FDA New Dietary Ingredient Guidance Status

The law requires an NDI notification to show, with the evidence behind it, that a dietary supplement containing the new dietary ingredient "will reasonably be expected to be safe" when used under the conditions recommended or suggested in its labeling. That evidence can be a "history of use or other evidence of safety" ^[5]. Neither the statute nor the regulation lists required study types. FDA's detailed recommendations on what evidence to submit are in the October 2026 final guidance, which I couldn't open.

What the statute requires (FD&C Act section 413, 21 U.S.C. 350b(a)(2))

• There must be a history of use or other evidence of safety showing that the ingredient, used under the labeled conditions, will reasonably be expected to be safe ^[5].
• At least 75 days before the product is introduced into interstate commerce, the manufacturer or distributor must give FDA "information, including any citation to published articles, which is the basis on which the manufacturer or distributor has concluded" that the supplement will reasonably be expected to be safe ^[5].
• When no notification is needed: the supplement contains only dietary ingredients that have been in the food supply as an article used for food, in a form that has not been chemically altered (350b(a)(1)) ^[5].
• Which ingredients count as "new": one that was not marketed in the US before October 15, 1994 (350b(d)) ^[5].
• Anabolic steroids: if FDA finds a notification inadequate because the article may be, or may contain, an anabolic steroid or an analogue of one, FDA "shall notify" the DEA (350b(c)(1)) ^[5].
• Optional petition route: anyone may petition for an order setting the conditions under which an NDI will reasonably be expected to be safe. FDA must decide within 180 days (350b(b)) ^[5].

What the regulation says the notification "shall include" (21 CFR 190.6(b), eCFR, up to date as of 10/22/2026)

These items set the context the safety case is judged against:

1. The name and complete address of the manufacturer or distributor.
2. The name of the NDI, including the Latin binomial name (with the author) of any herb or other botanical.
3. A description of the supplement(s) containing the NDI, including:
   • (i) the level of the NDI in the supplement;
   • (ii) the conditions of use recommended or suggested in the labeling, or, if the labeling gives none, the ordinary conditions of use.
4. The safety evidence itself: the history of use or other evidence of safety, including any citations to published articles or other evidence that the safety conclusion rests on. Rules on supporting material:
   • Published references "shall be accompanied by reprints or photostatic copies."
   • Any material in a foreign language "shall be accompanied by an accurate and complete English translation."
5. The signature of the person designated by the manufacturer or distributor.

Procedure under 190.6

• Filing date and 75-day wait: the date FDA receives the notification is the filing date, and the product must not enter interstate commerce for 75 days after it (190.6(c)).
• Amendments: if you send a substantive amendment, FDA assigns a new filing date, which restarts the 75 days (190.6(d)).
• Disclosure: FDA keeps the notification confidential for 90 days after filing. After that it goes on public display, except trade secrets and confidential commercial information (190.6(e)).
• No response is not approval: if FDA does not respond, that is not a finding that the NDI is safe or the product is not adulterated (190.6(f)).

FDA's recommendations

• The October 2026 final guidance finalises three sections of the 2016 revised draft:
  • VI.A, identity information;
  • VI.B, history of use or other evidence of safety;
  • VI.C, summary of the basis for your conclusion of safety.
• That guidance is where FDA explains which study types it recommends and when. I couldn't open the guidance PDF (https://www.fda.gov/media/195770/download) or FDA's "Important Aspects of the NDIN Process" (https://www.fda.gov/media/185995/download), so I can't summarise their study recommendations here.

Approach: I read 21 U.S.C. 350b in the U.S. Code edition of the FD&C Act, and 21 CFR 190.6 on eCFR because Part 190 is not in the datasets. The FD&C Act text I searched is the 2023 U.S. Code edition.

Sources:

• eCFR: 21 CFR 190.6, Requirement for premarket notification
• FDA: Guidance for Industry: NDI Notifications and Related Issues; Identity and Safety Information About the NDI

FDA's notice in the Federal Register (FR Doc. 2026-21453, published October 20, 2026) lists four changes from the 2016 revised draft. The biggest is that the "comprehensive safety profile" is gone, and FDA now recommends one "safety narrative" for every NDI notification.

The changes, in FDA's words

1. It's now a separate document. The final guidance "finalizes in a stand-alone document the identity and safety recommendations" that were in Sections VI.A ("Identity Information about the NDI and the Dietary Supplement"), VI.B ("History of Use or Other Evidence of Safety") and VI.C ("Summary of the Basis for Your Conclusion of Safety") of the 2016 draft. FDA's announcement says that finalising single sections this way "is responsive to public comments received on that guidance and is intended to facilitate ease of use."
2. One safety narrative replaces the comprehensive safety profile. "To help alleviate the burden of submitting separate documents regarding the safety data submitted in an NDIN, we eliminated the references to a 'comprehensive safety profile' and, instead, recommend use of a single 'safety narrative' for all NDINs."
3. More detail in three areas. FDA "made changes to provide additional clarity and description regarding":
   • what the safety narrative should contain;
   • when additional evidence of safety should be submitted;
   • what types of studies are recommended to support an NDIN.
4. Wording. The guidance also "contains editorial changes to improve clarity."

What stays the same

• The rest of the 2016 draft is still draft. FDA has marked up the 2016 revised draft to show which parts are final and which are still draft.
• The legal basis is unchanged. The information collections are still those in 21 CFR 190.6, approved under OMB control number 0910-0330.
• Status of the guidance. It is not binding, and you may use another approach if it meets the statute and regulations.

What this doesn't tell you: the notice describes the changes only in general terms. It doesn't give the new narrative contents or the study recommendations themselves. Those are in the guidance text, which I couldn't open last time (https://www.fda.gov/media/195770/download). So I can't tell you which recommendations were added, removed or reworded.

Approach: I searched FDA's Human Foods Program guidance catalogue, which lists the guidance titles but doesn't describe what changed. I also searched the FDA Federal Register records I can query, which don't yet include this notice. So I read the notice of availability and FDA's announcement directly on the official sites.

Sources:

• Federal Register notice of availability, FR Doc. 2026-21453 (public inspection PDF)
• Federal Register: NDI Notifications and Related Issues; Identity and Safety Information About the NDI
• FDA announcement: FDA Issues Guidance on Identity and Safety Information for New Dietary Ingredient Notifications