Mylan Pharmaceuticals is expanding its consumer-level voluntary US recall of valsartan-containing products to include all lots of valsartan-containing products within expiry. In November 2018, Mylan issued a voluntary recall to the consumer level of select lots of valsartan-containing products due to detected trace amounts of an impurity, N-nitrosodiethylamine (NDEA) contained in the active pharmaceutical ingredient (API), valsartan. NDEA is a substance that occurs naturally in certain foods, drinking water, air pollution, and industrial processes, and has been classified as a probable human carcinogen, according to the International Agency for Research on Cancer.

The 104 additional lots include 26 lots of amlodipine and valsartan tablets, USP (including the 5-mg/160-mg, 10-mg/160-mg, 5-mg/320-mg and 10-mg/320-mg strengths), 51 lots of valsartan tablets, USP (including 40-mg, 80-mg, 160-mg and 320-mg strengths), and 27 lots of valsartan and hydrochlorothiazide tablets, USP (80-mg/12.5-mg, 160mg/12.5-mg, 160-mg/25-mg, 320-mg/12.5-mg and 320-mg/25-mg strengths). These batches were distributed in the US between March 2017 and November 2018. 

The valsartan API used in the recalled products was manufactured at one of Mylan’s plants in India. Teva Pharmaceutical Industries also announced a recall in November 2018 when it detected NDEA in the valsartan supply it received from Mylan’s plant in India.

These recalls follow several other recalls of “sartan” APIs in the US and European Union. In November 2018, Sandoz, the generics arm of Novartis, voluntarily recalled in the US one lot of losartan potassium hydrochlorothiazide tablets (USP 100 mg/25 mg) due to a trace amount of NDEA found in the API. The API was manufactured by Zhejiang Huahai Pharmaceuticals (ZHP), a Linhai, China-based pharmaceutical company. The US Food and Drug Administration (FDA) issued a Warning Letter issued to ZHP on December 11, 2018 that outlined several manufacturing violations at ZHP’s Chuannan, China facility, including those relating to impurity control, change control, and cross contamination from one manufacturing process line to another. The agency is still looking into the root cause of the impurity.

Earlier this year, the FDA and the European Medicines Agency (EMA) began their initial investigations into the “sartans” after the EMA learned that ZHP had detected N-nitrosodimethylamine (NDMA) and NDEA, two probable human carcinogens, in several batches of its valsartan API. The FDA’s investigation began when a manufacturer of valsartan products detected NDMA in its API supplied from ZHP, which followed with other companies recalling valsartan products, including Teva. The EU’s detection of the two impurities led to an EU-wide review of all valsartan medicines marketed in the EU. The review was subsequently extended to other “sartan” medicines when very low levels of NDEA were found in losartan made by Hetero Labs, a Hyderabad, India-headquartered pharmaceutical company. In October 2018, the EMA updated that it was evaluating the APIs, candesartan, irbesartan, losartan, and olmesartan, marketed in the EU in addition to its investigation into valsartan products. After low levels of NDEA were found in irbesartan, supplied to a US pharmaceutical company by Aurobindo Pharma, a Hyderabad, India-headquartered generics and API manufacturer, the FDA expanded its investigation to include both valsartan and irbesartan. An investigation of losartan followed in November.

Source: Mylan