In an October 2012 Report, the Office of Inspector General (OIG) of the Department of Health and Human Services (HHS) charges that "structure/ function" (S/F) claims made for dietary supplements are inadequately substantiated and inconsistently notified to the U.S. Food and Drug Administration (FDA), as required. The OIG investigation was triggered by concerns expressed by the Government Accountability Office and public interest groups and is based upon the examination of substantiation for weight loss and immune function claims made for 127 dietary supplements. The supplements were purchased from the Internet and from retail stores.
The OIG Report recommends: that FDA seek explicit statutory authority to review substantiation for S/F claims to determine whether they are truthful and not misleading; that FDA improve the notification systems for S/F claims; and that the agency expand market surveillance to enforce the use of disclaimers for S/F claims and to detect unauthorized disease claims.
S/F claims for dietary supplements describe the role of a nutrient or dietary ingredient that is intended to affect the structure or function of the body or characterize the mechanism by which a nutrient or dietary ingredient acts to maintain a structure or function of the body, for example, "calcium builds strong bones." Because many of these claims would previously have been covered by the drug definition in section 201(g)(1)(C) of the Food, Drug Cosmetic Act (the Act), section 201(g)(1) of the Act was amended to provide that a dietary supplement "for which a truthful and not misleading statement is made in accordance with section 403(r)(6) is not a drug solely because the label or the labeling contains such a statement."
FDA does not pre-approve S/F statements permitted under section 403(r) (6) of the Act, but the Act requires the manufacturer of a dietary supplement bearing a structure/function claim to notify FDA, no later than 30 days after the first marketing of the dietary supplement with the statement, that such a statement is being made for the product. Regulations implementing these requirements are codified at 21 C.F.R. § 101.93.
In addition, the manufacturer must possess substantiation that the statement is truthful and not misleading, and must include in the labeling the following disclaimer: ‘‘This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.’’
OIG received 1,624 documents, of which 557 were human studies, from the manufacturers of 55 supplements. However, of the 34% of substantiation documents that were human studies, OIG concluded that none met all four of the elements that FDA recommends for competent and scientific evidence:
- a relationship between the evidence and the claim, e.g., have the studies specified and measured the dietary supplement that is the subject of the claim?
- the quality of the evidence, e.g., is there competent and reliable scientific evidence derived primarily from human studies (observational or interventional), as well as other background information, to substantiate a claim?
- does the totality of all relevant research, both favorable and unfavorable, tend to support the claim?
- does the evidence support the meaning of the claim, including each implied and express claim or reasonable interpretation?
Criteria for substantiation and applicable examples are discussed in FDA’s Guidance for Industry: Substantiation for Dietary Supplement Claims Made Under Section 403(r) (6) of the Federal Food, Drug, and Cosmetic Act.1
In addition to inconsistent substantiation of S/F claims, OIG investigators also report that the majority of notification letters to FDA were missing attestations that the claims submitted were substantiated, truthful and not misleading and that FDA was often unable to determine whether the notification had been sent within the 30 – day timeframe. Furthermore, 7% of the sampled supplement products were missing the required disclaimer and that 20% of the supplements in the sample bore what OIG concluded were prohibited claims purporting to treat diseases, such as the flu, the common cold or herpes and HIV, or they claimed to reduce cholesterol or prevent diabetes. The report urges FDA to extend its industry surveillance of electronic and print media and the internet to include retail establishments.
In response to the OIG Report, FDA indicated that it will consider whether to seek statutory authority to review substantiation for S/F claims and pointed out that FDA may at any time under existing law request that manufacturers voluntarily submit substantiation, although responses to such requests are not always made. In regard to the Notification System, however, FDA concurs with the OIG’s recommendation and has initiated a feasibility study to determine whether using existing IT programs could be adopted to provide FDA full access to all notification submissions and will consider amending the regulations "as resources and priorities allow." In response to the suggestion that the agency expand market surveillance of dietary supplements to enforce the use of disclaimers and to detect disease claims, FDA stated that it will look for opportunities to enforce supplement requirements. FDA pointed out that agency staff currently attend industry gatherings, to among other activities, obtain information about manufacturers’ compliance with FDA requirements, but that it does not intend at present to include retail establishments because the agency is "better able to address violations by conducting inspections at dietary supplement manufacturers’ facilities." FDA stated that it will focus enforcement on disease claims because they "pose the greatest threat to public health."
What should Supplement Marketers do?
Supplement manufacturers and marketers should review product claims made on the label and in promotional materials, including the quality and extent of substantiation for those claims. The OIG Report is unlikely to effect a major change in FDA’s enforcement priorities or methods, unless the agency receives additional resources to implement the OIG recommendations. However, FDA may be expected to turn its attention to the existence and timeliness of S/F claim notifications and to substantiation for S/F claims in the course of its normal enforcement activities. These will continue to be dietary supplement facility inspections, industry meetings/exhibits, and Internet surfing, with an emphasis on supplements that bear disease claims, that fail to bear required label statements, or that use claims or ingredients that may adversely affect the public health. In most cases, the products or claims are discontinued and substantiation is not always an issue for FDA.
Other Potential Fall-Out from the OIG Report
Dietary supplement marketers should consider the real possibility that the OIG Report may encourage an increase in private and state law suits against supplement marketers based upon allegations of false and misleading S/F claims for which substantiation may not exist. Knowing where the lines are drawn and what is required to successfully defend against consumer, competitor, and state government misleading advertising charges can save money and reputations.