On August 11, 2026, the U.S. Food and Drug Administration (FDA) published in the Federal Register the proposed rule titled “Substances Generally Recognized as Safe” (Docket No. FDA-2025-N-3262; RIN 0910-AJ02), which would substantially change the current regulatory framework for substances considered Generally Recognized as Safe (GRAS).

The proposal would amend 21 CFR Parts 170 and 570, converting the voluntary GRAS notification program into a mandatory requirement for covered uses in human and animal food. The rule is open for public comments through December 9, 2026, after which the FDA will determine whether, and in what form, to issue a final rule.

Current GRAS framework: two pathways

Under current law, a substance may qualify as GRAS when its safety, under the intended conditions of use, meets the standard set out in Section 201(s) of the Federal Food, Drug, and Cosmetic Act (FD&C Act). GRAS status does not necessarily require an FDA submission. Companies may currently pursue two pathways:

• Self-affirmed GRAS: the company independently concludes that the intended use is GRAS, based on applicable scientific evidence and FDA’s criteria, with no obligation to notify FDA.
• Voluntary GRAS Notification to FDA: the company voluntarily submits a GRAS Notice to FDA, which reviews the submission and may respond with a “No Questions Letter”, if a substance is deemed GRAS.

The current system does not offer “FDA-approved GRAS”: voluntary notification constitutes no premarket approval or formal affirmation of GRAS status.

Proposed shift to mandatory notification

Should the regulatory proposal be finalized, companies could still reach their own GRAS determinations, including through the scientific procedures currently used for self-affirmed GRAS. However, where a use is purported to be GRAS and falls within the scope of the requirement, submitting a GRAS Notice to FDA would also become mandatory, unless an exemption applies.

• FDA’s stated Objective & Transparency: FDA seeks visibility into substances entering the market under independent conclusions, aiming to prevent potentially unsafe substances from reaching the market without the agency’s prior review. Once filed, notices will be published within weeks in the public GRAS Notice Inventory.
• Noncompliance as a Trigger for Review: if the notification requirement introduced by this new provision is not met for a substance’s conditions of use, FDA states it would be a factor in prioritizing the substance for post-market review.
• A Key Point (No Premarket Approval): the mandatory notification requirement would not create a premarket approval system comparable to that applicable to food additives. Companies could still market a presumed GRAS substance before submitting the notice, and before FDA files it. The primary purpose of the notification would be to support FDA’s post-market review, helping the Agency identify uses that may not actually meet the GRAS criteria and could therefore require authorization as a food additive.

Scope

The requirement would apply to substances used in human and animal food that are presumed to be GRAS under their intended conditions of use. This includes substances intentionally added to food, as well as substances introduced indirectly, for example, through migration from food-contact articles.

Two categories of substances would potentially be covered:

• New substances, not yet introduced into the U.S. food supply.
• Substances already on the market, currently marketed on the basis of an independent (self-affirmed) GRAS conclusion – i.e., without prior FDA review.

Proposed exemptions

A GRAS Notice would not be required where:

• The substance’s GRAS status has already been recognized by FDA — whether through a “No Questions Letter” on a prior GRAS Notice, formal listing/affirmation under 21 CFR Parts 182, 184, or 186, qualification under §170.30(d) or (i)(1), or consideration through another established FDA process with no identified need for further notice;
• The use qualifies for a Threshold of Regulation (TOR) exemption under section 170.39, or is covered by an effective Food Contact Notification (FCN), provided the substance originates from the manufacturer/supplier identified in that FCN.
• The use is included on the public list under the transitional pathway described below, absent a contrary FDA determination.

A substance-specific analysis of identity, specifications, manufacturing process, intended conditions of use, and existing FDA regulatory status would therefore remain necessary in each case.

The proposal would also revise the procedural rules governing the Threshold of Regulation (TOR) exemption for human food, updating the scientific criteria and extending its scope to uses of substances both in food and as food-contact substances (FCS).

Transitional pathway for existing self-affirmed GRAS substances

For substances already marketed on a self-affirmed GRAS basis, the proposal introduces a time-limited streamlined submission pathway (proposed section 170.305), of one year following the effective date of the final rule.

All the submissions will be publicly listed in a database; however, inclusion does not constitute a formal GRAS determination and FDA may still require a full GRAS notice or food additive petition later.

Extension of FDA’s review period

In addition to the current 180-day evaluation period and one possible 90-day extension, FDA proposes a second 90-day extension, bringing the maximum total review period to 360 days, to accommodate the expected increase in submissions under a mandatory system. FDA would need to notify the notifier of any second extension before the first one expires.

Practical implications & Outlook

Until the new regulation takes effect, current provisions remain valid. The proposal does not alter companies’ current legal obligations during the public comment period (open through December 9, 2026). If finalized, the mandatory notification requirement would take effect 60 days after publication of the final rule, with an 18-month compliance period for covered substances.

Within this window, FDA proposes a streamlined transitional pathway for substances already marketed on a self-affirmed GRAS basis, available only during the first 12 months. The six-month gap between the two deadlines is intentional: FDA states that additional time is needed to process incoming submissions and publish them on a public list, which companies could then use to verify whether their substances qualify for the corresponding notification exemption.

Companies relying on self-affirmed GRAS conclusions should assess their existing portfolios to:

• Verify the legal and scientific basis, manufacturing specifications, and specific conditions of use for each ingredient;
• Evaluate eligibility for existing exemptions (codified status, No Questions letters, FCN, TOR) or the one-year streamlined transitional pathway.

For pipeline developments, preparing and submitting a GRAS Notice will become a standard regulatory requirement. While industry would retain the ability to reach independent GRAS determinations, mandatory notification will increase regulatory transparency without introducing a conventional premarket approval requirement.

SOURCE:

FDA – Proposed Rule “Substances Generally Recognized as Safe”

21 CFR Parts 170 and 570;
Docket No. FDA-2025-N-3262;
RIN 0910-AJ02