As questions about suspected carcinogens in drugs continue to roil the supply chain, the FDA last month said its testing of metformin did not find any with unacceptably high levels of NDMA. But testing laboratory Valisure has challenged those findings in a new Public Citizen petition, saying it discovered problems in 42% of the batches it checked. It contends the situation is likely to get worse as the COVID-19 outbreaks wreak havoc on supply chains.
Valisure said it tested 38 batches of diabetes medicine metformin from 22 companies and found 16 batches from 11 companies had the suspected carcinogen NDMA exceeding the FDA’s acceptable daily level of 96 ng. In fact, the petition (PDF) says it found several batches contained levels that were 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 reports Emery came to the same conclusions. The petition calls on the FDA to recall the batches in which Valisure found issues.
“This certainly underscores the prevalence of existing pharma quality problems, which may end up becoming even worse as coronavirus continues to derail Chinese drug manufacturing, where the majority of U.S. drugs originate from,” Valisure CEO David Light said in an email. “Many of these existing safety and quality issues, like the ones we identified in metformin, likely stem from overseas manufacturers cutting corners. It is certainly possible that many more corners may be cut in the scramble to ramp up production and fill backorders.”
This comes after the FDA in February reported its testing of “some metformin” products determined that the levels of NDMA in metformin products tested range from not detectable to low levels, and no sample had NDMA above the acceptable daily intake level set by the agency. “FDA has not recommended metformin recalls in the U.S.,” it said.
In an email Monday, the FDA said: "We will respond directly to the petitioners."
This is the third petition filed by the testing laboratory and online pharmacy. It earlier called on the FDA to pull Zantac and its ranitidine generics after finding potentially cancer-causing impurities in some batches. It has also filed a petition that calls on the agency to set a standard for a certain solvent used in some drug manufacturing, saying it is clear its use has contributed to NDMA and other impurities showing up in the U.S. drug supply.
The problems with NDMA and similar impurities being produced during manufacturing first appeared in 2018 in “sartan” blood pressure drugs. The surprise findings set off global recalls of hundreds of lots of valsartan, irbesartan and losartan and an intensive FDA investigation into how it could have happened and the dangers it posed to U.S. consumers. It also led the FDA to file warning letters to some manufacturers. The FDA has since been testing a number of drugs that might be expected to have the same issues.
Valisure says “contamination in these batches of metformin appears to be similar to the issues that continue to plague blood pressure medications like valsartan and losartan.”
It says it is clear that self-testing isn't working, and the FDA can't do it all. It suggests mandatory third-party testing may be necessary, a move that would potentially benefit its own business.
“Valisure urges FDA and industry to take swift and broad action to clean up the U.S. supply of metformin, a drug that tens of millions of Americans rely on,” it says.
“We must strive to avoid a repeat of over year-long rolling recalls that patients and practitioners still endure with blood pressure medications,” Light said in a press release.