By Mark L. Itzkoff
In a recent blog post, we discussed the realignment among some public advocacy groups that resulted in several researchers moving from the Pew Charitable Trusts (Pew) to the Natural Resources Defense Council (NRDC). At the time, we noted that the review process for food ingredients that are generally recognized as safe (GRAS) had been a focus of the PEW researchers, and that this development might have serious complications for companies who voluntarily submit GRAS Notices for FDA review. The exact nature of these complications is now becoming clear.
As detailed in the blog post cited above, substances that are GRAS for a specific application are not subject to the pre-market clearance requirements in the Federal Food, Drug, and Cosmetic Act, (FFDCA), 21 USC §§ 321(s), 342(a)(1)(C)(i),. 348. Under the GRAS Notification Program, a company may submit information notifying FDA tit has made a determination that a substance is GRAS, and providing the basis for the determination. If FDA concludes that the information in the Notice provides a sufficient basis for the GRAS determination and information otherwise available to FDA does not lead the agency to question the safety of the proposed use, FDA will issue a letter stating that it has “no questions” regarding the Notice. (FDA, About the GRAS Notification Program, (March, 2009).
On March 29, 2013, McCormick & Company (McCormick) submitted a GRAS Notice (GRN 466) informing FDA that the company had determined that the emulsifier polyglycerol polyrinioleic acid (PGPR) is GRAS for additional emulsifier applications (PGPR is the subject of 4 previous GRAS Notices). Specifically, McCormick determined that PGPR is GRAS for use in condiments and spreads, flavors and cheese powders used to produce snack foods.
On October 18, NRDC submitted a 7-page letter commenting on the GRAS Notice. In its letter, NRDC enumerates several concerns regarding the scientific procedures used to “justify” the GRAS determination, specifically questioning the dietary exposure calculation, the validity of the toxicology studies used to support the determination and reiterating a concern from a recent Pew study regarding the potential conflict of interest of the scientist who prepared the determination. (For more information on the Pew study, see our August 27, 2013 blog post.) NRDC concludes that “the claim that PGPR is GRAS for the intended uses is incorrect.”
The purpose of this blog post is to discuss some of the general policy issues related to the GRAS Notification Program raised in the NRDC letter. NRDC’s comments regarding the scientific/technical basis for the GRAS determination are questions more properly addressed by the Notifier.
At the beginning, we note that comments on GRAS Notices are highly unusual and it is unclear what NRDC intends to accomplish with its letter. While one objective may be to encourage FDA to require more supporting data from the submitter, that does not appear to be the only purpose. NRDC does not ask FDA to take specific action, such as requesting additional data or issuing a letter stating that the Notice does not provide a sufficient basis for the GRAS determination. In addition, it is our understanding that the NRDC intends to file similar comment letters on other GRAS Notices currently under review. Thus, it is likely that the October 18 comment letter is part of a long-term strategy to have FDA or Congress modify or eliminate the GRAS Notification Program, rather than an effort targeted at one self-affirmed GRAS ingredient.
One specific NRDC area of concern detailed in the letter is the so-called “conflict of interest” that was the subject of the Pew Study. Both the Pew Study and the NRDC comments claim that a conflict of interest arises when the scientist performing the GRAS review or members of a panel (a “GRAS panel”) are employed by the Notifier or by a consultant that is paid by the Notifier. Specifically, they claim the conflict of interest is prohibited under FDA’s draft guidance policy, Guidance for the Public, FDA Advisory Committee Members, and FDA Staff on Procedures for Determining Conflict of Interest and Eligibility for Participation in FDA Advisory Committees.
The policy set forth in that guidance document does not and should not apply to scientists performing GRAS determinations. As the title of the document makes clear, the guidance is intended to apply only to scientists participating in FDA Advisory Committees. A GRAS Panel is not an advisory committee; in fact, since the Notifier makes the determination, the GRAS Panel is actually formed to advise the Notifier, not FDA. Members of FDA advisory committees are either regular government employees or special government employees, while the scientists performing a GRAS determination are employed by either the Notifier or an agent of the Notifier. It is an essential element of the GRAS Notification Program that the GRAS determination has been made by the Notifier, not by FDA (see 21 CFR 170.36(a)(1) proposed). Thus, it is appropriate that any person preforming the determination be compensated by the Notifier.
Further, FDA has announced that it is preparing a guidance document addressing conflict of interest in GRAS determinations, and it is likely that the restrictions set forth in the new document will differ significantly from those in the guidance for advisory committees. NRDC should wait and comment on the new guidance document, rather than ask FDA to impose conflict of interest requirements that were not developed or intended to address the personnel involved in the preparation of GRAS determinations.
Another motive for the NRDC comments may be to establish the basis for future lawsuits against either FDA or individual food processors. NRDC states that the FDA “no questions” letters that are issued when the agency has completed its review of a GRAS Notice and has not identified any problem with the Notice is “an agency action.” Agency action is a prerequisite for most lawsuits against a government agency.
Finally, we note that instead of strengthening the GRAS Notification Program the NRDC comments may actually undermine it. By submitting the comments, NRDC is publicly questioning both the actual safety of PGPR and McCormick’s determination that there is a consensus in the scientific community that would concur with the safety assessment. While it is well established that the “general recognition” required for GRAS status does not require a unanimous opinion among the scientific community and that a “mere conflict among experts” does not preclude GRAS status (see FDA, The GRAS Proposal, 62 Fed Reg 18938, 39 (April 17, 1997)), public debate over the safety of a food ingredient is likely to deter some food processors from its use. Rather than risk being pulled into a public debate over the GRAS Notification Program, ingredient suppliers may opt to market their products based on self determinations without notifying FDA of the determinations. This would mean that FDA would have less information on food ingredients and where/how the ingredients are used.
