FDA to Apply Ephedra Rule to NDI Evaluations?

During the recent UNPA conference on the FDA draft guidance for New Dietary Ingredients, the agency suggested that industry take another look at the ephedra rule and its application of "unreasonable risk." Indeed industry should. Here is what that 2004 "Final Rule Declaring Dietary Supplements Containing Ephedrine Alkaloids Adulterated Because They Present an Unreasonable Risk" says in the introduction:

By its plain language, section 402(f)(1)(A) of the act requires evidence of "significant or unreasonable risk'' of illness or injury. There is no requirement that there be evidence proving that the product has caused actual harm to specific individuals, only that scientific evidence supports the existence of risk. The Government's burden of proof for "unreasonable risk'' is met when a product's risks outweigh its benefits in light of the claims and directions for use in the product's labeling or, if the labeling is silent, under ordinary conditions of use. "Unreasonable risk,'' thus, represents a relative weighing of the product's known and reasonably likely risks against its known and reasonably likely benefits. In the absence of a sufficient benefit, the presence of even a relatively small risk of an important adverse health effect to a user may be unreasonable.

In other words, the agency must evaluate the benefits of a product in order to evaluate whether there is an "unreasonable risk." The ephedra rule declaring all products containing this ingredient to be adulterated is based on the agency's conclusion that the ingredient's risks outweigh its benefits. And if the agency is not convinced that an ingredient or product has any proven benefits, then even a very small potential of risk is enough to conclude there is "unreasonable risk."

But why would the agency reference this ephedra rule when speaking about the NDI draft guidance? The NDI language from DSHEA makes no mention of weighing risk versus benefit. In fact it simply requires the notifier to provide the information that forms the basis for the conclusion of a reasonable expectation of safety. Is the FDA over-reaching in this area and suggesting that NDI notifications should include information about benefits of ingredients that the agency can use to compare risk to benefit? I think we need some clarification from the FDA on this point. What is the relevance to the NDI process of the ephedra rule and the risk-benefit evaluation that it used to determine "unreasonable risk"?

For more info about the NDI guidance situation, be sure to sign up for our upcoming live webinar with CRN, RSVP for our free Town Hall Meeting on the NDI Draft Guidance at SupplySide West, and check out AHPA's Congress on NDIs taking place in Chicago.