FDA Proposes Mandatory GRAS Notification Framework

On August 11, 2026, the U.S. Food and Drug Administration (FDA or Agency) published its highly anticipated proposed rulemaking that would fundamentally revise the regulatory framework governing Generally Recognized as Safe (GRAS) determinations for substances used in human and animal food (the Proposed Rule). The Proposed Rule, if finalized, would revise the GRAS regulations in 21 CFR parts 170 and 570 to require mandatory submission of GRAS notices for human and animal food substances claimed to be GRAS, unless an exception applies. This includes both direct food ingredients and substances introduced indirectly, such as through food packaging. Substances that are already in the market based on an independent GRAS determination would be eligible for a “time-limited, streamlined submission requirement.”

Among other exceptions, FDA would not require a new submission for substances that are already listed or affirmed as GRAS for the intended use by regulation, or those for which FDA has issued a “no questions” letter in its GRAS notice inventory. The Agency further proposes to expand the Threshold of Regulation (TOR) exemption framework, currently limited to indirect food additives, to substances added directly to foods. FDA would be required to maintain a public-facing GRAS notice inventory for all substances subject to mandatory notification, reflecting their intended conditions of use.

The release of the Proposed Rule comes after Robert F. Kennedy Jr., Secretary of Health and Human Services (HSS), directed FDA to explore rulemaking to eliminate the “self-affirmed” GRAS pathway on March 10, 2025. This rulemaking has also been highlighted in both the Make America Healthy Again (MAHA) Assessment and Strategy reports as a cornerstone in the Trump Administration’s health policy agenda. FDA states that the proposal is intended to increase transparency and oversight of substances entering the food supply and improve the Agency’s ability to identify and address potential safety concerns in accordance with its statutory responsibilities.

For a review of the current GRAS framework, please see our in-depth analysis here.

Key Provisions of the Proposed Rule

Mandatory GRAS Notification

The Proposed Rule would significantly revise the current regulatory framework by replacing FDA's voluntary GRAS notification program with a mandatory notification requirement with limited exceptions. Under the existing framework, manufacturers are not required to notify FDA before marketing a substance they have independently determined to be GRAS, although they may choose to submit a voluntary GRAS notice and seek a "no questions" response from the Agency. Under the Proposed Rule, manufacturers that market a substance based on an independent GRAS conclusion would be required to notify FDA and submit its basis for that conclusion. While the GRAS notice is mandatory, FDA states that the proposal does not establish a premarket review program for GRAS substances because manufacturers continue to be allowed to market a purported GRAS substance before submitting the required notice or before FDA files the submission as a GRAS notice. However, FDA will consider a company’s noncompliance with the mandatory GRAS notification as a factor in its prioritization of food substances for post-market review. As a practical matter, if a self-concluded GRAS substance is marketed in the absence of a FDA “no questions” letter, or is not in accord with an exception or other regulatory pathway outlined in the GRAS Proposed Rule, such as the food contact notification (FCN) pathway, and FDA later determines through post-market review that the substance is an unapproved food additive, the Agency can use its existing enforcement authorities to take action against the substance as an adulterated food, including the issuance of warning letters, seizure of adulterated product, and criminal penalties, among others. This legal enforcement authority has not changed under the Proposed Rule.

FDA proposes a 45-day period for conducting its initial review and determining whether a submission qualifies for filing as a GRAS notice. A notifier's obligation would generally be satisfied once the submission is accepted by FDA for filing under the proposed framework. FDA would retain the current 180-day evaluation timeline after the notice is filed for the GRAS determination, as well as the 90-day extension. The Agency is proposing to add a second 90-day extension it could invoke when additional review time is needed. If FDA ceases evaluating a filed notice at the notifier's request, the submission would not satisfy the notification requirement, and the notifier would remain out of compliance until a new notification is submitted and filed by FDA. Companies would be required to comply with the mandatory notification requirements within 18 months of the final rule’s effective date.

Time-Limited Streamlined Submission Pathway for Existing Marketed Uses
FDA proposes a streamlined, time-limited notification process for substances that are already on the market based on a self-determination of GRAS status before the final rule takes effect. Eligible manufacturers could submit basic information regarding the substance and intended use rather than a complete GRAS notice, provided FDA has not previously raised concerns regarding the substance or use.

The streamlined notification submission must contain the following information:

1. name and address of the submitter;
2. name of the substance;
3. intended use of the substance, including levels of use, purposes for which the substance is used, and the foods in which the substance is used or is in contact with;
4. evidence of presence of the substance in interstate commerce prior to the final rule’s effective date; and
5. if the FDA sent a “cease to evaluate letter” in response to a prior GRAS notice (GRN), the GRN file number.

The submitter may identify the statutory basis for its GRAS determination in the submission but is not required to do so.

Any entity seeking to use the streamlined notification process would be required to submit its notification within one year of the final rule's effective date. FDA is proposing to publish the information gathered from these submissions in a publicly available database.

Expansion of Threshold of Regulation (TOR)

The Proposed Rule would expand FDA’s TOR framework for human food substances by broadening the categories of substances eligible for TOR exemptions beyond food-contact substances. The TOR exemption was historically limited to substances used in food contact articles, such as food packaging and food processing equipment, which are present in food at very low levels. Under the proposed framework, any substance used in food, whether added directly or indirectly, would qualify for a TOR, provided that the substance has not been shown to be a carcinogen and dietary concentration and exposure of the substance for its intended use fall within applicable thresholds.

Importantly, if FDA grants a TOR exemption for a substance's intended use, the manufacturer would not be required to submit a mandatory GRAS notification for that use. Because TOR submissions do not require a full safety narrative, the TOR pathway may be a viable alternative to mandatory GRAS notification for certain ingredients such as processing aids, where the submitter can establish that the intended use would not exceed the dietary exposure threshold in the final food product.

Other Exceptions to Mandatory Notification

The Proposed Rule contains several exceptions under which a manufacturer would not be required to submit a GRAS notification to FDA:

• Existing FDA “No Questions” Letter: A manufacturer would not be required to submit a new GRAS notification if FDA has already issued a "no questions" letter for the same substance and intended conditions of use. This exception applies only to the uses covered by the existing notification. If the intended use, manufacturing process, or other relevant conditions differ from those addressed in the prior submission, the manufacturer remains responsible for demonstrating that the substance is GRAS for the new use. FDA considered, but tentatively declined to adopt, a streamlined notification process for substances that have previously received a "no questions" letter but are being used under modified conditions, although the Agency is specifically seeking comments on this issue.
• Substances Already Recognized as GRAS by Regulation: The notification requirement would not apply to substances that are already listed or affirmed as GRAS in FDA regulations under the conditions of intended use.
• Certain Historically Consumed Natural Substances: FDA proposes an exception for substances of "natural biological origin" that were widely consumed in the United States for their nutritional properties before January 1, 1958, without known detrimental effects. Eligible substances may only be subject to conventional processing as practiced before 1958, for which no known safety hazards exist.
• Substances Evaluated Through Other Regulatory Pathways: A GRAS notification would not be required when FDA has already evaluated the substance through certain other regulatory programs and did not recommend submission of a GRAS notice. These programs include Voluntary Premarket Consultations, Voluntary Premarket Meetings, Animal Cell Culture Consultations, and TOR submissions. Similarly, manufacturers with an effective Food Contact Notification (FCN) would not be required to submit a GRAS notification for that food contact substance, although this exception applies only to the manufacturer or supplier identified in the FCN.
• Public List of Previously Submitted Notifications: A GRAS notification would not be required if information about the substance and its conditions of use has already been submitted to FDA through the time-limited streamlined submission pathway and is included on the public list maintained by the Agency. Other manufacturers could rely on a listed submission for the same conditions of use without filing a separate notification unless FDA subsequently determines that a GRAS notice or food additive petition is necessary for that use.
• Animal Food Ingredients Listed in the 2024 “Official Publication” of the Association of American Feed Control Officials, Inc. (AAFCO): The Proposed Rule would also exempt certain animal food ingredients from the mandatory GRAS notification requirement if the ingredient and its intended use are listed in the 2024 Official Publication of the Association of American Feed Control Officials (AAFCO). Ingredients first listed or updated in editions subsequent to the 2024 Official Publication would not be eligible for this exception.

Statutory Authority to Mandate GRAS Reviews and Practical Challenges

FDA’s Proposed Rule to mandate GRAS notifications may face legal challenges. The Federal Food, Drug, and Cosmetic Act (FDCA) does not grant explicit authority to eliminate the self-affirmed GRAS pathway. Instead, the FDCA exempts GRAS substances from premarket review, as Congress has never required mandatory GRAS submissions. Historically, FDA has acknowledged this limitation, stating in the 2016 GRAS rule preamble that it “lack[s] express statutory authority to require companies to submit GRAS notices.”¹ Courts have upheld the voluntary system, finding FDA’s interpretation reasonable given decades of congressional inaction.²

FDA contends that the Proposed Rule would not establish a premarket approval system because a manufacturer could still independently conclude that a substance is GRAS and market the substance before submitting a GRAS notice. However, FDA also states that it would consider a company's failure to submit a GRAS notice when prioritizing post-market ingredient reviews. This appears to be the only new action that FDA is proposing it will take for failure to file a mandatory GRAS notice. But prioritization could result in an FDA finding that the ingredient is an adulterated food additive subject to action under existing enforcement authorities. Regardless, the Proposed Rule, if finalized, would represent a significant departure from FDA’s longstanding approach to GRAS determinations and could require the Agency to justify how the rule aligns with the FDCA, as well as FDA’s well-documented historical position on mandatory GRAS notices.

Finally, the proposal could also raise practical concerns regarding FDA’s ability to review a substantially larger number of GRAS submissions. FDA has previously emphasized that “resource-intensive” GRAS affirmation will deter petitions, and mandatory notification would slow innovation and delay new food products reaching the market.³ A delay in GRAS review timeframes would likely be further compounded, given the widespread reductions in force (RIFs) conducted throughout the FDA, which impacted both the Human Foods Program and the Center for Veterinary Medicine.

Next Steps and Considerations for Industry

• Prepare and submit comments on the Proposed Rule. Public comments on the Proposed Rule are due by December 9, 2026. Consider submitting comments to the Agency that address implementation challenges, reasonableness of proposed compliance deadlines, economic impact data, and sufficiency of proposed exceptions
• Inventory all self‑affirmed GRAS substances. Review all self-affirmed GRAS substances currently in use and evaluate whether they qualify for the time-limited, streamlined notification pathway.
• Assess substantiation supporting self-affirmed GRAS status. Review ingredient dossiers to ensure they meet the level of scientific evidence FDA would expect for a mandatory GRAS submission.
• Monitor regulatory and litigation trends in this area. Adopt a proactive approach to monitoring developments related to GRAS reform. In addition to the Proposed Rule, legislation has been introduced at both the state and federal levels to address GRAS reform (see our detailed analysis here). Given the rapidly evolving landscape, stakeholders should also be prepared for potential litigation challenging the proposed changes.

Footnotes

1. 81 Fed. Reg. 54981.

2. Center for Food Safety et al v. Price et al. No. 1:17-CV-03833 (SDNY Sept. 30, 2021).

3. 62 Fed. Reg. 18,938, 18,941 (1997), https://www.govinfo.gov/content/pkg/FR-1997-04-17/html/97-9706.htm.