FDA Publishes Proposed Rule to Mandate GRAS Notification

Mandatory GRAS notification—but not premarket approval

The proposed rule would replace the current voluntary notification process with a mandatory GRAS notification framework for self-determined GRAS uses.

If the proposed rule is finalized, companies would be required to notify FDA when marketing a substance based on a self-determined GRAS conclusion, unless an exemption applies. The requirement would extend to substances used directly in food and to food contact substances. FDA would not need to complete its review of the GRAS notice before the company markets the substance. FDA’s filing of the notice would satisfy the notification requirement, and the company may continue to market the substance while FDA conducts its substantive review.

Qualifying existing self-GRAS uses could use a streamlined submission

A self-determined GRAS use for a substance already in interstate commerce before the final rule’s effective date could qualify for streamlined submission during a one-year window. The company would provide the substance’s identity, conditions of use, and evidence of prior marketing without initially submitting the underlying GRAS safety analysis. FDA would place qualifying submissions on a new public list of existing GRAS uses and could later require a full GRAS notice or food additive petition.

Eligibility would turn on whether the relevant use entered interstate commerce before the final rule’s effective date—not simply on when the company completed its GRAS analysis. Companies should preserve evidence of interstate commerce prior to the anticipated effective date of the final rule and consider the timing of current and planned commercialization. Placement on FDA’s public list would not signify FDA review or acceptance of the GRAS conclusion.

New self-GRAS uses would require a full GRAS notice

For self-determined GRAS uses that do not qualify for an exemption or the streamlined submission pathway, a company would need to submit a full GRAS notice addressing the substance’s identity and conditions of use; the substance’s manufacturing, specifications, technical effect, and dietary exposure; the safety and general-recognition basis; and the supporting data and information.

A full GRAS notice requires a developed safety and regulatory record, not simply notice to FDA that the company reached a GRAS conclusion. Companies should assess whether their self-GRAS files contain the information necessary to support a complete notice.

FDA would establish a 45-day filing timeline after initial submission

FDA would have 45 days after submission to determine whether to file the submission as a GRAS notice. FDA would then have 180 days to evaluate the notice, with up to two 90-day extensions.

FDA proceeding to file a submission as a GRAS notice would satisfy the mandatory GRAS notification requirement. Filing would not reflect FDA’s substantive assessment of the GRAS conclusion, which would occur during FDA’s subsequent review.

Certain existing FDA reviews and regulatory statuses (the exemptions) would eliminate the need for a new GRAS notice

For human food, a company generally would not need to submit a new GRAS notice where the relevant use is covered by an FDA no-questions letter; an FDA regulation listing or affirming the use as GRAS; specified existing GRAS provisions; certain established, publicly documented FDA reviews that did not identify a need for a GRAS notice; a Threshold of Regulation (TOR) exemption; an effective Food Contact Notification (FCN); or the streamlined pathway for existing uses.

The exemptions turn on the particular substance and conditions of use. Companies should confirm that the manufacturing process, specifications, food categories, use levels, technical effect, and other relevant conditions fall within the scope of the applicable exemption.

A company may be able to rely on another company’s no-questions letter or streamlined listing

The proposed rule generally would permit reliance on a no-questions letter that covers the same substance and conditions of use, even if another company submitted the original notice. A company also may rely on a use included on FDA’s streamlined public list under the same conditions of use. An FCN operates differently because it generally applies only to the manufacturer or supplier identified in the notification.

A company should confirm that its substance and conditions of use fall within the scope of the no-questions letter or streamlined listing on which it intends to rely. This assessment should consider manufacturing, specifications, food categories, use levels, technical effect, and other relevant differences.

FEMA GRAS and other non-FDA GRAS determinations would not, by themselves, exempt a use from notification

The proposed rule does not separately exempt FEMA GRAS conclusions or other non-FDA expert-panel determinations. A self-GRAS use supported by one of those conclusions would require a GRAS notice unless another exemption applies. Existing uses may qualify for the streamlined pathway.

Companies should identify uses supported solely by FEMA GRAS or another non-FDA GRAS determination and determine whether those uses qualify for streamlined treatment or would require a full GRAS notice.

Failure to notify would not trigger a new standalone penalty

FDA does not propose a new penalty specifically for failure to comply with the GRAS notification requirement. FDA states that it would consider noncompliance when prioritizing substances for post-market review. If FDA determines that a use is not GRAS and instead involves an unauthorized food additive, FDA could rely on the FD&C Act’s existing food additive and adulteration authorities.

Failure to submit a required GRAS notice would not, by itself, mean that the substance is not GRAS or that its use is unlawful. FDA states that it would consider noncompliance when prioritizing substances for post-market review. If FDA ultimately determines that the use is not GRAS, existing food additive and adulteration authorities would apply.

FDA would expand the Threshold of Regulation pathway

FDA proposes to extend the TOR exemption beyond substances migrating from food-contact articles to qualifying direct and indirect uses in human food. FDA also proposes to replace the current 0.5-parts-per-billion dietary-concentration criterion with an exposure-based threshold of 0.025 micrograms per kilogram of body weight per day and to revise the criterion for carcinogenic impurities.

For substances associated with very low dietary exposure, the expanded TOR pathway may provide an alternative to a full GRAS notice. Companies should evaluate TOR alongside GRAS and, for food-contact substances, the FCN pathway.