FDA Advances Mandatory GRAS Notification Rule Following OMB Review

The Food and Drug Administration's proposed rule requiring mandatory notification of Generally Recognized as Safe (GRAS) determinations has moved to the Office of Management and Budget for interagency review as of December 2025, signaling a potential paradigm shift in how new food and supplement ingredients reach the market.

The proposed regulation would fundamentally alter the current voluntary notification framework, under which companies can either notify the FDA of their GRAS conclusions or begin marketing substances without any agency interaction. Industry observers note this change could represent the most significant evolution in food ingredient oversight since the GRAS provision was established under the 1958 Food Additives Amendment.

Understanding the Current GRAS Framework

Under existing regulations, companies have three pathways when introducing new food substances. First, they can submit a formal food additive petition requiring premarket approval—a process that typically takes years and significant resources. Second, they can conduct a GRAS determination and voluntarily notify FDA, receiving a "no questions" letter or other feedback within 180 days. Third, and most controversially, they can make a self-GRAS determination and introduce ingredients without any FDA notification or oversight.

According to regulatory experts, this third pathway has drawn increasing scrutiny from both lawmakers and public health advocates. The Senate Health, Education, Labor and Pensions (HELP) Committee highlighted this regulatory gap in recent oversight activities, noting that dozens of ingredients may enter the food supply annually through self-GRAS determinations with limited independent safety review.

Robert F. Kennedy Jr., recently appointed to a health policy advisory role, has publicly criticized what he characterizes as insufficient ingredient oversight, though the Senate HELP Committee's recommendations have focused on tightening procedures rather than eliminating self-GRAS determinations entirely.

Key Provisions of the Proposed Rule

While the full regulatory text remains under OMB review, industry sources familiar with the proposal indicate the mandatory notification requirement would apply to:

• All new GRAS determinations for substances not previously used in food or supplements
• Novel uses of existing GRAS substances at significantly higher concentrations
• Ingredients derived through new manufacturing processes or extraction methods
• Substances with limited consumption history in the United States, even if used internationally

The proposed rule would establish standardized documentation requirements, including comprehensive safety data, consumption estimates, and expert panel qualifications. Companies would need to submit notifications within a specified timeframe before commercial distribution, with FDA retaining authority to request additional information or issue safety concerns.

"This represents a fundamental shift toward proactive oversight rather than reactive enforcement," noted one Washington-based regulatory consultant who works with supplement manufacturers. "Companies will need to build notification timelines and potential FDA questions into their product development cycles."

Industry Response and Operational Impact

The supplement and functional food industries have expressed mixed reactions to the pending rule. Larger manufacturers with established regulatory affairs departments generally support increased standardization and transparency, viewing mandatory notification as a mechanism to level the competitive playing field and enhance consumer confidence.

However, smaller companies and ingredient suppliers have raised concerns about the administrative burden and timeline implications. Industry trade groups estimate that preparing comprehensive GRAS notifications can cost between $50,000 and $200,000 depending on the ingredient's complexity and available safety data.

The Natural Products Association has advocated for streamlined procedures for ingredients with substantial historical use documentation, while the Council for Responsible Nutrition has emphasized the importance of maintaining innovation pathways for novel ingredients backed by robust safety evidence.

For companies developing innovative supplement formulations, mandatory GRAS notification could add 6-12 months to product launch timelines, particularly if FDA requests additional information or clarification. This timeline consideration may influence strategic decisions about ingredient selection and reformulation priorities. Manufacturers can use tools like PharmoniQ's Supplement Checker to evaluate ingredient profiles and regulatory status as part of their product development process.

Looking Ahead: Implementation Timeline and Strategic Considerations

Following OMB review—which typically takes 90-180 days for significant regulatory actions—FDA will publish the proposed rule in the Federal Register, triggering a public comment period likely lasting 60-90 days. Based on historical precedent for major food safety regulations, a final rule could be issued 12-18 months after the comment period closes, with an additional transition period before enforcement begins.

Industry stakeholders should anticipate that any final rule will include provisions for substances already in commerce under self-GRAS determinations, though the specific treatment of these "legacy" ingredients remains a key question awaiting clarification.

Companies should begin evaluating their ingredient portfolios now to identify substances that may require GRAS notifications under the new framework. This preparation period offers an opportunity to gather safety data, establish expert panels, and develop notification documentation before compliance becomes mandatory. Understanding the regulatory landscape for supplements will be essential for navigating this transition successfully.

As the regulatory landscape evolves, proactive engagement with the rulemaking process through substantive public comments will be critical for shaping implementation provisions that balance safety oversight with innovation and market access considerations.