On the hunt for drugs contaminated with a likely carcinogen, the FDA initially tested and cleared generic diabetes med metformin. But now, after an independent lab challenged those findings, the FDA has identified that carcinogen in the widely used med, and broad recalls could be in the offing.

The FDA found carcinogen contamination in extended-release formulations of metformin, supporting outside laboratory Valisure’s findings in early March, a spokesman said Thursday.

Tested lots of extended-release metformin showed levels of N-Nitrosodimethylamine (NDMA)—a likely human carcinogen that’s led to recalls of “sartan” blood pressure drugs and the heartburn remedy Zantac—above acceptable limits, the FDA said. Those elevated levels weren’t found in samples of metformin’s immediate-release formula.

The FDA is contacting companies that sell extended-release metformin with NDMA levels that surpass the acceptable limit, a spokesman said. The agency declined to comment on whether recalls are likely for those products.

The agency’s newest findings come months after the FDA found no instances of NDMA contamination during generic metformin testing.

However, Valisure, an independent testing laboratory, disputed the FDA’s findings in March, saying it discovered NDMA contamination at unacceptable levels in 42% of the batches it checked.

In a Public Citizen petition (PDF), Valisure asked for an immediate recall of the contaminated products it identified and contended the situation was likely to get worse as COVID-19 wreaks havoc on supply chains.

Valisure said it tested 38 batches of metformin from 22 companies and found 16 batches from 11 companies had NDMA exceeding the FDA’s acceptable daily level of 96 ng. The laboratory found several batches that contained levels 10 times the daily acceptable intake limit.

It also found “significant variability from batch to batch, even within a single company,” which it says in its petition underscores the need for expanded testing of some drugs at the batch level. It had another testing lab, Emery Pharma, check its findings and Emery came to the same conclusions, Valisure said.

The discovery of NDMA contamination in metformin comes after the FDA launched a recall of generic and branded heartburn drug Zantac in April due to high levels of the same carcinogen.

In September, Valisure filed a separate citizen petition after tipping off regulators to the existence of the potentially cancer-causing impurity in Zantac and other heartburn medicines. It is the same impurity that led to a global recall of “sartan”-based blood pressure medicines over the past few years.

In early January, Emery Pharma filed its own citizen petition after confirming Valisure’s results, informing the FDA that its testing determined the level of the suspected carcinogen NDMA can increase if the drug is exposed to high heat, even after it has been packaged.

The discovery of NDMA contamination in metformin comes after the FDA launched a recall of generic and branded heartburn drug Zantac in April due to high levels of the same carcinogen.

In September, Valisure filed a separate citizen petition after tipping off regulators to the existence of the potentially cancer-causing impurity in Zantac and other heartburn medicines. It is the same impurity that led to a global recall of “sartan”-based blood pressure medicines over the past few years.

In early January, Emery Pharma filed its own citizen petition after confirming Valisure’s results, informing the FDA that its testing determined the level of the suspected carcinogen NDMA can increase if the drug is exposed to high heat, even after it has been packaged.

Source:  https://www.fiercepharma.com/manufacturing/fda-finds-likely-carcinogen-diabetes-drug-metformin-will-recalls-follow