An FDA letter underscores a challenge the agency has cited in enforcing a safety-related notification requirement for new dietary ingredients (NDIs): That an exemption may apply.
The exemption excuses dietary supplement manufacturers from having to provide evidence to FDA in a premarket notification that its NDI-containing product “will reasonably be expected to be safe.”
An April 28 letter from Cara Welch, the acting director of FDA’s Office of Dietary Supplement Programs (ODSP), stimulated a continuing debate over the exemption in Section 413(a)(1) of the Dietary Supplement Health and Education Act of 1994 (DSHEA).
Critics describe the exemption to the notification requirement as the so-called GRAS (generally recognized as safe) loophole. Section 413(a)(1) covers NDIs present in the food supply as an article used for food in a non-chemically-altered form.
Welch discussed the exemption in a letter denying a request by Natural Alternatives International Inc. (NAI) to enforce against “generic forms” of beta-alanine that have not been the subject of an NDI notification (NDIN).
She observed FDA bears the burden of showing the above-referenced exemption doesn’t apply. FDA hasn’t reached a final conclusion whether beta-alanine is exempted from the notification requirement based on Section 413(a)(1), but the agency is aware of evidence suggesting the ingredient is present in the food supply in energy drinks, she noted.
“The presence of beta-alanine in the food supply raises significant questions that would need to be answered before FDA would be in a position to demonstrate that certain imported beta-alanine appears to be adulterated,” Welch wrote to Kevin Bell, a lawyer with Arnall Golden Gregory LLP (AGG) and outside counsel to NAI.
Robert Durkin, an AGG lawyer who previously was deputy director of ODSP, suggested FDA could have made a final determination whether the exemption applies to other forms of beta-alanine.
“It seems like a rather weak reason to not take an enforcement or compliance action,” he said during an episode of “short legal briefs,” a video series produced by Natural Products Insider. “FDA has to make that determination for every warning letter, every import alert, every seizure. It just seemed like it was a rather capricious way to say that they didn’t know something before they would take an action.”
An attorney who helped to negotiate DSHEA—Scott Bass of Sidley Austin LLP—suggested it was an “inherent assumption” that most NDIs would go through FDA review, subject to “very limited exceptions of a true food having been on the market—not something that was on the market for six months in a drink.”
Yet FDA has only received about 1,200 NDINs over the last 27 years. Many NDIs in supplements presumably rely on GRAS self-affirmation to demonstrate ingredient safety. GRAS self-affirmation does not involve FDA review and is used for food ingredients.
“The majority of self-GRAS reports—the majority—are garbage,” Bass proclaimed in an interview. “Some are good, but how many? I’m guessing a very small percentage.”
Ashish Talati, a lawyer with Amin Talati Wasserman LLP, said he vigorously disagreed with that conclusion.
“I have worked on over 100-plus GRAS/self-GRAS projects and have seen a lot of them, and they’re not garbage,” he said in an interview. “They’re actually very well done.”
And if he notified FDA about those GRAS projects, the agency would not object to them, Talati predicted.
But many industry professionals have concluded the NDIN requirement is not working as intended by Congress.
“Folks who reasonably hoped that the NDI provision would be an acceptable pathway to ensure that FDA had visibility into the use and safety of new dietary ingredients would have to say that that provision has turned out to be a big disappointment,” attorney Stuart Pape of Polsinelli said in an interview.
He cited “loopholes” and challenges facing FDA “in developing any kind of enforcement strategy.”
“Anytime you let an exemption swallow a requirement, you run the risk that you’ve emboldened less responsible players to take advantage of an exemption that was never intended to be available to them,” Pape added.
Attorney Marc Ullman of Rivkin Radler LLP doesn’t blame the “GRAS loophole” for FDA’s reticence to enforce against generic forms of beta-alanine. Ullman blames FDA for not enforcing the NDIN requirement at the border, where the lawyer said the agency can require an importer demonstrate compliance. He further used words like “sloth,” “lazy” and “neglect” to describe the agency’s response to NAI’s request.
“It’s an outrageous statement evidencing scandalous neglect by a federal regulatory agency,” he said in an interview, commenting on Welch’s letter to Bell. “It’s basically an announcement of, ‘We have no intention of enforcing this part of the regulations until people start dropping dead. Then, we might care.’ And we all know that if there are consumer injuries, FDA will blame ‘the irresponsible dietary supplement industry.’”