By James Hoadley, Ph.D., EAS Senior Consultant
A new dietary ingredient (NDI) is a dietary ingredient that was not sold in the United States as a dietary supplement ingredient before October 15, 1994. Manufacturers of NDI-containing dietary supplements must notify FDA of their intent to market a NDI-containing supplement at least 75 days before the supplement is marketed in the U.S. The NDI Notification must thoroughly identify the NDI, how it is used in the NDI-containing supplement, and present the evidence the manufacturer relied upon to determine their use of the NDI in the supplement is reasonably expected to be safe. The NDI Notification requirement applies to every NDI-containing dietary supplement regardless of whether other firms have submitted NDI Notifications on the same substance. There is an exemption to the NDI Notification requirement provided for dietary supplements containing only NDIs that have been used for food in the same chemical form as is being used as a NDI (21 U.S.C. 350b(a)(1)). FDA has codified these requirements at 21 CFR 190.6.
FDA discussed its positions on NDI related issues in a draft guidance. One Q&A in the FDA’s guidance speaks directly to whether a NDI Notification would be required for a NDI that also has a GRAS food ingredient use. FDA noted that a substance legally marketed as a food ingredient in conventional food would be exempt from the NDI notification requirement because it has been present in the food supply as an article used for food in a form in which the food is not chemically altered. Submission of a GRAS Notification will establish a basis for a NDI to be legally marketed as a food ingredient.
The NDI Notification process intended in DSHEA for FDA to have some oversight on dietary supplement manufacturers’ safety assessments of their NDI-containing dietary supplements. However, in some situations it may make more sense to submit a generally recognized as safe (GRAS) Notification for NDIs.
Dietary Ingredients, are defined (21 U.S.C. 321(ff)(1)), include (a) vitamins, (b) minerals, (c) herbs or other botanicals, (d) amino acids, (e) dietary substances for use by man to supplement the diet by increasing the total dietary intake, or (f) concentrates, constituents, extracts, or combinations of the (a) through (e) ingredient categories.
Something such as a new, patented bacteria strain does not qualify as a dietary ingredient because it is not one of the categories named in (a) – (d), nor is it a “dietary substance” (category (e)) because it has never been in the human diet. Thus, FDA is likely to reject a New Dietary Ingredient (NDI) Notification for the new bacteria strain on the basis that the substance is not a dietary ingredient.
Submitting a GRAS Notification for food ingredient applications of the new bacteria strain establishes food ingredient uses for the new bacteria strain. A substance’s GRAS Notification becomes the basis to assert that the substance is a ‘dietary substance for use by man to supplement the diet’ and thus eligible as a dietary ingredient use.
When the substance of interest for dietary ingredient use is NOT clearly in one of the (a) – (e) dietary ingredient categories, then submitting a GRAS Notification will be imperative because there is a great risk that a new dietary ingredient (NDI) Notification would be rejected outright on the basis that the substance does not qualify as a dietary ingredient and thus cannot be a NDI.
Taking the GRAS Notification path allows supplement manufacturers to side-step the need for filing multiple NDI Notifications for each NDI-containing dietary supplement.
Section 413 of the FD&C Act states that a NDI Notification is not required of a dietary supplement containing only dietary ingredients which have been present in the food supply as an article used for food [413(A)(1)].
Submitting a GRAS Notification for food ingredient and dietary ingredient applications of a substance establishes there are recognized uses of the substance “as an article used for food.” Dietary supplements are not subject to the NDI Notification requirement when they contain only dietary ingredients which have been present in the food supply as an article used for food. A substance’s GRAS Notification becomes a basis to assert that the substance is in the food supply as an article used for food and therefore exempt from the NDI Notification requirement.
The NDI Notification requirement applies to each dietary supplement containing a NDI irrespective of how many previous NDI Notifications have been submitted for the same NDI. It would be advantageous for a dietary ingredient supplier to submit a GRAS Notification for a NDI substance (establishing the NDI substance to be in the food supply) and thereby exempting the NDI from the NDI Notification requirement.
Posted in Dietary Supplements, EASeNews, Issue of the Month and tagged Dietary Ingredient, James Hoadley.