European medicines authorities take further action in ongoing review of sartans

date: 17/10/2018

European medicines authorities have placed the Chinese company Zheijiang Huahai under increased supervision and the Indian company Aurobindo Pharma is no longer allowed to supply irbesartan to EU member states.

In July 2018, the detection of impurities – NDMA (N-nitrosodimethylamine) and NDEA (N‑nitrosodiethylamine) – in valsartan from Zhejiang Huahai led to an EU-wide review of all valsartan medicines. The review was subsequently extended to other sartan medicines when very low levels of NDEA were found in losartan made by Hetero Labs in India.

Both NDMA and NDEA, which have not been found in any of Zheijiang Huahai’s other products, are classified as probable carcinogens. A preliminary risk assessment for NDMA in valsartan indicated that the risk of cancer is low.


Zheijiang Huahai under increased supervision
European medicines authorities have placed the Chinese company Zheijiang Huahai under increased supervision following European and US inspections which revealed weaknesses in quality management at the company’s Chuannan site in Linhai, China.

The inspection findings included deficiencies in the way the company investigated impurities in its valsartan products and led EU authorities to issue a statement of non-compliance with Good Manufacturing Practices (GMP), prohibiting the use of valsartan from this company in EU medicines.

This latest action means that European medicines authorities will supervise the manufacture of other active substances produced by Zhejiang Huahai more closely. Authorities will monitor corrective measures being implemented by the company on a regular basis and increase the frequency of inspections of the site. In addition, marketing authorisation holders for EU medicines will be required to perform additional tests on all active substances supplied by Zhejiang Huahai.


Aurobindo Pharma is no longer allowed to supply irbesartan in the European Union
Low levels of NDEA have also been found in irbesartan produced by the Indian company Aurobindo Pharma. On 8 October 2018, the EDQM (European Directorate for the Quality of Medicines & HealthCare) suspended Aurobindo Pharma’s CEP (certificate of suitability to the monographs of the European Pharmacopoeia), effectively stopping the supply in the EU of medicines containing irbesartan from this company.

National medicines authorities in the EU are currently considering whether to recall medicines containing Aurobindo Pharma’s irbesartan from pharmacies as a precaution.

The review into the presence of impurities in sartans and their potential effects in patients is ongoing. EMA (European Medicines Agency) will continue working with national medicines authorities, international partners and the EDQM and will provide updates as more information becomes available.


Situation in Belgium
Based on the information available at FAMHP level:

  • medicines containing valsartan from the Chinese company Zhejiang Huahai and available  in Belgium have been removed from the market in July 2018;
  • no medicine placed on the market in Belgium contains irbesartan from the Indian company Aurobindo Pharma.


More about the medicines
The ongoing review is evaluating candesartan, irbesartan, losartan, olmesartan and valsartan, which belong to a class of medicines known as angiotensin-II-receptor antagonists, also known as sartans.

These medicines are used to treat patients with hypertension (high blood pressure) and those with heart failure or who have had a recent heart attack. Sartans work by blocking the action of angiotensin II, a hormone that constricts blood vessels and causes blood pressure to rise.


More about the procedure
The review of valsartan medicines was triggered by the European Commission on 5 July 2018 under Article 31 of Directive 2001/83/EC.

On 20 September 2018, the review was extended to include medicines containing candesartan, irbesartan, losartan and olmesartan.

The review is being carried out by EMA’s CHMP (Committee for Medicinal Products for Human Use), responsible for questions concerning medicines for human use, which will adopt the EMA opinion. The CHMP opinion will then be forwarded to the European Commission, which will issue a final legally binding decision applicable in all EU member states.

Last updated on 17/10/2018