FDA Releases Draft Guidance for Industry on Substantiation Needed for Dietary Supplement Structure/Function Claims

Date: Nov 12, 2004

On November 9, 2004, the Food and Drug Administration (FDA) officially announced a series of new initiatives concerning its regulation of dietary supplements. One of these efforts is a Draft Guidance for Industry on the scientific data necessary to substantiate "structure/function claims" (among certain others) made for dietary supplements. The Draft Guidance for Industry is available at: http://www.cfsan.fda.gov/~dms/dsclmgui.html.

Although the Draft Guidance focuses on dietary supplements, there is no apparent reason why these substantiation recommendations would not also apply to structure/function claims made for conventional foods. Thus, the Draft Guidance appears to provide FDA's current thinking on claims substantiation issues generally, although the current focus is on dietary supplements. Manufacturers of conventional foods would do well to pay attention to FDA's activities, which could be setting the stage for expanded food enforcement activities in the future.

Overall, FDA appears to be articulating a high standard that it expects dietary supplement manufacturers to meet to substantiate product claims. Essentially, the appropriate substantiation is expected to consist of relevant, high-quality data from studies involving humans. In the Draft Guidance, FDA does not acknowledge the substantial cost or time involved in generating such data, and the likelihood that many companies will not be in a position to expend these resources.

It is worth noting that, even before the release of the Draft Guidance, FDA appears to have increased its enforcement activities against unsubstantiated claims for dietary supplements. Several manufacturers of weight loss products received Warning Letters in August and October 2004, asserting that their products' claims lacked adequate substantiation. This represents a new direction for the Agency's enforcement efforts, which previously have focused on whether dietary supplements were making impermissible "drug" claims.

The Draft Guidance is part of a larger "strategy for dietary supplements" that FDA announced at the same time. This new regulatory strategy is discussed in more detail in the article available here.

Background on Claims Substantiation

Section 403(r)(6) of the Federal Food, Drug, and Cosmetic Act (FDC Act) permits manufacturers of dietary supplements to make claims describing their products (1) convey a benefit related to a classical nutrient deficiency; (2) are intended to affect the structure or function of the body; or (3) promote general well-being through consumption. Any party making such a claim must have substantiation that the claim is truthful and not misleading, or else the product is deemed "misbranded" and potentially subject to regulatory action. However, the FDC Act does not define what constitutes "substantiation" for these claims.

The Federal Trade Commission (FTC) has jurisdiction over advertising claims for dietary supplements, which claims must be adequately substantiated. FTC applies a standard of "competent and reliable scientific evidence" when determining whether an advertising claim meets the substantiation requirements.

Draft Substantiation Guidance

FDA has released a Draft Guidance for Industry entitled "Substantiation for Dietary Supplement Claims Made Under Section 403(r)(6) of the [FDC Act]." The Agency stated that it intends to apply a standard that is consistent with the one used by FTC. FDA claims that its approach "provides manufacturers flexibility in the precise amount and type of evidence that constitutes adequate substantiation." However, this purported flexibility is likely to be the source of continuing uncertainty over whether adequate substantiation, in fact, exists for a particular claim. FDA acknowledges that there is "no general rule for how many studies, or what combination of types of evidence, is sufficient to support a claim."

In determining whether the substantiation standard has been met with competent and reliable scientific evidence, FDA recommends that firms consider the following issues: (1) the meaning of the claim(s) being made; (2) the relationship of the evidence to the claim; (3) the quality of the evidence; and (4) the totality of the evidence. The Draft Guidance outlines these factors through a number of examples, most of which illustrate when the proposed substantiation is not adequate.

A. Meaning of the Claim(s)

First, manufacturers are expected to understand the meaning of each claim and to identify express and implied claims. If a claim can have more than one reasonable interpretation, FDA recommends that each interpretation be substantiated. Apart from the individual claims, FDA believes that the overall message of the statements taken together must also be substantiated. For example, if a dietary supplement claims to promote weight loss, it likely would not be sufficient to just have evidence showing an effect on a surrogate marker (e.g., metabolism rate) that is not conclusively tied to weight loss. Similarly, general statements such as "Recommended by Scientists" or "studied for years" might imply a broad consensus in the scientific community supporting the claim. FDA expects manufacturers to have evidence supporting such implied claims.

B. Relationship of the Evidence to the Claim

Second, the relationship of the evidence to the claim is essential to determining whether the claim is substantiated. A number of factors can go into evaluating the relationship, including: (1) Did the studies specify and measure the dietary supplement? (2) Did the studies measure and specify the structure/function that is the subject of the claim? (3) Were the studies based on a population similar to the one which will be consuming the dietary supplement? (4) Does the claim adequately convey the extent, nature, or permanence of the effect and the level of scientific certainty for that effect?

FDA notes there may be a number of concerns with the relevance of the data. For example, studies examining the effect of an ingredient administered as a topical product may not support a claim for the same effect in a dietary supplement (which must be ingested). Data showing effects in foreign populations should take into account potential confounding differences from a US population (e.g., initial lower blood levels of certain minerals in the foreign subjects). An effect measured in elderly patients may not be applicable to children.

C. Scientific Quality

Third, the scientific quality of a study is important in determining whether the study supports a claim. Quality is based on a number of factors: (1) study population; (2) study design and conduct; (3) data collection methods; (4) statistical analysis; and (4) outcome measures. Study design factors that can affect the quality of a study include bias, quality assessment criteria, the population studied, exposure and outcomes, data analysis, and peer review. FDA recommends a "randomized, double blind, parallel group, placebo-controlled trial design" as the "gold standard," but notes that this may not always be possible or ethical.

As a general matter, FDA expects the competent and reliable scientific evidence to be derived primarily from human studies. Additional sources of information may provide additional support but, by themselves, generally would not be adequate to substantiate a claim. These sources include: (1) animal studies; (2) in vitro (laboratory) studies; (3) testimonial/anecdotal evidence; (4) meta-analyses of numerous reports (although there might identify primary studies); (5) review articles (again, these may identify primary sources of support); (6) comments and editorials; and (7) product monographs prepared by manufacturers with information such as product specifications.

D. Totality of the Evidence

Finally, manufacturers should consider the totality of the evidence available to support a claim. Studies presenting conflicting or inconsistent results may raise questions about whether a particular claim is satisfied. Varying study results may be explained by different concentrations of the dietary supplement, different test methodologies used, different study populations, or other factors. However, in the absence of valid scientific explanations for differing or inconsistent results, some favorable information will not be sufficient to substantiate a claim in the face of other information that fails to support the claim.


Overall, the Draft Guidance for Industry on claims substantiation and the new "strategy for dietary supplements" represent much higher-visibility regulatory policies with respect to dietary supplements. Product manufacturers can expect FDA to increase its scrutiny of claims made for dietary supplements and to be more aggressive in pursuing enforcement action against products that do not meet the current standards.

For further information about claims substantiation requirements for dietary supplements, or FDA's regulation of these products generally, please contact Frederick A. Stearns at 202-434-4288 or via e-mail at stearns@khlaw.com.