FDA agrees to finalize the GRAS Notification process

By George Misko in Regulatory on January 06, 2015

Many packaging materials are used on the basis that they are “generally recognized as safe” (GRAS) by the U.S. Food and Drug Administration (FDA), a process which can quickly clear the way for products to be used commercially. However, the GRAS review process itself has been under review for some time, and FDA has now agreed to bring it to a conclusion.

Under a Consent Decree issued by the U.S. District Court for the District of Columbia, FDA has agreed to issue a final rule on its GRAS review program by Aug. 31, 2016. The Decree was entered as part of a settlement of a lawsuit filed by the Center for Food Safety (CFS) against FDA in February 2014.

CFS claimed that FDA was operating its GRAS Notification Program under a 1997 proposed rule that was never subject to final rulemaking, essentially making the program illegal under the Administrative Procedure Act (APA). The Center petitioned the court to vacate the 1997 proposed rule. To understand the significance of this latest activity, a little history lesson is in order.

 

Born in the USA

The GRAS concept was born with the Food Additives Amendment Act of 1958, which exempted substances from the definition of a "food additive" and formal preclearance requirements, if they are “generally recognized, among experts qualified by scientific training and experience to evaluate [their] safety, as having been adequately shown through scientific procedures (or, in the case of a substance used in food prior to Jan. 1, 1958, through either scientific procedures or experience based on common use in food) to be safe under the conditions of its intended use.” (21 U.S.C. §321)

FDA mandates that the same quality and quantity of scientific data required to support a food additive petition are needed to support a GRAS determination. It also requires that the critical data supporting the conclusion (usually, toxicology data) be published (in a peer review journal, for example) or otherwise available to the relevant scientific community. However, there is no requirement that the data be provided to FDA prior to marketing a product on this basis. (See 21 CFR §170.30)

In 1958, FDA published a list of GRAS substances, which was originally incorporated into 21 C.F.R. Part 182. Since many substances that were considered GRAS by industry were not included on the GRAS list, manufacturers would write FDA and request the Agency’s opinion on the GRAS status of a substance. FDA would respond with an informal opinion letter. Importantly, these letters were often only available to the requestor and were not binding on the agency. FDA discontinued issuing informal GRAS opinion letters in 1970.

Following a comprehensive review of GRAS substances, FDA conducted a rulemaking in 1972 to establish a voluntary GRAS affirmation petition process. Under the process, an individual could petition FDA to review the GRAS status of a substance. FDA would publish a notice of the filing in the Federal Register, request comments, conduct a comprehensive review and then publish a final rule in the Federal Register, if warranted. However, by the late 1980’s, once a GRAS petition was "accepted for filing," petitioners would start marketing their products and FDA often did not bother to take final action on the petition.

 

Birth of the GRAS Notification (GRASN) process

The GRAS affirmation petition process was ineffective and created a backlog of petitions, which led to the 1997 GRAS Notification proposed rule, explained FDA’s Dr. Antonia Mattia, director, Division of Biotechnology and GRAS Notice Review at a 2013 Food and Drug Law Institute meeting. While the rule was never finalized, the agency started accepting GRASNs in 1998 as a substitute for GRAS Affirmation Petitions. In December 2010, FDA requested further comments on the proposed 1997 GRASN procedure with an eye to taking final action on the proposal.

Under the GRASN procedure, a company may notify FDA that a particular use of a substance has been determined to be GRAS, and provide the same type and quality of data to the agency as in the petitioning process. In this case, though, FDA is under no obligation to grant or deny a petition as part of a regulatory process.

Instead, after evaluating  the data, FDA will inform the notifier that: (1) the agency has no questions for the notifier with respect to its GRAS determination at this time, or (2) the agency has determined that the notice does not provide a sufficient basis for a GRAS determination. FDA may also cease to evaluate the GRAS notice at the notifier's request. The GRASN and FDA’s response are published on the agency’s website.

To date, there have been almost 500 GRAS Notifications submitted to FDA. Of those received by December 31, 2012, FDA had “no questions” for 79%, and determined that 4% did not provide a sufficient basis for a GRAS determination. The notifier stopped the process in 17% of the cases.

With settlement of the suit, it appears that the GRASN program will continue to live in the way that it has since 1998, and continue to serve FDA’s goal of eliminating resource-intensive rulemakings and providing manufacturers with an incentive to inform FDA of their GRAS determinations, as FDA’s Dr. Mattia put it. It is just that now, it will be done through a program that has been adopted by the agency through more regular procedures.

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