As we previously reported in a March 2025 advisory, the Department of Health and Human Services (HHS) ordered the Food and Drug Administration (FDA) to explore formal rulemaking to revise the generally recognized as safe (GRAS) regulatory framework to eliminate the self-affirmed GRAS pathway. Yesterday, the FDA announced a proposed rule that, if finalized, would increase FDA oversight of substances in the human and animal food supply.
The proposed rule would amend 21 C.F.R. Parts 170 and 570 to require any person introducing a substance into interstate commerce under the GRAS provisions of the Federal Food, Drug, and Cosmetic Act to notify the FDA of the basis for their conclusion that the substance is GRAS under the conditions of its intended use, unless an exception applies. This includes both substances added directly to food and substances added indirectly (e.g., food contact substances migrating from packaging). HHS Secretary Robert F. Kennedy, Jr. characterized the proposed rule as an effort to “close the GRAS loophole once and for all” and restore federal visibility into substances entering the food supply.
Key Requirements
GRAS substances introduced into interstate commerce for use in food for the first time would be subject to mandatory FDA notification unless subject to an exception. The FDA intends to make the GRAS notices publicly available by publishing them in the GRAS notice inventory. Once the FDA issues a “no questions” letter, a notice may be relied on by others if the identity, manufacturing process, and conditions of use are not significantly different.
The proposed rule includes several exceptions that generally fall into two categories:
- Prior FDA review: Substances with uses addressed in an existing “no questions” letter, “threshold of regulation” exemption, effective food contact notification, or established FDA review process.
- Existing regulatory status: Substances already listed or affirmed as GRAS in FDA regulations or otherwise qualifying under longstanding safe-use provisions (e.g., Section 170.30(d) for natural biological ingredients consumed before 1958).
Despite eliminating the self-GRAS pathway, the proposed rule states that the proposed notification program generally “do[es] not establish a premarket review program for purportedly GRAS substances.” Companies may reach a GRAS conclusion about a new use of a substance and introduce the substance into interstate commerce before submitting a GRAS notice. However, noncompliance with the notification requirement would be a factor the FDA considers in prioritizing food substances for post-market review.
GRAS Substances Already on the Market: Proposed Streamlined Submission Pathway
Substances already in interstate commerce before the final rule’s effective date would be eligible for a time-limited streamlined submission pathway. Under this pathway, companies would not need to submit a full GRAS notice. Instead, they would submit identifying information about the substance, its conditions of use, and evidence that the substance was present in interstate commerce before the final rule’s effective date. The time-limited submission would be due within 12 months after the effective date.
The streamlined pathway would not be available if (1) the substance’s conditions of use were previously the subject of an insufficient basis letter; or (2) the FDA has already determined that the substance is not GRAS under the conditions of its intended use. For any substances submitted under this streamlined pathway, the FDA would post information about the substance on a public list, and any person could rely on that listing for the same conditions of use—unless the FDA later determines that a full GRAS notice or food additive petition must be submitted for that substance.
Timing Considerations
- If finalized, the proposed rule would take effect 60 days after publication in the Federal Register.
- Once effective, the rule has an 18-month compliance period.
- After a GRAS notice is submitted, the FDA would have 45 days to conduct an initial evaluation to determine whether the submission is adequate for filing.
- Once filed, the FDA would have 180 days to evaluate the GRAS notice, with the option to extend the evaluation period twice for 90 days each.
Next Steps for Industry
Food and beverage manufacturers, distributors, and ingredient suppliers that distribute food containing self-affirmed GRAS substances will be implicated by this rulemaking should the proposed rule become final. As initial next steps, regulated entities should consider:
- Taking an inventory of and assessing current ingredients to understand their regulatory status and evaluate safety data dossiers.
- Engaging with suppliers to discuss preparing GRAS notices or a submission through the time-limited pathway for FDA review or reformulating products to include only ingredients that have a suitable regulatory status, as needed.
- Participating in the public comment period to provide industry perspectives. Comments on the proposed rule are due December 9, 2026.
Our Food, Beverage & Agribusiness Team, which provides both regulatory and litigation services to our clients, will continue to monitor regulatory developments related to the GRAS pathway for human and animal food substances.
If you have any questions, or would like additional information, please contact one of the attorneys on our Food & Beverage team.
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