FDA released on July 5th the highly anticipated Draft Guidance on New Dietary Ingredients (NDIs). The guidance document was intended to assist companies in determining when a 75-day premarket notification is required for dietary ingredients not “grandfathered” under the DSHEA. We previously announced the publication of this guidance here. We will be commenting on the NDI guidance document over the next few weeks, breaking down the more significant aspects of FDA’s latest policy dictation. For now, we note that the document is in draft format. Companies seeking to lay groundwork for future challenges should consider filing objections with the FDA during the 90 day comment period. Legal arguments should be presented before the FDA first to establish standing and preserve the issues for appeal to a federal court.
In response to many questions concerning the guidance, we can say that the document is legally objectionable, but not surprising. Most of the regulatory interpretations appearing in the draft guidance are consistent with FDA’s position taken in enforcement proceedings over the past few years. The FDA has for the first time, however, expressly stated what most in industry tacitly understood. FDA claims that its latest policy proclamation responds to unreasonably low numbers of NDI notifications, despite the agency’s belief that industry should have provided notices in greater frequency. FDA’s heavy-handed response is an overcorrection. And given the agency’s perspective, we doubt a final document will differ drastically from the current draft. In any event, the FDA cannot unring the regulatory bell concerning many administrative conclusions in the existing draft.
We examine today the FDA’s position on dietary ingredients with a history of use in conventional food. The statute (21 U.S.C. § 350b(a)(1)) exempts from certain adulteration provisions of 21 U.S.C. § 342 dietary supplements that contain “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.” Dietary supplements are generally regulated as sub-categories of food. So what is an “article used for food”? The answer to that question may determine whether an ingredient is NDI. If the dietary ingredient itself can be labeled a “food” sold or present in the food supply, then the ingredient would be exempt from NDI notification. Apparently, according to FDA, all foods are comprised of dietary ingredients, but not all of those dietary ingredients are “articles used for food.” The definition of “food” is amorphous. Under 21 U.S.C. § 321(ff)(2)(B), the term “dietary supplement” is defined as a product that, inter alia, “is not represented for use as a conventional food or as a sole item of a meal or the diet.” But the distinction is not always black and white, as seen by FDA’s awkward attempt to guide industry on the differences between a liquid dietary supplement and conventional beverage, available here. FDA eventually rested on its administrative discretion, explaining that it “considers a liquid product’s name, packaging, serving size, and recommended conditions of use…” to determine whether the product is a conventional food or dietary supplement. In other words, FDA will tell you whether the product is a food. Industry can look only at the exclusionary definition in Section 321(ff)(2)(B), whereby a food is an article represented as the sole item of a meal or diet.
The first step in analyzing the NDI exemptions must be, therefore, to determine exactly how the dietary ingredient has been presented to consumers. If it was marketed as a food, or sold to consumers for its specific properties (e.g., oranges marketed as a good source of vitamin C), then an NDI notification can be avoided, provided the ingredient is not chemically altered.
FDA’s decision that specific ingredients must have been marketed directly to consumers is an administrative construct. The Congress through DSHEA sought to expand access to dietary supplements that were proven safe by a history of use in the food supply. FDA’s requirement that a dietary ingredient be specifically identified to consumers is inconsistent with the underlying premise of DSHEA; a semantic distinction of little relevance to the safety of a dietary ingredient that was consumed through the food supply.
Dietary ingredients that satisfy the first prong must be sold without chemical alteration. That second prong is perhaps the most controversial aspect of FDA’s draft guidance because FDA suggests that existing NDIs would require new notifications based on changes in dose, conditions of use, and/or manufacturing methodologies. FDA identifies a series of manufacturing methods that would or would not result in chemical alteration. In the end, companies seeking to avoid the burdensome NDI regulations should consider laboratory analysis to create a record showing the chemical similarities between the original and finished ingredient. In most cases, the record will be part of, or folded into, cGMP record-keeping.
Finally, FDA states that a company may need separate NDI notifications for supplements containing the same NDI when: (1) the daily intake level recommended or suggested in the labeling of the new supplement will be greater than that specified in your prior NDI notification, (2) the new supplement includes dietary ingredients that were not included in your original NDI notification, (3) the target populations (e.g., children or pregnant or lactating women) are different than the target populations specified in your original notification, (4) other conditions of use are different or less restrictive (e.g., more intended uses, longer duration of use) than the conditions of use described in your prior NDI notification, and/or (5) FDA expressed safety or other concerns in response to your prior NDI notification.
As with a drug product, FDA believes a new condition of use or target population would trigger the regulations under Section 350b anew. FDA derives this language from 21 U.S.C. § 350b(a)(2), wherein Congress exempted ingredients that were safe “under the conditions recommended or suggested in the labeling.” If enforced exactly as written in the guidance, the FDA would impose substantial barriers to market entry for new ingredients. NDI notifications are costly to prepare and may require detailed safety data. A requirement to submit separate notifications could require generation of different data sets. The separate notification requirement should concern only those dietary ingredients that cannot meet the exemption criteria in 21 U.S.C. § 350b(a)(1). And, even with new conditions of use or concentrations, an article that was used for food in a form in which the food is not chemically altered should be exempt. That definition appears to include certain dietary ingredients that were once established through the NDI notification process. After all, if a dietary ingredient proceeds through a 75-day notification, and is then sold to consumers as an article used for food, then subsequent sales of that ingredient should be exempted under Section 350b(a)(1), regardless of whether, for example, the target population changes. The FDA’s approach appears to foreclose the possibility that an NDI proceeding under Section 350b(a)(2) must always then be subject to that statutory section. Are we to believe that the separate notification requirement only concerns dietary supplements brought simultaneously to market? We will see whether FDA can reconcile its guidelines with the statutory text in the final guidance document.
Peter Arhangelsky can be reached at (202) 466-6937 or firstname.lastname@example.org.
 The pertinent part of 21 U.S.C. § 350b is as follows:
(a) IN GENERAL.—A dietary supplement which contains a new dietary ingredient shall be deemed adulterated under section 402(f) unless it meets one of the following requirements:
(1) 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.
(2) There is a history of use or other evidence of safety establishing that the dietary ingredient when used under the conditions recommended or suggested in the labeling of the dietary supplement will reasonably be expected to be safe and, at least 75 days before being introduced or delivered for introduction into interstate commerce, the manufacturer or distributor of the dietary ingredient or dietary supplement provides the Secretary with information, including any citation to published articles, which is the basis on which the manufacturer or distributor has concluded that a dietary supplement containing such dietary ingredient will reasonably be expected to be safe.