Contributor: Mark L. Itzkoff
Principal, The Law Office of Mark Itzkoff, firstname.lastname@example.org
On November 15, 2017, FDA released a proposed guidance document, Best Practices for Convening a GRAS Panel: Guidance for Industry. The Guidance is, in part, a response to 2013 criticism of the GRAS exemption for food ingredients from the Pew Charitable Trust, the Natural Resources Defense Council, and others (for more information on the criticism, see previous blog posts here, here, here and here) regarding the GRAS process in general and the potential for the conclusions of a GRAS panel to be influenced by a conflict of interest. The Guidance would impose substantial new obligations on the company asking for the GRAS panel (the “proponent”) and the consultants and scientists taking part in the panel.
Among the areas discussed in the draft Guidance are (1) the proper considerations for assembling a GRAS panel, including assuring that the panel members have the proper expertise; (2) avoiding real and perceived conflicts of interest; (3) proper operation of the panel and documentation of the deliberations; and (4) honoraria paid to the members of the panel. The agency recommends that companies and consultants working on GRAS issues develop a written GRAS policy that addresses conflict of interest and other issues discussed below. Several of FDA’s recommendations are likely to result in significant cost increases for companies trying to establish the GRAS status of new food ingredients/uses without any corresponding public safety benefit.
The draft Guidance recommends that GRAS panels include members with specific areas of expertise, which could expand the size of the panels, and that the basis for selecting panel members be set forth in the GRAS policy. For example, FDA recommends that panels reviewing the status of botanically-derived substances include a member with expertise in plant chemistry. Currently, a GRAS panel is typically comprised of toxicologists who rely on the chemical analysis of the botanically-derived substance to identify the composition of the new ingredient. The toxicologists focus their GRAS evaluation on published data on the safety of these constituents. Under the proposed guidance, the GRAS panel would include additional members to review the chemistry involved in the botanical reactions that result in the new ingredient. FDA makes similar expertise recommendations for enzymes produced by microorganisms, potential allergens, and other food substances.
FDA identifies several examples of potential conflicts of interest that might disqualify a scientist form participating on the GRAS panel, including ownership interests in the proponent; a role as a director, officer, or employee of the proponent; research funding from the proponent; or a debt relationship between the panel member and the proponent. The conflicts pertain to the panelist as well as the spouse and minor children. FDA also lists situations where there is an appearance of a conflict that should be avoided, such as when the result of the evaluation will have a “direct and predictable effect on the current financial interest of a household member, including adult children and parents, as well as non-relatives in residence.” The agency recommends that policies for managing conflict issues and establishing procedures for screening potential panel members for possible conflicts be included in the GRAS policy.
FDA includes consulting services as an example of a potential conflict of interest. However, FDA does not discuss the overlap between GRAS panelist and business consultants. For example, a panel may review a new ingredient and conclude that additional studies on substances formed during digestion are needed to support a GRAS conclusion. The proponent conducts the additional studies and re-submits the data to the GRAS panel. Do panelists become “consultants” by recommending the additional studies? If so, are they no longer eligible to remain on the GRAS panel?
The agency also sets out new recommendations on the operation of the GRAS panel. Included is a recommendation that the panel document the basis for each member’s determinations and the panel’s deliberations. Currently, it is common practice for the panel to issue a consensus opinion that is signed by all panel members and the basis for the final determination should be fully detailed in the GRAS opinion. Requiring each panel member to prepare an independent statement of the basis for their opinion will increase the time each panel member spends on the review and, thereby, increase the costs to the proponent without any apparent public safety benefit.
In terms of honoraria provided to members of the GRAS panel, FDA recommends that payments to panel members be detailed in the written GRAS policy (discussed above) and that payments not be tied to results, i.e., that panelists not be paid a bonus if they find that a substance is GRAS for the suggested uses. In practice, panel members are often paid for the time spent reviewing the material and reaching a consensus on the GRAS status. If the panelists conclude that a substance is not GRAS, no formal opinion is issued. When a substance is found to be GRAS, a formal opinion is prepared and reviewed, resulting in additional time and fees.
FDA is asking that comments on the draft guidance be submitted to the agency by May 15, 2018.