On October 19, the U.S. Food and Drug Administration (FDA) finalized guidance on the identity and safety information that should go into new dietary ingredient (NDI) notifications (NDINs). This finalizes Section VI of FDA's broader draft guidance; the other portions are still in draft. Unless an exception applies, a manufacturer or distributor must submit an NDIN at least 75 days before marketing a supplement containing an NDI. The NDIN must show that the supplement will reasonably be expected to be safe (FD&C Act § 413(a)). The guidance is nonbinding. Overall, it gives companies more flexibility on safety evidence and asks for more information on identity and manufacturing. For a detailed discussion of each change, read our full alert.
Key Changes
- Targeted testing. FDA no longer lists multi-generation reproductive, teratology, or chronic-toxicity/carcinogenicity studies as standard studies. Which studies are appropriate now depends on the specific gaps in the evidence, and companies should explain the studies they chose and why others were unnecessary. For repeat-dose animal studies, FDA now prefers oral gavage. Feeding and drinking-water studies remain acceptable if actual intake is documented.
- Alternatives to animal testing. FDA supports "new approach methods," such as in vitro and in silico testing, when they produce reliable evidence. FDA cautions that these methods are unlikely to establish safety on their own.
- History of safe use. Twenty-five years of use remains the general benchmark when a company relies on history alone. A shorter period may be enough if other information supports it. Evidence from traditional medicine now needs to address only the gaps between traditional use and the proposed use.
- Single safety narrative. One comprehensive narrative replaces the separate NDI profile and finished-product narrative. Companies may select one NOAEL, with an explanation, to use in their safety calculations.
- Identity and manufacturing. FDA now expects more analytical data supporting identity and specifications, details on starting materials for extracts, and documentation of manufacturing controls. On degradants, companies may identify expected degradants and support their safety, rather than showing that none form.
What Companies Should Do Now
- Review the guidance before commissioning new studies. Existing literature, history of use, or a targeted testing program may be enough.
- Define the conditions of use precisely and keep them consistent with the labeling. Unless the NDIN states restrictions, FDA assumes daily lifetime use by all populations at the highest serving size.
- Get sufficient analytical and manufacturing information from suppliers early.
- Check whether marketed products contain NDIs for which a required NDIN was never submitted. Enforcement may increase now that the guidance is final.
For a more detailed analysis of the final guidance, see our full alert, FDA Finalizes NDIN Guidance on Identity and Safety Information: What Industry Needs to Know. If you have questions or would like help evaluating whether an NDIN is required, developing a safety strategy, or preparing an NDIN, Venable's FDA team is here to help.