Three generic drug companies across Europe have recalled dozen lots of high blood pressure medication after a contamination was found in a common active pharmaceutical ingredient (API).
Bristol Laboratories, Brown & Burk and Teva announced the recall of irbesartan and losartan, both angiotensin II receptor blockers, following detection of 5- (4 ‘- (azidomethyl) -[1,1’-biphenyl] -2-yl) -1H-tetrazole (AZBT), which over time may increase a patient’s risk of cancer. Since there is no evidence of immediate danger or harm to the patient and only minor contamination was found, the recall was only issued for pharmacies and wholesalers.
A spokesman for the UK Medicines and Health Products Regulatory Authority (MHRA), which has recalled 31 lots from the three manufacturers, confirmed the contamination was caused in the manufacture of one active ingredient for both drugs as well as valsartan. ‘[The contamination] was seen as potentially formed during the finished product manufacturer’s evaluation of an alternative API source and was confirmed during testing of the current API lots used by that finished product manufacturer, ”the spokesman said.
This recent recall follows several problems with members of the sartan drug family, and more generally, caused by impurities introduced during drug synthesis. Most of these involved nitrosamines, especially the potential carcinogen No-Nitrosodimethylamine (NDMA) associated with various factors including processing conditions and solvent recovery techniques. As a result, companies have been looking for alternative methods to avoid this contamination. However, treating the problem has proven difficult, especially in the case of the dyspepsia drug ranitidine, with research by GlaxoSmithKline last year showing that the contamination can arise from the slow breakdown of the ranitidine molecule itself.
The situation has been exacerbated by regulators in Europe and North America imposing stricter contamination limits to identify and remove potential contaminants. In Great Britain, the current limit values for AZBT (33 ppm for losartan and 66 ppm for irbesartan) are only provisional standards and are being discussed by the MHRA Commission for Human Medicine.
In response to the recent Sartan recall, Teva confirmed that Chemistry worldIt had recalled 41 batches of losartan across Europe and was already considering adapting its processes to avoid further problems. “At the manufacturing level, Teva is waiting for approval [the European Directorate for the Quality of Medicines and Healthcare] of its submitted plan to change the process of its API manufacturing, “said a spokesman.