FDA NDI guidance finalized for identity and safety evidence

FDA NDI guidance for identity and safety evidence

The FDA NDI guidance issued on October 19, 2026, gives final recommendations on identity and safety evidence for new dietary ingredient notifications (NDINs). It finalizes three sections of the 2016 revised draft and replaces the "comprehensive safety profile" with one "safety narrative" (FDA update). There is no compliance date.

The full title is "New Dietary Ingredient (NDI) Notifications and Related Issues; Identity and Safety Information About the NDI: Guidance for Industry" (FDA guidance page). The Federal Register notice of availability came out on October 20, 2026, as FR Doc. 2026-21453 under docket FDA-2025-D-6501 (Federal Register). Comments on the docket are accepted at any time.

What FDA finalized, and what is still draft

The new document stands alone. It finalizes Sections VI.A (identity of 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 safety conclusion) of the August 2016 revised draft (FR notice PDF). Section V of the 2016 draft, on procedures and timeframes, was already finalized in March 2024 (procedures guidance). The other, unfinalized sections remain draft under docket FDA-2011-D-0376 (2016 revised draft). FDA plans to prioritize finalizing the rest, and it gave no date.

What changed from the 2016 draft

FDA lists the changes in the notice itself (FR notice PDF). The main change: "we eliminated the references to a 'comprehensive safety profile' and, instead, recommend use of a single 'safety narrative' for all NDINs." The aim is to ease the burden of separate safety documents. FDA also clarified the narrative's contents, when more safety evidence is needed and which studies it recommends. Update templates that still call for a separate "comprehensive safety profile."

When the guidance applies

The guidance reflects FDA's current thinking from the day it was issued, and it "does not establish any rights for any person and is not binding on FDA or the public" (final guidance PDF). You can use another approach if it meets the statute and the regulations.

Those legal requirements did not change. The duty to notify comes from section 413 of the FD&C Act, codified at 21 U.S.C. 350b, and from 21 CFR 190.6.

New dietary ingredient definition and notification law

A new dietary ingredient is a dietary ingredient "not marketed in the United States before October 15, 1994" (21 U.S.C. 350b(d)). You don't need to notify if the supplement contains only dietary ingredients "present in the food supply as an article used for food in a form in which the food has not been chemically altered" (21 U.S.C. 350b(a)(1)).

Otherwise, there must be a history of use or other evidence of safety showing the NDI "will reasonably be expected to be safe" under the labeled conditions of use. The manufacturer or distributor must send FDA that information at least 75 days before the product enters interstate commerce (21 CFR 190.6(a)).

Under 21 CFR 190.6(b), the notification must include:

• the name and full address of the manufacturer or distributor
• the name of the NDI, with the Latin binomial (including the author) for a botanical
• a description of the supplement, with the NDI level and the conditions of use in the labeling (or ordinary conditions of use)
• the history of use or other evidence of safety, with citations, copies of published references and English translations of foreign-language material
• the signature of a designated person

The 75 days run from FDA's receipt of the notification. A substantive amendment gets a new filing date, restarting the clock. FDA keeps the NDIN confidential for 90 days after filing. It then makes it public, except for trade secrets and confidential commercial information (21 CFR 190.6(c)-(e)).

"FDA does not approve NDI notifications," the guidance says (final guidance PDF). And if FDA doesn't respond, that "does not constitute a finding" that the NDI is safe (21 CFR 190.6(f)). A supplement that needed an NDIN and didn't have one is deemed adulterated under section 402(f). Filing one does not cure inadequate safety evidence (final guidance). FDA's response letters include acknowledgment without objection, incomplete, objection and other regulatory issues. An incomplete NDIN does not satisfy the notification requirement in section 413(a)(2) (procedures guidance).

Identity information FDA recommends

The final guidance asks for more than 190.6 lists (final guidance PDF). Expect to give the trade name, a physical and chemical description, analytical verification of identity, batch-to-batch controls, impurities and contaminants, and the identity and level of the other ingredients.

Specifications should set out tests, acceptance criteria and analytical methods, ideally in a table. A chromatogram that just "matches the reference sample" is not specific enough. Known toxic components should carry a "less than" limit. On manufacturing, FDA wants enough detail to understand the process and in-process controls, with the focus on what affects identity and safety.

What else you provide depends on the ingredient:

• Chemical entities: name, formula, molecular weight, structure, CAS number and UNII, plus stereochemistry for isomers.
• Botanicals: Latin binomial with author citation, plant part, taxonomic identity testing, cultivation, origin and harvest details, a voucher specimen, and known adulterant species and toxins in related plants.
• Live microbials: strain identity, for example by whole genome sequencing.

The guidance also covers extracts and concentrates, metabolites, enzymes and fermentation products. Unless your NDIN restricts use, FDA assumes lifetime daily use by all age groups at the highest serving. That assumption drives the intake numbers in your safety case, so state the limits you intend.

Safety evidence and the safety narrative

The final guidance recommends one safety narrative: an objective evaluation that pulls the evidence together. Cover total daily intake, toxicity concerns (excipients included) and comparisons with related test articles. Explain the no-observed-adverse-effect level (NOAEL), acceptable daily intake (ADI) and margin-of-safety figures (final guidance PDF).

For history of use, FDA looks for consumption by large, genetically diverse populations with limited or no adverse events. Give intake data as the mean and the 90th percentile. Historical intake should be at or above your proposed intake. When history of use is the only basis, FDA "generally recommends 25 years of widespread use." A shorter period needs justification (final guidance PDF).

Other evidence fills the gaps that history of use leaves. The final guidance describes:

• a genetic toxicity battery of two or three tests
• a 90-day oral study when the existing evidence is insufficient
• reproductive and developmental evidence where use in pregnancy or lactation is possible
• chronic studies when the findings call for them

Human studies are not required by the Act. New approach methods are unlikely to be enough on their own, but they can fill gaps. Appendix A gives an illustrative testing table (final guidance PDF). The guidance also flags antibiotic resistance and toxins in live microbials, and it encourages early contact on nanomaterials.

The estimated daily intake (EDI) uses the maximum proposed daily intake. The margin of safety is the NOAEL divided by the EDI, or the historical safe intake divided by the EDI. The ADI is the NOAEL divided by the combined safety factors, and the EDI should not exceed the ADI. Read the final guidance for the safety-factor method.

Submitting an NDIN

FDA prefers electronic filing through its Centralized Online Submission Module, also called COSM (How to Submit NDINs). Paper notifications go to the Office of Dietary Supplement Programs (HFS-810), 5001 Campus Drive, College Park, MD 20740-3835, as an original plus two copies. General questions go to NDIN@fda.hhs.gov (NDI Notification Process). Pre-NDIN meeting requests go to NDITeam@fda.hhs.gov (procedures guidance).

RegAffairs AI provides a cited answer on the final NDI guidance.

Before you write your own, look at FDA's list of submitted 75-day premarket notifications. It runs from 1995 to the present, with links to the regulations.gov dockets.