GRAS from the ground up: Review of the Interim Pilot Program for GRAS notification.

After publication of the draft Generally Regarded As Safe (GRAS) rule in 1997, the United States (US) Food and Drug Administration (FDA) initiated an Interim Pilot Program encouraging the notification to FDA of GRAS determinations. This paper analyzes GRAS notifications submitted during the Interim Pilot Program along with warning letters issued during the same time period to better understand the evolution of the program and anticipate the future GRAS landscape. The success of the GRAS Notification program is demonstrated by the increasing rate of GRAS Notifications submitted to the FDA during the Interim Pilot Program, as well as the shift from a primarily domestic process to a process featuring an equal to greater contribution of GRAS Notifications from companies outside the US. Analysis of the first 600 GRAS Notifications revealed a number of interesting trends regarding the inclusion and composition of GRAS Expert Panels; differences in notifications for substances with nutritive, processing aid, or effect; and the duration of GRAS Notifications. The review of FDA warning letters associated with GRAS issues provides additional insight into GRAS notices, from the perspective of ongoing post-market emphasis on food safety with the implementation of the GRAS Final Rule.