FDA recently released an updated version of its draft guidance on new dietary ingredients (NDIs), Dietary Supplements: New Dietary Ingredient Notifications and Related Issues.1 The lengthy draft guidance details FDA’s thinking on determining whether an NDI notification is required, including how to determine if a substance is an NDI, exceptions to the notification requirement, NDI notification procedures and timeframes, what to include in an NDI notification, and a decision tree for NDI notification that helps companies determine whether an ingredient is an NDI and if notification is necessary.
A “dietary ingredient” is an ingredient used in a dietary supplement. NDIs are a subset of dietary ingredients that were not in the US food supply as dietary ingredients before October 15, 1994. The new draft guidance represents the FDA’s current thinking on NDIs and amends and supersedes the original 2011 draft guidance.
In October 1994, the Dietary Supplement Health and Education Act (DSHEA) was signed into law and amended the Federal Food, Drug, and Cosmetic Act (FD&C Act), and therein added requirements for NDIs. A manufacturer of an NDI or food containing an NDI must submit a safety notification to FDA at least 75 days before marketing. No such notification is required for dietary ingredients that were marketed before October 15, 1994 (“grandfathered” dietary ingredients).
Because FDA does not maintain a recognized list of grandfathered dietary ingredients, determining whether a dietary ingredient is “new” is an internal company decision. Industry trade associations such as the United Natural Products Alliance and the Council for Responsible Nutrition have published lists of grandfathered ingredients that serve as a reference for companies when determining the status of a dietary ingredient. However, in the new draft guidance, FDA maintains its position that an ingredient’s inclusion in a list of grandfathered dietary ingredients prepared by industry is not evidence of marketing status before October 15, 1994. Rather, FDA committed to developing an authoritative list of grandfathered dietary ingredients. Such a list will eliminate much of the flexibility that manufacturers have in determining whether a dietary ingredient constitutes an NDI; yet, an FDA-approved list will provide manufacturers with more certainty regarding the regulatory status of their dietary ingredients. FDA is seeking comments from industry to help generate the list.
FDA will also require documentation—such as written business records, promotional materials, or press reports—establishing that an ingredient was marketed as a dietary ingredient prior to October 15, 1994. Specifically, sales records, manufacturing records, commercial invoices, magazine advertisements, mail order catalogs, or sales brochures are acceptable records. Documentation should include adequate information to establish (1) that marketing took place in the United States prior to October 15, 1994, (2) the marketed ingredient’s identity and form, and (3) whether the ingredient was marketed as a dietary ingredient or for some other purpose. Pursuant to the guidance, affidavits alone are inadequate to show that an ingredient is not an NDI. However, FDA will consider Generally Recognized as Safe and food additive regulations as documentation that a substance was marketed as a dietary ingredient before October 15, 1994.
The draft guidance also provides examples of when changes to the manufacturing process and combination of ingredients in a prior notification transform a grandfathered dietary ingredient to an NDI. Manufacturing changes that “alter the physicochemical structure or properties, purity and impurities, or biological properties (such as bioavailability or toxicity) of the ingredient will result in an NDI.” For example, using a different part of a plant would create an NDI. A new NDI notification is also required if there is no existing notification describing the specific combination of ingredients. That is, if an NDI is combined with dietary ingredients other than those that were in the dietary supplement evaluated in the original NDI notification, a new notification is required. This suggests that combinations of dietary ingredients that already have NDI notifications but would be combined in a new way not covered in any previously existing notification would also require new notification.
FDA invites comments on the draft guidance and, in particular, information evidencing that a dietary ingredient was in the US food supply prior to October 15, 1994, to support the list of grandfathered ingredients it is generating. The deadline for submissions is October 11, 2016. Visit www.regulations.gov to submit your comments.