FDA's aggressive move on tainted 'sartan' leads to shortages

Scott Gottlieb FDA
FDA Commissioner Scott Gottlieb. (FDA)

The FDA took aggressive action when it learned that some “sartan” drugs contained a probable carcinogen which developed during manufacturing. Now the long list of recalls has caught up to supply, leaving some products in short supply and the FDA trying to decide how to balance exposure versus going without a medication.

In a statement released Friday, FDA Commissioner Scott Gottlieb and CDER Director Janet Woodcock, both medical doctors, reported that the blood pressure medication valsartan is currently in short supply and other medications may soon fall into shortage.

“That’s why the agency has also evaluated safety data for NDMA and NDEA to determine interim acceptable intake levels for these impurities in the ARB class of medicines,” the statement said.

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Medicines that contain NDMA or NDEA above certain limits pose an “unacceptable risk to patients, and ARBs that contain impurities above these levels are being recalled,” the FDA said.

But the bottom line is that the FDA says the risk is generally very small and patients should continue to take their meds, even recalled products, “until their pharmacist provides a replacement or their doctor provides an alternative treatment option.”

RELATED: FDA berates Chinese drugmaker tied to global valsartan recall

Not all of the drugs in this class contain the impurities, the FDA pointed out. The FDA has also figured out how manufacturers can test for and avoid the impurity problems so that going forward, the drugs should be free from N-Nitrosodimethylamine (NDMA) and N-Nitrosodiethylamine (NDEA), the two contaminants that led to the current problems, the statement said.  

The initial discovery of one of NDMA in sartan prodcuts, came this summer at a U.S. drug manufacturer that had used valsartan API from China’s Zhejiang Huahai Pharmaceutical. Since then, the FDA made a discovery: NDMA and the similar NDEA, can be created in certain manufacturing situations for sartan drugs, including the reuse of solvents, a fact the agency had been completely unaware of before.

The surprise findings set off global recalls of hundreds of lots of valsartan, irbesartan and losartan—ubiquitous drugs used to lower blood pressure—and an intensive FDA investigation into how it could have happened and the dangers it posed to U.S. consumers.

RELATED: The valsartan carcinogen mess taught pharma a surprise manufacturing lesson. Will 2019 bring more?

The agency banned the valsartan APIs produced by Huahai and savaged the Chinese company in a warning letter for changing its manufacturing processes without thoroughly evaluating the risks. The FDA said that when Huahai altered its manufacturing process in 2011 to include a solvent suspected of producing the impurity, it didn’t even consider that the changes might lead to the formation of mutagenic impurities in its valsartan APIs. The levels of impurities in its drugs far exceeded levels considered safe.

But the FDA has since learned that the impurities were found in the APIs of other drugmakers, including Aurobindo and Mylan, and in finished products from Sandoz, Teva and others. This has led to more and more recalls, and now shortages.

Just days ago, drugmaker Torrent Pharmaceutical for the second time expanded its losartan and losartan combo drug recall, bringing the total recall to 16 lots. It said it is only recalling lots in which the contaminant level is above acceptable levels. The drugmaker has already recalled all of its valsartan products.

Others have done the same. According to the FDA’s drug shortages website, Mylan reports it has no valsartan supplies available after a recall of all of its lots of valsartan last month and Novartis' Sandoz is not currently supplying valsartan after after its recall.