Sandoz, Torrent Pharmaceuticals Recall Products for Nitrosamine Impurities

Sandoz, the generics arm of Novartis, and Torrent Pharmaceuticals, an Ahmedabad, India-based pharmaceutical company, have made voluntary recalls of certain products, respectively ranitidine and losartan, for containing certain nitrosamine impurities.

Sandoz has issued a voluntary recall of 14 lots of prescription ranitidine capsules distributed due to a nitrosamine impurity, N-nitrosodimethylamine (NDMA), which was found in the recalled medicine. Ranitidine is an H2 (histamine-2) blocker used in over-the-counter and prescription drugs, including the brand-name drug, Zantac, to decrease the amount of acid created by the stomach. NDMA is classified as a probable human carcinogen.

Earlier this month, the FDA reported that it had detected that certain ranitidine products contained NDMA at low levels. In addition to the FDA, the European Medicines Agency initiated an review in the European Union of ranitidine. 

The FDA says it is testing ranitidine products from multiple manufacturers and assessing the possible effect on patients who have been taking ranitidine, as well as what manufacturers can do to reduce or eliminate nitrosamine in drugs. As part of the FDA’s investigation, the agency recently posted a testing protocol, which can be used by regulators and industry to detect nitrosamine impurities in ranitidine. The FDA is asking companies to begin their own laboratory testing to examine levels of NDMA in ranitidine and to send samples of ranitidine to the FDA to be tested by agency scientists.

In a separete development, Torrent Pharmaceuticals has expanded its earlier recall (April 2019) for losartan potassium tablets USP and losartan potassium/hydrochlorothiazide tablets USP to the consumer level due to trace amounts of N-methylnitrosobutyric acid (NMBA), a probable human carcinogen. The recall includes an additional three lots of losartan potassium tablets USP and two lots of losartan potassium/hydrochlorothiazide tablets USP.

The impurity was detected while testing finished product batches manufactured using active pharmaceutical ingredients (APIs) manufactured by Hetero Labs Limited using an older route of synthesis, according to information from Torrent. Torrent is only recalling lots of losartan-containing products that contain NMBA above the acceptable daily intake levels released by the US Food and Drug Administration. The products were distributed nationwide to Torrent’s wholesale distributor, repackager and retail customers.

Losartan is used to treat hypertension, hypertensive patients with left ventricular hypertrophy and for the treatment of nephropathy in Type 2 diabetic patients. Losartan potassium and hydrochlorothiazide tablets USP is used to treat hypertension and hypertensive patients with left ventricular hypertrophy.

In April 2019, Torrent expanded a recall for losartan potassium tablets USP and losartan potassium/hydrochlorothiazide tablets due to the detection of NMBA. That recall included 36 lots of losartan potassium tablets USP and 68 lots of losartan potassium/hydrochlorothiazide tablets, USP. Earlier (January 2019), Torrent voluntarily recalled certain lots losartan products due to the detection of N-nitrosodiethylamine (NDEA), a probable human carcinogen.  

A series of recalls for nitrosamine impurities found in sartan APIs dating back to 2018 and the now recent impurities in ranitidine led the European Medicines Agency to announce earlier this month (September 2019) that it will develop guidance to marketing authorization holders for avoiding the presence of nitrosamine impurities in human medicines containing chemically synthesized APIs, which companies should consider alongside their knowledge of the manufacturing processes for their products. 

Source: Torrent Pharmaceuticals and FDA; Sandoz and FDA

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