FDA ‘enforcement discretion’ on NDIs takes back seat to finalizing overall NDIN guidance

The Food and Drug Administration disclosed in a recent letter to a U.S. congressman that it is continuing to review comments submitted regarding a draft guidance of enforcement discretion targeting delinquent ingredient notifications that are applicable to distributors and manufacturers of supplements.

The goal of the May 2022 guidance was to encourage companies to correct past failures to submit a notification to FDA for new dietary ingredients (NDIs) marketed in supplements. As noted by an FDA official three years earlier, “an effective NDI notification process represents FDA’s only opportunity to evaluate the safety of a new dietary ingredient before it becomes available to consumers.”

It’s now clear that finalizing the 2022 document is less of a priority for FDA than completing various sections of its overall NDI notification guidance. FDA is finalizing the NDIN guidance in discrete sections starting with a guidance published in March on NDI time frames and procedures.

“The FDA continues to review comments submitted regarding the draft guidance on enforcement discretion for never filed NDINs as part of our consideration of a final guidance,” an FDA spokesperson told Natural Products Insider in an email. “However, based on some initial reactions to the draft guidance, we are prioritizing our efforts to finalize the different sections of the overall NDIN draft guidance to ensure the dietary supplement industry has our current thinking on how to prepare and submit NDI notifications.”

Related:FDA NDI guidance: Five key takeaways

This pivot by FDA is consistent with what some industry trade associations advocated for: addressing the substantive NDIN guidance first. In the words of Council for Responsible Nutrition (CRN) President and CEO Steve Mister, one of several people to be interviewed for this article, the agency “put the cart before the horse” by issuing an enforcement discretion guidance before detailing circumstances in which firms must file a notification.

“FDA must provide the clarity that we’re looking for so that companies can make an educated decision of whether their ingredient is new,” Mister said. “And then let’s talk about how you have enforcement discretion after the fact to go clean up the things that are out there that people thought they didn’t have to file on.”

Perhaps FDA officials realized “they got ahead of their skis” and determined they would put the enforcement guidance on the back burner, he added.

Robert Marriott, director of regulatory affairs with the American Herbal Products Association (AHPA), said FDA should clarify its expectations and standards on evaluating notifications before issuing a final guidance on enforcement discretion. After FDA implements a period of enforcement discretion, it must start “enforcing consistently” based on expectations it sets with the industry, “and that means more strictly than [officials] have in the past,” he added.

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“I found it strange that FDA came out with the enforcement discretion guidance before going final with meaningful portions of the 2016 NDIN draft guidance,” said Bob Durkin, a lawyer with Arnall Golden Gregory LLP and a former FDA official with the Office of Dietary Supplement Programs (ODSP).

If part of regulated industry is reticent to file NDI notifications with FDA based on a “lack of understanding of the 2016 guidance,” FDA should clear up the confusion prior to issuing a final document on enforcement discretion, he said.

He added not all firms that have failed to file are similarly situated.

“There are some players on the market that should have filed NDINs that haven’t because they’re confused, and then there are some on the market that haven’t filed NDINs, and they’re not at all confused,” Durkin said. “They know exactly what has to be done and they’re choosing not to do it.”

United Natural Products Alliance (UNPA) President Loren Israelsen suggested that a final guidance regarding enforcement discretion could be meaningful if FDA clarified and backed away from many of its positions in the 2016 NDIN guidance that industry found controversial, such as the myriad manufacturing changes triggering an NDI.

“If we have clarity on those issues, [and] if FDA were to back away from that thinking, and then say, ‘Here’s a moratorium, we tried to respond and give you most of what you objected to,’ then we may have something interesting,” he said.

If those circumstances don’t materialize, Israelsen found it difficult to conceive of a circumstance in which someone would choose to file a delinquent NDI under an amnesty period.

“It would have to be a really important ingredient that has high commercial potential,” he said. “Bottom line, it just feels like the traffic flow has established itself. You know what speed basically you need to stay within and for the regulator not to ‘red flag’ you, and I just don’t see many companies stepping out of that traffic flow.”

Mister suggested an enforcement discretion guidance could offer benefits to firms uncertain about whether an ingredient is subject to the notification requirement, though he agreed some substances “clearly fall within the notification requirement, and there are some companies that are just ignoring it.”

He said his trade organization is frustrated “that there are so many examples of things where companies should be filing and are not. And I don’t think enforcement discretion is going to make them come forward.”

FDA must use “a stick in those cases,” he proclaimed. “A carrot’s not going to work.”

In a May 28 letter to Rep. Jeff Duncan (R-S.C.), FDA acknowledged noncompliance with the notification requirement.

“As you noted, FDA is aware that some manufacturers and distributors have marketed products for which a premarket notification under section 413(a)(2) of the FD&C Act was required, but never submitted,” Erin O’Quinn, acting associate commissioner for legislative affairs, wrote to Duncan. “The goal of the enforcement discretion policy discussed in the draft guidance is to encourage firms to correct past failures to submit an NDI notification, to increase the amount of safety information we have about NDI-containing dietary supplements in the marketplace, and to promote risk-based regulation.”

O’Quinn made clear the enforcement discretion policy, when finalized, would not apply to products introduced to the market after May 20, 2022, the date the draft guidance was published.

‘Smoke and mirrors’

When FDA published the document two years ago, some people thought (or were hopeful) that it signaled a coming wave of crackdowns against unfiled NDIs.

“Was the draft guidance truly a sign or signal that the FDA was getting its house in order and planning on actually enforcing the law, or was it yet another delay tactic? Two years later, we have our answer,” said Pieter Cohen, M.D., associate professor of medicine at Harvard Medical School, in a follow-up email to an interview with Natural Products Insider. “It was just more smoke and mirrors.”

Cohen has been spearheading studies on dietary supplements — and related analysis of the Dietary Supplement Health and Education Act of 1994 (DSHEA) — for about 15 years starting with an article (“American Roulette — Contaminated Dietary Supplements”) published in October 2009 in the New England Journal of Medicine. He described the situation with FDA’s enforcement discretion policy as “Kafkaesque,” or “a bureaucracy that is so convoluted and tangled on itself it can’t even make a decision.”

“Not only has FDA not enforced the law for a decade or more, but now the FDA is saying that their plan to offer an amnesty is in permafrost — with signaling to the manufacturers that apparently in the meantime, you can do whatever you want to do because it might take us another multiple years to clarify that we won’t be enforcing the law,” Cohen said in the interview.

FDA may have gotten ahead of itself with the enforcement discretion guidance, based on an expectation that Congress would pass its legislative proposal to require a listing of all dietary supplement products with the agency, according to former ODSP official Sibyl Swift, Ph.D., chief science officer and VP of regulatory affairs with cbdMD Inc.

Mandatory product listing (MPL) legislation moved through Congress in 2022, but ultimately died amid negotiations to reauthorize FDA user-fee programs.

“It would be a good thing to issue if [FDA] had received mandatory product listing. ‘Hey, by the way, everyone’s going into a database. We’re going to know. You might as well submit what you have,’” Swift said, commenting on the agency’s possible thinking at the time FDA officials worked on the guidance. “That makes sense. Otherwise, what is this?”

Executives with the Natural Products Association (NPA) don’t believe FDA’s 2022 guidance will promote its stated objectives in the draft document — including encouraging firms to submit late notifications — especially if it’s never implemented.

“It’s just like the [FDA] warning letters. If you’re not going to follow up on the warning letter,” what good is it? asked Kyle Turk, NPA’s director of government affairs.

When asked if a final guidance on NDI enforcement discretion would make a difference, Swift responded, “I would love to say ‘yes,’ but I’m going to go with ‘no.’ … Look at [FDA’s] track record, and unless they pivot significantly, their track record says no.”