The howls of dissatisfaction and quantity of comments relating to the Food and Drug Administration’s (FDA) recent New Dietary Ingredient (NDI) draft guidance has led many to explore alternate routes to market for their ingredients.
Bob McQuate, PhD, CEO and co-founder of Oregon-based GRAS Associates, LLC, told NutraIngredients-USA that his company has seen an “uptick in GRAS determinations inquiries and landed projects,”
“We have had potential clients approach us for self-affirmed GRAS for an ingredient, and they are really interested in dietary supplement use.
“I think it’s going to continue.”
FDA stance
In a recent webinar hosted by the United Natural Products Alliance (UNPA), FDA’s Daniel Fabricant, PhD, stressed that self-affirmed GRAS was not a way around NDI status, but he did concede that he thinks there is “some confusion” in the industry over the issue.
If the ingredient has GRAS status (with or without FDA notification) then the statute states that it needs to have been previously used in foods, said Dr Fabricant, and a company should not think that “GRAS gets submitted and it goes in a supplement”.
Quoting from the NDI draft guidance, Dr Fabricant asked, “Has the ingredient been used in the food supply and is to be used as a NDI without being chemically altered?”
The road to grief?
Loren Israelsen, executive director of UNPA and host of its recent webinar said that the current state of knowledge on this topic “starts with confusion”.
“My understanding is that GRAS affirmation provides exemption to NDI status, and this will allow a company to take a different pathway to establish a lawful ingredient.”
“But if companies are going to consultancies and using GRAS as a surrogate to NDI status because they consider it easier, then they need to have the history of use somewhere in the world, and the additional toxicological data.”
Ashish Talati from Chicago-based law firm Amin Talati, LLC, agreed that companies do need to show usage in food.
“What companies can do is self-affirm the GRAS status and then sell the ingredient as a conventional food. The ingredient is then exempt from the NDI process, assuming the conditions of use are the same as for GRAS,” said Talati.
Central depository
So if companies can self-affirm, how does FDA know? It doesn’t, said Israelsen. There is not central depository or composite listing of which ingredients are self-affirmed GRAS. The only public record of this would be if a company makes a public disclosure.
(There is an exception to this: The Flavor and Extract Manufacturing Association (FEMA) has been doing its own GRAS determinations and sharing this with FDA.)
So what happens if FDA sees a dietary supplement with an ingredient that is self-affirmed GRAS? The ingredient supplier obviously considers that is has fulfilled its regulatory burden.
FDA, on the other hand, would see a product that contains an ingredient that is neither an old nor new dietary ingredient, and the agency has also not been notified about the GRAS status of the ingredient.
“If the Agency cannot find a status for the ingredient, then is the default position for FDA that it is an unapproved substance and therefore an adulterant?” asked UNPA’s Israelsen. “Does this road lead to grief at some point?”
Ashish Talati said FDA would have to contact the company, and would say “we [FDA] think this is an NDI”. The company would then prove the ingredient is self-affirmed GRAS, he said.
Dr McQuate explained that self-affirmed GRAS shifts the burden of proof to FDA. “FDA cannot challenge this unless it has evidence to suggest the ingredient is not safe.
“The ingredient is legal and can be marketed without a food being ‘adulterated’.”
“If you submit a GRAS notification to FDA and the Agency doesn’t agree, the ingredient’s self-affirmed status still holds [based on ‘reasonable certainty of no harm under the intended conditions of use’],” he noted.
Rigor
Another concern raised by Dr McQuate is the presumption that self-affirmed GRAS is as rigorous as a GRAS notification to FDA. “This is questionable,” he said.
Dr McQuate noted that he has experience firsthand of this, with a potential client unhappy with his requests for greater characterization of a substance being met with the potential client ‘shopping around’ until it found a consultancy willing to self-affirm the GRAS status of the poorly characterized material.
“Self-affirmation of GRAS status does present an opportunity for abuse.”
GRAS Associates has one standard for GRAS, whether it’s for self-affirmation or FDA notification, said Dr McQuate. The company operates a two-step evaluation. The preliminary GRAS assessment is light weight (and the cost is also light) and if this is positive, then the client can choose to advance to the second, comprehensive GRAS assessment, which can yield self-affirmation or notification to FDA.