Health Canada has found the Chuannan manufacturing site of Zhejiang Huahai Pharmaceuticals located in Linhai, China, to be non-compliant with requirements for Good Manufacturing Practices (GMPs) for the manufacture of active pharmaceutical ingredients. Health Canada’s decision is based on a review of information from a recent inspection conducted by the US Food and Drug Administration (FDA).
GMPs are internationally accepted standards that help ensure that drugs are consistently manufactured, tested, stored and distributed in a way that meets Canada’s high safety and quality standards.
A non-compliant rating means that Canadian companies can no longer import drugs that contain active pharmaceutical ingredients from this site unless they are medically necessary. Health Canada will allow the continued importation of medically necessary drugs under conditions that verify their safety, such as additional testing. At this time, no products containing active pharmaceutical ingredients from this site have been identified as medically necessary.
Health Canada is assessing what impact the non-compliant rating may have on products in Canada. This includes assessing possible effects on drug supply and whether measures may be needed to mitigate supply concerns or protect the health and safety of Canadians.
No products are being recalled at this time. It is important to note that a non-compliant rating does not necessarily indicate a product safety concern. It means that the Department has identified issues with how the company is following good manufacturing processes and procedures. Health Canada continues to monitor the situation. If at any point a safety concern is identified involving products from this site, Health Canada will take action and inform Canadians.
Zhejiang Huahai Pharmaceuticals is the manufacturer of the valsartan active pharmaceutical ingredient that, to date, is the only active ingredient from this site found to contain the impurities N‑nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA). Health Canada reviewed the FDA inspection as part of its continuing assessment of the issue with valsartan. All drugs containing valsartan manufactured by Zhejiang Huahai Pharmaceuticals have already been recalled in Canada.
Please refer to the following website in Health Canada for details:
http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/../67870a-eng.php
In Hong Kong, there are 253 registered pharmaceutical products containing valsartan (83 products), candesartan (19 products), irbesartan (64 products), losartan (70 products) and olmesartan (17 products). 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 the detection of impurities in sartan-containing products 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 2 Oct 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 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.
Regarding the announcements issued by various overseas drug regulatory authorities on the detection of the second impurity of NDEA in the valsartan API produced by Zhejiang Huahai, there should be no local impact as all valsartan products manufactured using API produced by Zhejiang Huahai have been recalled from the market.
Regarding the European Medicines Agency’s announcement on the detection of NDEA in losartan in the API produced by Hetero Labs Limited, the DH has contacted the certificate holders of all registered candesartan, irbesartan, losartan and olmesartan products and will continue to follow up on the impact of NDEA impurities on the products available in the local market.
So far, the DH has received 13 cases of adverse drug reaction related to valsartan, candesartan, irbesartan, losartan and olmesartan. None of them are concluded to be related to the presence of NDMA and/or NDEA. 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/Wednesday, Oct 3, 2018
Issued at HKT 15:00
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