FDA Finalizes Guidance on Identity and Safety Information for New Dietary Ingredient Notifications

On October 19, 2026, FDA announced the release of a final guidance addressing the identity and safety information that manufacturers and distributors should include in new dietary ingredient notifications (NDINs). The guidance provides a detailed roadmap for preparing the portion of an NDIN intended to establish that a dietary supplement containing a new dietary ingredient (NDI) will reasonably be expected to be safe under its proposed conditions of use.

Industry stakeholders have long sought more practical guidance regarding the identity and safety information necessary to support a successful NDIN. The new guidance contains detailed recommendations concerning ingredient characterization, manufacturing information, history of use, toxicology and clinical evidence, safety calculations, and the organization of the notifier’s safety narrative.

FDA first issued a draft NDI guidance in 2011 and issued a revised draft in 2016. Since then, FDA has finalized discrete portions of the 2016 draft guidance. In March 2024, FDA issued final guidance focused primarily on the procedures and timeframes for submitting and reviewing NDINs. FDA also issued draft guidance in April 2024 regarding NDIN Master Files. This new final guidance finalizes 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of Use or Other Evidence of Safety,” and VI.C, “Summary of the Basis for Your Conclusion of Safety,” of the 2016 draft guidance. Other portions of the 2016 draft guidance remain in draft form.

The guidance addresses a range of issues in detail, several of which we highlight below:

• Identity and manufacturing information. FDA recommends that an NDIN provide sufficient information to establish the identity of the NDI, including the ingredient’s physical and chemical characteristics, relevant marker substances, batch to batch standardization, impurities and contaminants, relevant manufacturing steps, and specifications. FDA also provides example specification tables identifying tests, acceptance criteria, and analytical methods.
• A single, integrated safety narrative. FDA recommends that each NDIN contain a “safety narrative” that objectively evaluates the history of safe use and other available safety evidence and explains why that evidence supports the safety of the notified article under the proposed conditions of use. FDA replaced references in the draft guidance to a separate “comprehensive safety profile” with a single safety narrative to help alleviate the burden of submitting separate documents regarding the safety data submitted in an NDIN.
• History of safe use. FDA describes the information it expects regarding dose and total daily intake, duration and frequency of consumption, the consuming population, and the relationship between the historically consumed article and the notified ingredient. If a notifier is relying on history of use alone, FDA generally recommends at least 25 years of widespread use, although the guidance recognizes that additional evidence could help demonstrate that a shorter timeframe is sufficient. When supported by appropriate evidence, a history of use in traditional medicine may also help establish a reasonable expectation of safety.
• Other evidence of safety. The guidance discusses genetic toxicity testing, alternative methods such as in vitro biochemical or cell-based assays and in silico modeling, preclinical animal studies, and human clinical studies, including tolerability and absorption, distribution, metabolism, and excretion studies. Although FDA does not explicitly require human clinical studies, FDA may recommend them where existing history of safe use data, safety data, and data on population exposure do not provide a sufficient basis to conclude that the article will reasonably be expected to be safe for its intended use. FDA emphasizes that the appropriate supporting evidence will depend on the nature of the specific data gap.
• Safety calculations. FDA recommends that safety narratives address relevant safety endpoints, identify and justify the selected no observed adverse effect level in animal studies, and include appropriate margin of safety and acceptable daily intake calculations.
• Bridging and data gap analyses. Where the notified ingredient and test article differ, FDA recommends a qualitative and quantitative comparison in the safety narrative. FDA notes that the more different the composition is between the test article and the notified article, the more difficult it will be to establish that the study supports the notified article’s safety.
• Information for particular ingredient types. The guidance provides additional recommendations for specific types of ingredients, including configurational isomers, salts, covalently modified derivatives, botanicals, extracts and concentrates, metabolites, enzymes, fermentation derived ingredients, and live microbials. For example, for fermentation derived ingredients, FDA recommends discussing the safety of the fermenting organism for use in food production.
• Emerging technologies. FDA provides additional recommendations for live microbial dietary ingredients and NDIs that contain nanomaterials or otherwise involve nanotechnology. For nanotechnology modified ingredients, FDA cautions that safety data for a conventional form may not adequately support the modified form. FDA recommends contacting the Agency before submitting an NDIN involving nanomaterials or nanotechnology.

The guidance also comes as FDA is separately reconsidering its oversight of substances that are generally recognized as safe (GRAS). In August, FDA proposed requiring the submission of GRAS notices for certain uses of substances in human and animal food. In the dietary supplement context, an ingredient’s prior presence in the food supply, including use as a GRAS substance, may be relevant to determining whether an NDIN is required. Although the GRAS proposal and the final NDIN guidance address distinct regulatory frameworks, both reflect FDA’s focus on the evidence used to establish an ingredient’s identity, history of use, and safety. Taken together, these actions signal increased FDA attention to the regulatory status and safety substantiation of novel ingredients. As a reminder, comments on FDA’s proposed GRAS rule are due December 9, 2026.

If you have any questions concerning the material discussed in this client alert, please contact the following members of our Food, Beverage, and Dietary Supplements practice.