FDA Issues Final Guidance on Best Practices for Convening a GRAS Panel

FDA Issues Final Guidance on Best Practices for Convening a GRAS Panel

December 22, 2022, Covington Alert

On December 21, 2022, FDA released its final guidance on best practices to follow when convening an expert panel to evaluate whether a substance is “generally recognized as safe,” or GRAS, under the conditions of its intended use in human or animal food. The final guidance retains many of the core elements of FDA’s 2017 draft guidance, with some notable exceptions discussed below.

In FDA parlance, a GRAS panel refers to a panel 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 food. The panel’s determination can help support the conclusion that a substance is GRAS under section 201(s) of the Federal Food, Drug, and Cosmetic Act (FDCA),[1] and therefore does not require FDA pre-market approval as a food additive. Specifically, a GRAS panel provides food ingredient developers with a mechanism to show that the safety of a substance under the conditions of its intended use is “generally recognized by qualified experts,” often referred to as the “general acceptance” prong of a GRAS determination.

In November 2017, FDA released draft guidance on best practices for convening a GRAS panel. The draft guidance addressed longstanding concerns from consumer, health, and food safety groups that the voluntary GRAS system presented an inherent conflict of interest by allowing manufacturers to decide for and by themselves whether a substance is safe to be added to food. To provide industry with best practices for reducing the risk that bias will affect the credibility of the GRAS panel’s conclusion, the draft guidance focused on the following topics:

• identifying GRAS panel members with appropriate and balanced expertise;
• taking steps to reduce the risk that bias will affect the credibility of the GRAS panel’s output including by identifying conflicts of interest and developing strategies to manage and document any conflicts; and
• limiting the data and information provided to a GRAS panel to publicly available information.

Covington’s detailed summary of the draft guidance is available here.

II.      Notable Changes in Final Guidance

FDA received 13 comments on its 2017 draft guidance. Based upon these comments, FDA modified the draft guidance by:

• emphasizing that GRAS panels are not necessary in many instances, and may be insufficient in others;
• expanding background information regarding the value of a GRAS panel in providing evidence to support the “general acceptance” aspect of eligibility for GRAS status through scientific procedures; and
• clarifying policies about evaluating and managing the conflicts of interest, appearance issues, and honoraria for panel participants.

A.        Necessity and Sufficiency of GRAS Panels

Comments on the draft guidance suggested that use of GRAS panels may make the GRAS notification process too burdensome. FDA’s response clarified that “[i]n most cases, a well-supported GRAS conclusion will not need an analysis by a GRAS panel as evidence of general acceptance,”[2] and included new examples in the final guidance to illustrate situations in which a GRAS panel may be unnecessary or insufficient. FDA also clarified that a GRAS panel analysis will typically not be required to demonstrate general acceptance when certain other types of evidence are available, including:

• published peer-reviewed primary studies consistent with generally accepted safety assessment strategies unless the data raises unresolved safety questions;
• secondary literature, such as a review of published primary literature; and
• findings of an authoritative body such as the opinion or recommendations of the National Academy of Sciences.

That said, FDA explained that there may be other circumstances in which a well-constructed GRAS panel may provide the type of evidence needed to conclude that published safety data are generally accepted. One example, as described by the agency, is when multiple studies bearing on the safety of the substance have been published but there are “no secondary sources that evaluate these studies and draw general conclusions based on this comprehensive body of knowledge.”[3] Another example is if “the published results of a particular safety study raises safety questions that require additional data to be resolved.”[4]

In contrast, FDA noted that the use of a GRAS panel does not necessarily guarantee that the “general acceptance” prong of the GRAS standard will be satisfied. GRAS panels may be insufficient, for example, when there is ongoing scientific controversy about safety concerns raised by available data, or when the safe level of intake is only within a narrow range.

B.        Background Information About the Value of a GRAS Panel

FDA clarified that the “primary function” of a GRAS panel “is to reflect the views of the broader scientific community, rather than to reach a scientific judgment on specific data and information.”[5] The panel’s value “is bound up with the extent to which it appears likely that most other scientists with similar training would reach a similar judgment.”[6] FDA carries this explanation forward throughout the final guidance, aiming to distinguish GRAS panels from FDA advisory committees and other bodies that provide independent expert advice to the agency on unresolved scientific, technical, and policy issues.

C.        Evaluating and Managing Conflicts of Interest in GRAS Panels

The final guidance updates and reaffirms various points from the draft guidance on evaluating and managing conflicts of interest to optimize the value of a GRAS panel. New best practices identified in the final guidance include:

• documenting the waiver or monetary thresholds for acceptable conflicts of interest;
• further stressing the need to limit a GRAS panel’s exposure to confidential information to mitigate accusations of bias or perceptions that the panel’s conclusion do not match generally accepted scientific consensuses; and
• clarifying that compensation for panel members is independent from the outcome of the panel’s deliberation.

What Can You Do?

Companies should refer to the final guidance when deciding whether and how to convene GRAS panels when making GRAS determinations for human and animal food ingredients. Interested stakeholders can also submit comments to the docket for the final guidance.

 

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If you have any questions concerning the material discussed in this client alert, please contact the members of our Food, Beverage, and Dietary Supplements practice.