United Natural Products Alliance (UNPA) President Loren Israelsen was an instrumental player in the negotiations leading to passage of the Dietary Supplement Health and Education Act of 1994 (DSHEA).

In an April 19 interview at the SupplySide East trade show in Secaucus, New Jersey, Israelsen discussed DSHEA reform, drug preclusion, FDA enforcement and other regulatory challenges facing the supplement industry.

“DSHEA was built with a physical world in mind, and what we have is a world that has really become virtual in so many ways,” he said. “So that has created some challenges with DSHEA and hence the conversation, ‘Do we need to change it?’ The risk has always been, once you lift the hood, anybody can get a wrench and get in there.”

MPL

Israelsen said he was not surprised by recent survey results that revealed few industry professionals prefer mandatory product listing (MPL) of dietary supplements with FDA as their top legislative priority. Top-level findings from the survey, which was conducted by Natural Products Insider and SupplySide, in collaboration with New Hope Network’s custom research team, were presented at SupplySide East.

“As we’ve had a chance to understand what FDA means by mandatory product listing and what they want as part of that, I think that has caused a lot of hesitation,” Israelsen remarked.

UNPA adopted a “neutral” position with a willingness to listen to FDA’s proposal, he explained, but when his organization learned “what FDA really wanted, we said, ‘That’s a no-go with us.’

“It included aspects and regulatory authority that go well beyond just product listing.”

Israelsen responded to arguments by some that FDA’s legislative proposal for MPL would help promote the idea that the industry is strongly regulated.

The notion, he said, “would fade over time.”

“I think there might be an [initial] little blip, but I don’t think it’s FDA’s goal to say, ‘Oh yes, the industry is now much more regulated with MPL than before,’” Israelsen concluded.

Institutional bias at FDA?

He also addressed the perception by many industry stakeholders that FDA has an institutional bias against dietary supplements.

“If you look at the record, they have good reason to be concerned about bias at the agency. That for sure has been true in the past,” Israelsen said, noting such concerns go back decades.

“DSHEA was a shocking defeat for FDA,” he reflected. “Part of DSHEA repudiates FDA directly and revokes [its] authority,” reflecting a “direct slap in the face” to the agency.

“And it took the agency a number of years to basically catch their breath and recover from that,” Israelsen said. “But more than anything, our category of supplements just [doesn’t] fit into the binary structure of FDA. So, we’re just a problem fundamentally.”

This binary structure, he confirmed, is the universe of food and drugs.

“The world isn’t that simple,” Israelsen commented. “[It] never was and we regard ourselves as the original food and medicine, and that what FDA set up is an artificial distinction. As Hippocrates said, ‘let food be [thy] medicine.’”

FDA tends to view the supplement industry “as both an inconvenience, and also we’re … the tectonic shift point in the plates,” he said. “This is where the action is always going to happen.”

“We have novel ideas of what we should be able to say that FDA says on the food side, ‘Hey, that’s a drug claim. You can’t make that. You’re going to get a warning letter.’ Then, we have encroachment from the drug side trying to take over exclusive rights to sell certain dietary ingredients that have been available to people for thousands of years. So, there’s always going to be a point of friction,” Israelsen said.

“That friction may be called bias by many,” he continued. “[I] don’t disagree. I see it as simply the reality of us not fitting into a binary system of foods and drugs that is still in the process of reconciliation, and whether it’s ever resolved, I can’t say. Most other countries in the world have resolved it, but we haven’t gotten there yet in the U.S.”

[Below, UNPA President Loren Israelsen (right) discusses a host of regulatory challenges facing the dietary supplement industry, during an interview with Josh Long at the SupplySide East trade show in April in Secaucus, New Jersey].

Reagan-Udall Foundation report

Israelsen said he and his colleagues did not “get a satisfactory answer” from FDA officials concerning why dietary supplements were excluded from a report on FDA’s human foods program facilitated by the Reagan-Udall Foundation. This topic was the subject of a two-part series of articles published in January by Natural Products Insider.

He articulated two theories for why supplements were excluded from the report.

“One is that the Reagan-Udall Foundation would have been highly critical of FDA had they reviewed dietary supplement programs,” Israelsen said. “That to me is the most plausible.”

The other possible reason for excluding supplements, he said, is FDA’s view that these products are subject to special legislation, namely DSHEA.

“I can tell you at the highest levels of FDA, there’s a very, very limited understanding of dietary supplements—very,” he said.

FDA enforcement

That many industry professionals don’t believe FDA enforcement is adequate—another finding that emerged in the SupplySide/Natural Products Insider regulatory survey—also does not surprise Israelsen.

“FDA slow walks enforcement so the industry looks bad. Then, the media will do their job, pick up the story and carry it,” he said. “The other [scenario] is the agency truly is underfunded. They don’t have the resource to get out and put cops on the beat. I think it’s a combination of both. There is more that the agency could do I think quite efficiently.”

The marketplace also has evolved, with e-commerce becoming “a dominant part of the industry,” Israelsen said. “That is the hardest place to regulate for everybody.”

The lax FDA enforcement has forced industry to attempt to “self-police” the market, he observed.

“That is inherently not our job,” Israelsen said, though he added, “We spend a lot of time collectively trying to do that.”

FDA accountability

In the context of enforcement, Israelsen responded to a question on whether specific FDA officials should be held accountable.

One of the challenges, he commented, is many officials are tapped as acting directors—as the commissioner of FDA, for example, or elsewhere within the agency’s ranks, such as acting director of the Office of Dietary Supplement Programs (ODSP).

“The majority of time, it appears that they’re not confirmed. They don’t have full authority,” Israelsen said, describing such FDA officials as “caretakers.”

“That’s a real problem. That’s a procedural problem,” he said.

Israelsen found it “lamentable” that FDA can’t hire someone permanently for a position and say, “OK, it’s your job to get these things done.”

“Then, it’s much easier to hold them accountable,” he explained. “When you get an acting [director], and they go before Congress … they just say, ‘Hey, I’m just doing my best. I’m basically just keeping the seat warm.’

“That’s got to change,” he continued. “I say that. I don’t think it will.”

Individuals at “the highest levels of the agency” must be put into permanent jobs and held accountable, he suggested.

“That’s really in the commissioner’s office,” Israelsen said. “They set the tone. They set the beat. And they’re the ones, if they said, ‘Look, we’re going to get some things done with this supplement area,’ it’s more than likely going to happen.”

CBD stalemate

Asked to comment on FDA’s denial of three CBD citizen petitions in January, Israelsen responded, “Disappointed would be a massive understatement.”

“It didn’t need to take five years for them to reach this conclusion, and in the meantime, they bled dry the majority of the CBD industry that was on a clock,” he said. “They had investment money that was burning down, and they were not getting new money because of all this uncertainty at FDA.”

If the plan was to “wait out the category” and let the CBD industry “suffocate,” the objective was achieved, said Israelsen.

“I just think this is an extraordinary example of administrative failure on the part of the agency not to address an issue and reach resolution in a timely way,” he concluded.

Drug preclusion

Israelsen raised concerns over a race-to-market provision in DSHEA between supplements and drugs. Under this provision, FDA has determined several ingredients are excluded from dietary supplements because they were either first approved as a drug or authorized for investigation as a new drug before being lawfully marketed in supplements. CBD, NAC and NMN are among the ingredients FDA has found are precluded in supplements due to their approval or study as a drug.

FDA’s interpretation of the drug preclusion provision, Israelsen said, “is not what was envisioned—because I was in the room when that section was written.”

The provision “wasn’t intended to go rummaging around and finding something from five, 10, 20 even 30 years or older and say, ‘Oh … look what we found’ that has no relevance [to] today’s market and then knock out a dietary ingredient because of that. That is not what was envisioned,” he said. “It was [to] present a short look back and a look forward to see if there was something that was in true commercial conflict … that would stifle drug research.”

A company that is poised to demonstrate the safety of a new dietary ingredient (NDI) through a pre-market notification to FDA, he said, faces uncertainty over concerns that the agency could find the ingredient is excluded from supplements.

This “stifles new dietary ingredient innovation and notification,” Israelsen said. “FDA keeps saying, ‘Well, how come nobody submits NDIs?’ Pretty simple. It’s become such a risky proposition. From a business perspective, it doesn’t make sense. FDA says, ‘We’re overusing the GRAS [generally recognized as safe] provision.’ Well, if you think so, why don’t you take a look at the NDI provision and see if we can’t rectify that, get it to where it’s supposed to be and make it what it was intended to assess—the safety at a reasonable level—and take a look around in a certain scope of area of whether there is a relevant drug-related conflict that would be pertinent to 2023?”

Israelsen was asked whether he prefers federal legislation or fighting FDA in court over the legality of specific ingredients to address FDA’s interpretation and enforcement of the drug preclusion provision in DSHEA.

“Neither one thrills me,” he responded. “I don’t think Congress would get to it in a realistic time. I think litigation is highly risky partly because we’d have to rely on such a thin fact record. Thirty years down the road, we just don’t have an evidentiary basis strong enough for either side. And then, you leave it in the hands of a judge."

Israelsen observed most judges typically defer to FDA.

“This is one of the harder problems we have to work out,” he said. “To be honest, there have been discussions about this at length to the point of truly trying to model out language of how this could be rectified.

“It’s still a work in process,” Israelsen added. “We’ll continue to work on it because it’s really important for a couple of reasons.”

For instance, he identified “new-generation dietary ingredients that are probably more bioactive than we have seen in the past,” increasing the likelihood of conflict with the pharma industry.

These ingredients, Israelsen added, “are going to be the engine products for our industry, and I don’t want to see them get blown up in the NDI process.”