FDA Issues Long-Awaited Revised Dietary Supplement NDI Draft GuidanceAugust 14, 2016
By Etan J. Yeshua –
Last week, FDA issued for the dietary supplement industry a draft guidance document that largely doubles-down on controversial positions the Agency has previously taken. The draft guidance – “Dietary Supplements: New Dietary Ingredient Notifications and Related Issues” – replaces the draft of the same name that was issued in July 2011. As we blogged about at the time (here and here), FDA’s 2011 draft guidance reflected a regulatory approach that many considered to be inconsistent with the requirements and intent of the Dietary Supplement Health and Education Act (“DSHEA”), which amended the Federal Food, Drug, and Cosmetic Act (“FD&C Act”). The 2011 draft elicited a host of comments (including two from us, here and here) about key issues in FDA’s approach to implementing DSHEA. The “updated” draft guidance is likely to elicit much the same criticism, as it largely reiterates the Agency’s previous positions on key issues (which we describe below).
In a Federal Register notice announcing the updated draft guidance, FDA identified the “major topics on which we have revised or added questions and answers,” including:
- manufacturing changes that create a new dietary ingredient (“NDI”);
- synthetic substances;
- the definition of “chemical alteration”;
- the definition of “NDI” and the list of “grandfathered” dietary ingredients;
- structuring notifications efficiently and relying on data from prior notifications and master files;
- identity information to include in an NDI notification;
- electronic submission;
- PDF form for NDI notifications submitted on paper; and
- safety information to include in an NDI notification.
For the most part, however, the Agency’s revisions and additions restate controversial positions that FDA took in the 2011 draft guidance—positions about which the Agency received numerous comments from industry and Congress. These positions include:
- “Grandfathered” ingredients. The Agency narrowly construes the category of “grandfathered” (or “old”) dietary ingredients, i.e., those that are not NDIs, and therefore do not require NDI notification, because they were marketed in the United States before October 15, 1994. In the updated guidance, FDA maintains its position that, in order to be grandfathered, an ingredient must have been marketed before that date as a dietary ingredient (rather than, e.g., as a conventional food or an over-the-counter drug) further narrowing the class of “grandfathered” ingredients. FDA also continues to maintain that certain changes in manufacturing methods may cause an otherwise grandfathered ingredient to become an NDI.
- In addition, FDA states in the new draft guidance that it is open to compiling a (non-exclusive) list of grandfathered ingredients, but that the burden for establishing the grandfathered status of an ingredient would largely fall to industry: “[W]e are prepared to develop an authoritative list of [grandfathered] ingredients, based on independent and verifiable data. Because FDA does not generally have access to marketing records for dietary ingredients and dietary supplements, the documentation of pre-DSHEA marketing would have to be supplied by industry. . . . The mere fact that an ingredient is not on the list would not, however, establish that the ingredient is an NDI . . . . Rather, the omission of an ingredient from the list would be regarded as neutral and would not affect the ingredient’s regulatory status.” (Emphasis in original).
- Definition of “dietary ingredient.” Section 201(ff)(1)(E) of the FD&C Act includes as a dietary ingredient “a dietary substance for use by man to supplement the diet by increasing the total dietary intake.” FDA maintains its position that this category includes only substances that are “commonly used as human food or drink,” thereby excluding many novel substances, as well as many dietary substances that are not “commonly used,” from inclusion in a dietary supplement.
- NDIs exempt from the notification requirements. The FD&C Act exempts from the notification requirement NDIs that are “present in the food supply as an article used for food in a form in which the food has not been chemically altered,” and FDA continues to interpret this exemption narrowly. For example, the updated draft guidance again considers an NDI to have been “present in the food supply” only if it is present as an ingredient in conventional foods; presence in a dietary supplement would not exempt the ingredient from the notification requirement.
- A new concept in the draft guidance is the option to submit a confidential “NDI master file.” The master file would contain “the manufacturing, specifications and other identity information needed to completely describe the ingredient” and may be incorporated by reference into later NDI notifications.
- Responsibility for submitting NDI notifications. FDA maintains its position that, except in limited circumstances, a dietary supplement manufacturer must submit a separate notification for each supplement that contains an NDI and generally cannot rely on a previously-submitted notification. The Agency again asserts that a notification must be submitted for a dietary ingredient even if the ingredient’s manufacturer or another supplement manufacturer previously submitted a notification for that ingredient, except when virtually all conditions of use are identical (including, for example, that “[t]he new supplement does not combine the NDI with other dietary ingredients that were not included in [the] original NDI notification,” the target consumer population is the same, etc.).
- Synthetic ingredients. The Agency continues to consider most synthetic copies of botanicals (and synthetic constituents and extracts of botanicals) as falling outside the definition of “dietary ingredient” and, thus, as impermissible in dietary supplements, even if the synthetic ingredient is chemically identical to the natural ingredient.
- Although the new draft guidance explicitly states that “synthetic vitamins, minerals, and amino acids qualify as dietary ingredients . . . regardless of [their] source,” it reiterates that “a synthetic copy of an herb or other botanical does not qualify as a dietary ingredient under section 201(ff)(1)(C) of the FD&C Act” and that “[f]or more than a decade, FDA has consistently interpreted section 201(ff)(1)(F) of the FD&C Act as not including synthetic copies of botanical constituents, extracts, and concentrates.”
- The new draft guidance provides a limited exception: “a synthetic copy of a botanical ingredient [or constituent] may qualify as a dietary ingredient under section 201(ff)(1)(E) if the synthetic copy has been used as a lawfully marketed ingredient in the conventional food supply.” In other words, if a synthetic botanical or synthetic botanical constituent is on the market in conventional foods (e.g., vanillin), then that synthetic ingredient could be used as a dietary ingredient in a dietary supplement. Of course, in order to lawfully be on the market in a conventional food, the ingredient would have to be either an FDA-approved food additive or Generally Recognized As Safe (“GRAS”) in accordance with FDA regulations.
FDA has stated that comments to the draft guidance should be submitted by October 11, 2016 in order to ensure that the Agency considers them before it begins work on the final version of the guidance.