Number of unfiled NDIs is hard to pin down in supplement sector

Here’s my burning question: Over the last three decades, how many new dietary ingredients (NDIs) should have been reviewed by the Food and Drug Administration but were not since distributors and manufacturers never filed the paperwork? 

Before you make up a number, keep in mind that not even the all-knowing, all-powerful government of the United States of America can answer that question with absolute certainty. Enter Steven Tave, a long-time FDA official and attorney who ran the Office of Dietary Supplement Programs (ODSP) for a number of years. 

During a 2019 public meeting, while serving as ODSP’s director, Tave calculated based on what FDA considered conservative estimates that at least 46,000 dietary supplement products had been introduced to the U.S. market since 1994—when Congress passed the Dietary Supplement Health and Health Education Act (DSHEA). 

“Let’s say 90 percent of these products did not require a notification," he said. “That still leaves 10 percent of the products that did require a notification.” 

That means the distributors or manufacturers of 4,600 products were obligated to notify the Food and Drug Administration, providing evidence that their NDI is reasonably expected to be safe. However, only about 1,100 NDINs (new dietary ingredient notifications) had been submitted to FDA since the law was signed, Tave reported at the time. 

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

By his math — and keep in mind this is a conservative FDA estimate — more than 75% of ingredient notices that were supposed to have been filed with FDA had not been, depriving the U.S. government of its only legitimate chance to review the safety of an NDI before consumers start swallowing those pills, capsules or gummies. 

In a May 28 letter to Rep. Jeff Duncan (R-S.C.), FDA acknowledged noncompliance with the notification requirement while discussing a 2022 draft guidance that proposed to exercise NDI enforcement discretion. As I reported yesterday, finalizing the 2022 draft policy is less of a priority for FDA than completing sections of its overall NDIN guidance. 

“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, FDA's 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.” 

FDA’s NDIN database tracing submissions back to November 2023 lists a total of 1,316 notifications since 1995. 

To put that number into context, FDA estimates the U.S. market contains as many as 100,000 different products, with 75% of Americans taking a dietary supplement at least occasionally. 

Before you send me a scathing email, I’ll concede FDA itself is the first to admit it has no real idea of the true number of dietary supplement products sold in the U.S., much less than the number of NDIs that should have been filed but were not.  

In comments filed with FDA in 2022, the Council for Responsible Nutrition (CRN) expressed concern that FDA’s “estimate, based on assumptions that 46,000 products were brought on the market since 1994 and 10 percent of those products required an NDI notification, is not supported by evidence. To avoid misleading the public, FDA should rescind this estimate.” 

CRN President and CEO Steve Mister told me recently his group stands by those comments. For instance, he noted a large part of the dietary supplement market consists of products containing old dietary ingredients or a combination of these grandfathered ingredients that are exempt from the notification requirement. 

What’s his estimate of the number of unfiled NDIs? 

“We’re not going to speculate on what the number is, but what we’re going to say is what we said in 2022,” Mister responded. “FDA shouldn’t put numbers out there that can be used and weaponized against the industry when they don’t know either — and that’s what they’ve done.” 

Bob Durkin left FDA in October 2019 to join the law firm of Arnall Golden Gregory LLP (AGG) after spending more than 12 years at the agency, most recently as deputy director of the Office of Dietary Supplement Programs.  

I recently asked him about Tave’s numbers. Durkin acknowledged no one knows the actual number of unfiled NDIs though believed Tave’s estimates were conservative. Durkin said he was aware of Tave’s plan and basis for his numbers at the time and had discussed it with him. 

“I think it’s likely that there have been more than 4,600 NDIs on the market that have required a notification,” Durkin told me. “I don’t know that all of them are still on the market. I’m sure some are, and I’m sure some of those present a risk to the public health — and it’s that portion of those violative NDIs that have to be identified and gone after.”  

It’s hard to argue with Durkin. Certainly, FDA must prioritize enforcement against those novel ingredients in supplements — and products marketed as supplements but that contain drugs — that pose the greatest risks to public health, but what about all the other unfiled NDIs that may be safe or unsafe? What, if anything, should FDA do to tackle that beast? And if the agency does not plan to enforce on this issue, what is the incentive for companies to comply? 

We’ll explore those questions in the next column. Thanks for checking in.