Zhejiang Huahai Pharmaceutical Co. Ltd. has been placed under increased supervision after European and U.S. inspections found that its manufacturing facility for the heart medicine valsartan was not in compliance with good manufacturing practices.
The European Medicines Agency began a review of valsartan-containing drugs by the Chinese manufacturer in July, after traces of N-nitrosodimethylamine and N-nitrosodiethylamine impurities were detected in its products. N-nitrosodimethylamine and N-nitrosodiethylamine — NDMA and NDEA, respectively — potentially cause cancer in humans.
Valsartan was developed by Novartis AG and sold under the name Diovan. The drug is used to treat high blood pressure and heart failure.
The discovery of impurities in Zhejiang Huahai's products led to an EU-wide review of all valsartan medicines, which was later expanded to include other "sartan" medicines including candesartan, irbesartan, losartan and olmesartan, according to the agency. Low levels of NDEA have since been discovered in irbesartan products manufactured by India's Aurobindo Pharma Ltd., which has been prohibited from supplying irbesartan in the EU. According to EMA, the agency is now considering recalling medicines containing Aurobindo's irbesartan from pharmacies as a precautionary measure.
Now, the regulators have cited weaknesses in quality management at Zhejiang Huahai's Chuannan site in Linhai, China. Specifically, inspectors found deficiencies in the way the company investigated impurities in its valsartan products. EU authorities issued a statement of non-compliance with good manufacturing practice and prohibited the use of Zhejiang Huahai's valsartan in EU medicines.
Zhejiang Huahai's manufacturing operations for its other active substances will now be under close scrutiny by EU authorities. Any corrective measures carried out by the Chinese manufacturer on a regular basis will be monitored, and the agency will conduct more frequent site inspections. The European drug authority is also requiring market authorization holders for EU medicines to conduct additional tests on all active substances from Zhejiang Huahai.