CVM GRAS Notification Finally Arrives

On Friday, June 4, the FDA Center for Veterinary Medicine (CVM) published an announcement regarding a Generally Recognized as Safe (GRAS) Notification program (Substances Generally Recognized as Safe Added to Food for Animals; Notice of Pilot Program).[1]  However, while the announcement is a good start and pledges fidelity to the Center for Food Safety and Applied Nutrition’s (CFSAN) 1997 “Substances Generally Recognized as Safe; Proposed Rule”[2], there are some inconsistencies with the CFSAN Proposed Rule and some issues left unaddressed that have been foci of concern for both CVM and the stakeholders.

Early in the announcement, there appears to be an incongruity regarding eligibility for participation, in that at the header titled “DATES” the following language is used: “Submit written requests to participate in the pilot program”.  However, the first line in Section III of the announcement indicates that “Any person may notify FDA of a claim [for GRAS exemption]…”  Presumably, this is not an inconsistency, but an encouragement to prospective Notifiers for a pre-Notification meeting with CVM. However, does this pre-Notification meeting represent an opportunity for CVM to head off a potential Notification of a substance CVM has decided embodies too much “risk”? In the past (as recent as September, 2009), FDA personnel described GRAS as a pathway for substances of low priority for regulation (much akin to those currently eligible for “regulatory discretion” letters). Does this mean that those substances with potentially higher “risk” would be forced into the food additive petition queue?  Presumably, heading a GRAS determination off at the pass before it is declared GRAS and subsequently Notified, would prevent a potentially embarrassing high rejection rate as is seen with CFSAN’s New Dietary Ingredient Notification program (~70% rejection rate).  But, such a pre-GRAS determination selection process infringes on the entitlement of any manufacturer to determine the statutory route by which his substance may become compliant i.e., GRAS or Food Additive Petition.  Judgment of a Notification or validity of a GRAS determination solely on the basis of CVM’s determination of potential “risk” is not a call CVM is empowered to make; this is a GRAS Notification process (proposed 21CFR170.36), not a GRAS Affirmation process (21CFR170.35 or 570.35).

The announcement also engages in some redefining the working practices at CFSAN in section I.B. “Elements of the GRAS Standard”.  First, the announcement declares that “…use of a substance that is GRAS requires both technical evidence of safety and a basis to conclude that this technical element of safety is generally recognized.”  The “technical element” refers to the rigor of test data supporting the determination and the cases cited are generally rooted in the Weinberger v. Hynson et al.[3] decision, wherein the “substantial evidence” doctrine is applied: