The proposed FDA GRAS rule is out for a 120-day comment period: what will change if the rule is adopted

FDA has proposed a significant change to the Generally Recognized as Safe (GRAS) framework for substances used in human and animal food. Under the proposed FDA rule, companies introducing certain substances to the US market on the basis of a GRAS conclusion would be required to notify the FDA and provide supporting information for that conclusion.

At present, manufacturers may independently determine that a substance is GRAS under its intended conditions of use without notifying the FDA, a process commonly referred to as a self-GRAS conclusion. The proposed rule would replace the current voluntary notification system with a mandatory notification programme, subject to certain exceptions.

See also our previous blogs and webinar for more information.

Proposed mandatory GRAS notification: what does it mean?

The mandatory system would authorise FDA to review substances on the market, including new and existing substances introduced into food and feed that are purportedly GRAS under the conditions of their intended use, and to assess whether these substances are not GRAS but instead constitute food additive uses that require a food additive petition to be marketed lawfully.

FDA would establish procedures to conduct an initial evaluation of the GRAS submission before determining whether to file it as a GRAS notice. FDA is proposing that this initial evaluation would be completed within 45 days.

During this preliminary assessment to determine whether the submission is adequate to file, FDA would not evaluate the GRAS status of the substance under its intended conditions of use, and the filing of a GRAS notice would not mean that the substance that is the subject of the GRAS notice is GRAS under its intended conditions of use.

Within two days following the 45-day period, FDA would send a letter setting out its decision to file or not to file the submission as a GRAS notice. FDA also proposes to clarify that it may contact a notifier with questions related to the notice, including questions about the data and information used to support a GRAS conclusion, during FDA’s evaluation of a GRAS notice. Currently, the evaluation period is 180 days from filing, plus an additional 90 days if needed. In its proposal, FDA would add a second 90-day extension period, if necessary. The notifier would be informed in due time.

If FDA agrees with the GRAS conclusion, it would issue a “no questions letter” in response to a GRAS notice, as it does currently. The letter would state that, based on the information provided by the notifier, as well as other information available to FDA, FDA has no questions at that time regarding the notifier’s conclusion that the notified substance is GRAS under its intended conditions of use. FDA also proposes to include language clarifying that a no questions letter is not an affirmation by FDA that the notified substance is GRAS under its intended conditions of use. GRAS notices would continue to be published on FDA’s website, as they are currently.

Time-limited option for self-GRAS food substances: what is it?

For self-GRAS substances currently on the US market, FDA proposes a pathway for submitting certain information during a time-limited option. Companies with self-GRAS substances may choose to participate in this time-limited option to qualify for an exception from the GRAS notice submission requirement.

FDA proposes this exception because it recognises that many companies have relied on marketing substances based on an independent conclusion of GRAS status. FDA therefore offers this alternative to submitting a GRAS notice only for substances already in US interstate commerce. In addition, requiring GRAS notices for all such uses of substances would likely overburden FDA’s administrative resources for evaluating and responding to GRAS notices.

FDA proposes a one-year deadline to make these submissions.

What would such a submission be required to contain?

Food-GRAS:

• the name and address of the submitter, so that FDA can ask questions about the submission
• the name of the substance, using an appropriately descriptive term
• the conditions of intended use of the substance, including the foods in which the substance is used, the levels of use and the purposes for which the substance is used
• evidence that the substance was present under its intended conditions of use in US commerce before the effective date of the final rule resulting from the proposed FDA rule
• a GRAS notice file number, if FDA sent a “cease to evaluate” letter in response to the submitter’s previous GRAS notice for the same intended conditions of use of the substance

Feed-GRAS:

• the name and address of the submitter, so that FDA can ask questions about the submission
• the name of the substance, using an appropriately descriptive term
• the intended conditions of use of the substance, including the target animal species
• the foods in which the substance is used, the levels of use in such foods and the purposes for which the substance is used
• where the intended use is in food for food-producing animals, the quantities of residues to which humans may be exposed in edible animal tissues
• evidence that the substance was present under its intended conditions of use in US commerce before the effective date of the final rule resulting from the proposed FDA rule
• a GRAS notice file number, if FDA sent a “cease to evaluate” letter in response to the submitter’s previous GRAS notice for the same intended conditions of use of the substance

FDA does not propose requiring submissions to include underlying data or information pertaining to a conclusion of GRAS status.

The submission would be included on a public list maintained by FDA, unless FDA issues a determination that a GRAS notice or a food additive petition must be submitted for the intended use of the substance.

The proposal contains certain specific provisions for feed-GRAS substances

No GRAS notice submission would be required if the intended use of the substance has been the subject of an established animal food ingredient consultation (AFIC) process with FDA, and if a summary document made publicly available by FDA through that consultation process indicates that FDA has no questions or concerns about the safety of the substance for the intended use.

In addition, for animal food ingredients that are listed in and used in accordance with Chapter 6 of the 2024 edition of AAFCO’s “Official Publication”, FDA is proposing an exception from the requirement to submit a GRAS notice, provided that FDA has not publicly expressed a concern about the GRAS status of the use of the ingredient.

FDA notes that Chapter 6 of the 2024 edition of the “Official Publication” contains a comprehensive list of animal food ingredients, many of which include definitions established through AAFCO’s ingredient definition request process. Because most states adopt the ingredient definitions listed in the “Official Publication” under their state laws, the publication facilitates the marketing of animal food ingredients under those state laws.

FDA further notes that it has reviewed many of the ingredients for safety under their intended conditions of use in animal food through its former participation in the AAFCO ingredient definition request process under a memorandum of understanding (MOU) that expired in October 2024. Moreover, for ingredients that were reviewed as part of the AAFCO ingredient definition request process but were not specifically reviewed by FDA under the MOU process, FDA is not aware of any safety issues associated with them, and many have a long history of use in animal food.

For animal food ingredients listed in editions of the AAFCO OP other than the 2024 edition, and for animal food ingredients that are used in accordance with the 2024 AAFCO OP but are the subject of a public FDA statement expressing concern regarding their GRAS status, the proposed exception would not apply. In those cases, FDA would require submission of a GRAS notice if the substance is being introduced into US interstate commerce under the GRAS provision in section 201(s) of the FD&C Act.

Medfiles supports clients with GRAS strategy, scientific substantiation and regulatory planning for the US market, helping clients prepare for upcoming changes and remain compliant as requirements evolve. The regulatory experts at Medfiles bring nearly 30 years of experience in food and feed safety regulation and over 10 years of hands-on experience with food and feed registrations in the US.

Mari Eskola, Ph.D. | Team leader, Regulatory Science and Reports // Senior Regulatory Affairs Expert, Food and Feed

Mari Eskola joined Medfiles in 2021 and leads the Regulatory Science and Reports Team. Since starting at Medfiles, she has been involved in a wide range of projects relating to food, feed, and cosmetics safety.

Mari has nearly 30 years of broad international expertise in the chemical and regulatory safety of food and feed, acquired across the European Union, national authorities, and industry. At Medfiles, she brings over 15 years’ experience as a regulatory food and feed risk assessor. Mari developed her risk assessment expertise working for 10 years at the European Food Safety Authority (EFSA), where she conducted regulatory risk assessments of contaminants in food and feed. She also served as Acting and Deputy Head of the EFSA Contaminants Unit. She is a food chemist specialising in analytical chemistry and obtained her PhD in food science in 2002.

In addition, Mari has extensive food and feed research and regulatory experience from several European institutes, including the European Commission Joint Research Centre (EC JRC), the European Chemicals Agency (ECHA), Teagasc in Ireland, the University of Natural Resources and Life Sciences in Austria, and the former Finnish Food Safety Authority. She has international experience in project and people management and has authored numerous scientific publications, including many EFSA scientific opinions and risk assessments.

You may be interested in:

• GRAS reform in the US is evolving – the latest developments
• Generally Recognised As Safe (GRAS) – the faster regulatory pathway to food and feed market
• Is the self-affirmed GRAS pathway coming to an end?

References:

• Substances Generally Recognized as Safe. A Proposed Rule by the Food and Drug Administration on 11 August 2026. US Federal Register. https://www.federalregister.gov/documents/2026/08/11/2026-16296/substances-generally-recognized-as-safe/