- A generic blood pressure medicine containing a potentially dangerous impurity has been voluntarily recalled from markets by manufacturers, with support from the Food and Drug Administration and the European Medicines Agency.
- The cancer-causing compound N-nitrosodimethylamine (NDMA) was found in active pharmaceutical ingredient valsartan manufactured by Chinese company Zhejiang Huahai Pharmaceuticals. The impurity appears to date back to a manufacturing change by the company in 2012, according to the EMA.
- Zhejiang Huahai has stopped distributing its valsartan API and authorities are working with the company to reduce or eliminate the impurity from future products. NDMA risk is long-term, and patients should not stop their treatments without a doctor's advice, both the EMA and FDA said.
NDMA, a liver toxin and probable carcinogen, is most often known for its low-level presence in tobacco smoke and in cured meat and fish. Its presence in pharmaceuticals is a worrying finding, and the authorities have moved quickly to address the issue.
"When we identify lapses in the quality of drugs and problems with their manufacturing that have the potential to create risks to patients, we're committed to taking swift action to alert the public and help facilitate the removal of the products from the market," said FDA commissioner Scott Gottlieb.
Not all valsartan-containing medicines in the U.S. contain API manufactured by Zhejiang Huahai, the FDA noted. Even so, three generic drugmakers — Teva Pharmaceuticals USA, Prinston Pharmaceutical (Solco Healthcare), Major Pharmaceuticals — are voluntarily recalling their products from shelves as well.
"The presence of NDMA was unexpected and is thought to be related to changes in the way the active substance was manufactured," the FDA said, regarding product produced by Zhejiang Huahai.
Notably, that change appeared to have taken place in 2012, according to European authorities. The EMA is working with toxicology experts to understand the impact of NDMA, and to find out how long and at what levels patients might have been exposed to NDMA.
Recalling drugs can lead to shortages, something the FDA has been working hard to avoid this year. Since valsartan is used to treat high blood pressure and heart failure, the agency doesn't recommend patients stop taking the drug until they have a replacement product.
Novartis, which manufactures and sells branded valsartan as Diovan, said there would be no impact on its drug.
"There's no negative impact on branded Diovan," said Paul Hudson, CEO of Novartis Pharmaceutical on a second quarter earnings call Wednesday.
Hudson said the Swiss pharma would be prepared to meet any increase in demand for branded Diovan that could result from the recalls of generic versions.
Valsartan is also contained in Novartis' new heart drug Entresto, which pairs the API with sacubitirl in a film-coated tablet.
"This has absolutely no impact on Entresto at any point in any process. So we are confident in how we go-forward in preparation with Diovan and indeed with Entresto for the rest of the year," Hudson said.
While the root of this problem appears tied to just the one Chinese manufacturer, GMP violations in the export-heavy generic industries of India and China have come under increased FDA scrutiny in recent years.