FDA proposes mandatory GRAS notifications in major overhaul of US food ingredient oversight

The US Food and Drug Administration has proposed requiring companies to notify the agency when they rely on a conclusion that a substance is generally recognized as safe (GRAS), in a major overhaul of the system governing ingredients used in human and animal food. The proposal, scheduled for publication in the Federal Register on August 11, would replace the current voluntary notification framework with a mandatory system, subject to a series of exceptions.

• FDA proposed replacing voluntary GRAS notifications with mandatory submissions for companies introducing substances into interstate commerce on the basis of a GRAS conclusion.
• The proposal created exceptions for certain previously reviewed substances and established FDA processes, including its consultation pathway for foods produced from cultured animal cells.
• Companies with qualifying substances already on the market would have access to a one-year streamlined submission window, while the proposed mandatory requirements would carry an 18-month compliance period.

Under existing US regulations, a company can conclude independently that the intended use of a food substance is GRAS and place it on the market without submitting that conclusion to FDA. Companies can voluntarily file a GRAS notice containing the scientific evidence supporting their conclusion, but notification is not currently required.

FDA's proposal would change that. Any person introducing a substance into interstate commerce under the GRAS provision of the Federal Food, Drug, and Cosmetic Act would generally have to notify the agency of the basis for concluding that the substance was GRAS under its intended conditions of use. The requirement would cover substances already present in the food supply as well as substances being marketed for food use for the first time.

The change could be particularly significant for developers of novel food ingredients, including ingredients produced through fermentation and other emerging food technologies, where GRAS conclusions have become an important route to the US market.

Importantly, however, FDA was not proposing to turn GRAS notification into a conventional premarket approval process. A substance that legitimately qualifies as GRAS under its intended conditions of use remains exempt from food additive premarket review and approval. Companies would also retain the ability to reach their own GRAS conclusions. The principal change is that, in most circumstances, those conclusions could no longer remain solely within the company: they would have to be submitted to FDA.

FDA argued that the voluntary system had left significant gaps in its knowledge of substances entering the food supply.

The agency explained that nearly 30 years of experience with voluntary notification had shown that it did not always know what substances companies were marketing on the basis of independent GRAS conclusions. As of March 25, 2025, FDA's Human Foods Program had filed more than 1,200 GRAS notices, but those represented only substances companies had chosen to bring to the agency.

FDA maintained that those gaps had sometimes prevented early engagement with companies over new food substances and hampered its ability to carry out its food safety responsibilities. The agency also pointed to an increasingly diverse food supply driven by changes in consumer demand, manufacturing and ingredient development.

Mandatory notification would give FDA and the public considerably greater visibility into the ingredients entering US foods. Filed GRAS information would be added to FDA's public GRAS Notice Inventory, with the agency expecting information to become publicly accessible within weeks of filing.

The system would also give FDA an opportunity to determine whether the scientific evidence actually supported a GRAS conclusion or whether a substance instead constituted a food additive requiring premarket approval.

FDA stressed that an independent GRAS conclusion – including claims that a company had independently 'certified' a substance as GRAS – did not itself establish that the substance legally qualified as GRAS. The agency could determine from the evidence that a substance was not GRAS or constituted an unapproved food additive.

Under the proposed procedure, FDA would have 45 days after receiving a submission to conduct its initial evaluation and decide whether to file it as a GRAS notice. Once filed, FDA would normally respond within 180 days, although the agency could extend that period by 90 days on as many as two occasions where necessary.

That distinction matters for companies planning commercialization. Filing the notice would satisfy the proposed notification requirement; companies would not necessarily have to wait for FDA's final response before complying with the notification obligation.

FDA could ultimately issue a 'no questions' letter, conclude that the notice did not provide a sufficient basis for GRAS status, or cease its evaluation at the notifier's request. Under the proposal, if FDA ceased evaluating a notice, the mandatory notification requirement would no longer be considered met.

The proposal also established several exceptions intended to prevent companies from having to duplicate regulatory work FDA had already undertaken.

An existing FDA "no questions" letter covering the substance and its intended conditions of use would qualify for an exception. Substances already listed or affirmed as GRAS under applicable regulations would also be excluded, as would qualifying substances covered by the proposed threshold-of-regulation process or an effective Food Contact Notification.

One of the most important provisions for the cell-cultivated food sector concerned FDA's existing consultation system for foods made from cultured animal cells.

FDA proposed an exception where the agency had already considered a substance's intended use through an established process designed to evaluate the possible presence of unapproved food additives and its publicly available documentation did not recommend or otherwise identify the need for a GRAS notice.

The agency specifically identified its Animal Cell Culture Consultations, alongside its biotechnology consultation processes for foods from new plant varieties, as qualifying established processes.

During an Animal Cell Culture Consultation, FDA already considers whether a food might contain a substance requiring separate review under the food additive or color additive provisions of federal law. If that process concludes without FDA identifying the need for a separate GRAS notice, the proposed rule would not require another GRAS submission for the particular use reviewed by the agency.

The exception is significant because it means the overhaul would not automatically add another regulatory submission to the established FDA pathway for cell-cultivated meat and seafood.

It is narrower than a blanket exemption for cell-cultivated foods, however. The exception depends on FDA having reviewed the particular intended use through the established consultation process and its documentation not identifying the need for separate GRAS evaluation. If FDA determined during consultation that a substance required review through another regulatory program, that route would still have to be followed.

For precision fermentation and other novel ingredient companies relying on GRAS, the practical effect could be more direct. The proposal does not identify precision fermentation as a separate regulatory category or provide it with a technology-specific exemption. A company introducing a qualifying fermentation-derived substance under an independent GRAS conclusion would therefore fall within the general mandatory notification framework unless one of the proposed exceptions applied.

Companies with substances already on the market would receive a transitional route.

FDA proposed a time-limited pathway allowing certain substances introduced into interstate commerce before the effective date of a final rule under an independent GRAS conclusion to be registered through a streamlined submission rather than immediately requiring a complete GRAS notice.

Companies using that route would have to provide information including the substance's name, its intended conditions of use, the foods in which it was used or contacted, use levels and purpose, and evidence showing that it was in interstate commerce before the final rule's effective date.

Inclusion on FDA's resulting public list would not amount to an agency determination that the substance was GRAS. FDA could subsequently determine that a full GRAS notice or food additive petition was required.

The streamlined option would be available for one year following the effective date of a final rule. FDA proposed making any eventual final rule effective 60 days after its publication, while the mandatory notification provisions would have a compliance date 18 months after that effective date.

The scale of the transition could be substantial. In its paperwork analysis, FDA estimated 967 respondents associated with independent GRAS conclusions for human food and calculated that approximately 2,418 streamlined submissions could result from those respondents. It estimated another 155 submissions associated with animal food. FDA assumed that preparing a streamlined submission would take approximately 32 hours, compared with an estimated 180 hours for a GRAS notice.

FDA acknowledged that the wider proposal could impose significant costs, particularly on smaller businesses. Its regulatory analysis concluded that the economic impact could exceed 3% of annual revenue for small entities and therefore have a significant economic impact on a substantial number of them.

The agency estimated the present value of the proposal's costs at approximately US$89.6 million over 10 years at a 3% discount rate, with a range of US$34.9 million to US$210 million. Annualized costs were estimated at approximately US$10.5 million under the same discount rate.

FDA also acknowledged potential commercial consequences if mandatory submissions exposed weaknesses in existing GRAS conclusions. The agency noted that its review could result in an "insufficient basis" determination for a substance used in certain products, potentially transferring market share and revenue toward competing products using different ingredients. FDA did not attempt to quantify those effects because it could not determine which substances might ultimately receive such a response.

The proposal would also increase transparency around the scientific evidence underpinning GRAS conclusions. Companies claiming that safety-related information in a notice was exempt from disclosure under the Freedom of Information Act would have to identify it when submitting the notice. For non-public safety information supporting a GRAS conclusion, the notifier would also have to explain how general recognition of safety could exist when qualified experts did not have access to that information.

FDA has invited comments not only on the proposed rule itself but on alternatives that could reduce the regulatory burden while still increasing transparency and helping the agency identify potentially unsafe food substances. One example raised by FDA was whether streamlined submissions could be permitted more broadly for substances purported to be GRAS.

The proposal remains just that - a proposal. The mandatory system will not take effect unless FDA completes the rulemaking and publishes a final rule, and the information collection requirements will additionally require approval from the Office of Management and Budget.

Comments are due 120 days after publication of the proposal in the Federal Register under docket FDA-2025-N-3262.

For companies developing new proteins and ingredients for the US market, the proposal would nevertheless represent a substantial change in how GRAS is used. Independent GRAS conclusions would remain possible, but the ability to rely on them without telling FDA would, with limited exceptions, disappear.

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