On August 17, the US Food and Drug Administration (FDA) published a Final Rule on the Generally Recognized as Safe (GRAS) notification program, a voluntary premarket notification program for products used in food substances. This Final Rule comes 19 years after the FDA proposed the GRAS notification program in a Proposed Rule, which was intended to shift the premarket program from the GRAS petition process, which involved formal rulemaking, to the less burdensome GRAS notice process. Although the Final Rule is extensive, human food manufacturers can rest assured that the changes to the GRAS notice are not.
The Final Rule provides for nearly the same GRAS Notification as the Proposed Rule, with format being the focus of the changes, rather than substance. The new notification now divides the GRAS notice into seven parts, all of which must be addressed, regardless of applicability:
- Part 1: Signed Statements and Certifications
- Part 2: Identity, Method of Manufacture, Specifications, and Physical/Technical Effect
- Part 3: Dietary Exposure
- Part 4: Self-Limiting Levels of Use
- Part 5: Experience Based on Common Use in Food Before 1958
- Part 6: Narrative
- Part 7: List of Supporting Data and Information in the GRAS Notice
The methods for demonstrating the GRAS status, through common use prior to the 1958 Food Additives Amendment to the Federal Food, Drug, and Cosmetic Act, or through scientific procedures remain unchanged. Establishing a GRAS conclusion through scientific procedures is the most common format for the GRAS notice. This type of notice includes a thorough discussion of the safety of the purported GRAS substance through published scientific literature as well as safety studies conducted by the submitter, where applicable. The Final Rule does not require external studies be performed, but allows for a comprehensive safety profile to be demonstrated through “accepted scientific data, information, or methods, which ordinarily are published, as well as the application of scientific principles, and may be corroborated by the application of unpublished scientific data, information, or methods.”
Note that all information used in the development of the GRAS conclusion must be listed in Part 7, and the narrative in Part 6 is required to include a discussion of any negative data that may exist in the scientific community that is relevant to a conclusion of safety. However, this change is nothing new to those who have filed a notice in the recent past, because this has long been an FDA expectation.
Another interesting aspect of the Final Rule is the ability to include trade secret information and declare that information exempt from Freedom of Information Act requests. But take this with a great deal of caution—first, the FDA may not agree with the claim of exemption. Second, and perhaps more important, if confidential trade secret information is included, the submitter must explain how there can be a general consensus of safety regarding the intended use of the substance in the GRAS notice without considering this data. Therefore, if you can make the GRAS conclusion without using confidential information, you should exclude the information from the notice.
Although formatting changes may be required, those companies familiar with the GRAS process will see little alteration in their notices. For those new to the GRAS process, the Final Rule contains clarifying information that was absent in the Proposed Rule, making the path toward a “No Objection” letter more straightforward.