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Guidance Issuing OfficeCenter for Veterinary MedicineCenter for Food Safety and Applied Nutrition
This guidance document is intended to provide our recommendations on best practices for convening a “GRAS panel.” By “GRAS,” we mean “generally recognized as safe.” See section II.A for a discussion of the GRAS provision of the Federal Food, Drug, and Cosmetic Act (FD&C Act). By “GRAS panel,” we mean 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 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.
In general, FDA’s guidance documents do not establish legally enforceable responsibilities. Instead, guidances describe FDA’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in FDA guidances means that something is suggested or recommended, but not required.
In this document, we refer to a person who is responsible for a conclusion that a substance may be used in food on the basis of the GRAS provision of the FD&C Act as the “proponent” of GRAS status for that substance under the conditions of its intended use. In many cases, the process whereby the proponent evaluates whether the available data and information support a conclusion that a substance is GRAS under the conditions of its intended use need not include a GRAS panel. However, in some cases, the proponent might decide that the opinion of a GRAS panel may be useful. Depending on the outcome of the GRAS panel’s analysis, the proponent could either reach a conclusion regarding the safety of the substance under the conditions of its intended use, or be advised of one or more issues (such as gaps in the data and information, or alternative interpretations of the available data and information) that warrant investigation before a conclusion can be drawn about whether the substance is safe under the conditions of its intended use.
Importantly, the outcome of a panel’s deliberations does not create or confer general recognition of the safety of the use of an ingredient. Rather, it could provide evidence supporting the proponent’s contention that there is general acceptance based on generally available information among relevant scientific communities. When the outcome of the GRAS panel’s analysis supports the proponent’s conclusion that a substance is safe under the conditions of its intended use, in essence the proponent is relying on the members of the GRAS panel to act as a representative sample of the larger scientific community knowledgeable about the safety of substances directly or indirectly added to food. In so doing, the proponent relies on the outcome of the GRAS panel’s analysis to support the proponent’s conclusion that the safety of the intended use is “generally recognized” by qualified experts. Whether a GRAS panel is a sufficiently representative sample with respect to the larger scientific community depends on a number of factors, such as the subject matter expertise of the members of the GRAS panel and whether the members of the GRAS panel are representative of experts qualified by scientific training and experience to evaluate the safety of the substance under the conditions of its intended use. For example, a “GRAS panel” opinion published by scientists without expertise appropriate to address the applicable safety questions could not provide evidence that the conclusions in the publication are “generally accepted.” Unless both criteria, i.e., “generally available” and “generally accepted,” are satisfied, there would be no basis for a conclusion of GRAS status based on a “GRAS panel” opinion (see Response 11, 81 FR 54960 at 54974, August 17, 2016).
A GRAS panel is just one mechanism that proponents have used to provide evidence of general acceptance in support of their GRAS conclusion. In most cases, a well-supported GRAS conclusion will not require an analysis by a GRAS panel (see Figure 1). We suggest that proponents considering whether a GRAS panel would be useful in supporting their GRAS conclusion consult with FDA before embarking on such an effort. In addition, we realize that it can be challenging to identify, screen, and select a comprehensive panel of qualified experts when specialized expertise applicable to the scientific considerations associated with the intended conditions of use of a food substance is needed, given the potentially finite number of experts who would be both qualified and available to serve on a GRAS panel. Thus, it may be worth considering whether the effort to convene a GRAS panel is warranted in any particular case before allocating resources to it.
This guidance document is intended for and directed to:
- Those proponents who intend to consider the opinion of a GRAS panel in reaching a conclusion that the intended use of a substance in human food or animal food is GRAS;
- Those persons who assemble a GRAS panel and provide the framework for its deliberations (“organizers”); and/or
- Those persons who are interested in our views and recommendations on best practices for convening a GRAS panel.
The recommendations in this guidance address best practices for convening a GRAS panel to:
- 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; and
- 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).
The recommendations in this guidance reiterate certain statutory and regulatory considerations that we have previously discussed regarding the use of a GRAS panel in addressing the GRAS provision of the FD&C Act related to food and food additives (81 FR 54960 at 54966, 54994, and 55000). However, this guidance document is not intended to address the statutory and regulatory criteria that govern eligibility for classification of a substance as GRAS under the conditions of its intended use or to describe the proponent’s responsibilities for complying with those statutory and regulatory criteria. For the most recent discussions of those statutory and regulatory criteria, see the final rule entitled “Substances Generally Recognized as Safe” (81 FR 54960 (the GRAS final rule)) and our guidances entitled “Regulatory Framework for Substances Intended for Use in Human Food or Animal Food on the Basis of the Generally Recognized as Safe (GRAS) Provision of the Federal Food, Drug, and Cosmetic Act: Guidance for Industry” (the regulatory framework guidance) (Ref. 1) and “Frequently Asked Questions About GRAS for Substances Intended for Use in Human or Animal Food: Guidance for Industry” (the GRAS FAQs) (Ref. 2).
Rather, this guidance includes recommendations for GRAS panels that are informed by federal law, regulations, and FDA guidance documents related to FDA advisory committee members. Our reference to these requirements and guidances is solely for the purpose of discussing concepts that are relevant to conflict of interest issues for GRAS panels (the topic of this guidance), rather than to imply that FDA bears the same organizing role in relation to a GRAS panel as it does for an FDA advisory committee or to imply that the processes are wholly analogous. In addition, for more background and information, this guidance notes some available conflict of interest policies from other organizations. This guidance is intended to support the organizers of GRAS panels in their own development of procedures for convening GRAS panels
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Food and Drug Administration
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All written comments should be identified with this document's docket number: FDA-2017-D-0085.