By Riëtte van Laack –
The Food Safety Modernization Act ("FSMA") required that FDA, within 180 days of enactment of the FSMA, publish guidelines clarifying the definition of a new dietary ingredient ("NDI") and requirements for NDI notifications. FDA just made that deadline when it released the “Draft Guidance for Industry: Dietary Supplements: New Dietary Ingredient Notifications and Related Issues” on Friday July 1, 2011 (the Federal Register notice of availability was published on July 5, 2011). It will take some time to distill the information contained in this long-awaited draft guidance. However, from an initial read it appears that FDA’s interpretation of the statutory requirements applicable to NDIs is more restrictive than the statutory language contemplates and would create substantial hurdles for manufacturers.
The FDC Act defines a NDI as one not marketed in the U.S. before October 15, 1994. The manufacturer or distributor of an NDI (or a dietary supplement that contains an NDI) must notify FDA at least 75 days before the marketing of the product, unless the NDI has “been present in the food supply as an article used for food in a form in which the food has not been chemically altered.” The notification must provide the basis for the manufacturer’s conclusion that its product “will reasonably be expected to be safe.”
FDA estimates that there are more than 55,000 dietary supplements on the market and, annually, another 1000 new dietary supplements introduced. Yet, since 1995, FDA has received only approximately 700 NDI notifications. FDA has pointed to these numbers as evidence that NDI notifications are not being submitted in cases when they should be. Further, FDA has indicated many of the 700 notifications that FDA has so far received did not provide the information required by FDA’s regulations. In part, the guidance is intended to address these issues. The draft guidance consists of more than 120 Q&As regarding the determination of whether a dietary ingredient is an NDI, and, if it is, whether a notification is required and what information should be included in the notification. FDA’s draft guidance also includes a decision tree to help determine whether an NDI notification is needed, as well as an NDI Notification Form providing a template that a manufacturer may use for submission of its NDI notification.
As is clear from the high percentage of NDI notifications that FDA regards as deficient and the more than 70 Q&As that address the contents of a notification, preparing an NDI notification is no small task. Smaller companies may not be able to afford a notification, and larger companies should be prepared to devote substantial resources to the effort. Consequently, the determination of whether an NDI needs a notification, or whether the NDI is present in the food supply in a form in which it has not been chemically altered, is a critically important issue when deciding whether to incorporate a dietary ingredient in a supplement. Under FDA’s proposed interpretation of the NDI requirements, one or more notifications could be required for the majority of NDIs. According to the draft guidance, circumstances under which a notification may be required include:
- a change in the manufacturing process resulting in a change of the specifications of the NDI that previously has been notified to FDA;
- an NDI for which another manufacturer already submitted an NDI notification;
- use of solvents other than water or aqueous alcohol;
- preparation of an extract by removal of some components of a solution in water; and
- use of a different fermentation medium to grow a microorganism.
The requirement that a notification be submitted even where an NDI is the subject of a previous notification appears especially problematic for the inefficiencies it would generate – and for the lack of statutory authority upon which to base such a requirement. FDC Act § 201(ff) specifically states that a dietary supplement is a food, with certain exceptions not applicable here. Given that provision, isn’t a previously notified NDI “present in the food supply as an article used for food,” and therefore exempt from notification?
The determination of whether a dietary ingredient is an NDI must be preceded by a determination of whether the substance in question qualifies as a dietary ingredient within the meaning of FDC Act § 201(ff). On several occasions, FDA has objected to NDI notifications because, according to the Agency, a substance did not qualify as a dietary ingredient. In the draft guidance, FDA asserts that a substance does not necessarily qualify as a dietary ingredient merely because it occurs in food. Instead, a substance that is not a vitamin, mineral, botanical or amino acid, qualifies as a dietary ingredient only if it is consumed as a component of the diet. Therefore, contaminants of food products (including pathogenic microorganisms), food contact substances and other indirect food additives usually do not qualify as dietary ingredients. According to FDA, whether and when a synthetic substance qualifies as a dietary ingredient depends on the nature of the substance and the particular provision of the dietary ingredient definition under consideration. Although the draft guidance rejects the proposition that a synthetic substance can be a “constituent” or “extract” of an herb or other botanical, the guidance states that the “enzymatic or synthetic processing of cysteine or any other dietary ingredient would be an appropriate method for the manufacture of a metabolite of a dietary ingredient like taurine for use in a dietary supplement.”
As noted above, the requirements for the contents of the NDI notification are addressed in 71 Q&As. The purpose of the NDI notification is to provide FDA with information that forms the basis on which the manufacturer has determined that the dietary supplement(s) containing the NDI will reasonably be expected to be safe. Therefore, it is not surprising that 43 of these 71 Q&As address what FDA believes constitutes “history of use or other evidence of safety” to support the safety of the NDI. The guidance provides a table with FDA recommendations regarding safety testing for an NDI depending on the proposed level of use and the documented historical use levels. This table includes references to the specific Q&A for further discussion of FDA’s recommendation.
Comments on the draft guidance are due by October 3, 2011.