/>iOn March 5, 2024, the US Food & Drug Administration (FDA) released final guidance titled “Dietary Supplements: New Dietary Ingredient Notification Procedures and Timeframes: Guidance for Industry.” The guidance is meant to help manufacturers and distributors of new dietary ingredients (NDIs) and dietary supplements navigate the process of submitting new dietary ingredient notifications (NDINs) to the FDA. The guidance finalizes Section V of the 102-page 2016 draft guidance and answers questions related to other sections of the draft guidance. The FDA indicated that the decision to separate the finalized versions of the 2016 draft guidance into discrete sections for ease of use is responsive to comments received on the draft guidance. As the FDA continues to review and analyze the remaining sections of the draft guidance, it will issue those sections as separate final guidance.
IN DEPTH
BACKGROUND
Under the Federal Food, Drug, and Cosmetic Act (FD&C Act), NDIs are considered dietary ingredients that have not previously been used in food or dietary supplements. Dietary ingredients include vitamins, minerals, amino acids, concentrates and extracts that were not marketed in the United States before October 15, 1994.
Currently, under Section 413(a)(2) of the FD&C Act, a manufacturer or distributor of an NDI must submit a premarket safety notification (known as an NDIN) to the FDA at least 75 days before selling the product through interstate commerce. The NDIN must provide citations to published articles that support the safety of the NDI or the dietary supplement containing the NDI. If a manufacturer or distributor does not submit an NDIN and receives approval as required, the dietary supplement containing the NDI is considered to be adulterated.
The NDIN must include the following:
- Name and address of the notifier
- Name of the NDI, including the Latin name for botanicals
- Description of the dietary supplement
- Level of the NDI in the dietary supplement
- Recommended or suggested conditions of use for labeling
- Ordinary conditions of use of the supplement if there are no recommended conditions
- History of the use or other evidence supporting the safety of the dietary ingredient
- Authorized signature of the manufacturer or distributor
FDA regulations also provide the administrative procedures for filing an NDIN. After filing a notification, the notifier is prohibited from introducing the product into interstate commerce for 75 days from the filing date. Notably, the newly released guidance clarifies that submitting additional information that is deemed substantive will change the filing date to the date on which the additional information was submitted.
KEY TOPICS
Who needs to submit an NDIN?
Manufacturers or distributors of a dietary supplement with an NDI are required to submit an NDIN.
How should the information be presented in the NDIN?
The NDIN should be well organized to promote efficiency in review. The FDA encourages notifiers to submit electronically, although paper submissions are also permitted. A single NDIN may cover multiple dietary supplements. The NDIN should include a description of the NDI and the manufacturing process; documentation of the NDI’s physical, chemical and molecular composition and structure; and a specification sheet identifying the safety attributes of the NDI. For example, a botanical has different chemical and physical properties based on the part of the botanical from which the ingredient is derived. An NDIN should specify whether the NDI comes from the root or the leaf of the botanical, along with its properties. The description should also explain how the NDI will be used, specify the level of the NDI per serving, identify other dietary and non-dietary ingredients in the supplement that will be interacting with the NDI and, most importantly, provide any data or other evidence that supports the safe use of the NDI.
NDINs must also include a full copy of any publications referenced in the notification in support of the NDI’s safety. Abstracts are not accepted.
What information should not be included in the NDIN?
The FDA reminded notifiers that information included in the NDIN should be relevant to the NDI and should not include information that falls outside the scope of safety, context for use and/or the manufacturing process.
When should an NDIN be submitted?
NDI manufacturers and distributors must submit an NDIN at least 75 days prior to marketing the dietary supplement via interstate commerce.
Notifiers may contact the FDA at NDITEAM@fda.hhs.gov with the subject line “[Firm Name] Pre-NDIN Meeting Request” to get preliminary and nonbinding feedback on a potential NDIN.
What happens after the NDIN is submitted?
The filing date of the NDIN is when the FDA receives a complete NDIN. An incomplete NDIN does not satisfy the notification requirement in Section 413(a)(2) of the FD&C Act. Therefore, if the dietary supplement is placed on the market, it will be deemed adulterated until the review process is complete. The FDA will contact the notifier with questions or requests for amendments during the review process.
When will the NDIN be posted publicly?
For 90 days after the filing date, the FDA will not disclose the content or existence of the notification. After 90 days, however, the notification will be publicly available on the NDIN docket on www.regulations.gov. As the public posting of the NDIN will exclude any trade secrets or confidential commercial information, notifiers should clearly identify any information they believe is a trade secret or confidential in a separate document that accompanies the NDIN.
NEXT STEPS
Although it has been eight years since the FDA issued guidance on the dietary supplement notification and review process, the recently released guidance indicates a renewed focus on this topic. Interested stakeholders are encouraged to take advantage of this opportunity to submit to the FDA any electronic or written comments they have regarding the final guidance or the remaining sections of the draft guidance that have yet to be finalized.
