What is Needed for a Successful GRAS? Part II

“It is not remarkable that consumer confidence in food safety has decreased markedly in the past few years.” (Howard Roberts, Acting Director of the Bureau of Foods, 1976[1])

In his drop-quote below, Director Roberts actually refers to food ingredient safety – and GRAS. Even 18 years after the act passed, FDA and industry still struggled with the meaning of “generally recognized as safe.” By the 1970s, the “easy” GRAS determinations had been added into FDA GRAS lists, and FDA worked on anything missing an agreed upon and clear understanding.

Complicating matters was the recent finding that cyclamate (long held to be GRAS), was a carcinogen and that at least one corrupt animal testing facility had faked data. Accord-ing to Roberts, “the ranks of anti additive consumers are [increasing] every day by constant pressure from activists and a barrage of … misinformation from the media.”

GRAS was under constant attack and FDA couldn’t offer definition for “generally recognized,” nor could the legislative history. Like art or pornography, everyone knew it when they saw it, but no one could describe it to the satisfaction of all. Over time, there have been attempts to redefine GRAS. Most recently, FDA uses the term “technical element” when discussing technical evidence of safety (e.g., animal studies, etc.) and “common knowledge element” when discussing general knowledge and safety acceptance.

In this context, publication of “technical elements” might fulfill the “general knowledge” component, but is still inadequate to demonstrate GRAS because acceptance had not yet been demonstrated. It could well be that “acceptance” would assume primacy in a GRAS determination. This conundrum has been revived in the GRAS Notification proposal wherein criteria for rejection of a Notification includes “… (3) does not convince the agency that there is the requisite expert consensus about the safety of the substance for its intended use or, (4) is so poorly presented that the basis for the GRAS determination is not clear.”

Now, if the agency formalizes the GRAS Notification process without change, will it have Congress’ support to withstand “anti-additive consumer” assaults? Will a lack of acceptance be a barrier to GRAS?

Acceptance is more subjective. Activist claims for a lack of acceptance may rest in the argument that the ingredient is “unhealthy,” citing the phrase “otherwise unfit for food” in §402(a)(3), an argument tried earlier against fatty- and sugar-laden foods that FDA rejected. With the help of the concept of acceptance, it might have renewed traction, though.

Going forward, if the final rule for GRAS Notification maintains the provision for acceptance, what will be the standard? It had been established that that general recognition of safety doesn’t mean totality within the scientific community, but where is the tipping point on safety acceptance and will there be a provision for a standard of “healthiness?” The burden of proof of safety is necessary for a GRAS determination, and the 100% “no objection” rate to Burdock Group’s GRAS Notifications responds to No. 4, stated earlier. However, the additional burden on the GRAS for “acceptance” places a new emphasis on the burden of persuasion in a submission. The burden of persuasion is included in Burdock Group’s GRAS dossiers as a discussion of the theory of approvability, where the totality of information is integrated – not just a record of substance identification, detection and safety. It provides readers with an understanding of why and how the substance can be GRAS. We achieve this with thorough research, a team approach to dossier preparation, selection of the appropriate expert panel members and nearly 30 years of GRAS/ingredient safety experience.

Reference

[1] Roberts, H.R. Food Drug Cosmetic Law Journal 31:404, 1976.