Generally Recognized as Safe (GRAS): Panels and Self-Affirmation

An ingredient is “generally recognized as safe,” or GRAS, when qualified scientific experts agree it causes no harm at the levels and in the ways it’s actually used in food. That agreement exempts the ingredient from the FDA’s premarket approval process, which is otherwise required for food additives. The concept dates to the 1958 Food Additives Amendment, and one feature of the system surprises most people who encounter it: a company can reach a GRAS conclusion on its own and start selling the ingredient without ever notifying the FDA.

What the Law Actually Says

The definition sits in Section 201(s) of the Federal Food, Drug, and Cosmetic Act. A “food additive” is any substance intentionally added to food, but the statute carves out anything “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.”¹ For substances used in food before January 1, 1958, experience based on common use can support that recognition instead of formal scientific procedures.

The consequence of the classification is stark. If a substance is GRAS, it isn’t a food additive and doesn’t need FDA premarket approval. If it doesn’t qualify as GRAS, it is a food additive under 21 U.S.C. § 348, and using it without an approved food additive petition makes the food adulterated under federal law.² A wrong call on GRAS status can turn a legal product into an illegal one.

How a Substance Qualifies

Two pathways to GRAS status appear in 21 CFR 170.30. The first is scientific procedures: published studies, toxicological data, and other technical evidence that together demonstrate reasonable certainty of no harm at intended use levels. The second applies only to substances used in food before January 1, 1958, and relies on a history of common use rather than formal toxicology.³

The safety standard is the same either way, and it’s identical to what a formal food additive petition would require. The evidence must produce “common knowledge throughout the scientific community” that the substance is not harmful under the conditions of its intended use.³ A handful of favorable studies aren’t enough if the broader expert community hasn’t reached the same conclusion.

For substances entering the food supply after 1958, the scientific-procedures pathway is the only option, and the evidence has to be publicly available so that experts outside the sponsoring company can evaluate it.⁴ Unpublished proprietary safety data can’t anchor a GRAS conclusion. For the pre-1958 pathway, if common use occurred primarily outside the United States, the documentation requirements tighten: use history must be supported by generally available information and corroborated by a second, independent source.³

Who Decides: The Expert Panel

Because GRAS status turns on expert consensus, the composition and independence of the panel that evaluates the data matter a great deal. FDA guidance recommends that panels include, at minimum, expertise in the identity and properties of the substance (chemistry or microbiology), toxicology, and exposure assessment. Depending on the substance, additional expertise may be needed in areas like allergy, pediatric nutrition, or specialized manufacturing.⁵

Conflict of interest is where panels draw the most scrutiny. The FDA recommends that employees of the sponsoring company, the company’s attorneys, and anyone with a direct financial stake in the outcome not serve as panel members. Financial interests that can be “directly and predictably affected” by the panel’s work create a disqualifying conflict, and even relationships that merely look like bias warrant management. The agency recommends each panel organizer keep a publicly available written policy for identifying and handling these issues.⁵

Self-Affirmed GRAS: The Part Most Consumers Don’t Realize Exists

A company can conclude on its own that a substance is GRAS and start marketing it without ever notifying the FDA. The Federal Food, Drug, and Cosmetic Act doesn’t require a company to submit anything to the agency before using a GRAS substance, and the FDA’s 2016 final rule kept the notification procedure voluntary.⁶ A manufacturer can assemble an expert panel, reach a favorable conclusion, file the documentation internally, and go to market.

The FDA encourages companies to submit a GRAS notice rather than rely on self-affirmation, and recommends that companies making independent conclusions follow the same documentation framework used for formal notices.⁷ Encouragement isn’t a mandate. If the FDA later determines that a self-affirmed substance doesn’t meet the GRAS standard, the substance becomes an unapproved food additive, and the food containing it is adulterated. The company carries the full legal risk of that judgment call.

Notifying the FDA

Companies that do choose to notify the FDA submit a GRAS notice organized into seven parts under 21 CFR Part 170, Subpart E. Part 1 identifies the notifier, names the substance, describes the intended conditions of use (food categories, use levels, target populations), and states the statutory basis for the safety conclusion. The notifier must certify that the submission is complete, representative, and balanced, including any unfavorable information. Nothing in Part 1 can be treated as a trade secret; it all becomes public.⁸

The remaining parts cover substance identity and method of manufacture, dietary exposure, the safety narrative, supporting data, references, and any information that could contradict the safety conclusion. That last requirement is worth emphasizing: the notifier has to affirmatively include unfavorable data.⁹

What a “No Questions” Letter Actually Means

The FDA’s response to a GRAS notice is not an approval. When the agency doesn’t take issue with the notifier’s conclusion, it issues what’s commonly called a “no questions” letter. The FDA states plainly that this letter “is not an affirmation” of GRAS status; it simply means the agency found no reason to challenge the notifier’s determination at that time.¹⁰ The legal responsibility for the safety conclusion stays with the company.

If the FDA finds the notice doesn’t support a GRAS conclusion, it says so by letter. The notifier can also ask the FDA to cease evaluating the notice at any point before that final response, which avoids a public record of the agency rejecting the safety basis. The FDA acknowledges the request and makes the acknowledgment public, so the withdrawal itself isn’t invisible, and it doesn’t prevent a later resubmission.⁹ Some companies that withdraw a GRAS notice later resubmit through a food additive petition.

When GRAS Claims Fail

The FDA can and does act when it decides a substance marketed as GRAS doesn’t qualify. Because a substance that fails the GRAS standard is an unapproved food additive, the food is adulterated, and the agency’s enforcement tools include warning letters, seizure, and injunction.

Common triggers include:

Inadequate safety data to support the GRAS conclusion for the conditions of use.
Published literature showing that qualified experts have raised concerns at the intended use levels.
Conditions of use that diverge sharply from the ones covered by existing safety data, such as adding caffeine to alcoholic beverages when the safety data covered its use in cola-type drinks.

The FDA has said that when new uses emerge without any premarket engagement, judging whether consumption patterns remain safe becomes much harder for the agency.⁶ That’s the tension built into the system: the voluntary process means the FDA often learns about a substance only after it’s already on the market, sometimes only when a problem surfaces.

GRAS Versus a Food Additive Petition

A food additive petition requires FDA approval before the substance can be marketed. The agency reviews the petition and, if satisfied, issues a regulation authorizing specific uses.² That process can take years.

A GRAS notice is voluntary and produces no regulation and no formal approval. The safety standard is the same in both routes: reasonable certainty of no harm. The GRAS pathway requires that safety evidence be publicly available and that qualified experts broadly agree, while a food additive petition can rely on proprietary data.⁴ The trade-off is speed and autonomy against regulatory certainty. A GRAS determination gets a product to market faster and leaves the legal risk with the company; a food additive regulation provides a definitive government authorization.

What’s Public and What Isn’t

The FDA maintains a public GRAS Notice Inventory covering every notice filed since 1998, when the agency received its first submission under the notification procedure. Entries list the tracking number, substance name, date of closure, and the type of response letter, and link to full detail pages and, in some cases, to related food additive petitions when a withdrawn notice was resubmitted through that route.⁹

Part 1 of every GRAS notice is fully public. The notifier can request that specific information in the later parts be withheld under the Freedom of Information Act, typically proprietary manufacturing details, but the safety narrative and core technical data generally remain accessible. That means competitors, researchers, and consumer groups can scrutinize any GRAS conclusion that comes through the notification process.⁸ Self-affirmed GRAS determinations that never reach the FDA have no public record at all.

1
Office of the Law Revision Counsel. 21 USC 321 – Definitions; Generally
2
Office of the Law Revision Counsel. 21 USC 348 – Food Additives
3
eCFR. 21 CFR 170.30 – Eligibility for Classification as Generally Recognized as Safe (GRAS)
4
U.S. Food and Drug Administration. Understanding How the FDA Regulates Food Additives and GRAS Ingredients
5
U.S. Food and Drug Administration. Best Practices for Convening a GRAS Panel: Guidance for Industry
6
Federal Register. Substances Generally Recognized as Safe
7
U.S. Food and Drug Administration. Guidance for Industry: Regulatory Framework for Substances Intended for Use in Human Food or Animal Food on the Basis of the Generally Recognized as Safe (GRAS) Provision of the Federal Food, Drug, and Cosmetic Act
8
eCFR. 21 CFR 170.225 – Part 1 of a GRAS Notice: Signed Statements and Certification
9
eCFR. 21 CFR Part 170 Subpart E – Generally Recognized as Safe (GRAS) Notice
10
U.S. Food and Drug Administration. How U.S. FDA’s GRAS Notification Program Works