How to File a GRAS Notification with the FDA

A GRAS Notification is a voluntary submission in which a company tells the FDA that it has concluded a substance is Generally Recognized As Safe (GRAS) for a particular use, and provides the evidence behind that conclusion. The FDA reviews the notice and responds with a letter. The process is defined in 21 CFR Part 170, Subpart E and described on the FDA's how the GRAS Notification program works page.

This is an overview of what goes into a notice and how it is filed. It is not legal advice, and the scientific conclusion at the center of a notice must be made by qualified experts.

Notification is voluntary, but valuable

A company may determine on its own that a use is GRAS and market the substance without ever contacting the FDA. So why file? Because a favorable FDA response, the "no questions" letter, provides public, documented assurance that the agency has reviewed the company's conclusion and does not object. That assurance matters to customers, retailers, and downstream manufacturers. The trade-off is the work of assembling a complete, defensible notice.

The seven parts of a GRAS notice

The FDA specifies a seven-part structure, each part with its own section in the regulations:

1. Signed statements and certification (170.225): the GRAS conclusion, who is making it, and the required certifications.
2. Identity, method of manufacture, specifications, and physical or technical effect (170.230): exactly what the substance is and how it is made.
3. Dietary exposure (170.235): how much of the substance people will consume from its intended uses.
4. Self-limiting levels of use (170.240): whether the substance naturally limits its own use level.
5. Experience based on common use in food before 1958 (170.245): if the GRAS conclusion rests on a long history of food use.
6. Narrative (170.250): the reasoned argument that the available data establish safety and general recognition.
7. List of supporting data and information (170.255): the references and evidence relied on.

A complete notice is internally consistent across all seven parts. The exposure estimate has to match the intended uses, the specifications have to match the substance the safety data describe, and the narrative has to actually rest on the cited evidence.

How a notice is submitted

GRAS notices are submitted to the FDA's Center for Food Safety and Applied Nutrition (CFSAN). Submissions are increasingly handled electronically through the FDA's Electronic Submissions Gateway rather than on paper. Once filed, the notice is logged, and if the FDA accepts it for review, it eventually appears in the public GRAS Notice Inventory, where anyone can see the substance, the notifier, and the FDA's response.

What the FDA sends back

After review, the FDA responds with one of a few outcomes. The one notifiers want is a letter stating the agency has no questions about the GRAS conclusion. The FDA may also respond that the notice does not provide a sufficient basis for a GRAS conclusion, or the notifier may ask the FDA to cease evaluation. The agency generally aims to respond within about 180 days.

Where software fits

The scientific conclusion, and the signature on it, must come from qualified people; software does not and should not replace that. What software does well is the assembly and transmission: organizing the seven parts, checking internal consistency, formatting the packet, and transmitting it electronically to the FDA. Ambrose's regulatory compliance platform assembles the GRAS packet and transmits it through the FDA gateway, while the notifier of record and the signed scientific conclusion remain the client's. The result is a faster, more repeatable path from a finished safety assessment to a filed notice.

Sources

• FDA, How the U.S. FDA's GRAS Notification Program Works
• FDA, Generally Recognized as Safe (GRAS)
• FDA, GRAS Notice Inventory
• eCFR, 21 CFR Part 170, Subpart E (GRAS)