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 certificate of suitability to the monographs of the European Pharmacopoeia (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.
Please refer to the following website in EMA for details:
http://www.ema.europa.eu/en/news/eu-inspection-finds-zhejiang-huahai-site-non-compliant-manufacture-valsartan
In Hong Kong, there are 83 registered pharmaceutical products containing valsartan, and all
products are prescription-only medicines.
Regarding impurities in valsartan, a public announcement was issued on 6 Jul 2018, and letters to inform local healthcare professionals were issued by the Department of Health (DH) on 6 Jul 2018, 9 Jul 2018, 25 Jul 2018 and 3 Aug 2018. Related news for impurities in valsartan was also previously issued by various overseas drug regulatory authorities, and was posted on the Drug Office website since 6 Jul 2018, with the latest update posted on 22 Sep 2018.
In summary, there are four manufacturers, namely Zhejiang Huahai, Zhejiang Tianyu and Zhuhai Rundu in China and Hetero Labs Limited in India, reported to have detection of trace amounts of NDMA and/or NDEA in the valsartan Active Pharmaceutical Ingredient (API) by various overseas drug regulatory authorities.
The DH contacted the certificate holders of all registered valsartan products to follow up on the local impact regarding valsartan API produced by the above mentioned manufacturers.
For API produced by Zhejiang Huahai, there are 5 affected products (HK-61786, HK-61787, HK-61784, HK-61785 and HK-60794) marketed in Hong Kong. The DH instructed the certificate holders to recall all the products from the market as a precautionary measure on 6 Jul 2018, and the DH noted that all the recalls have been completed.
For API produced by Zhejiang Tianyu, amongst the registered pharmaceutical products containing valsartan, there is only one product namely Retoni Tablets 80mg (HK-65604) registered by Swiss Pharmaceutical Co Limited (Swiss Pharmaceutical) which has used API produced by Zhejiang Tianyu and is available in the local market. As confirmed with Swiss Pharmaceutical, the API was tested by the Taiwan Food and Drug Administration (TFDA) and the company has not received any notice from the TFDA for NDMA contamination. The DH collected samples of Retoni tablets for analysis and no NDMA was detected.
For API produced by Zhuhai Rundu and Hetero Labs Limited, the certificate holders confirmed that the valsartan products available in local market are not manufactured using API produced by Zhuhai Rundu or Hetero Labs Limited.
So far, the DH has not received any adverse reactions related to the above products affected by the recall.
The DH will keep vigilant on any further updates on the matter issued by overseas regulatory authorities.
Patients who are taking the above products should not stop taking the medicines, but should seek advice from their healthcare professionals as soon as possible for proper arrangement.
Ends/ Saturday, September 29, 2018
Issued at HKT 14:30
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