Millions of Americans take medication daily to control their blood pressure. We recently found that some generic versions of one medication, valsartan, contain an impurity that doesn’t meet FDA’s safety standards. Valsartan is an angiotensin II receptor blocker (ARB) that treats high blood pressure and heart failure. The FDA currently has a major operation underway to investigate and address this troubling finding. This investigation is led by a dedicated task force of experts focused solely on this important work. Their mandate is to oversee the investigation and track new developments and information coming in from valsartan manufacturers. This multidisciplinary team of chemists, toxicologists, medical doctors, pharmacists, investigators, communication specialists, and analytical lab staff coordinates across the FDA, and acts on the newest available information.
As our investigation continues to identify the root cause of this impurity, we want to take the opportunity to describe to the public what we are doing to find the cause of the impurity, to prevent a recurrence of this episode and to protect patients who need this medication.
On June 19, a U.S. manufacturer of valsartan products, Prinston Pharmaceuticals Inc., contacted the FDA‘s Center for Drug Evaluation and Research (CDER) about its products containing valsartan active pharmaceutical ingredient (API) manufactured by Zhejiang Huahai Pharmaceutical Co. (ZHP). Prinston informed CDER that they had stopped making valsartan products because ZHP had detected an impurity in the API – a chemical known as N-nitrosodimethylamine (NDMA). NDMA is a probable cancer-causing chemical found in trace amounts in water and some foods. However, the levels of NDMA in ZHP’s valsartan API – while still trace amounts – were unacceptable.
Although the risk to patients taking the affected products is extremely low, we take matters of pharmaceutical quality very seriously. We took immediate steps to address these findings.
Shortly after initiating our investigation, we learned that a foreign regulator was also reviewing medications containing valsartan API manufactured by ZHP and considering a recall. We have closely coordinated with the European Medicines Agency, European Directorate for the Quality of Medicines, Regulatory Operations and Regions Branch and Therapeutic Products Directorate of Health Canada, and the Pharmaceuticals and Medical Devices Agency in Japan since that time, sharing information about our investigation with them and other regulatory bodies and learning about their findings.
We recognized that we had to find answers to several important questions: How many U.S. valsartan products are affected? Where did the impurity come from? What are the potential health consequences of the impurity? How many patients are affected? How long have patients been exposed to NDMA? How do we ensure that patients and providers are informed so that health care is minimally disrupted? How do we prevent drug shortages? And could similar drugs also contain this impurity?
Our first priority was to inform patients and health care providers. To do this, we had to verify the information about ZHP’s API to understand the risk to U.S. patients and the scope of APIs and products potentially affected by this impurity. We identified four manufacturers using valsartan API from ZHP for the U.S. market. We contacted them to ask if they knew about NDMA in their products and to recommend recalls of affected products. In addition to ZHP, we identified 13 other API manufacturers who supply more than 20 drug companies that make valsartan for the U.S. market. We made plans to determine if their products could also contain NDMA.
By July 13, we had the information we needed to issue a press release stating that three companies had products containing NDMA and were voluntarily recalling them. One of the four manufacturers we initially identified required further investigation, but has since voluntarily recalled its products.
However, we did not want patients taking valsartan to hear this news and abruptly stop their medications, possibly suffering serious medical issues, such as stroke. We needed to let patients know the specific products impacted by the recalls, so they could talk to their health care providers and get prescriptions for products that had not been recalled. W...
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