• On October 19, 2026, FDA released a final guidance document titled “New Dietary Ingredient (NDI) Notifications and Related Issues; Identity and Safety Information About the NDI” (Safety Guidance). The Safety Guidance finalizes various sections of the general revised draft guidance on NDI Notifications (General Guidance) (updated in October 2026 to reflect the Safety Guidance).
  • The Safety Guidance is in a question-and-answer format and details the information that manufacturers and distributors should provide in a new dietary ingredient notification (NDIN) and specifically finalizes the following sections of the General Guidance:
    • General Guidance Section VI.A, Identity Information about the NDI and the Dietary Supplement:
      • Finalized as Section IV in the Safety Guidance, this section details the type of identity information that should be included in an NDIN, including the name of the ingredient and its specifications. The Safety Guidance provides further information on what is needed to identify certain ingredients such as salts, covalently modified derivatives of dietary ingredients, botanicals, metabolites, enzymes, ingredients produced by fermentation, and live microbial ingredients.
    • General Guidance Section VI.B, History of Use or Other Evidence of Safety:
      • Finalized in Sections VI and VII in the Safety Guidance, these sections describe the type of information needed to demonstrate an NDI’s safe history of use. FDA recommends a period of at least 25 years of widespread use when relying on history of safe use alone. The Safety Guidance recommends citing to published articles, providing examples of sufficient documentation to establish history of safe use. Other evidence of safety could include things like genetic toxicity tests, animal studies, and human studies. This type of evidence is needed when there is not sufficient history of safe use to support the NDIN. The Safety Guidance further details characteristics of a quality study.
    • General Guidance Section VI.C, Summary of the Basis for Your Conclusion of Safety:
      • Finalized in Section V in the Safety Guidance, this section explains what safety information is required, including what should be included in the “safety narrative.” The safety narrative should contain an “objective evaluation of the history of safe use or other evidence of safety, along with an explanation of how the evidence of safety provides a basis” to conclude the NDI is reasonably expected to be safe. It should include an estimated daily intake of the substance, as well as describe the function of each non-dietary ingredient.
  • Under the Dietary Supplement Health and Education Act of 1994, dietary supplement manufacturers generally do not need FDA premarket approval before marketing a product. However, unless a limited exception applies, manufacturers must submit an NDIN at least 75 days before marketing a dietary supplement containing a dietary ingredient that was not marketed in the United States before October 15, 1994. The notification must contain information supporting the manufacturer’s conclusion that the ingredient can reasonably be expected to be safe under the recommended conditions of use.
  • FDA issued its last major revision to the General Guidance in 2016. Since then, industry and stakeholders have submitted nearly 2,000 public comments, and FDA has issued a series of guidance documents addressing discrete aspects of the NDIN process, including notification procedures and master files. This new Safety Guidance continues the Agency’s phased approach of finalizing discrete sections of the General Guidance.
  • Keller and Heckman will continue to monitor developments related to FDA’s evolving NDIN framework and will provide updates as additional guidance and policy developments become available.