Pharmacy takes FDA to task in citizen petition over tainted valsartan

The FDA has tied the contamination of blood pressure drugs by probable carcinogens to an approved switch in manufacturing to a process that uses certain solvents. Now an online pharmacy says it has discovered the solvents are as bad as the impurities they have been creating and has criticized the FDA for not taking steps to limit their use.

In a citizen petition, the New Haven, Connecticut-based Valisure says the FDA has established acceptable limits for impurities such as those commonly known as NDMA and NDEA after they were discovered in heart drugs last year, leading to massive global recalls.

But it claims the FDA has not lowered the acceptable level for the solvent DMF, although it “has become apparent that the switch in the manufacturing industry to the use of the DMF solvent may be largely responsible” for the appearance of the impurities in the U.S. drug supply.   

“This disparity lacks a rational basis and is of significant concern, particularly because of Valisure’s recent findings that high levels of DMF exist in certain on-market lots of valsartan medication,” Valisure’s petition says.

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The petition says the FDA needs to investigate the use of the solvent N,N-Dimethylformamide (DMF) in drug manufacturing since it is classified as a Class 2 carcinogen. It should lower the acceptable level of its use in the U.S. drug supply and requested the FDA seek the recall all of the drugs in which it is found in levels that exceed its guidance.

Valisure, which stakes its reputation on testing all of the drugs it sells, says it has discovered DMF at high levels in more than 20 lots of valsartan distributed by a number of companies, including Aurobindo and Novartis. Some of those remain on the market.

Valisure says it will not sell those drugs because of what it considers the risk of exposure to consumers but can’t get a refund because FDA standards allow them to be on the market. As a result, the company says it will take a loss on those drugs.

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FDA spokesman Jeremy Kahn in an email said it will review the petition but does not comment on third-party research. He said the agency is committed "to ensuring adequate and safe supply of ARB medicines to improve access for patients."

The FDA and regulators in Europe last year first uncovered the impurity NDMA in a valsartan API made by China’s Zhejiang Huahai Pharmaceutical, leading to a global recall. A deeper dive uncovered that the contaminants NDMA, then NDEA and finally NMBA can form through specific and commonly used manufacturing processes that include certain solvents.

As each new impurity was discovered, more drugs were recalled, leading to shortages of some of the ubiquitously prescribed blood pressure medicines including valsartan and losartan. This prompted the FDA to determine what it considers an acceptable level of the impurities. It also has led the agency to recommend consumers continue to take their drugs, even if they are suspected of contamination, saying the risk to stopping is greater than the risk of getting cancer.