FDA’s Recently Issued Guidance on Dietary Supplement Claims: A Peek Under the Hood

By Ricardo Carvajal –      

FDA has announced the availability of a guidance for industry titled “Substantiation for Dietary Supplement Claims Made Under Section 403(r)(6) of the Federal Food, Drug, and Cosmetic Act.”  Under certain conditions, section 403(r)(6) permits manufacturers of dietary supplements to make nutritional deficiency, structure/function, or general well-being claims in the labeling of dietary supplements, provided those claims are truthful and not misleading.  The guidance issued by FDA is very similar to a draft guidance that FDA issued under the same name in 2004, but there are some interesting differences that suggest a possible tightening of FDA's standards with respect to the types of evidence that constitute adequate substantiation. 

In addressing animal and in vitro studies, FDA has eliminated qualifying language that was present in the draft guidance.  For example, the draft guidance stated that, "Generally, without any data from human studies, the results of animal studies alone are not sufficient to substantiate a claim."  The recently-issued guidance omits the qualifier "generally."  Also, the draft guidance stated that, "The strongest in vitro evidence would be based on data that have been reproduced in different laboratories, but this evidence alone would ordinarily not be adequate to substantiate a claim."  The recently-issued guidance changes the last phrase in that sentence to state that "this evidence alone would not substantiate a claim."  These two omissions suggest that FDA is likely to demand data from one or more human studies for substantiation (but note that FDA does not address structure/function claims that include qualifying language, a point briefly addressed further below). 

As to the weight that can appropriately be given to a single study, Example 20 in the draft guidance stated that a single positive study involving a small number of subjects likely would be insufficient to substantiate a claim in the face of several high-quality studies that produce negative results.  The recently-issued guidance omits any reference to the number of subjects as a relevant factor.  This suggests that, in the absence of explanatory circumstances, FDA may view a single positive study as insufficient to substantiate a claim in the face of several unfavorable studies, even if that study involved a substantial number of subjects.

There is additional material of interest in the footnotes of the guidance.  First, FDA responds to comments raising First Amendment concerns by concluding that the statutory substantiation requirement in section 403(r)(6) is constitutional under the analysis governing commercial speech in Central Hudson Gas & Electric Corp. v. Public Service Commission of New York (447 U.S. 557 (1980)).  The guidance states that the "misleading nature of a claim made under section 403(r)(6) that is not substantiated cannot be cured by a disclaimer stating that the claim lacks support."  However, FDA sidesteps the question of whether a claim made under section 403(r)(6) that includes qualifying language can be substantiated.  Second, FDA takes the position that a study using a conventional food or a multi-nutrient supplement would not substantiate a single ingredient dietary supplement claim, and that a disclaimer wouldn’t work in such situations.  In support of its position, FDA notes that “recent scientific studies have shown that nutrients in food do not necessarily have the same beneficial effect when taken in the form of a dietary supplement,” and may either have no benefit or show “an increased risk for the very disease the nutrients were predicted to prevent.”