A proposed rule that would effectively eliminate the self-affirmed GRAS pathway has been with the Office of Management and Budget (OMB) since December 1, with a Notice of Proposed Rulemaking (NPRM) expected soon.
This will be followed by a public comment period before publication of a final rule, says the Dept of Health and Human Services (HHS). This would “require the mandatory submission of GRAS notices for the use of human and animal food substances that are purported to be GRAS.
“Food substances that are listed or affirmed as GRAS for the intended use by regulation, or for which FDA has already issued a no questions letter… would be exempted. The proposed rule would clarify that FDA maintain and update a public-facing GRAS notice inventory for all substances that are the subject of mandatory GRAS notice… The proposed rule would also clarify the process under which FDA would determine that a substance is not GRAS.”
According to Bob Durkin, partner at law firm Amin Wasserman Gurnani, “Word is there was a significant push back on this, both directly to FDA/HHS and at OMB. OMB has meeting on the proposed rule scheduled for April 20, so I don’t think we can expect anything prior to that.”
We caught up with Durkin and other experts to find out what the proposed changes could mean, what firms should be doing to prepare, and whether the FDA has the legal authority to eliminate self-GRAS without Congress, which is currently considering two bills that would effectively do the same thing (click here and here).
What does GRAS mean?
The GRAS (Generally Recognized as Safe) designation applies to substances added to food that are considered safe under the conditions of their intended use. Unlike food additives, GRAS substances are not subject to FDA pre-market approval; however, they must meet the same safety standards.
Currently, companies can independently determine their ingredient is GRAS through self-affirmation after convening an expert panel to review relevant safety data or they can submit a dossier to the FDA for review. Should the FDA be satisfied with the submission, it will come back with a ‘no questions’ letter, which is publicly available on the FDA website along with the applicant’s GRAS notice.
In cases where a company has self-affirmed its ingredients as GRAS, there is no requirement to notify the FDA and no public database of self-GRAS ingredients, something some commentators have long argued is a “loophole” that needs closing.
The scientific rigor underlying the GRAS determination is—or should be—the same whether the ingredient is self-affirmed GRAS or the subject of an FDA ‘no questions’ letter.
What should firms be doing now to prepare?
According to Brian Sylvester, partner at law firm Morrison Foerster, companies should “ensure their GRAS determinations are fully documented and defensible, and that the underlying dossiers could withstand FDA scrutiny if required.”
As the standards for self-GRAS and GRAS notices to the FDA are the same, adds Durkin, “There should be a very low burden in using a well-done self-affirmed GRAS as the basis for a GRAS Notice.”
One pressing questions relates to the status of self-GRAS ingredients already on the market, he says.
“The proposed rule was somewhat ambiguous on this point. It’s hard to think that a new rule would force ingredients that followed the existing rules off the market.
“If anything, I think it is more likely that ingredients currently on the market through the self-affirmed pathway might at some point have to make a future notification or at least list self-affirmed ingredients with FDA in a way that would allow the agency to conduct some sort of strategic review of these ingredients based on certain risk factors.”
Can HHS do this without amending the FDCA?
At the same time, says Sylvester at Morrison Foerster, firms should “not assume that mandatory submissions will ultimately be required” as there are “credible legal questions as to whether FDA has the legal authority to eliminate self-GRAS.”
Notably, under the Food, Drug, and Cosmetic Act (FDCA), a substance is a food additive unless it is generally recognized, among qualified experts, as safe under its intended conditions of use, he says. Substances that are GRAS are not food additives, and do not therefore require premarket approval.
“If FDA requires submission in every case—and especially if companies must wait for FDA review before marketing—that begins to look like mandatory premarket review,” says Sylvester, which the FDCA explicitly says is not required for GRAS substances.
“There is a real legal issue here, and a rule eliminating self-GRAS would likely face credible challenge if FDA proceeds without Congress amending the FDCA.”
He adds: “Industry stakeholders are already questioning whether FDA has the legal authority under the FDCA to impose a mandatory notification system and warning that a rule requiring companies to wait for FDA review could invite legal challenge.”
Durkin adds: “My opinion is that FDA does not have authority, under the Act as currently written, to eliminate self-affirmed GRAS. Whether FDA does or doesn’t will only come into question if the rule tries to do so. At that point, it’s a question that will likely be answered in court.”
Does FDA have the resources to deal with changes to the GRAS rule?
On a more practical level, the FDA—which like all government agencies has been hollowed out by the Trump administration—will need to significantly increase resources to administer any proposed changes, adds Jonathan Emord, general counsel at advocacy group the Alliance for Natural Health (ANH).
The devil, as always, will be in the detail, he says.
“If the proposed rule includes a pre-market approval system or a requirement for self-GRAS determinations to be re-evaluated substantively by the government, that would be a worst-case scenario, potentially creating huge bottlenecks beyond FDA resources and imperiling consumer access to historically safe additives, resulting in denial of consumer choice and loss of certain health enhancing ingredients, adversely affecting health outcomes.”
If it just includes a notice provision, he says, “that would eliminate a lot of industry concern unless it suffers from regulatory creep that causes it to be ‘notice’ in name only and instead to be a substantive new proof of safety requirement. That would have effects similar to those in the worst-case scenario above.”
In the end, claims Emord, the FDA will “have to conform to the Supreme Court’s Loper Bright Enterprises decision, which denies FDA any deference in its interpretation of the FDCA and compels the agency to ensure that the GRAS provisions of the statute are interpreted in accordance with their plain and intended statutory meaning.”
Put simply, he claims, “FDA does not have much wiggle room.”
Other options: A risk-based evaluation of a self-GRAS list
The best measure, argues Emord, “would be one that gives dispositive weight to a long history of safe use in the market, only requiring proof beyond that history case by case in specific instances where there is credible evidence that the dietary ingredient presents an unreasonable risk of illness or injury or of actual injury.”
According to Durkin: “I think a possible middle ground, between full elimination of self-affirmed GRAS and keeping the status quo might be some sort of requirement to list self-affirmed ingredients with FDA.
“The agency could require the listing to include information about the ingredient, its intended use, and the basis for safety. FDA could then review these, perhaps with some of the new AI tools either developed or being developed, and use a risk-based evaluation to identify certain ingredients for a full review by FDA.”
