The implementation of a “generally recognized as safe” (GRAS) notification process for animal feed ingredients has been eagerly awaited for years. It is not surprising, then, that the announcement by the US Food and Drug Administration (FDA) Center for Veterinary Medicine (CVM) of its intent to start accepting notifications this past summer was met with great enthusiasm by the petfood industry.
However, many in the industry are confused as to how to take advantage of this process. I have been told by outside parties that the notifications submitted to FDA to date have not been of suitable quality to effectively evaluate the safety of the substance in question.
To help address this problem, Cantox Health Sciences International
recently held a workshop entitled “How to utilize the ‘new’ GRAS process for
animal food ingredients.” I was honored to be invited to speak at a workshop along
with Cantox employees and a representative from the Association of American
Feed Control Officials (AAFCO). While the audience was relatively small, the
attendees were very enthusiastic and not at all shy in asking questions.
The “new” process is not really that new. In fact, FDA first proposed the GRAS notification process to replace the GRAS affirmation process over a decade ago. Although the regulations proposed in 1997 have yet to be finalized, the center within FDA responsible for human food safety evaluation has been accepting GRAS notifications for many years. However, it was only a few months ago when CVM started doing the same for animal feed ingredients.
Legally, a company has had the ability to conduct a self-determination of GRAS without submission to FDA since enactment of the Food Additives Amendment Act of 1958. However, the newly implemented notification process, wherein a summary of the data considered in the GRAS determination is voluntarily submitted to FDA, has distinct advantages.
While FDA review of the submission does not constitute formal approval by the agency, it does offer some reassurance to the company that its determination of GRAS was not without basis. Also, by public acknowledgement that a reviewed substance raised “no questions” with FDA, there is a means by which consumers and state regulators can verify that the data to support safe use have been evaluated by someone other than the company itself.
The first step in GRAS notification is to compile a dossier of all available information on the substance. To be generally recognized as safe, the bulk of information—and particularly, all of the pivotal data to support safe use—must be in the public domain (e.g., published in peer-reviewed scientific journals). Components of a dossier may include:
- Description of the substance (name, composition, physical form, etc.);
- Description of the manufacturing process;
- Stability, methods of analysis, other specifications;
- Intended use (utility, species, inclusion rates, etc.);
- Data to support safety (target animal, human, environmental); and
- Any evidence that potentially contradicts safe use.
An unbiased expert panel must then review the dossier. A minimum of three panelists should vary in expertise so all aspects are covered. For example, a veterinary nutritionist, a veterinary toxicologist and a scientific authority on the substance in question may be a good complement of expertise for evaluating many petfood ingredients.
The panel discusses the dossier and may ask for more information or investigate further on its own. The panel must reach a consensus that there is reasonable certainty of no harm under the intended conditions of use before a determination of GRAS may be reached. Only then may the sponsor submit the GRAS notification to FDA.
AAFCO definitions rely on “enforcement discretion,” not a formal approval or notification process. Concern has been raised about having so many feed ingredients exist in this regulatory limbo. Thus, with implementation of the GRAS notification process, FDA has indicated its desire to phase out the AAFCO definition process, possibly by the time the FDA/AAFCO Memorandum of Understanding expires in 2012.
In fact, there is discussion that many of the existing AAFCO definitions (especially those established after 1958) will eventually need to be reexamined, and some ingredients may be deleted if safe use cannot be resubstantiated.
FDA intends to post GRAS notifications and the agency’s responses on its website. It is hoped that AAFCO will include in its Official Publication a list of those substances to which FDA had “no questions.” The listing of GRAS notifications through this venue would be of great service to state feed control officials, the petfood industry, consumers and others who may use this resource for determining acceptability of petfood ingredients.