Is this the end of the road for self-affirmed GRAS?

From an EU perspective, it can be hard to grasp that in the USA, innovative food ingredients may lawfully enter the market via the generally recognized as safe (GRAS) pathway. Under this approach, companies can conclude – based on publicly available evidence and expert consensus – that their ingredient is safe without pre-market approval. Self-affirmation offers a fast and flexible route to market, reflecting a regulatory paradigm where an ingredient can be sold unless safety concerns arise. This contrasts with the EU, where safety must be established before market entry.

On 4 August 2025, the Food and Drug Administration (FDA) proposed rulemaking (RIN 0910-AJ02) to amend GRAS regulations and effectively eliminate the self-affirmed route, requiring notification of all GRAS conclusions to the FDA. Reform efforts are not new, but with this initiative prioritized by Health and Human Services Secretary Robert F. Kennedy Jr. – alongside several Bills introduced to reform or end the GRAS pathway – self-affirmation could be nearing its end.

The GRAS pathway originated as a statutory exemption from the food-additive premarket approval requirement created by the 1958 Food Additives Amendment. Congress recognized that some substances did not need formal regulation if their safety was established by qualified experts, leading to the creation of the GRAS list in 1958. In 1969, the Nixon administration directed the FDA to review all substances on the list. That task was outsourced to the Select Committee on GRAS Substances (SCOGS), which took 10 years to produce 151 detailed reports covering more than 400 substances.

Self-affirmation could be nearing its end, but much will depend on how the FDA drafts the rule and manages the transition

In 1972, the FDA conducted rulemaking to establish procedures (21 CFR 170.35) for affirming the GRAS status of substances and created a petition process whereby companies could ask the FDA to review substances not already listed. Then, in 1997, the FDA proposed eliminating the resource-heavy affirmation process, replacing it with the notification procedure used today. Since then, more than 1,200 GRAS notices have been voluntarily submitted, averaging about 75 per year.

This is not the first time the GRAS pathway has evolved, but what are the timelines and implications for the current proposal? The notice of proposed rulemaking is expected in October 2025, followed by public consultation, with a final rule estimated during 2026-2027.

In practice, companies selling under self-affirmation will need to prepare for FDA submission. For some, this may mean reformatting dossiers and refining narratives. For others, it could require generating and publishing pivotal data. The bigger concern will be timelines. With more than 1,000 ingredients thought to be sold under self-affirmed GRAS, a sudden shift to mandatory notification risks creating a substantial review backlog.

Key questions loom. Will the FDA provide a compliance window for transition? Will t hire additional reviewers? Could it triage notices – prioritizing higher-risk substances – or consider grandfathering or phased requirements for low-risk ones? And for products already on the market under self-affirmation, will companies have to withdraw pending a ‘no-questions’ letter, or will interim enforcement discretion apply? Much will depend on how the rule is drafted and, critically, how the FDA decides whether a substance is unsafe.

To prepare, companies should assess gaps in their current dossiers and datasets against FDA requirements and begin shaping a regulatory strategy to minimize disruption. There is still time, and the outcome is not yet certain. But calm preparation for notification, including strategic timing of submissions – especially for companies with multiple ingredients – will be key.

So, is this truly the end for self-affirmed GRAS – or is it just the beginning of a new version of it?

Dr Hannah Lester is the CEO of Atova Regulatory Consulting and also Head of Regulatory Strategy at Gourmey. This article is republished from the Q3 2025 edition of Protein Production Technology International, the industry's leading resource for alternative proteins. To subscribe to all future editions, please click here