This is the first in a series of articles about the FDA’s attempts to increase its visibility on the safety of new dietary supplement ingredients in the US market.
An FDA plan to give supplement makers a chance to rectify their failure before going to market to notify the agency of new dietary ingredients (NDIs) in their products represents “an excellent opportunity to… right that wrong,” an FDA official said. in an interview.
In orientation project published in May, the FDA revealed its intention to exercise enforcement discretion for 180 days regarding the requirement to timely file an NDI notification (NDIN) with the agency. This amnesty period would begin after a notice is published in the Federal Register announcing the availability of final guidance.
The NDIN requirement is intended to ensure that new ingredients are “reasonably” expected to be safe, and is an essential part of FDA market surveillance, as it is the agency’s only chance to review the safety of NDI in supplements before they are available to consumers. . By comparison, a manufacturer of a conventional food ingredient must establish “reasonable certainty of harmlessness under the conditions of intended use” to meet the GRAS (generally recognized as safe) standard.
Cara Welch, who heads the FDA’s Office of Dietary Supplement Programs (ODSP), said she hopes “a number of notifications” will be submitted to the FDA during the 180-day period “because this provides the security data we are looking for”.
“The focus, however, is on safety data, so we can get a better picture of the safety of products currently on the market,” she told Natural Products Insider in an exclusive interview.
She said the FDA was not looking for a specific type of ingredient or product, but rather NDINs that should have been submitted to the agency but were not.
Welch’s predecessor, Steve Tave, estimated in 2019 that the FDA should have received at least 4,600 notifications since the 1994 Dietary Supplement Health and Education Act (DSHEA) was passed, but none had received just over 1,100.
His estimate was based, in part, on an assumption that the United States contained 50,000 dietary supplement products — the bottom of the number of products (50,000 to 80,000 or more) that the FDA estimated to be on the market.
When asked why the FDA is issuing the guidelines now, Welch replied, “I don’t know if there’s any particular ‘why now’ reason other than this is…one of the many steps we’re taking to …advancing and modernizing the way we’ regulate the dietary supplement industry.
The more notifications the FDA receives “reduces the number of those who have not complied with NDI’s notification requirement,” she said. “This will help the FDA identify those who continue to be in violation and take the next step, making it easier for enforcement to meet the NDI notification requirement.”
Welch added: “We want to see who is willing to submit in order to determine how small this pool of notifications that have not been submitted will be. And then we can focus our enforcement actions.
FDA stakeholders have for many years criticized the agency for not vigorously enforcing the NDIN requirement, including in response to a batch of recently issued warning letters. The guidelines could be interpreted as a signal that the FDA intends to strengthen its enforcement of NDIs – and Welch did not disagree with such an assumption.
“The purpose of this policy is to provide an opportunity for supplement manufacturers and distributors to correct past failure,” she said. “Those who … choose not to correct this failure and continue to be in violation would be an area where we hope to see more enforcement action.”
She did not elaborate on specific enforcement strategies likely to be employed, such as whether the FDA would go beyond warning letters to legal actions requiring collaboration with the US Department of Health. Justice.
Welch suggested that the FDA seeks to foster “active participation” in the NDIN process not only to rectify past behavior, but also to modify future behavior.
“At first, we … allow this temporary delay to submit your late notification, which will encourage people to submit them on time in the future and identify for the FDA companies that simply choose not to comply, even when we let’s kind of take away the fear of retaliation for late notification,” she said.
Stakeholder reaction
Pieter Cohen is a physician and associate professor of medicine at Harvard Medical School who has studied potentially harmful new ingredients marketed in dietary supplements, including higenamine. He doubted the grace period would open the floodgates for ingredient submissions to the FDA. He and other FDA critics argue that the FDA has a history of lax enforcement against non-compliant companies.
FDA officials “have not prosecuted companies for the past 28 years, so the notion of a ‘grace period’ honestly doesn’t make much sense to me,” Cohen said in an interview. is performance art.”
He added, “What we need to see is whether or not the FDA is going to pull the thousands – maybe tens of thousands of products – from the market that contain…a new food ingredient that hasn’t gone through the appropriate channels. .”
American Herbal Products Association (AHPA) President Michael McGuffin isn’t surprised by Welch’s remarks about FDA enforcement.
“That’s exactly what she should be saying, isn’t it,” he said in an interview. “There is no reason to issue a declaration of temporary enforcement discretion unless the next day or shortly thereafter you terminate the enforcement discretion and apply it in place.”
If the FDA steps up enforcement, McGuffin wondered which ingredients it would target. For example, would the FDA step up its fight against kratom, which is already the subject of import alertor ingredients that the agency has reported on a listing published online, some of which are NDIs, including Acacia rigidula, cesium chloride and DMBA?
McGuffin supports the FDA’s active enforcement of various dietary supplement requirements, including, for example, cGMP (current good manufacturing practices), serious adverse event reporting requirements, and NDINs.
“We think this is a very well regulated and safe class of goods,” McGuffin said, “but it’s only as well regulated as the enforcement.”
Marc Ullman doesn’t hold his breath that the FDA’s hope to elevate its enforcement action against non-compliant NDIs will bear fruit. He is an attorney at Rivkin Radler LLP, whose attorneys, including Ullman, advise dietary supplement companies on FDA regulations, including the NDIN requirement.
“When I spoke with the FDA about residual formaldehyde in my customers’ counterfeit astaxanthin, I was hopeful of an application. Nothing happened,” he said in a statement. interview.”When I walked in and met with the FDA to discuss the presence of a variety of unknown spikes and counterfeits of my client’s PQQ, I was hopeful that there would be some application . Nothing happened.”
Ullman added: “Why would we think they would do anything but complain about needing more authority?”
The FDA’s goal “should not be simply to accumulate NDIN numbers,” according to Bob Durkin, a former ODSP official who practices law in the nation’s capital with Arnall Golden Gregory LLP (AGG).
Rather, its goal should be to “identify offending products” that pose “a risk to public health” and remove them from the market, he said in an interview.
Durkin’s colleague, AGG partner Kevin Bell, expressed doubt that the FDA’s enforcement discretion policy would move the needle on compliance significantly.
Bell’s request to the FDA last year to apply generic forms of beta-alanine made in China was denied in a letter signed by Welch. Like Ullman, Bell had raised concerns with the FDA about so-called counterfeit or copycat ingredients that haven’t been reviewed by the FDA but look like NDIs who invested in safety and got letters from ” recognition” from the FDA after notifying the agency.
“I don’t think there are any teeth in there [draft guidance] because so what,” Bell said. “If it artificially inflates some numbers for a while, it doesn’t mean anything,” he said. “It’s like saying I’m going to put more speed limit signs on the highway. “Don’t worry because no one will ever get a ticket. We’ll just put up more signs.”
