On November 15, the US Food and Drug Administration (FDA) published a draft guidance on best practices to help parties interested in convening a panel of experts to evaluate whether a substance is “generally recognized as safe” (GRAS) under the conditions of its intended use.
Background
As previously discussed, the FDA last year published a Final Rule on the GRAS notification program, a voluntary premarket notification program for products used in food substances (GRAS notification procedure). This Final Rule was promulgated 19 years after the FDA established the “interim” GRAS notification program in a Proposed Rule.
A substance that is GRAS under the conditions of its intended use is not a “food additive” and is therefore not subject to mandatory premarket review by FDA under section 409 of the Federal Food, Drug, and Cosmetic Act (the FD&C Act). For a substance to be GRAS under the conditions of its intended use, two criteria must be met:
- The use of the substance must meet the same safety standard as a food additive: there must be a reasonable certainty of no harm under the conditions of its intended use; and
- The use of the substance must meet the general recognition standard: the intended use of the substance in food must be recognized as safe by qualified experts based on publicly available scientific information.
One method that proponents of a substance may use to establish that their substance is GRAS is through the use of a “GRAS panel.” A GRAS panel is a group of qualified experts who independently evaluate whether the available scientific data, information, and methods establish that a substance is safe under the conditions of its intended use in human food or animal food as part of an evaluation of whether adding that substance to food is lawful under the GRAS provision of the FD&C Act.
Guidance Document
The draft guidance document provides the following best practices for convening a GRAS panel:
- Identify GRAS panel members who have appropriate and balanced expertise
- Take steps to reduce the risk that bias (or the appearance of bias) will affect the credibility of the GRAS panel’s output (often called a “GRAS panel report”), including the assessment of potential GRAS panel members for conflict of interest and the appearance of conflict of interest
- Limit the data and information provided to a GRAS panel to public information (e.g., by not providing the GRAS panel with information such as trade secret information)
Takeaways
One of the most interesting takeaways from the draft guidance document is that it includes considerable discussion on the notion of bias and/or the appearance of bias affecting the credibility of the GRAS panel’s final output. FDA understands and anticipates the possibility of proponents “stacking” their GRAS panels with experts that would inevitably give them a favorable conclusion on their proposed substance. Thus, while a GRAS panel is not a federal advisory committee under the Federal Advisory Committee Act (5 U.S.C. App.), the FDA strongly suggests that GRAS panel organizers develop conflict of interest policies and look, to the extent possible, at the relevant statutory and regulatory requirements applicable to federal advisory committees (found in 18 U.S.C. § 208(b), 21 U.S.C. § 379d-1, 5 C.F.R. Part 2640, and 5 C.F.R. § 2635.502), as well as policies adopted by other relevant organizations (e.g., National Academies of Sciences, Engineering, and Medicine (NASEM), National Academy of Medicine (NAM) the Flavors and Extract Manufacturers Association of the United States (FEMA)). Such material can assist in the determination of whether a GRAS panel member has a potential conflict, or the appearance of a conflict, of interest and whether participation in a panel meeting is appropriate. At the same time, FDA recognizes that there may be instances in which the need for an individual’s service outweighs the potential for a conflict of interest or appearance issue in order to provide the GRAS panel with essential expertise.
Continuing with the theme of transparency and integrity in the process, another interesting takeaway from the draft guidance document was an emphasis surrounding concerns over providing non-public information (e.g., confidential and trade secrets) to the GRAS panel to inform their deliberations. As discussed in our blog post on the GRAS Final Rule, while a general recognition of safety may be corroborated by the application of non-public information, the proponent for the substance must explain how there can be a general consensus of safety regarding the intended use of the substance without considering this data. An exception to this concerns non-public information that could raise a question about the safety of the substance under the conditions of its intended use. Hence, to the extent possible, GRAS panel organizers should minimize the amount of non-public information provided to GRAS panels.
Conclusion
The draft guidance is available for public comment until by May 15, 2018 (Docket No. FDA-2017-D-0085). Feel free to reach out to the authors of this post for more information or assistance with drafting comments.