U.S. FDA GRAS Certification: Challenges, Success Factors, and Strategies

As global demand for clean-label and compliant food products continues to rise, the FDA GRAS certification has become a widely recognized benchmark for product safety in the U.S. market. While self-affirmed GRAS remains legally permissible, the FDA-notified GRAS pathway offers stronger regulatory credibility and can significantly enhance a product’s market acceptance.

However, navigating the GRAS process is far from straightforward. An in-depth analysis of GRAS notifications submitted over the past five years reveals common pitfalls that often result in FDA evaluation delays or terminations, and highlights what successful applicants are doing differently.

What Is GRAS Certification?

GRAS (Generally Recognized As Safe) is a regulatory category defined by the U.S. Food and Drug Administration (FDA). It applies to food substances that are generally recognized, among qualified experts, to be safe under the conditions of their intended use.

There are two recognized GRAS pathways:

• Self-Affirmed GRAS: A company assembles a qualified expert panel to evaluate and document the safety of the substance. No FDA notification or public disclosure is required.
• FDA-Notified GRAS: The company submits a GRAS dossier to the FDA for formal review. If the FDA has no objections, the notification is published, giving the product greater transparency and market trust.

Why Pursue FDA GRAS Notification?

While self-affirmed GRAS allows for lawful market entry in the U.S., FDA notification provides third-party validation and enhanced regulatory credibility. This is especially important for:

• International product exports
• Gaining retail and distributor trust
• Reducing compliance risk
• Supporting clean-label marketing claims

Top Reasons GRAS Applications Fail: What the FDA Objections Reveal

Between January 2019 and January 2024, the FDA discontinued evaluations of 62 GRAS notifications. A closer review of 54 dossiers (excluding 8 with limited feedback) revealed the following common causes for termination:

Key Takeaways:

• The Safety Narrative is the most critical and frequently challenged section. Issues include lack of robust data, incomplete comparisons with similar substances, or insufficient toxicology.
• Dietary exposure assessments are often flagged for using outdated data, flawed models, or incorrect assumptions.
• Substance-specific details—such as manufacturing methods and product specifications—are often lacking in clarity or depth.

What Successful GRAS Notifications Have in Common？

To understand what differentiates successful submissions, we analyzed 72 FDA “No Questions” responses issued between January 2023 and the present. Here’s what the data shows:

What This Means:

• Nearly all successful GRAS dossiers (97.2%) made updates to substance characterization, including identity, production method, and technical specifications.
• Corrections to exposure models, use conditions, and safety analysis were also common.
• Successful applicants were often able to resolve FDA concerns related to substance data, but safety narrative weaknesses were much harder to overcome.

How to Strengthen Your GRAS Dossier: Practical Tips

Build a Robust Safety Narrative

• Include comprehensive toxicological studies (acute, subchronic, genotoxicity, ADME, etc.)
• Provide a thorough literature review with both supporting and contrary data
• Reference regulatory opinions from EFSA, JECFA, or other authorities when available

Ensure Exposure Estimates Are Scientifically Sound

• Use updated food consumption data
• Clearly link use levels with exposure calculations
• Justify assumptions and include margin of safety calculations

Present Substance Characteristics Fully

• Include three non-consecutive batch analyses for specs
• Disclose production parameters, raw material quality, and any use of GMOs
• Address potential contaminants such as heavy metals, solvents, mycotoxins

Beware of Confidentiality Risks

When pursuing FDA GRAS notification, any data submitted—including proprietary manufacturing processes or in-house studies—may become public. If the FDA raises questions that touch on commercial secrets, applicants must either disclose the information or withdraw the notification.

Pre-submission planning is essential to balance transparency and trade secret protection.

Conclusion: FDA GRAS Is Achievable—With the Right Strategy

The path to FDA GRAS approval is complex but manageable with the right technical and regulatory approach. Understanding the common pitfalls—and aligning your submission to FDA expectations—will significantly boost your chances of success.

Need Help with GRAS Certification?

REACH24H’s regulatory experts offer end-to-end GRAS consulting services, including:

• Feasibility analysis
• Data gap assessments
• Toxicology and exposure modeling
• Dossier preparation and FDA submission

Let our experience support your product’s success in the U.S. food market.

Contact us to learn more about our one-stop GRAS certification services.