On October 19, 2026, the U.S. Food and Drug Administration (FDA) issued final guidance addressing the identity and safety information manufacturers and distributors should include in new dietary ingredient notifications (NDINs) for dietary supplements. The guidance provides more detailed recommendations on how companies can establish the identity of a new dietary ingredient (NDI), substantiate its safety, and explain the scientific basis for concluding that the ingredient is reasonably expected to be safe under its intended conditions of use.
The guidance finalizes three sections of FDA’s 2016 revised draft guidance, addressing ingredient identity, history of use or other evidence of safety, and the basis for safety conclusions. Although the guidance does not impose new legally binding requirements, it clarifies FDA’s expectations for the scientific evidence supporting NDIN submissions and may have important implications for companies developing or marketing supplements containing NDIs.
Under the Dietary Supplement Health and Education Act of 1994, manufacturers and distributors generally must submit an NDIN at least 75 days before introducing an NDI or a dietary supplement containing an NDI into interstate commerce, unless an applicable statutory exception applies. The notification must provide the basis for concluding that the ingredient will reasonably be expected to be safe under the conditions of use recommended in the supplement’s labeling.
Key Takeaways
- FDA provides more detailed expectations for ingredient identity. The guidance outlines the information FDA recommends including to adequately characterize an NDI, including ingredient names, specifications, composition, and manufacturing-related information. It provides additional recommendations for specific categories of ingredients, including botanicals, enzymes, metabolites, fermentation-derived ingredients, and live microbial ingredients. For these ingredients, FDA recommends information sufficient to establish their identity and distinguish them from potentially different substances. Companies should ensure that the ingredients described in their notifications are adequately characterized and correspond to the ingredients evaluated in supporting safety studies.
- A history of safe use should generally reflect at least 25 years of widespread consumption when relying solely on historical safety evidence. FDA recommends at least 25 years of widespread use when a company relies solely on historical consumption to establish safety. The agency also emphasizes that the number of consumers, frequency and levels of consumption, and characteristics of the population consuming the ingredient are important to establishing a meaningful history of safe use. A shorter history is not automatically insufficient, but companies should provide additional information demonstrating why the available evidence adequately supports safety. The guidance also identifies potentially useful documentation, including scientific literature, consumption surveys, and historical food production records.
- FDA clarifies when additional safety studies may be warranted. Where historical use is insufficient, FDA recommends supporting NDINs with other evidence of safety, which may include genetic toxicity testing, animal studies, human clinical studies, or other scientifically appropriate alternative testing methods. The guidance discusses appropriate study designs, testing methodologies, and the relevance of study findings to the proposed conditions of use. Importantly, FDA emphasizes that safety data involving a related ingredient may require additional justification to establish that the results apply to the specific NDI being marketed.
- FDA recommends consolidating safety information into a single “safety narrative.” In its Federal Register notice, FDA explained that it eliminated references to a separate “comprehensive safety profile” to reduce duplicative documentation and instead recommends a single safety narrative for all NDINs. The narrative should objectively evaluate the available safety evidence and explain how that evidence supports a reasonable expectation of safety. FDA recommends addressing estimated daily intake, potential toxicity concerns, relevant safety margins, and the effects of other ingredients or components on the safety of the finished supplement. The change may streamline submission preparation, but companies must still provide a scientifically supported explanation of their safety conclusions.
Practical Considerations
The final guidance highlights several aspects of NDIN preparation that dietary supplement manufacturers and distributors may wish to evaluate:
- Review existing and planned NDIN submissions. Companies developing supplements containing NDIs should evaluate whether their ingredient characterization, specifications, and supporting safety information align with FDA’s finalized recommendations, particularly for ingredients involving complex manufacturing processes or novel formulations.
- Assess the adequacy of historical safety evidence. Companies relying on traditional use or prior human consumption should determine whether available documentation sufficiently establishes the duration, extent, and conditions of use. Where historical evidence is limited, additional safety data or scientific justification may be warranted.
- Evaluate whether additional studies are needed. Companies should assess whether existing toxicological and clinical evidence adequately supports the proposed ingredient, dosage, and target population. Where studies involve related but different substances, companies should be prepared to explain the relevance of those findings to the NDI.
- Update safety narratives and supporting documentation. Companies preparing NDINs should consider organizing safety evidence into a consolidated narrative that addresses the proposed conditions of use, explains any data gaps, and provides a clear scientific rationale for the conclusion of safety. This may be particularly important for products containing multiple NDIs or other ingredients that could affect the product’s overall safety profile.
Looking Ahead
The final guidance is part of FDA’s ongoing effort to finalize discrete portions of its broader 2016 revised draft guidance on NDINs. FDA has indicated that it intends to finalize additional sections as it completes its review, meaning further clarification of the NDIN framework may follow.
Although the guidance is nonbinding and does not alter the statutory notification requirements, it provides a more detailed framework for understanding how FDA evaluates identity and safety information submitted in NDINs. Companies should consider incorporating these recommendations into their ingredient development and notification strategies to address potential deficiencies before submission.
MoFo’s Food Regulatory team will continue monitoring FDA’s implementation of the guidance and further developments concerning NDIN requirements. If you have questions about how the finalized guidance may affect your dietary supplement products or notification strategies, please contact the authors.