September 29, 2022

Even after manufacturers were hit with FDA warning letters, about 30% of supplements with banned ingredients remained available for customers to purchase online, researchers found.

Among 31 products with FDA warning letters, only one had been recalled by the manufacturer, and nine (29%) were still available to buy online a mean 6 years after those warning letters, reported Pieter Cohen, MD, of Cambridge Health Alliance in Somerville, Massachusetts, and colleagues in a research letter in JAMA.

“What I find interesting here is that the law is clear. These products are illegal,” Cohen wrote in an email to MedPage Today. “However, the FDA doesn’t use the authority that it has to enforce it, even in these crystal-clear cases of violations.”

Cohen said that while the agency flexes its muscle by sending warning letters, it also needs to follow up: “If these products are not immediately recalled, the agency should request a voluntary recall (which didn’t happen here). Then if the firm still doesn’t comply, the FDA should have mandated a recall (all powers that they have).”

Cohen and his team have long been studying banned or unapproved ingredients in supplements and how the FDA regulates this multi-billion-dollar industry. In several previous studies, he and his team have found other examples of where FDA’s oversight of supplements has lagged. That includes a recent report that found that weight-loss and sports supplements contained cocktails of banned and unapproved stimulants that weren’t on FDA’s radar.

For this latest study, Cohen and colleagues focused on warning letters sent to companies regarding three compounds: the amphetamine analogue beta-methylphenethylamine (BMPEA), the ephedrine analogue methylsynephrine, and the dimethylamylamine analogue octodrine (DMAA).

The warning letters around these compounds were issued in 2015, 2016, and 2019, respectively, and all mandated that manufacturers respond to the agency and outline the steps that will be taken to correct the problem and prevent similar issues in the future.

Cohen and team then scoured the internet for evidence of recalls for these products. They then purchased the nine products still available online and analyzed their contents.

They found four of the nine products listed at least one prohibited ingredient on the label. One product declared that it contained the same prohibited ingredient that prompted the letter, and the other three products said they contained other FDA-prohibited ingredients.

In liquid chromatography-mass spectrometry testing, five of the nine products actually contained at least one FDA-prohibited ingredient, and two of those products contained the exact same banned ingredient for which the FDA issued the warning letter in the first place, they reported.

As for the other 21 products, Cohen said it’s nearly impossible to know what happened to them. He expects one of two scenarios: either the manufacturers “quietly phased out the product at any time over the years since the warning letters were issued,” or they renamed the product.

“There’s nothing in the law that prevents a manufacturer from doing this, and then the FDA would be back at square one needing to issue a new warning letter,” Cohen told MedPage Today.

In addition to warning letters, FDA can request voluntary recalls and publish public notices about problematic supplements. However, previous research has shown that about 10% of supplements were still available after a voluntary recall, and another study found 75% of products still contained banned substances years after public notices, the researchers reported.

The agency can also mandate a recall, they noted, but it appears to be rare. “FDA should consider ways to ensure that prohibited drugs are removed from supplements, perhaps by testing products sold after warning letters and mandating recalls whenever products remain adulterated,” they noted.

The study was limited by its small sample size, and by the fact that only one sample of each supplement was analyzed, so the results may not be generalizable to all dietary supplements subject to FDA warning letters. It is also unclear whether the presence of banned substances may vary by batch or over time, they noted.

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    Kristina Fiore leads MedPage’s enterprise & investigative reporting team. She’s been a medical journalist for more than a decade and her work has been recognized by Barlett & Steele, AHCJ, SABEW, and others. Send story tips to [email protected] Follow

Disclosures

Cohen reported receiving grants from Consumers Union and Pew Charitable Trusts and being subject of a civil suit brought by Hi-Tech Pharmaceuticals, a supplement company, regarding BMPEA (the jury found in Cohen’s favor).

No other disclosures were reported.