundry that are placed on others.’’).) The protection for the good will’’ (Hanover business could inure. Here, the regulations will help ensure a level Star Milling Co. v. Metcalf, 240 U.S. 403, government is not taking any trademark playing field in the dietary supplement 414 (1916)), only if a regulation takes or trade name for its own use, nor is it market because no manufacturer will be the owner’s goodwill as well would the shutting down the businesses that own able to make an implied disease claim regulation be a taking. It is not apparent, them. Therefore, the goodwill without prior FDA review under the however, that these regulations will symbolized by the trademark or trade health claim or new drug standard. deprive manufacturers of any goodwill. name will remain with these businesses. Previously, unreviewed implied disease Manufacturers will be faced with a Finally, although trademarks and claims on dietary supplements choice as to whether to change their trade names can be property when they proliferated, in part because of trademark or trade name or to seek symbolize and protect the goodwill uncertainty about the line between approval for their products as drugs. In associated with a business, there can be structure/function claims and disease some cases, they will also have a third no property interest in an illegal claims. option: Seeking authorization to make a product. Dietary supplements that bear These regulations are rationally health claim. If they are able to obtain claims to treat or prevent disease are related to, and substantially advance, drug approval for the intended use misbranded and are also unapproved FDA’s legitimate interest in promoting suggested by the trademark or trade new drugs (unless the claim is an and protecting the public health by name, they will not have to change the authorized health claim). As such, they ensuring the safety and efficacy of trademark or trade name, provided that may not legally be sold in interstate products promoted for use in treating or the name is not confusingly similar to commerce (see section 301 (a) and (d) of preventing disease. (See Keystone, 480 the name of another drug or otherwise the act. There can be no taking of an U.S. 470 at 485; Monsanto, 467 U.S. at misleading (see section 502(a)(1) of the illegal article. (See Meserey v. United 1007.) By clarifying that such products act (21 U.S.C. 352(a)(1)); and States, 447 F. Supp. 548, 554 (D. Nev. may not be marketed under the § 201.10(c)(3) and (c)(5).) Similarly, if 1977) (‘‘Plaintiff has not been denied his structure/function claim regime, FDA is they are able to obtain authorization to property. He is denied the right to seeking to ensure that they are regulated make a health claim for the intended introduce his goods into commerce through the drug approval or health use suggested by the trademark or trade unless they are in compliance with the claims authorization process, as name, they will not have to change the [Federal Food, Drug, and Cosmetic] appropriate. trademark or trade name unless it is Act.’’).) Moreover, it has always been The effect of the regulations cannot be misleading. (See section 403(a)(1) of the illegal to market dietary supplements or characterized as a taking of property. act.) Even if a manufacturer chooses to other foods with disease claims, except Dietary supplement companies will not change its trade name or trademark, it that since 1990 the act has permitted be precluded from using terms that will not be deprived of the goodwill authorized health claims. These imply a disease claim in their underlying them but only of that regulations merely clarify the line trademarks and trade names. If they particular symbol of the goodwill. The between acceptable structure/function wish to continue using trademarks and manufacturer will still be able to claims and prohibited disease claims. trade names that imply a disease claim, transfer the goodwill associated with its (See Lucas, 505 U.S. at 1030 (‘‘The use they may do so, provided that they first products to another trade name or of [property] for what are now expressly meet the safety and efficacy standards trademark. prohibited purposes was always and other regulatory requirements Case law on the treatment of goodwill unlawful, and * * * it was open to the applicable to drugs or, in appropriate under the Takings Clause supports the State at any point to make the cases, provided that they obtain view that no taking will occur as a result implication of those background authorization to make a health claim. of these regulations. The general rule is principles of * * * law explicit’’ without (As discussed below, only non- that the owner of a place of business to paying compensation) (emphasis in misleading trademarks and trade names which the government takes title is not original).) For this reason and the other may be used.) entitled to compensation for loss of reasons previously discussed, the first Even if these regulations could be said goodwill (United States v. General factor of the takings analysis indicates to prevent a business from using a Motors Corp., 323 U.S. 373, 379 (1945)). that these regulations effect no takings. trademark or trade name on its dietary The reason for the rule is that the b. The economic impact of the supplements, such a result still would business may reopen at another location government action. The second factor to not constitute a taking of the trademark to which the goodwill may be consider is the economic impact of the or trade name. The purpose of giving transferred (Kimball Laundry Co. v. government action. This impact is not to trademarks and trade names legal United States, 338 U.S. 1, 11–12 (1949)). be considered piecemeal by dividing a protection is to prevent one Only where the government operates the property interest ‘‘into discrete

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Since of the interference with rights in the however, FDA believes that the 1938, drugs (with certain narrow property as a whole. (See Penn Central, economic impact of that loss of goodwill exceptions) have been subject to a 438 U.S. at 130–31; Andrus v. Allard, is outweighed in the takings analysis by premarket approval requirement. Given 444 U.S. at 65–66.) Thus, here the total lack of reasonable investment-backed this longstanding history of close impact of the regulations on property expectations in being able to make regulation, it cannot be reasonable for a rights should be considered, rather than disease claims in trademarks and trade manufacturer or distributor to expect to only whether a business can or cannot names. be able to make disease claims without continue to use a particular trademark c. Interference with reasonable prior authorization from FDA. or trade name. It is clear that a investment-backed expectations. The Moreover, it has always been illegal to regulation’s economic impact may be final factor to consider is whether a market dietary supplements or other great without rising to the level of a company has a reasonable investment- foods with disease claims, except that taking. (See Pace Resources, Inc. v. backed expectation in continuing to use since 1990 authorized health claims Shrewsbury Township, 808 F.2d 1023, a trademark or trade name. To be have been permitted. These regulations 1031 (3d Cir.), cert. denied, 482 U.S. 906 reasonable, expectations must take into merely clarify the line between (1987) (citing Hadacheck v. Sebastian, account the power of the state to acceptable structure/function claims 239 U.S. 394 (1915) (reduction in value regulate in the public interest (Pace and prohibited disease claims. (See from $800,000 to $60,000); Euclid v. Resources, 808 F.2d at 1033). Lucas, 505 U.S. at 1030 (‘‘The use of Ambler Realty Co., 272 U.S. 365 (1926) Reasonable expectations must also take [property] for what are now expressly (75 percent diminution in value)).) into account the regulatory prohibited purposes was always In assessing whether a regulation environment, including the unlawful, and * * * it was open to the effects a taking, the Supreme Court has foreseeability of changes in the State at any point to make the considered whether the regulation regulatory scheme. ‘‘In an industry that implication of those background denies an owner the ‘‘economically long has been the focus of great public principles of * * * law explicit.’’).) viable’’ use of its property. (See, e.g., concern and significant government Companies in the dietary supplement Keystone, 480 U.S. at 499.) Although it regulation,’’ Monsanto, 467 U.S. at 1008, industry should have been aware that is undeniable that compliance with the possibility is substantial that there FDA was likely to issue such a these regulations will cost money and will be modifications of the regulatory clarification, not only because of the may mean that certain trademarks and requirements. ‘‘Those who do business regulatory environment generally but trade names must be altered, companies in the regulated field cannot object’’ if also for several specific reasons. First, will not be denied the economically the regulatory scheme is ‘‘buttressed * * the passage of DSHEA, which added viable use of their property. As * to achieve the legislative end’’ section 403(r)(6) to the act, created a previously discussed, some firms may (Connolly v. Pension Benefit Guar. likelihood that FDA would issue be able to obtain new drug approval or Corp., 475 U.S. 211, 227 (1986) (citation health claim authorization for those omitted)). The lack of a reasonable regulations ‘‘to achieve the legislative products that bear trademarks or trade investment-backed expectation can end’’ of permitting structure/function names that include disease claims. If outweigh the other takings factors and claims without premarket review, while approved as new drugs or authorized to be determinative in whether a taking continuing to prohibit disease claims bear a health claim, in many cases these has occurred (Monsanto, 467 U.S. at lacking FDA authorization (see products could continue to bear the 1005). Connolly, 475 U.S. at 227 (citation original trademark or trade name. This Companies that use trademarks or omitted)). Second, the Commission on approach would, however, require the trade names that include disease claims Dietary Supplement Labels specifically company involved to make significant lack a reasonable investment-backed encouraged FDA to clarify the expenditures of time and money to expectation that they will be able to appropriate scope of structure/function submit a new drug application (NDA) or continue to use those trademarks and statements (Ref. to Commission report, health claim petition to FDA. The trade names. First, the Supreme Court p. 38). Third, the rapidly expanding financial burden required to comply has said that it is unreasonable to have dietary supplement market and the with such requirements is not a taking high expectations in personal property proliferation of implied disease claims under these circumstances, however, (i.e., property other than land): ‘‘[I]n the in labeling should have put the industry just as it is not a taking to require other case of personal property, by reason of on notice that FDA might take action. companies to comply with applicable the State’s traditionally high degree of For all these reasons, there can be no requirements before marketing a new control over commercial dealings, [the reasonable investment-backed drug or a food bearing a health claim. property owner] ought to be aware of expectations with respect to trademarks Obtaining new drug approval or the possibility that new regulation and trade names that include disease authorization to make a health claim might even render his property claims. Thus, the third factor of the may be costly, but it is not the kind of economically worthless * * *.’’ (Lucas v. takings analysis weighs strongly against economic impact that leads to a taking. South Carolina Coastal Council, 505 finding a taking of property that requires ‘‘Requiring money to be spent is not a U.S. at 1027–28). Second, the dietary compensation under the Fifth taking of property’’ (Atlas Corp.) v. supplement and drug industries are a Amendment. Moreover, the three United States, 895 F.2d 745, 756 (Fed. ‘‘focus of great public concern and factors, taken together, show that these Cir.), cert. denied, 498 U.S. 811 (1990)). significant government regulation’’ regulations do not effect such a taking. As previously noted in the discussion (Monsanto, 467 U.S. at 1008). A product Therefore, FDA concludes that the of the first factor of the takings analysis, that bears a disease claim, whether that comments arguing the contrary are case law indicates that the regulations claim appears in a trademark, trade unpersuasive.

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IV. Implementation Plan FDA has decided, however, that it will to assess all costs and benefits of The preamble to the proposed rule not treat manufacturers who have not available regulatory alternatives and, discussed FDA’s tentative conclusions notified the agency of their claims when regulation is necessary, to select regarding the effective date of a final differently from other manufacturers. At regulatory approaches that maximize rule and the agency’s implementation least some of those manufacturers who net benefits (including potential plan. In general, the preamble to the did not submit 30-day notifications to economic, environmental, public health proposed rule stated that a final rule the agency may have failed to do so and safety, and other advantages; would become effective 30 days after believing that notification was not distributive impacts; and equity). The the date of the final rule’s publication in necessary under section 201(g)(1)(C) of Regulatory Flexibility Act requires the Federal Register. Any product that the act. Therefore, all manufacturers agencies to examine the economic is marketed for the first time after will have 11 months after the effective impact of a rule on small entities. The publication of the final rule, and any date of the final rule to come into Unfunded Mandates Reform Act requires agencies to prepare an new claims made for an existing compliance, and small businesses will assessment of anticipated costs and product for the first time after the have 17 months after the effective date benefits before enacting any rule that publication of the final rule, will be of the final rule. The agency believes may result in an expenditure in any one expected to be in compliance beginning that these compliance periods, year by State, local and tribal 30 days after publication of the final uniformly applied, are sufficiently long governments, in the aggregate, or by the rule. However, small businesses that that it is not necessary to extend the private sector, of $100 million (adjusted marketed a product as of the date of effective date to 6 months after publication in the Federal Register. annually for inflation). publication of a final rule would have FDA concludes that this final rule is had an additional 17 months to bring For a limited transition period, FDA does not intend to take enforcement consistent with the principles set forth existing claims (i.e., claims already in in the Executive Order and in these two the products’s labeling on January 6, action against firms who have relied on the agency’s September 1997 preamble statutes. The agency has determined 2000 for those products into that the rule is a significant regulatory compliance, provided that the small statements to make a structure/function claim for a dietary supplement under action as defined by the Executive business had notified FDA of the claim Order, because it raises novel policy as required by section 403(r)(6) of the section 201(g)(1)(C) of the act. To allow a reasonable time for the necessary label issues. FDA has further determined that act and § 101.93(a) and that FDA had the final rule may have a significant not objected to the claim. For all other changes, the transition period will last until the applicable compliance date for economic impact on a substantial products that were on the market as of number of small entities. This section the date of publication of a final rule, the rest of the rule; i.e., small businesses will have 18 months from publication to constitutes the agency’s final regulatory FDA would have allowed an additional flexibility analysis as required under the 11 months beyond the effective date to comply, and other firms will have 12 months. As of the applicable Regulatory Flexibility Act. Because this bring existing claims for those products rule imposes no mandates on into compliance, provided that the firm compliance date, firms that have been making structure/function claims under government entities and will not result had notified FDA of the claim as in private expenditures of $100 million required by section 403(r)(6) of the act section 201(g)(1)(C) must either remove the claim or comply with the in any one year, the Unfunded and § 101.93(a) and that FDA had not Mandates Reform Act does not require objected to the claim. Any product requirements of section 403(r)(6) of the act and § 101.93, including notifying the agency to prepare a cost-benefit marketed for the first time after the date analysis. of publication of the final rule, and any FDA of the claim and relabeling to add new claim made for an existing product the required disclaimer. New structure/ B. Benefits of the Labeling Requirements for the first time after publication of the function claims are not subject to this The primary purpose of the rule is to final rule, would have been expected to transition period; any firm that makes a provide a consistent standard for be in compliance beginning 30 days structure/function claim in the labeling distinguishing between claims that may after the date of publication of a final of a dietary supplement after the be made in labeling without prior rule. effective date of this rule must comply review by FDA and claims that require (112.) Two comments suggested with section 403(r)(6) of the act and prior authorization as health claims or extending the compliance period to 6 § 101.93. prior review as drug claims. The larger months after the date of publication of V. Environmental Impact goal is to ensure that information about a final rule. The comments also non-disease-related effects of a dietary advocated that there be no distinction The agency has determined under 21 supplement on the body may be freely between large and small businesses for CFR 25.30(h) and (k), that this action is disseminated in labeling, while at the compliance dates. The comments of a type that does not individually or same time guaranteeing that claims for further suggested that FDA give cumulatively have a significant effect on use of a dietary supplement to treat or businesses whose products were on the the human environment. Therefore, prevent disease are not made without market as of the date of publication of neither an environmental assessment prior review to ensure that the a final rule 15 months (instead of 11 or nor an environmental impact statement supplement is safe and effective for that 17 months) to comply. Another is required. use. comment suggested that the final rule VI. Analysis of Impacts Although dietary supplements can become effective 12 months, rather than play a valuable role in consumer health, 30 days, after its publication date. A. Background the agency recognizes that, when FDA believes that the proposed FDA has examined the impacts of the inappropriately labeled, they can pose compliance periods of 11 and 17 final rule under Executive Order 12866, unnecessary risks. Such risks arise months following the effective date of the Regulatory Flexibility Act (5 U.S.C. when the product labeling: (1) the final rule are reasonable and fair, 601–612), and the Unfunded Mandates Encourages consumers to self-treat for a and that the distinction between large Reform Act of 1995 (Public Law 104–4). serious disease without the benefit of a and small businesses is appropriate. Executive Order 12866 directs agencies medical diagnosis, or to self-treat for a

VerDate 04-JAN-2000 16:16 Jan 05, 2000 Jkt 190000 PO 00000 Frm 00046 Fmt 4701 Sfmt 4700 E:\FR\FM\06JAR4.XXX pfrm11 PsN: 06JAR4 Federal Register / Vol. 65, No. 4 / Thursday, January 6, 2000 / Rules and Regulations 1045 serious disease by substituting a dietary FDA anticipates, therefore, that the need to be relabeled to conform with the product of uncertain value for a medical final rule will clarify the dividing line proposed criteria for structure/function therapy that has been shown to be safe between acceptable structure/function claims. The cost categories included and effective; (2) encourages consumers claims and disease claims, and thereby administrative, analytical, and to feel sufficiently protected from a reduce the number of inappropriate inventory disposal activities. serious disease (e.g., cancer) that they disease claims in dietary supplement FDA acknowledged that estimates of delay, or possibly forego, regular labeling. The defined standard for the number of dietary supplement screening or early medical attention that structure/function claims under section products were approximate, but may be critical to improved odds of 403(r)(6) of the act will help to avoid projected that the proposed rule would patient survival; or (3) increases the risk instances of inappropriate substitution cover about 29,000 products, with about of adverse reactions due to interactions of dietary products for timely disease 75,000 distinct labels, or stock keeping with other chemical compounds (e.g., screening or medical treatment, and of units (SKU’s). The agency also prescription medications) taken by the adverse interactions or explained that the rule would directly patient. As consumer spending on contraindications of drug-supplement affect from 500 to 850 manufacturers of dietary supplements continues to rise, combinations. In addition, the rule may dietary supplement products. the need for an information standard promote the development of data and To estimate the lower-bound costs of that minimizes these risks becomes information for the support of new the proposed rule, FDA assumed that more acute. health or drug claims. Although FDA the 2,300 notifications initially received The rule may also benefit consumers cannot quantify these regulatory from dietary supplement manufacturers by encouraging manufacturers of dietary benefits, the agency expects that this adequately represented the number of supplements to develop the safety and standard will positively support the products with structure/function claims. effectiveness data needed to support a effective integration of dietary The agency had already objected to 150 health or drug claim. Where disease supplements into consumers’ overall notifications because they contained claims can be made without this programs of wellness and self-care. obvious disease claims, but identified an additional 60 notifications demonstration of safety and C. Costs of Compliance effectiveness, product manufacturers containing one or more claims that have less incentive to develop the The costs to industry are the direct might not have met the newly proposed substantial documentation needed to costs of compliance, which are criteria for structure/function claims. receive this agency authorization. The primarily the costs of the needed Consequently, FDA’s lower-bound availability of additional products with product relabeling; and the indirect direct cost estimate included label authorized health or drug claims would costs of compliance, which include the changes for 60 dietary supplement be extremely useful to the many potential loss of product sales due to the products. The estimated administrative, consumers who have difficulty elimination of disease claims. The redesign, and inventory losses distinguishing among the variety of following section details the agency’s associated with these 60 label changes products now marketed for particular calculation of the direct costs of totaled between $91,400 and $123,400. health concerns. compliance. FDA has been unable, FDA also presented an upper-bound The dietary supplement industry has however, to estimate the extent of the $8.5 million estimate of the direct costs grown rapidly, with estimated sales in indirect costs of this rule. As explained of the proposed rule, based on the 1996 of $10.4 billion for all dietary below, the agency estimates that over likelihood that many additional dietary supplements, including $4.9 billion for 800 dietary supplement products will supplements are marketed with vitamins and $3.0 billion for need to be relabeled due to this rule. structure/function claims. For this nonprescription herbal products (Ref. The substitution of a valid structure/ estimate, the agency concluded that 8). FDA has limited information on the function claim for a disease claim may, about 30 percent, or 22,500, of the number of products and quantities sold, in fact, lead to a decrease in the sale of estimated universe of 75,000 dietary or on the age, gender, and disease status certain products. The magnitude of this supplement labels contain structure- of persons currently using dietary impact, however, is unknown, as most function claims. Assuming that the supplements. However, a 1997 survey of firms will replace the disease claim with proportion of disease claims on all 43,000 households, conducted by the a structure/function claim that appeals labels containing structure/function Hartman and New Hope research to many of the same consumers. It is claims equals the proportion of disease organization, indicates that also possible that some firms will avoid claims in the 2,300 notifications approximately 70 percent of all a potential drop in sales by developing containing structure/function claims, households reported using vitamins, the safety and effectiveness data needed the agency calculated that up to 585 minerals, or herbal supplements in the to obtain either a new drug approval or labels (60/2,300 x 22,500) could need to past 6 months (Ref. 9). Among survey authorization from FDA to make a be changed if the proposed rule became respondents, those under age 30 health claim. The agency cannot final. The higher costs of the upper- accounted for only 8 percent of all quantify the probability of these bound estimate resulted both from the households with a member using occurrences, however, and no industry substantially increased assumed number dietary supplements; ages 30 to 39 comment includes such data. of affected labels and from the impact of accounted for 21 percent, ages 40 to 49 1. Proposed Rule the significantly shorter compliance accounted for 22 percent, ages 50 to 59 In the preamble to the proposed rule period (30 days) for manufacturers that accounted for 18 percent, and ages 60 or (63 FR 23624), FDA had projected that had not notified FDA of their structure/ older accounted for 30 percent (Ref. 10). the direct costs of compliance would function claim by the publication date Although the oldest group of survey range from $0.1 million to $8.5 million. of the final rule. respondents were, on the whole, less This figure largely reflected agency 2. Final Rule knowledgeable about individual estimates of the average cost of A number of the comments submitted products, they reported more regular relabeling a typical dietary supplement in response to the proposed rule product use and more use for specific product multiplied by the number of specifically addressed FDA’s analysis of conditions than younger respondents. dietary supplement products that would compliance costs. As a result, the

VerDate 04-JAN-2000 16:16 Jan 05, 2000 Jkt 190000 PO 00000 Frm 00047 Fmt 4701 Sfmt 4700 E:\FR\FM\06JAR4.XXX pfrm11 PsN: 06JAR4 1046 Federal Register / Vol. 65, No. 4 / Thursday, January 6, 2000 / Rules and Regulations agency has altered several of its cost 75,000 distinct labels. The agency has product). As described in its earlier assumptions. In addition, FDA has used this estimate for its analyses of analysis, based on an average of the adjusted its analysis to reflect the dietary supplement rules over the past estimates provided in comments to modified provisions of the final rule. As several years (e.g., 60 FR 67211 earlier rules, FDA determined that the described below, the agency estimates December 28, 1995) and has received no average label redesign cost is about the total direct costs of the final rule to indication from industry that better $1,700 per dietary supplement SKU for be about $3.73 million, but presents estimates were available. Although the a 12-month compliance period, and sensitivity analysis to indicate that the agency’s preliminary analysis reported $1,300 for an 18-month compliance costs could rise to as much as $10.35 that an estimated 30 percent of the period. No industry comment million under certain worst-case products (8,700) carry structure/ questioned the reasonableness of these assumptions. function claims, more recent data from unit cost estimates. Although several industry comments a random survey conducted for FDA by The final rule sets compliance periods suggested that FDA had underestimated RTI of about 3,000 dietary supplement of 1 year for large firms (revenues above the costs of relabeling, no comments products indicates that this percentage $20 million) and 18 months for small objected to the specific elements that may have been too low (Ref. 11). firms (revenues below $20 million), were considered, i.e., administrative, Although RTI notes that the surveyed except that new claims (i.e., claims not redesign, and inventory disposal sample is too small to support made before the publication of the final activities. In response, FDA has retained quantitative inferences for the rule) must be in compliance as of the this format for its analysis of the final population of dietary supplements, FDA effective date. Such claims will not rule. One comment claimed that FDA finds the data to be the best available. necessitate relabeling, however. FDA had underestimated the number of The RTI report actually shows that 69 does not know the size of the firms that products that would be affected, but percent of the products in its sample will need to make label changes. RTI provided no evidence or basis for have claims, but this percentage (Ref. 12) reports that 95 percent of the determining a more accurate count. includes ‘‘diet supplementation’’ firms in the industry are small, but that Another comment stated that the claims. When adjusted to exclude ‘‘diet the 5 percent that are large account for agency’s cost estimates were not well supplementation’’ only 62 percent of the 80 percent of industry sales. The RTI explained and that all assumptions were products in the RTI data base include product data base also indicates that not disclosed. Consequently, FDA has relevant claims. Even this 62 percent approximately 25 percent of the sample revised its analysis to; (1) Simplify the figure is too high, however, because RTI products were manufactured by just 5 cost-estimating methodology, (2) clearly over-sampled herbal products, which percent of the companies. Thus, FDA present and describe each assumption, have a higher probablity of claims and has assumed that approximately one- (3) fully explain the derivation of the would not exceed 60 percent and has quarter of the affected products will estimated direct costs of compliance, used this figure as its final estimate. come from large firms and three- and (4) conduct sensitivity analysis for Of the first 2,300 notifications of quarters from small firms. the remaining areas of significant structure/function claims reviewed by Consequently, the total estimated label uncertainty. FDA, no more than 60, or 2.6 percent of redesign costs equal about $3.03 million a. Cost of designing new labels. the products with claims, would have (i.e., $1,700 x 0.25 x 2,164 SKU’s + Dietary supplements will no longer be needed labeling changes due to the $1,300 x 0.75 x 2,164 SKU’s). able to make claims whose status was criteria described in the proposed rule. previously unclear, but which now have Since that time, the total number of b. Administrative costs. One industry been defined as disease claims. Firms notifications with structure/function comment contended that FDA had not may comply either by obtaining new claims submitted to the agency has adequately explained the basis for its drug approval, by receiving increased to about 5,200. A subsequent company-specific administrative costs, authorization from FDA to make a review of all of the submitted claims estimated at $425 and $320 respectively, health claim, or by revising their indicates that the final rule could for 12-month and 18-month compliance product labeling to eliminate disease require about 1.9 times as many label periods. These figures were derived claims. Because the cost of submitting modifications as the proposed rule, from data presented in a 1991 RTI report adequate documentation to obtain new owing largely to the revised criteria for on the cost of FDA’s food labeling drug approval or health claim cholesterol claims in the final rule. FDA regulations (Ref. 13). They included authorization far exceeds the cost of estimates that the final rule may require costs associated with interpreting a modifying a label, this analysis assumes revised labels for about 4.81 percent of regulation, determining the manner of that the direct costs of the rule will be the 17,400 dietary supplement products compliance and managing the the costs of modifying labels with (29,000 x 60 percent currently estimated compliance method. RTI had estimated disease claims. As explained above, as marketed with structure/function that, on average, small firms would bear FDA recognizes that some firms may claims (Refs. 15 and 16). (Excluding administrative costs of $850 to comply choose to obtain health claim cholesterol claims would reduce this with the new food labeling rules for a authorization or new drug approval as figure to 1.74 percent of the products 1-year compliance period, and $650 for an alternative means of compliance, or with claims.) a 2-year compliance period. For its to improve the marketability of their The resulting label cost calculations analysis of the proposed rule, FDA products. The agency believes, however, are straightforward. First, the agency reduced this figure by fifty percent, that it is unlikely that the rule would be found that revised labels (for all claims based on the smaller administrative the determining factor in a large number including cholesterol) may be needed effort that would be needed to comply of instances. for approximately 837 products (17,400 with the proposed rule, compared to the No public comments provided products with claims x 4.81 percent). conventional food labeling regulations alternative estimates of the number of Because each product may contain evaluated by RTI in 1991. The affected dietary supplement products. roughly 2.6 distinct SKU’s (75,000 regulations that were the subject of the As noted above, FDA had estimated that SKU’s ÷ 29,000 products), labels for an 1991 RTI evaluation involved a broader the industry markets approximately estimated 2,164 SKU’s may need to be range of administrative options and 29,000 covered products with about modified (837 products x 2.6 SKU’s/ tasks, such as nutritional testing and

VerDate 04-JAN-2000 16:16 Jan 05, 2000 Jkt 190000 PO 00000 Frm 00048 Fmt 4701 Sfmt 4700 E:\FR\FM\06JAR4.XXX pfrm11 PsN: 06JAR4 Federal Register / Vol. 65, No. 4 / Thursday, January 6, 2000 / Rules and Regulations 1047 product reformulation. (The $320 of the dietary supplement products will with claims). Because relabeling costs estimate for the 18-month compliance require new labels as a result of this rule are reported to double for each halving period was determined by interpolating (837 ÷ 29,000) and that about three of the compliance period, compliance between the estimates for 12 and 24 quarters of the affected products are costs would have been eight times months.) The agency has raised these manufactured by small firms. Thus, greater for those products. For the final costs by about 27 percent to $540 and total inventory disposal costs are rule, all large firms will be expected to $407, respectively, to account for salary calculated at $281,000 (i.e., $8 million comply within 12 months, and all small inflation since 1991 (Ref. 14). x 2.89 percent x 0.75 + $15 million x firms within 18 months, regardless of FDA had initially estimated that 500 2.89 percent x 0.25). whether the firm has notified FDA of to 850 firms manufacture dietary d. Total direct compliance costs. As the structure/function claims on its supplements. The recent RTI study, described above, FDA has assumed the products. This change significantly however, has identified 1,050 direct compliance costs of this rule to be reduces the direct compliance costs of manufacturers (Ref. 12). This higher the costs associated with relabeling the final rule. number probably overestimates the size those dietary supplements whose e. Sensitivity analysis. Due to of the industry covered by this rule, labeling claims are considered disease uncertainty with respect to several because it includes homeopathic claims under the newly defined criteria. factors in the agency’s direct cost model, products, which are drugs by statutory Redesign costs are estimated at $3.03 FDA has prepared a sensitivity analysis definition, and ‘‘functional foods’’ and million, administrative costs at of other possible cost scenarios. First, sports nutrition products, which may be $413,000, and inventory disposal costs FDA tripled the percentage of product either conventional foods or dietary at $281,000. In sum, therefore, the total notifications assumed to be out of supplements depending on how they estimated direct compliance costs equal compliance with the new criteria for are marketed and used. For this final almost $3.73 million. structure/function claims. This change analysis, FDA has assumed that 1,000 In addition, there may be costs results in almost tripling the total direct companies manufacture the dietary associated with the discussion in the supplement products covered by this final rule concerning structure/function compliance costs of the regulation, rule. Although only a small fraction of claims made under section 201(g)(1)(C) raising the estimate from about 3.73 these establishments will need to of the act. (See response to comment 95 million to about 10.35 to about $5.93 implement changes in labeling due to in section III.A.1 of this document.) The million. Second, FDA doubled its this rule, the agency anticipates most agency believes that some firms have estimate of administrative costs. This firms will review the final rule to assess been making structure/function claims change raises the inital cost estimate to whether their labeling will be affected. for dietary supplements without about $4.14 million. Changing both The administrative costs of the final including a disclaimer statement or assumptions simultaneously raises the rule would likely be higher for those notifying FDA, based on FDA’s total estimated costs to about $11 firms that will need to revise labels and statements in a 1997 preamble (62 FR million. Finally, under the initial lower for those firms that do not. 49859 at 49860, 49863, and 49864). scenario, if all of the needed label Nevertheless, FDA assumes that, on Because the agency has not repudiated changes were assumed to affect only average, all large dietary supplement these statements, any firm that has small businesses, the total cost estimate manufacturers would incur costs of relied on them to make a claim for a rises to about $3.46 million. This $540 and all small dietary supplement dietary supplement will need to add the sensitivity analysis indicates that the manufacturers would incur costs of disclaimer to all applicable labels, as total direct costs of this rule would not $407. As noted above, RTI found that well as to notify FDA, according to the impose a major burden on this industry about 95 percent of the firms in this requirements of this section 403(r)(6) of even if the most uncertain cost factors industry are small. Thus, the agency the act and § 101.93. Because firms are doubled or tripled from FDA’s best calculated administrative costs to equal making such claims have not identified estimates. about $413,000 (i.e., 950 small firms x themselves to FDA, the agency does not D. Other Industry Comments $407 + 50 large firms x $540). FDA have a reliable database on which to notes that these estimates may overstate base a cost estimate of the number of Several comments insisted that FDA the incremental administrative costs of firms and products that may incur costs had not conducted a comprehensive this final rule, because dietary to comply with this new provision. cost-benefit analysis of the proposed supplement firms must already comply The costs to industry of the final rule rule, as required under Executive Order with DSHEA and this rule is meant to are substantially different from the costs 12866. These comments stated that clarify the meaning of that act, rather of the proposed rule, because of two FDA’s economic analysis ignored both than to add new requirements. important changes to the proposed the potential savings in consumer health Nevertheless, the agency’s sensitivity requirements. First, the final rule care expenditures that would be lost by analysis, presented below, doubles the requires more product labels to be restricting important labeling above cost estimates. changed, because it includes more information, as well as the likely c. Costs of inventory losses. The final specific parameters for acceptable negative effect of the proposal on the cost component involves the value of structure/function claims about growth of the dietary supplement lost inventory. FDA’s preliminary cholesterol. This change increases the industry. One industry comment, for analysis relied on information from an direct compliance costs of the final rule. example, declared that a substantive earlier nutrition labeling rule that Second, the proposed rule required cost-benefit analysis ‘‘must identify the affected the entire dietary supplement needed label modifications to be potential health benefits that are lost as industry. That information indicated completed within 30 days after a consequence of reduced consumer that inventory disposal costs for the publication of the final rule, for those access to useful information about the entire industry would be about $8 products without a properly submitted health-related properties of dietary million for an 18-month compliance claim notification. Roughly 70 percent supplements and ingredients.’’ It noted period and $15 million for a 12-month of all products with claims may have that FDA’s analysis ‘‘fails to consider compliance period. As explained above, fallen into this group (1–5,200 products the public health benefits associated FDA estimated that about 2.89 percent without notifications ÷ 17,400 products with ingesting dietary supplements as

VerDate 04-JAN-2000 16:16 Jan 05, 2000 Jkt 190000 PO 00000 Frm 00049 Fmt 4701 Sfmt 4700 E:\FR\FM\06JAR4.XXX pfrm11 PsN: 06JAR4 1048 Federal Register / Vol. 65, No. 4 / Thursday, January 6, 2000 / Rules and Regulations well as the losses to public health that incidents identified in the agency’s dietary supplement as a disease claim could result from consumers failing to adverse event database. Estimated only if the statement included an take appropriate dietary supplements benefits of the nutrition labeling rule express reference to a specific disease; due to uninformative structure/function were derived from epidemiological and (3) treating a statement about a claims.’’ That comment also maintains studies of the consequences of dietary dietary supplement as a disease claim if that ‘‘FDA’s failure to assess and fat. In each case, the agency believed the statement mentions an abnormality consider such benefits (and costs) that it had a reasonably reliable data of the structure or function of the body, stands in contrast with the specific base upon which to base conclusions, even if the abnormality was not finding of DSHEA that ‘appropriate use and each risk assessment dealt with the characterized by a set of signs or of safe nutritional supplements will risks of a single substance (tobacco, symptoms recognized as the disease. limit the incidence of chronic diseases, ephedra, and dietary fat). In contrast, These alternatives are fully discussed in and reduce long-term health care this structure/function rule governs the preamble to the proposed rule (63 expenditures’.’’ The comment also structure/function claims in the labeling FR 23624 at 23630) and alternative (2) points out that FDA has performed such for all dietary supplements. Although is also discussed extensively in section analyses in other rulemakings, e.g., the agency could conceivably analyze a II.E of this document. In brief, FDA tobacco, nutrition labeling, and ephedra few of the claims covered by the rule, finds that the public comment does not regulations. adequate data on the benefits and risks include evidence or arguments FDA disagrees. Although Executive of most of these products are not sufficient to persuade the agency to Order 12866 directs agencies to assess available. Consequently, the agency support these alternatives. the costs and benefits of economically believes that this rule will improve the Within the broad framework of the significant rules, the quantification of nation’s health, but concludes that it final rule, FDA weighed other policy these expected costs and benefits is cannot feasibly quantify the effects of changes that could affect the required only ‘‘to the extent feasible’’ the rule on the nation’s health compliance costs. One option would (58 FR 51735 at 51741, October 14, expenditures. have set the compliance period for all 1993). As described above, FDA believes One industry comment suggested that firms at 6 months and another at 12 that its final rule strikes the appropriate the regulatory system could impede months from the publication date of the balance with respect to health-related firms from conducting research to final rule. Other options would have claims in dietary supplement labeling. substantiate structure/function claims, if extended the compliance period beyond The rule classifies certain claims as DSHEA is construed so narrowly that it 18 months for small businesses, or acceptable structure/function claims excludes meaningful health-related completely exempted small businesses that may be made without prior FDA benefits. This comment noted, however, from the rule. Finally, the proposed rule review. Although the provision of that the absence of an enforceable legal would have permitted firms 12 or 18 structure/function information to standard for substantiation would months to comply, depending on consumers may reduce health care discriminate against companies that do whether they were large or small firms; expenditures, no health organization, research to support their claims and but only if they had submitted timely industry association, or any other would deter science-based companies notifications of their structure/function interested public or private group has from entering the market. Similarly, a claims to FDA and FDA had not presented information or data that patient organization and several objected to the claims. Other firms had would allow the agency to develop a pharmaceutical companies expressed only a 30-day compliance period. quantifiable estimate of the health care concern that the rule would permit Based on its model of food labeling benefits. The rule classifies other claims some products to escape regulation as costs, FDA assumes that compliance as disease claims that are subject to drugs and therefore diminish incentives costs double for each halving of the existing requirements for new drug for the costly clinical research compliance period (Ref. 13). Thus, the approval or health claim authorization conducted by pharmaceutical first option, which set a 6-month before a product may be marketed with companies and academic scientists. compliance date for all firms, results in the claim. FDA believes that classifying As stated previously in the document, average relabeling costs twice as high as claims into a category that requires FDA FDA is not aware of any evidence that that of the 12-month compliance period. review of safety and efficacy evidence, would indicate that the establishment of FDA decided that this additional burden where appropriate, will similarly reduce criteria for distinguishing structure/ was not warranted. The option of a 12- long-term health care expenditures. function claims from disease claims will month compliance period for small as Again, however, the agency has no adversely affect the conduct of scientific well as large firms was rejected because means of quantifying the probable research. In fact, FDA believes that the of the additional burden to small firms, health outcomes of this aspect of the final rule accords with the intent of which may find it more difficult to rule and therefore has no means of DSHEA in promoting the enhancements effect rapid shifts in labeling quantifying its impact on health care to consumer health expected from the procedures. The final rule provides expenditures. Because this analysis broad dissemination of structure/ small firms with an additional 6 months discusses the types of benefits and costs function information, while reducing to introduce these labeling changes. reasonably expected, and quantifies the risks to consumer health associated Extending the compliance date for small those that can be ‘‘feasibly’’ quantified, with the promotion of disease treatment firms beyond 18 months was rejected, the agency has, in fact, complied with and/or prevention uses for products because the agency did not believe that the direction of Executive Order 12866. whose safety and efficacy have not been the delayed consumer benefits would be FDA has attempted to quantify the demonstrated. balanced by the relatively modest benefits of some of its previous additional cost saving. Exempting all regulations. The agency’s estimated E. Regulatory Alternatives small firms was not acceptable, because benefits of the tobacco rule relied on a FDA has considered several major most firms covered by this rule are widely established risk assessment alternatives to the proposed rule as part small. The final option, which was to published by the American Cancer of the rulemaking process. These include the compliance periods Society. Estimated benefits of the include: (1) Taking no new regulatory specified in the proposed rule, required proposed ephedra rule were based on action; (2) treating a statement about a label changes within 30 days for

VerDate 04-JAN-2000 16:16 Jan 05, 2000 Jkt 190000 PO 00000 Frm 00050 Fmt 4701 Sfmt 4700 E:\FR\FM\06JAR4.XXX pfrm11 PsN: 06JAR4 Federal Register / Vol. 65, No. 4 / Thursday, January 6, 2000 / Rules and Regulations 1049 products bearing claims of which FDA manufacture products not covered by businesses, less than 0.1 percent of the had not been notified or claims to which this rule. FDA has projected the small firms (1 firm) would be likely to FDA had already objected. This option industry size for this rule at about 1,000 have more than 4 of these products and was rejected because it could have firms. The Small Business only about 3 percent (30 firms) to have increased costs per label for many small Administration (SBA) has determined more than 2 of these products. firms by a factor of eight. that dietary supplement manufacturers A small firm that needs to redesign with fewer than 500 employees are labels for three products (about eight F. Small Business Impacts small businesses. Because most data SKU’s) due to the rule will incur As stated above, the Regulatory sources characterize firms in this estimated one-time direct compliance Flexibility Act requires agencies to industry by sales revenues rather than costs of about $11,650. A small firm that analyze regulatory options that would employment size, and because company needs to redesign labels for 4 products minimize any significant impact of a revenues of less than $20 million (about 10 SKU’s) would incur costs of rule on small entities, unless the rule is correlate reasonably well with a 500 about $14,950, or roughly 1.2 percent of not expected to have a significant employee threshold, FDA has received average company revenue. Thus, the economic impact on a substantial approval from the SBA to use a less- assumption that these products are number of small entities. With this final than-$20 million sales revenue standard randomly distributed among small firms rule, FDA is defining the types of to represent small dietary supplement indicates that very few small businesses statements that can be made concerning manufacturers. Table 1 displays the would be likely to incur relabeling costs the effect of a dietary supplement on the reported size distribution of the dietary that are greater than 1 percent of average structure or function of the body. It also supplement manufacturing industry. small company revenue. It is possible, establishes criteria for determining As described above, FDA assumes however, that some firms will have a when a statement represents a claim to that all small manufacturers of dietary disproportionate number of labels to be diagnose, cure, mitigate, treat, or supplements will incur administrative revised. In the RTI database of 3,000 prevent disease and thus is not costs of about $407 per firm. In randomly selected products, only 3 acceptable as a structure/function claim. addition, a number of small companies (all large) have more than 24 The regulation was prepared in manufacturers of dietary supplements products. Although the data base response to the dietary supplement will need to alter some product labels, sample show a number of small industry’s request for clarification from at an average redesign cost of about companies with up to 24 products, it is FDA with respect to the distinction $1,300 per SKU, and an average very unlikely that all of these product between structure/function and disease inventory cost of about $107 per SKU. labels would need to be changed due to claims, and to guidance in the FDA further analyzed the dietary this rule. If a small company needed to Commission report suggesting that FDA supplement product data base described revise 10 products, however, its direct provide such clarification to industry. in the October 1999 RTI report (Ref. 11) costs of compliance would be about For its analysis of the proposed rule, to determine how these products may be $37,000. Moreover, although FDA FDA had estimated that between 500 distributed among small businesses. As cannot quantify the likelihood, some and 850 firms were involved in dietary noted earlier, FDA estimates that about small firms could lose product sales due supplement manufacturing. A more 628 of the 837 products (75 percent) to the necessary removal of a disease recent industry survey reports that 1,050 needing revised labels due to this rule claim from a product label. Thus, FDA companies manufacture dietary are manufactured by small firms. If finds that this rule may have a supplements; although as explained these 628 products were randomly significant economic impact on a above, some of these companies may distributed among the 950 small substantial number of small companies.

TABLE 1.ÐESTIMATED NUMBER OF DIETARY SUPPLEMENT MANUFACTURERS AND REVENUES, BY SIZE CATEGORY 1

Size Category Number of Companies Revenues ($ in billions) Percentage of Market

>$100 million 16 3.32 55% $20 to $100 million 38 1.54 25% <$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 and the Secretary of the Department of 8. Economic Characterization of the Health and Human Services, November 1997. Dietary Supplement Industry, prepared for This final rule contains no collections 2. Dorland’s Illustrated Medical Dictionary, DHHS/FDA/CFSAN by Research Triangle of information. Therefore, clearance by 28th ed., W. B. Saunders Co., Philadelphia, Institute, Center for Economics Research the Office of Management and Budget p. 478, 1994. under Contract No. 223–96–2290: Task Order under the Paperwork Reduction Act of 3. Stedman’s Medical Dictionary, 26th ed., 3, Final Report, p. 5–2, March 1999. 1995 is not required. Williams & Wilkins, Baltimore, p. 492, 1995. 9. Herb and Supplement Usage Nears 70 Percent, Natural Foods Merchandiser, 4. The Encyclopedia Americana, VIII. References www.nfm-online.com/nfm backs/Feb 98/ International Edition, Grolier Inc., Danbury, Ð Ð herbusage.html. The following references have been p. 168, 1985. placed on display in the Dockets 10. Wyngate, P., Consumers Not 5. Black’s Law Dictionary, 6th ed., West Supplement Brand Savvy, Natural Foods Management Branch (address above) Publishing Co., St. Paul, p. 467, 1990. Merchandiser, www.nfm-online.com/ and may be seen by interested persons 6. The Merck Manual, 17th ed., Merck nfmÐbacks/MarÐ98/brandsavvy.html. between 9 a.m. and 4 p.m., Monday Research Laboratories, Whitehouse Station, 11. Dietary Supplement Sales Information, through Friday. NJ, p. 416, 1999. prepared for DHHS/FDA/CFSAN by Research 1. Commission on Dietary Supplement 7. Webster’s Encyclopedic Unabridged Triangle Institute, Center for Economics Labels, Report to the President, Congress, Dictionary, p. 1057, 1989. Research Under Contract No. 223–96–2290:

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Task Order 4, Final Report, pp. 5–8, October structure or function, provided that (A) The name of the product; 1999. such statements are not disease claims (B) A statement about the formulation 12. Research Triangle Institute, Economic under paragraph (g) of this section. If of the product, including a claim that Characterization of the Dietary Supplement the label or labeling of a product the product contains an ingredient Industry, p. 5–15. marketed as a dietary supplement bears 13. Research Triangle Institute, (other than an ingredient that is an ‘‘Compliance Costs of Food Labeling a disease claim as defined in paragraph article included in the definition of Regulations,’’ prepared for CFSAN/FDA by (g) of this section, the product will be ‘‘dietary supplement’’ under 21 U.S.C. RTI under Contract No. 223–87–2097, final subject to regulation as a drug unless the 321(ff)(3)) that has been regulated by report, pp. 5–3, 5–4, January 1991. claim is an authorized health claim for FDA as a drug and is well known to 14. U.S. Department of Labor, Bureau of which the product qualifies. consumers for its use or claimed use in Labor Statistics, BLS. (g) Disease claims. (1) For purposes of preventing or treating a disease; 15. Memorandum from R. J. Moore, FDA, 21 U.S.C. 343(r)(6), a ‘‘disease’’ is (C) Citation of a publication or to file, review of notifications made pursuant damage to an organ, part, structure, or to 21 U.S.C. 343(r)(6). reference, if the citation refers to a system of the body such that it does not disease use, and if, in the context of the 16. Memorandum from J. Lienesch, FDA, to function properly (e.g., cardiovascular file, calculation of relabeling cost estimate for labeling as a whole, the citation implies final rule on statements made for dietary disease), or a state of health leading to treatment or prevention of a disease, supplements concerning the effect of the such dysfunctioning (e.g., e.g., through placement on the production on the structure or function of the hypertension); except that diseases immediate product label or packaging, body, December 22, 1999. resulting from essential nutrient inappropriate prominence, or lack of deficiencies (e.g., scurvy, pellagra) are List of Subjects in 21 CFR Part 101 relationship to the product’s express not included in this definition. claims; Food labeling, Nutrition, Reporting (2) FDA will find that a statement (D) Use of the term ‘‘disease’’ or and recordkeeping requirements. about a product claims to diagnose, ‘‘diseased,’’ except in general statements Therefore, under the Federal Food, mitigate, treat, cure, or prevent disease about disease prevention that do not Drug, and Cosmetic Act, the Public (other than a classical nutrient refer explicitly or implicitly to a specific Health Service Act, and under authority deficiency disease) under 21 U.S.C. disease or class of diseases or to a delegated to the Commissioner of Food 343(r)(6) if it meets one or more of the specific product or ingredient; or and Drugs, 21 CFR part 101 is amended criteria listed below. These criteria are (E) Use of pictures, vignettes, as follows: not intended to classify as disease symbols, or other means; claims statements that refer to the (v) Belongs to a class of products that PART 101ÐFOOD LABELING ability of a product to maintain healthy is intended to diagnose, mitigate, treat, structure or function, unless the 1. The authority citation for 21 CFR cure, or prevent a disease; part 101 continues to read as follows: statement implies disease prevention or treatment. In determining whether a (vi) Is a substitute for a product that Authority: 15 U.S.C. 1453, 1454, 1455; 21 statement is a disease claim under these is a therapy for a disease; U.S.C. 321, 331, 342, 343, 348, 371. criteria, FDA will consider the context (vii) Augments a particular therapy or 2. Section 101.93 is amended by in which the claim is presented. A drug action that is intended to diagnose, revising the section heading and by statement claims to diagnose, mitigate, mitigate, treat, cure, or prevent a disease adding paragraphs (f) and (g) to read as treat, cure, or prevent disease if it or class of diseases; follows: claims, explicitly or implicitly, that the (viii) Has a role in the body’s response product: to a disease or to a vector of disease; § 101.93 Certain types of statements for (i) Has an effect on a specific disease (ix) Treats, prevents, or mitigates dietary supplements. or class of diseases; adverse events associated with a therapy * * * * * (ii) Has an effect on the characteristic for a disease, if the adverse events (f) Permitted structure/function signs or symptoms of a specific disease constitute diseases; or statements. Dietary supplement labels or class of diseases, using scientific or (x) Otherwise suggests an effect on a or labeling may, subject to the lay terminology; disease or diseases. requirements in paragraphs (a) through (iii) Has an effect on an abnormal Dated: October 26, 1999. (e) of this section, bear statements that condition associated with a natural state Jane E. Henney, describe the role of a nutrient or dietary or process, if the abnormal condition is Commissioner of Food and Drugs. ingredient intended to affect the uncommon or can cause significant or structure or function in humans or that permanent harm; Donna E. Shalala, characterize the documented (iv) Has an effect on a disease or Secretary of Health and Human Services. mechanism by which a nutrient or diseases through one or more of the [FR Doc. 00–53 Filed 01–5–00; 8:45 am] dietary ingredient acts to maintain such following factors: BILLING CODE 4160±01±F

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