The long-anticipated proposed rule on closing the so-called GRAS loophole is less onerous than some had feared but could still create major headaches for the food industry if not properly resourced and will almost certainly prompt legal challenges, say experts.
Under the proposed rule, firms would not in future be able to self-affirm substances as GRAS (Generally Recognized as Safe) and will be required to submit a full GRAS notice to the FDA.
However, for legacy self-GRAS ingredients already on the market, FDA is proposing a “streamlined” route designed to bring them out of the shadows without forcing each one through a full retrospective GRAS review.
This, says the FDA, “enables the agency to prioritize post-market safety evaluations while minimizing unnecessary regulatory burden.”
The proposal, which will be published in the federal register on August 11, will be subject to a 120-day comment period, after which the FDA will review them and develop a final rule. According to the document:
- From the effective date, GRAS notifications will be mandatory for ingredients not yet on the market. This means firms must submit a full dossier to the FDA. However, GRAS substances would remain exempt from premarket approval.
- For self-GRAS substances already on the market before the effective date, firms will have one year to make a streamlined submission identifying the substance and its conditions of use, without having to submit the underlying safety dossier. FDA estimates this will take about 31.5 hours to prepare, versus 180 hours for a full GRAS notice, and 11 hours to review.
- The FDA can then decide which if any of the substances subject to streamlined submissions warrant deeper review and may subsequently order firms to submit a full GRAS notice or a food additive petition.
- The FDA will put qualifying streamlined submissions on a public list but stresses that inclusion on the list does not mean it has reviewed or endorsed an ingredient’s GRAS status.
- FDA estimates there are 2,000+ self-GRAS and 1,740 FEMA GRAS* substances already on the market.
- FDA will treat failure to notify as a factor in prioritizing substances for post-market review.
- FDA estimates the mandatory regime will generate about 98 extra GRAS notices a year, on top of the 112 currently submitted voluntarily.
- The FDA proposes to complete initial evaluations of a notifier’s submission to determine whether to file it as a GRAS notice within 45 days.
- Proposed exceptions to mandatory notifications include uses covered by an existing “no questions” letter, substances listed as GRAS in FDA regulations, certain historical-use substances, uses reviewed through established FDA consultation processes, threshold-of-regulation exemptions, and uses covered by food-contact notifications.
Venable: ‘Your ‘no questions’ letter may not be as secure you think’
Right now, as firms are not obliged to inform the FDA that they have self-affirmed a substance as GRAS, FDA may only “become aware of the need to take action regarding unsafe food additives in food only after a public health concern emerges,” says the agency.
“A mandatory GRAS notification program would allow FDA to ensure that GRAS conclusions have a scientific basis and that appropriate documentation supporting those conclusions exists.”
The rule also clarifies FDA’s process for determining that a substance is not GRAS. For substances already listed/affirmed as GRAS in FDA regulations, FDA could propose in the federal register that a use is not GRAS, allow 60 days for comments, and if it concludes there is a lack of convincing evidence, amend or repeal the relevant GRAS regulation.
This is significant, noted law firm Venable in a note issued this afternoon: “Your ‘no questions’ letters may not be as secure as you think. FDA proposes authority to revisit, update, or rescind prior no questions letters if new information calls the GRAS conclusion into question.”
When might this come into effect?
Amaru Sanchez at law firm Akin told AgFunderNews that there is no clear timetable for a final rule. That said, there will be pressure to move in a timely fashion given the prominence of GRAS reform in the MAHA agenda, he predicted.
As properly conducted self-GRAS determinations should meet the same substantive standard as submitted GRAS notices, mandatory notification is more of an administrative change than a fundamental scientific hurdle, said Sanchez.
He also pushed back on the idea that companies choose self-GRAS because they have something to hide. Self-GRAS can provide legitimate flexibility for firms continually improving manufacturing processes, strains or formulations without repeatedly entering FDA’s notification process as long as they maintain dossiers as they go, he noted. It also generally involves a little less paperwork.
However, the science underlying the determination must be the same, he said: “If you’re a company that has been, taking shortcuts, then this is a big deal.”
Not all self-GRAS affirmations are equal…
Indeed, Some self-GRAS ingredients on the market today would likely struggle to meet FDA’s current GRAS standards, claimed Dr. George A. Burdock, president at consulting firm Burdock Group, which has worked with scores of firms on GRAS determinations.
Many legacy self-GRAS determinations would likely “not pass FDA’s requirements because they were done as an immediate reaction to the law in 1958 and the ingredients were not fully vetted and the person declaring a substance GRAS, was totally unqualified to do it,” he said.
“I have seen self-GRAS determinations consisting of a two-paragraph memo, signed by some totally unqualified person. Often the person signing off was the owner of the company, a quality assurance person or some chemistry professor at the local junior college.”
Failure to resource proposal could have direct commercial consequences
One of the biggest concerns for the industry, however, is resourcing, said Burdock. “FDA has never had the resources to review all these ingredients.”
Sanchez added: “Without more staffing or funding, this is going to be extremely challenging to implement.”
He noted that FDA already struggles to meet existing GRAS review timelines, with notices currently taking “about a year or more.” A surge in mandatory submissions could extend that timeline, which could have direct commercial consequences.
Although companies technically do not have to wait for a no-questions letter to market a GRAS substance, for example, many larger customers are reluctant to source ingredients without one. Any delay could make life harder for a startup with limited runway.
Sanchez said FDA’s food program has historically been constrained because it largely depends on congressional appropriations rather than industry user fees, and GRAS reviews were already challenging before recent staffing reductions.
He is also seeing more companies file GRAS notices now in anticipation that mandatory notification is coming one way or another, which is already increasing the workload.
Streamlined process for self-GRAS ‘less onerous’ than some feared
Jonathan Emord, general counsel at advocacy group the Alliance for Natural Health (ANH), noted that “this is a far less onerous regulatory requirement than were all companies forced to file full GRAS dossiers.”
However, legal challenges are likely given the absence of clear congressional authorization and the fact that the changes “are extensive enough to increase significantly the costs borne by industry,” he predicted.
The new rule also creates greater risk that in future FDA will be more active in refusing GRAS recognition for substances that, under the old rule, would have been allowed based on self-determination alone.
While the proposal will “likely not disable FDA,” he said, “It will tax existing resources.”
Advice to food companies
According to Brian Sylvester, partner at law firm Morrison Foerster: “My advice remains largely the same as before the proposed rule published today. Companies relying on self-GRAS conclusions only should ensure those determinations are fully documented and defensible and that the underlying dossiers could withstand FDA scrutiny if required.
“They should also identify the substances and uses for which they rely on independent GRAS conclusions and determine whether they can substantiate when those uses entered interstate commerce, given the proposed streamlined pathway for legacy substances.
“At the same time, companies should not assume that any mandatory submissions will ultimately be required… the legal question remains whether the FDCA [Food, Drug, and Cosmetic Act] actually gives FDA authority to impose a mandatory notification requirement without congressional action.”
Companies should also closely monitor congressional efforts to amend the statute, which could substantially reshape or supersede the rulemaking, said Sanchez at Akin.
“There are now several major bills on GRAS [proposed by lawmakers] and if Congress moves on any of those, that can change the game. And what surprised me, especially in the press announcement, was how candid FDA was about the limits of its own authority. It basically said, we may need a legislative fix as a backup.”
In the preamble to its 2016 GRAS final rule, he pointed out, the FDA also explicitly acknowledged that it “lacks express statutory authority to require companies to submit GRAS notices.”
He added: “Another thing to keep an eye on is what’s happening on the state level. New York being one example, which pretty much has a bill waiting on the governor’s desk to sign [the Food Safety and Chemical Disclosure Act, which among other things would impose a first-of-its-kind state-level mandatory reporting regime for self-affirmed GRAS substances used in food].”
CSPI: How will this be enforced?
Health advocacy group The Center for Science in the Public Interest (CSPI) welcomed the document but urged the FDA to “fully close the GRAS loophole by requiring premarket review for all new food chemicals.”
President Dr. Peter Lurie said it was also “unclear how FDA would enforce a notification provision the administration characterizes as mandatory. Mandatory without enforcement is not mandatory at all.”
Sign up for our weekly newsletter.
