By Robert Martin, Ph.D., EAS Senior Advisor for Food & Color Additive Safety
On August 17, 2016, FDA published a final rule which formally codifies the requirements for GRAS Notices that originated with the GRAS proposal published in 1997. FDA states that the expressed intent of this final rule is to “… clarify the criteria used to determine whether the use of a substance in human or animal food is generally recognized as safe (GRAS)” and applies to GRAS Notices submitted to the Center for Food Safety and Applied Nutrition (CFSAN) and/or the Center for Veterinary Medicine (CVM). The final rule addresses the scientific evidence that should be used to demonstrate safety, the availability of this data in the public domain, and the criteria for formulating this data into a GRAS Notice that would establish a consensus among experts that the material is safe in food and/or animals for its intended use(s).
Overall, this final rule is welcome. However, based on our reading of this document, there are some areas that will need to be clarified and addressed going forward, in particular, expert panels, conflicts of interest, and independent (self-GRAS) GRAS determinations. This document does not go into much detail regarding independent GRAS determinations as it is made clear that FDA prefers GRAS notices. FDA has indicated that it will issue guidance documents in these areas at a later date. The agency did not provide an option to comment on this final rule aside from requesting comments related to the Paperwork Reduction Act only.
The final rule will also change, and codify, some of the terminology used to describe certain actions. For example, “GRAS determination” in the previous GRAS notices will now refer to “GRAS conclusion” or “conclusion of GRAS status.” The new GRAS notices will refer to “signed statements” as opposed to a “claim” in earlier GRAS notices. FDA has established new sections in 21 CFR 170.203 and 21 CFR 570.203 that list the new definitions and terms to be used in future GRAS notices, for food and animals, respectively.
Notable in this final rule, as compared to the proposed rule, is the use of the word “required” by FDA for the new actions and many of the actions performed in GRAS notices based on the proposed rule and FDA guidance documents (See Table 2 – Summary of the Principal Changes to the Proposed Notification Procedure; 81 FR 54969 – 54970).
The format for future GRAS notices will now be divided into seven parts, all of which must be discussed in the document. FDA describes this format in new sections 21 CFR 170.225 through 170.255 and 21 CFR 570.225 through 570.255, respectively, for human food (CFSAN) and animal food (CVM).
One very troubling aspect of this final rule is that FDA has now expressly given itself the option of extending the targeted 180 day review/completion period for another 90 days “… on an as needed basis.” Most notifiers would prefer a shorter review/completion period rather than a longer one.
One predictable outcome of this final rule is that FDA is likely to receive more GRAS notices to review. As discussed, and implied, in the preamble to the final rule, one way for the agency to keep up with the workload is to refuse to accept submissions during their pre-filing review if, in FDA’s opinion, the document does not meet the requirements for GRAS or conform to the prescribed format. Coupling this with the agency’s ability to extend the review to 9 months could result in longer review times.
The GRAS final rule, which becomes effective on October 17, 2016, will present challenges and difficulties in understanding and making certain that all of the requirements are met. Going forward, EAS stands ready to assist all clients in successfully managing these requirements to secure a successful GRAS notice.