How The U.S. FDA’s GRAS Notification Program Works

Understanding GRAS, its history, processes, and strategic value for food-ingredient regulation

The U.S. Food and Drug Administration (FDA) play a pivotal role in regulating most of the food supply in America. Its Center for Food Safety and Applied Nutrition (CFSAN), particularly the Office of Food Additive Safety, evaluates the safety of food ingredients and packaging components. Among the regulatory paths available, “Generally Recognized as Safe” (GRAS) holds a unique position, allowing certain substances to be used without the full premarket approval required for food additives.

This article explains the GRAS concept, the mechanism of the GRAS Notification Program, how it differs from food additive approval, and strategic considerations for ingredient manufacturers.

1. Historical & Legal Background

• In 1958, Congress enacted the Food Additives Amendment to the Federal Food, Drug, and Cosmetic Act (FD&C Act). This required premarket approval for new food additives but also included an exclusion: substances recognized by qualified experts as safe under intended use (i.e. GRAS) are not regulated as “food additives.”
• A GRAS conclusion must be based on widely known, peer-reviewed data and broad expert consensus, such that the substance is excluded from the food additive definition if safe under its intended use.
• Because GRAS is an exclusion rather than affirmative approval, the manufacturer or notifier carries the burden to justify safety.

2. GRAS vs Food Additive: Key Distinctions

• A GRAS determination only holds under the intended conditions of use. If use changes (dose, food matrix, population), the safety must be reassessed.
• GRAS by “common use in food” is a historical pathway (for substances used before 1958) but is seldom used today. Most modern GRAS conclusions use scientific procedures.

3. GRAS Affirmation & Notification Evolution

• In the 1960s–1970s, FDA used a GRAS Affirmation Petition process to re-evaluate substances. However, this process proved resource intensive.
• In 1997, the agency proposed replacing affirmation with a GRAS Notification Program, which would allow a notifier to inform (not petition) FDA of a GRAS conclusion. FDA would review but would not formally “approve” or be bound to the timeline.

4. How the GRAS Notification Program Operates

4.1 Submitting a GRAS Notice

• A notifier may request a pre-submission meeting with FDA to clarify expectations.
• The submission must go to the Office of Food Additive Safety (CFSAN).
• The notice should include:
     • A GRAS exemption claim describing the substance, intended use, and the       

        basis for the GRAS determination (scientific procedures or common use).
   • Identity and chemical properties of the substance
   • Manufacturing process and specifications
   • Toxicological, metabolism, and exposure data
   • Safety studies or published literature supporting the GRAS status
   • Discussion of any conflicting or adverse data and rationale for concluding safety

4.2 FDA’s Response

• Within 30 days, the FDA acknowledges receipt of the notice. Then it evaluates whether the notice provides a sufficient basis for GRAS and whether there are questions of safety or data gaps.
• FDA issues one of three response letters:
    1. No questions currently — FDA does not question the notifier’s conclusion
    2. Insufficient basis” — FDA finds issues or data gaps that prevent supporting         the GRAS determination
    3. Cease evaluation at notifier’s request
• FDA also uses a public inventory of GRAS notices and responses, accessible online.

5. GRAS in Practice: Trends & Data

• As of 2024, FDA continues to receive dozens of GRAS notices per year; e.g. 57 substances submitted in 2024, most still pending.
• Many GRAS determinations never submit notices; the “self-affirmed GRAS” loophole has drawn regulatory scrutiny, and recent policy directions propose tightening oversight.
• The FDA aims to respond within 180 days under the food additive petition timeline, but GRAS notices often take longer due to complexity or resource constraints.

6. Strategic Considerations for GRAS Notifications

• Choose whether to submit a GRAS notice or rely on self-affirmation. Note that self-affirmation carries enforcement risk if challenged.
• Use a qualified expert panel and ensure safety data meets the same quality as that for food additives.
• Maintain transparency: include negative or conflicting findings and defend the overall safety case.
• Monitor scientific literature and regulatory developments (especially around GRAS reform) as FDA has been directed to examine the GRAS pathway.
• Use public GRAS inventory data to benchmark similar submissions and anticipate FDA concerns.

Conclusion: Ensuring GRAS Compliance with Confidence

Navigating the U.S. FDA’s GRAS Notification Program requires a deep understanding of regulatory science, risk assessment, and evolving policy landscapes. From preparing a scientifically robust safety dossier to managing expert evaluations and FDA correspondence, every step demands precision and transparency.

As global food innovation accelerates, aligning product development with GRAS and food additive regulations is not just a compliance requirement, it’s a strategic advantage that ensures market access, consumer safety, and brand credibility.

At Maven Regulatory Solutions, we specialize in simplifying complex regulatory pathways for food ingredients, offering end-to-end support in GRAS determination, dossier preparation, safety data evaluation, and FDA submission strategies. Our expertise ensures your innovations are both compliant and commercially viable in the dynamic U.S. market.

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