FDA Final NDI Guidance on Identity and Safety Narratives

The U.S. Food and Drug Administration (FDA) on October 19, 2026 finalized the part of its new dietary ingredient guidance that tells supplement companies what identity and safety information belongs in a premarket notification. The final guidance, titled “New Dietary Ingredient (NDI) Notifications and Related Issues; Identity and Safety Information About the NDI,” was announced in the Federal Register on October 20 under docket FDA-2025-D-6501.

The document turns three sections of a 2016 revised draft into final agency advice. For brands that sell newer botanicals, extracts, probiotics and other novel ingredients online, it is FDA’s most detailed statement so far of the evidence it wants to see before such a product reaches shoppers.

What a new dietary ingredient notification is

Under section 413 of the Federal Food, Drug, and Cosmetic Act, a new dietary ingredient (NDI) is a dietary ingredient that was not marketed in the United States before October 15, 1994. The maker or distributor of an NDI, or of a supplement containing one, must file a new dietary ingredient notification (NDIN) with FDA at least 75 days before the product enters interstate commerce. The exception is an ingredient that has been present in the food supply as an article used for food without being chemically altered.

The notification has to lay out why the company concluded its product will reasonably be expected to be safe. FDA repeats in the guidance that it does not approve these filings, and that “no FDA approval is required or issued at any point in this process.” A supplement that needed a notification and never had one is deemed adulterated under the statute.

Which parts of the 2016 draft are now final

FDA’s constituent update says the guidance finalizes Section VI.A (identity information about the NDI and the dietary supplement), Section VI.B (history of use or other evidence of safety) and Section VI.C (summary of the basis for the conclusion of safety). The agency says finishing the draft one piece at a time responds to public comments, and it has marked up the 2016 document to show which language is still in draft.

Not everyone sees the approach as tidy. Sidley Austin, in a client note, called the piecemeal finalization “highly unusual” and said it leaves the most contentious issues from the 2016 draft unresolved.

One safety narrative replaces two safety profiles

The main format change concerns how a company presents its safety case. According to the Federal Register notice, FDA removed references to a “comprehensive safety profile” and now recommends a single “safety narrative” for every notification, a move it says will “alleviate the burden of submitting separate documents.” That narrative should estimate total daily intake, interpret the history of use and any studies, describe toxicity concerns for vulnerable groups and explain the margin of safety.

How FDA wants history of use documented

When a notification rests on history of use alone, FDA “generally recommends 25 years of widespread use” as the minimum and asks for added support when the record is shorter. The guidance says the number of people who consumed an ingredient and how often they took it count at least as much as the number of years. The historical intake should also be the same as or higher than the dose the new supplement would deliver.

FDA’s list of acceptable records is notably down to earth. Alongside peer-reviewed studies and the National Health and Nutrition Examination Survey, it names cookbooks and published recipes, old advertisements, sales records, commercial invoices, product labels and chromatography or mass spectrometry results. Use in traditional medicine can help, but the agency warns that composition, dose and the people using a remedy often differ from a modern supplement, so a notifier should fill those gaps with other evidence and disclose traditional limits such as a one-week maximum.

Identity details now expected in a notification

The identity section asks for far more than an ingredient name. Botanicals still need the Latin binomial with the author citation, as the 1997 regulation at 21 CFR 190.6 requires. The guidance adds specific questions for salts, isomers, covalently modified derivatives, metabolites, enzymes, fermentation products and live microbial ingredients, and asks how a company rules out toxins found in related plants or microorganisms.

Sidley Austin pointed out that the manufacturing information FDA requests, including extraction solvents, drying steps, standardization and purification, would put the agency in a position to judge whether a substance has been chemically altered. That question often decides whether an ingredient needs a notification in the first place.

What the guidance means for online supplement sellers

The guidance speaks to companies that file notifications, but private-label brands and online retailers inherit the result. A brand buying a newer ingredient from a supplier can look it up on FDA’s list of submitted 75-day premarket notifications, which is searchable by ingredient, firm and dates and links each entry to its file on Regulations.gov. A listing only shows that FDA reviewed a filing. The agency’s response letter in that file is what records its view.

A notification also does not settle whether FDA treats a product as an unapproved drug, the issue at the center of EC4IM’s report on FDA warning letters to research-use-only peptide sellers.

The records FDA names have uses beyond the agency. A mushroom or botanical brand opening a supplement account with a high-risk acquirer through Organic Payment Gateways may face underwriting questions about the ingredients on its labels, and pre-1994 invoices, old labels or a supplier’s notification number are the same kind of proof the guidance describes.

Where the final guidance leaves supplement brands

FDA’s October guidance creates no new legal duty, and the agency says companies may take another approach that satisfies the statute and regulations. It does fix, in final form, how FDA wants identity, history of use and safety evidence presented, with one safety narrative per filing, 25 years of widespread use as the usual floor when history stands alone, and detailed manufacturing data for extracts and novel forms. Brands that sell ingredients introduced after 1994 now have a settled yardstick for their suppliers’ filings while FDA works through the rest of the 2016 draft. Comments on the guidance can be submitted at any time on Regulations.gov under docket FDA-2025-D-6501.

FDA Finalizes the Identity and Safety Sections of Its New Dietary Ingredient Guidance