FDA recommends that dietary supplement manufacturers and distributors voluntarily consult with it concerning the safety of supplements containing high amounts of new dietary ingredients (“NDIs”) that are approved direct food additives or GRAS.
An NDI notification must be submitted to FDA at least 75 days before selling a dietary supplement if the dietary supplement contains an NDI, i.e., a dietary ingredient that was not marketed in the U.S. prior to October 15, 1994. 21 U.S.C. § 350b(a), (d). An NDI notification is not required, however, if the dietary supplement “contains only dietary ingredients which have been present in the food supply as an article used for food in a form in which the food has not been chemically altered.” Id. at § 350b(a)(1).
FDA stated in its “Draft Guidance for Industry: Dietary Supplements: New Dietary Ingredients” (“NDI Draft Guidance”) that under this exception, an NDI notification is not required “for a dietary ingredient that has been listed or affirmed by FDA as generally recognized as safe (GRAS) for direct addition to food, self-affirmed as GRAS for direct addition to food, or approved as a direct food additive in the U.S.,” if the ingredient has been used in the food supply and will not be chemically altered.
Although an NDI notification is not required for such an ingredient, the NDI Draft Guidance states that the NDI adulteration standard will still apply if the ingredient was not marketed in the U.S. prior to October 15, 1994. Under the NDI adulteration standard, a dietary supplement containing a direct food additive or GRAS NDI is adulterated unless there is sufficient information to provide reasonable assurance that it does not present a significant or unreasonable risk of illness or injury. Id. at § 342(f)(1). FDA is particularly concerned about supplements containing a direct food additive or GRAS NDI in an amount much higher than that which results from conventional food use. In such situations, FDA recommends that manufacturers and distributors voluntarily submit an NDI notification to inform FDA of their basis for concluding that there is adequate information to provide reasonable assurance that the use of the NDI in the dietary supplement will not present a significant or unreasonable risk of illness or injury.
FDA’s interpretation of the NDI adulteration standard appears at odds with Congress’ intent when the adulteration standard is read in context with section 350b. Section 350b indicates that the purpose of NDI notification is to establish that the NDI is reasonably expected to be safe when used under the conditions recommended or suggested in the labeling of the dietary supplement. Id. at § 350b(a)(2). Because Congress chose to exempt supplements containing direct food additive or GRAS NDIs from the notification requirement, it is clear that Congress found such supplements to be categorically safe, regardless of the amount of the ingredient. Nonetheless, because of FDA’s position in the NDI Draft Guidance, manufacturers and distributors of dietary supplements containing food additives or GRAS NDIs should perform a safety analysis to confirm the safety of such products, especially when the ingredient is present in an amount much higher than that in conventional foods.
FDA has agreed to re-examine the proposed NDI Draft Guidance, but it is not clear, at this point, whether there will be any substantive changes to the guidance or to this particular provision within the guidance.