EMA and national authorities considering impact on other active substances produced at the site

An inspection by EU authorities in collaboration with EDQM has found that Zhejiang Huahai did not comply with good manufacturing practice (GMP) in the manufacture of valsartan at the Chuannan site in Linhai, China.

As a result, a statement of non-compliance for the manufacture of valsartan has been issued and the site is no longer authorised to produce valsartan (and its intermediates) for EU medicines. This means that marketing authorisation holders in the EU are prohibited from using valsartan from the site for the production of medicines.

This action comes after product recalls and the subsequent suspension of the company’s CEP* for valsartan (a certificate of compliance with European standards for quality testing) in July 2018. This already prohibited the supply of the company’s valsartan in the EU due to the presence of an impurity N-nitrosodimethylamine (NDMA).

The latest European inspection, which focused on the manufacture of valsartan and was completed in September 2018, found several weaknesses at Zhejiang Huahai, including deficiencies in the way the company investigated the presence of NDMA and another impurity N-nitrosodiethylamine (NDEA) in its valsartan products.

The non-compliance statement, which applies only to the manufacture of valsartan, is available on the EudraGMP website.

The site has recently also been inspected by the US Food and Drug Administration (FDA), which has issued an import alert stopping all active substances produced by Zhejiang Huahai’s Chuannan site and all medicines containing those active substances from entering the United States. FDA has not announced additional product recalls other than those already in place for valsartan medicines, similar to the recalls in the EU.

EMA and national authorities in the EU are now actively considering all available evidence, including the outcomes of the European and US inspections, as part of the ongoing process of evaluating the Zhejiang Huahai manufacturing site. This will determine what further EU action may be required for other active substances produced by the site.

The detection of NDMA (a substance that could cause cancer) in valsartan from Zhejiang Huahai led to an EU-wide review of valsartan medicines, which was subsequently extended to other sartans medicines.

This review is still ongoing. EMA will continue working with national authorities, international partners and EDQM and will provide updates as more information becomes available.

*CEP: certificate of suitability to the monographs of the European Pharmacopoeia

Posted on the EMA website on 28 September 2018