On March 5, 2024, FDA issued a final guidance on Dietary Supplements: New Dietary Ingredient Notification Procedures and Timeframes (Procedures and Timeframes Guidance). This new guidance finalizes Section V (“NDI Notification Procedures and Timeframes”) of the FDA’s 2016 revised draft guidance on new dietary ingredients (NDIs). It is directed to formal aspects of how a new dietary ingredient notification (NDIN) is to be filed, who should submit the NDIN, what information should and should not be included, how to identify information the submitter believes to be trade secret, and the potential for meetings between the submitter and FDA.
Other sections of the 2016 revised draft guidance remain in draft form. FDA has thus avoided updating its guidance on many of the most critical legal issues covered by the NDI Draft Guidance, such as how to determine whether a substance qualifies as a dietary ingredient at all and whether an ingredient is excluded from the need to submit an NDIN because it is either (1) a “pre-DSHEA” dietary ingredient marketed in the United States prior to October 15, 1994, or (2) an ingredient that 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” under section 413(a)(1) of the Federal Food, Drug, and Cosmetic Act (FDCA) (21 U.S.C. §350b(a)(1)). See our 2016 client alert discussing these issues.
FDA states in the Procedures and Timeframes Guidance that it understands the importance of finalizing the NDI Draft Guidance and will continue to finalize individual sections after “review and analysis of those sections.” Of course, FDA has been reviewing and analyzing those sections for eight years already, and it is unclear when any additional long-promised guidance on NDIs may be published.
Background
Under the Federal Food, Drug, and Cosmetic Act (FDCA), an NDIN to FDA is required where the exact substance that is the NDI has not been present in the food supply as an article used for food. Section 413(a)(2) of the FDCA states that “the manufacturer or distributor of the dietary ingredient or dietary supplement” must provide FDA with information “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.” (21 U.S.C. §350b(a)(2)). If an NDIN is required but has not been submitted, FDA can deem any dietary supplement containing that NDI to be adulterated. FDA’s regulation at 21 CFR 190.6 sets forth the information that must be included in an NDIN, and Section VI of FDA’s revised draft guidance continues to provide details about what to include.
Key aspects of the Procedures and Timeframes Guidance:
Who must submit an NDIN?
FDA takes the position that NDINs submitted by the manufacturers of the NDI itself do not eliminate the requirement for manufacturers or distributors of dietary supplements containing that NDI to submit an NDIN, unless the NDI manufacturer’s NDIN included information about the dietary supplement(s). The NDI manufacturer’s NDIN would need to include a description of the dietary supplement(s) and the history of use or other evidence of safety that formed the basis of the conclusion that the dietary supplement(s) would reasonably be expected to be safe under the labeled conditions of use.
Can you submit a single NDIN that contains safety data for a range of conditions of use and covers multiple products? If so, how should the NDIN describe the dietary supplement in which the NDI will be used?
Yes, an NDIN may cover multiple dietary supplements and include safety data for a range of conditions of use, and should include: (1) the NDI level per serving, (2) the identity and level of other dietary and non-dietary ingredients per serving (such as binders and fillers), (3) a description of the manufacturing process, including process controls, (4) a specification sheet describing critical safety attributes, and (5) the recommended conditions of use. The conditions of use include the serving form (e.g., tablet, capsule, powder, liquid), serving size, frequency and duration of use, instructions for use, target population and any excluded populations, and any other restrictions on use. These details and conditions are rather specific, and an ingredient supplier’s NDIN may not anticipate and cover a broad range of future forms or iterations of dietary supplements containing the NDI.
How should the NDIN describe the NDI?
NDINs have been rejected because the NDI was not sufficiently well characterized or the data supporting the notification did not closely match the specific NDI. In this final guidance, FDA advises that the NDIN submitter should:
(1) specify which of the dietary ingredient categories in section 201(ff)(1) of the [FDCA] the NDI belongs to and explain the basis for [that] conclusion; (2) describe the manufacturing process used to make the NDI, including process controls; (3) describe the physical properties and chemical or molecular composition and structure of the NDI; and (4) include a specification sheet (preferably in table form) that describes the critical identity and safety attributes of the NDI, including the purity and strength of the NDI and the identities and levels of any impurities and contaminants.
Further, FDA states that the NDI should be described at a level that communicates the basic nature and characterizing components of the ingredient. For example, the name for an herb or other botanical must include the Latin binomial name, including author citation, as well as the plant part that is the source of the NDI. If the NDI was the subject of a previous NDIN, FDA recommends that the previous NDIN number be included.
What information should not be in the NDIN?
An NDIN should not contain general or extraneous information that does not help identify the NDI or dietary supplement containing the NDI or help provide the basis for its safety. NDINs should not include data or information to substantiate claims, studies on a product where the NDI was a mere constituent and where such data may not be useful for assessing safety, or information about other products that are not specifically linked to the NDI or dietary supplement containing it.
Do you have to provide copies of publications cited in the NDIN to FDA?
Yes. All references offered in support of an NDIN must be included as reprints or photocopies, and abstracts and bibliographic citations will not be sufficient. Failure to provide full copies may cause an NDIN to be incomplete. For unpublished scientific work, FDA recommends providing a complete description of the data and methods of the unpublished study. In some cases, raw data should be provided in an NDIN.
How should you identify information in an NDIN that you believe is trade secret or confidential commercial information (CCI)?
Submitters should clearly identify any trade secret or CCI and explain the basis for this belief.
Meetings Between FDA and Notifiers
While voluntary, FDA provides that a submitter can request feedback on a potential NDIN by emailing NDITEAM@fda.hhs.gov, with the subject line “[Firm Name]– Pre-NDIN Meeting Request.”
Although this guidance is final, interested stakeholders can submit comments to the docket, FDA-2023-D-5280, at any time.
If you have any questions concerning the material discussed in this client alert, please contact the members of our Food, Drugs, and Devices practice.
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