Shifting Expectations: FDA Takes a First Step Toward Making GRAS Notifications Mandatory

On August 11, 2026, the U.S. Food and Drug Administration (FDA or Agency) released a long-anticipated proposed rule that would introduce new GRAS notification requirements for the food industry by mandating submission of a GRAS notification for use of an ingredient in human or animal food substance that is purported to be GRAS (GRAS Proposal). This broadened notification requirement is intended to give FDA more transparency so that FDA “can more efficiently determine if the use of a substance constitutes a food additive use that is subject to FDA review and approval” and take other steps to ensure the safety of food.¹

Under section 409 of the Federal Food, Drug, and Cosmetic Act (FDCA), any ingredient used or intended for use in food must either be authorized by FDA as a food additive under FDCA section 201(s) or qualify for one of the statutory exceptions to the definition of a “food additive.”² The key exception is for ingredients that are “generally recognized as safe,” or GRAS. For decades, FDA has explicitly permitted marketers to independently determine that the intended use of a food ingredient meets the statutory GRAS safety standard and go to market, without being required to engage with the Agency—a practice often referred to as “self-affirmation.” While FDA has amassed extensive information about many GRAS substances through voluntary submissions notifying the Agency of a manufacturer’s conclusion that a substance is GRAS under the current GRAS notification regulation, such submissions have never been mandatory. The GRAS Proposal moves to eliminate the voluntary nature of the GRAS notification program and thus is a fundamental change for the industry.

The GRAS Proposal states that notifications would be mandatory for new GRAS ingredients and would require a less substantial notification for self-affirmed GRAS substances currently on the market. FDA states that it has the authority to make this shift under FDCA section 409(d) which allows FDA “at any time” and “upon [its] own initiative” to declare that an ingredient is a food additive subject to a premarket petition and approval.³ FDA’s goal is to have information available so that it can assess whether a company must instead submit a food additive petition: “the proposed GRAS notification program would assist FDA’s post-market review of purported GRAS substances, enabling FDA to determine whether these substances are not GRAS and therefore require FDA review and approval under section 409 of the FD&C Act.”⁴

Important questions remain, including: (1) whether FDA’s stated authority under FDCA section 409(d) provides sufficient grounds for requiring GRAS notifications, and (2) whether FDA’s Human Foods Program has sufficient capacity to review the resulting influx of submissions and to identify companies that do not submit notifications. The full impact remains uncertain, as the GRAS Proposal does not specify that a notification for a new ingredient must be submitted prior to marketing or according to any specific timeline. Rather, FDA states that noncompliance would factor into prioritization for its post-market review.

From Voluntary to Mandatory: How Did We Get Here?

The statutory concept of “generally recognized as safe” dates to the 1958 Food Additives Amendment to the FDCA, which established a premarket approval requirement for “food additives,” defined under section 201 of the FDCA as:

[A]ny substance the intended use of which results or may reasonably be expected to result, directly or indirectly, in its becoming a component or otherwise affecting the characteristics of any food (including any substance intended for use in producing, manufacturing, packing, processing, preparing, treating, packaging, transporting, or holding food; and including any source of radiation intended for any such use), if such substance is not generally recognized, among experts qualified by scientific training and experience to evaluate its safety, as having been adequately shown through scientific procedures … to be safe under the conditions of its intended use[.]⁵

GRAS ingredients are thus expressly carved out of the definition of food additive. FDA has since consistently taken the position that premarket review is required for a food additive, but voluntary for a GRAS ingredient.⁶ Notably, food additives and GRAS substances derive from the same statutory foundation, and thus must meet the same rigorous scientific safety standard, requiring sufficient evidence to establish a “reasonable certainty in the minds of competent scientists that the substance is not harmful under the conditions of its intended use,” considering consumption, cumulative dietary effects, and appropriate safety factors.⁷ This standard is applied whether documented in a food additive petition, a GRAS notification, or a self-affirmation.

As FDA notes in the GRAS Proposal, over the years the Agency has revisited this statute and explored a variety of ways to work with stakeholders to identify GRAS ingredients, including first, an attempt to itemize and publish lists of GRAS substances, an approach ultimately concluded to be “impracticable.”⁸ FDA then began issuing informal GRAS “opinion letters” upon request, until it moved away from this approach—ultimately rescinding all such letters. In 1972, FDA introduced a GRAS affirmation petition rule which allowed interested parties to seek Agency confirmation of GRAS status via a premarket submission and resulting regulation. But by 1997, FDA ended this approach as well, labeling it as too slow and resource-intensive.

Finally, in 1997, FDA proposed instead the voluntary GRAS notification process that was ultimately finalized in 2016 and remains in place today. When finalizing the rule, FDA stated that it retained “the voluntary nature of the GRAS administrative procedure” because the Agency “lack[s] express statutory authority to require companies to submit GRAS notices.”⁹ FDA later defended this position in court, and the court confirmed that a GRAS notification is purely voluntary, stating:

Congress delegated “to FDA the responsibility of ensuring that our nation's food is safe and free from harmful substances.” If the FDA has delegated anything at all to manufacturers, it is simply the ability to notify FDA of a GRAS determination, with which FDA can agree or disagree. … As the Government aptly notes, “[i]f FDA had promulgated no rule at all, manufacturers would have the same option they have now: to act without notifying FDA and assume the risk of enforcement if FDA later determines that they violated the law. The Rule provides them no additional authority.”¹⁰

Faced with this clear legal history, the GRAS Proposal offers a limited shift toward mandatory notification.

GRAS Proposal Impacts

FDA’s GRAS Proposal, if finalized, would expand FDA oversight of food ingredients by requiring notification for all new ingredients, with exceptions for, among other things: (1) those ingredients that have already been the subject of a GRAS notification or affirmation for the same condition of use; and (2) for ingredients that have been considered under one of the other pathways, such as new plant varieties developed through biotechnology or foods from cultured animal cells. Other exceptions include, with some limitations, prior sanctioned substances, threshold-of-regulation exemptions, and uses covered by an effective food-contact notification. The GRAS Proposal takes a significant step toward ending GRAS self-affirmation.

1. Broadened Scope for Food Companies?

In addition to mandatory notifications for new food ingredients—and perhaps most significant—the GRAS Proposal would also require a slimmed down GRAS notification for purported GRAS ingredients already on the market. The GRAS Proposal offers a one-year phase-in window after the effective date of any final rule for submitting information about the existence and uses of such substances. Notably, these notifications do not need to include safety information.¹¹

The full impact remains uncertain, as the GRAS Proposal makes clear that there is no specific requirement that a notification be submitted prior to marketing:

Importantly, the proposed GRAS notification program generally … [does] not establish a premarket review program for purportedly GRAS substances. As explained elsewhere in this document, the FD&C Act allows a person to introduce a substance into interstate commerce if the substance is GRAS under the conditions of its intended use (see sections 201(s) and 409 of the FD&C Act). Thus, a company may continue marketing a purported GRAS substance before submitting a GRAS notice or after submitting a GRAS notice before it is filed by FDA. Similarly, a company may reach a GRAS conclusion about a new use of a substance and introduce the substance into interstate commerce before submitting a GRAS notice.¹²

FDA does not explain this timeline further, leaving significant uncertainty around the new mandatory notification requirement, stating only that “noncompliance … would be a factor in FDA's prioritization of food substances for post-market review.”¹³

2. Practical Considerations Amid FDA Resource Constraints

The GRAS Proposal maintains FDA’s existing voluntary notification program which already provides the Agency—and the public—with substantial visibility into GRAS substances and their intended uses, available on a public-facing FDA inventory. To date, there are over 1,200 substances that have been the subject of notifications to FDA under this program, and their intended use and basis for GRAS are fully available to the public. There are many reasons why companies decide to voluntarily submit their GRAS review, particularly for those earlier in the supply chain, who want to share their “no questions” letter from FDA with downstream customers. The voluntary nature of the process to date is often smooth and seamless, and provides FDA with substantial information. It is also worth noting, that in some cases, self-affirmed GRAS determinations involve already known ingredients evaluated for slightly different doses, uses, or target populations.

Against this backdrop, the GRAS Proposal raises practical questions about FDA’s capacity to administer a substantially expanded notification program within prescribed review timelines. At present, FDA regulations prescribe that the Agency “will respond” to a voluntary GRAS notification within 180 days of filing (which may be extended by 90 days as needed).¹⁴ Notably, FDA’s review of the 10 most recent GRAS notifications took an average of 264.4 days (ranging from 198 to 342 days), substantially exceeding the 180-day review period required by regulation. For mandatory notifications for new ingredients under the GRAS Proposal, FDA intends to impose new review timelines, including a new 45-day initial evaluation period for FDA to determine whether to file it as a GRAS notification.¹⁵ Whether FDA has the resources to meet these timelines—particularly given the substantial increase in submissions the GRAS Proposal would generate—remains an open question given current resources at the Agency.

3. Lack of Clarity for Dietary Supplements

Dietary supplement companies have come to rely on the voluntary self-affirmed GRAS process as a practical tool for bringing an ingredient to market, given that in draft guidance, FDA indicates that a GRAS conclusion may take the place of an NDI notification “as long as the … direct food additive or GRAS substance [] has been used in the food supply … and [] is to be used as a dietary ingredient without chemical alteration.”¹⁶ In that context, FDA affirms that a supplement company may market a substance that it determines is GRAS without informing the Agency. Consistent with this position, FDA has issued “no questions” letters in response to GRAS notices that expressly contemplate use of the notified substance in dietary supplements.

The GRAS Proposal reminds the industry that dietary supplements are not food additives, consistent with the Dietary Supplement Health and Education Act, but, confusingly, states that therefore the GRAS process is not available to dietary supplement ingredients:

Uses of substances that are excepted from the definition of a food additive under section 201(s)(1) through (6) of the FD&C Act cannot be the subject of a GRAS notice. Specifically, the term “food additive” does not include: … (6) an ingredient described in section 201(ff) of the FD&C Act in, or intended for use in, a dietary supplement (section 201(s)(1) through (6) of the FD&C Act). As such categories are excepted from the definition of “food additive” in section 201(s) of the FD&C Act, they are not eligible for classification as GRAS under the GRAS provision included in the definition of “food additive” (see proposed § 170.205(c)).¹⁷

It will be important for the dietary supplement industry to clarify that the GRAS pathway is available to food ingredients, broadly, including those used as dietary ingredients or “other ingredients” in dietary supplements.

4. Acknowledgment of Other Notification Pathways

FDA has introduced similar notification processes in the food sector, including for foods derived from new plant varieties developed through biotechnology (including gene-edited plants), and human food made with cultured animal cells. The GRAS Proposal acknowledges these pathways and identifies them as exempt from the new notification requirements, subject to some limitations where FDA can decide that the substance is appropriately reviewed as a food additive.

* * *

Given the changes FDA has proposed, companies should assess how the rule may affect their regulatory and market strategies, including whether and when existing self-affirmed GRAS determinations would require submission and how competitive dynamics across the supply chain may shift. It is also critical to monitor developing legislative changes, as there are currently multiple bills in Congress and the states that could impact the GRAS substances. Comments are due by December 9, 2026 on the proposal, and are essential to ensure FDA’s final rule reflects both scientific realities and operational challenges, so that the current FDA and future administrations have all the input needed to reflect on whether this shift in the law is sustainable. Finally, it remains to be seen whether stakeholders will mount legal challenges to the Agency’s assertion of mandatory authority after decades of taking a voluntary approach.

---

¹ 91 Fed. Reg. 51834, 51835 (Aug. 11, 2026).

² 21 U.S.C. § 348(a).

³ 21 U.S.C. § 348(d).

⁴ 91 Fed. Reg. at 51851.

⁵ 21 U.S.C. § 321(s).

⁶ See, e.g., 62 Fed. Reg. 18938, 18941-42 (Apr. 17, 1997); id. at 18945-46; id. at 18950-51; id. at 18956; 81 Fed. Reg. 54960, 54971 (Aug. 17, 2016).

⁷ 21 C.F.R. § 170.3(i).

⁸ 39 Fed. Reg. 34194, 34196 (Sept. 23, 1974) (finalized, 41 Fed. Reg. 53600 (Dec. 7, 1976)).

⁹ 81 Fed. Reg. at 54981-82.

¹⁰ Ctr. for Food Safety v. Becerra, 565 F. Supp. 3d 519, 531 (S.D.N.Y. 2021) (citations omitted).

¹¹ 91 Fed. Reg. at 51855-57.

¹² Id. at 51851.

¹³ Id.

¹⁴ 21 C.F.R. § 170.265(b)(1).

¹⁵ 91 Fed. Reg. at 51851.

¹⁶ FDA, Draft Guidance for Industry: Dietary Supplements: New Dietary Ingredient Notifications and Related Issues, at 23 (Apr. 2024).

¹⁷ 91 Fed. Reg. at 51850.