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New toxic drug impurities have been identified in some heart medications in US after being found in new heart drug inpurity

New toxic drug impurities have been identified in some heart medications in US after being found in new heart drug inpurity

Millions of blood pressure pills that contain a possible carcinogen have been recalled around the world in the last three years. As pharmaceutical firms examine a solution, theyve discovered severe problems: another potentially fatal chemical is appearing in the same drugs.

The new chemicals are called azido impurities and regulatory authorities claim theyre mutagenic, meaning they could alter someones DNA and increase cancer risk.

The impurities were found in blood pressure medications that were recalled earlier this year in Canada as well as Europe. US officials helped lead the way in the 2018 recalls of the same type of drugs contaminated with the probable carcinogen N-Nitrosodimethylamine, or NDMA, though they have yet to pull any for containing the azido impurities.

According to documents reviewed by Bloomberg, a US Food and Drug Administration inspector has determined that at least one large firm in India, Hetero Labs Ltd., has criticized skepticism about its process for controlling the impurities. According to the documents, Hetero hasn't adequately checked that a residue of impurities arent growing on production equipment, which may cross-contaminate subsequent batches.

In August, the FDA inspector visited Hetero Labs Ltd.'s manufacturing facility in the Sangareddy district in south-central India. The plant makes the active ingredient for the blood pressure drug valsartan, which it sells to other pharmaceutical firms to make a finished pill. Valsartan production may cause azido impurities. The firm has not responded to requests for comment.

Health Canada, the canada's drug regulator, announced recalls of valsartan, a drug class called an angiotensin II receptor blocker, in May for elevated azido levels. Losartan and irbesartran, two drugs in the same class, were recalled for the exact same impurities over the next few months. Sanofi, Novartis AGs generic drug unit Sandoz, and generic-drug giant Teva Pharmaceutical Industries Ltd. are among the companies implicated in the investigation.

According to the countrys Medicines and Healthcare products Regulatory Agency, Teva also recalled ARBs in the UK in June, followed by Sanofi in August. According to emailed answers to Bloomberg's questions, the MHRA is aware of three possible azido impurities in heart drugs. Other European countries, such as France, Switzerland, and Ireland, have also recalled ARBs containing azido impurities.

Sanofi recalled certain irbesartan drugs in Canada in June for higher azido impurities and sold some of those drugs to consumers in the United States, according to a spokesperson in an e-mail response to Bloomberg. The drug maker informed the FDA and didn't receive any further responses, according to the spokesperson.

Sanofi is close to completing the testing of all batches of irbesartan-containing medicine produced between 2018 and 2020. Most of the samples have not contained azido impurities above the threshold considered acceptable. The business plans to work with health authorities in mid-October to recommend recalls of any non-conforming batches, according to a spokesperson.

Sanofis irbesartan tested since January has not contained unacceptable azido impurities, according to the spokesperson.

Sandoz originally recalled 40 batches of ARBs in Canada in May, and it has since rerecalled 49 batches for certain losartan pills in the United States. The active ingredient for the drugs was made by a different firm, according to an emailed statement from spokesman for parent company Novartis, though the company wasnt named.

Sanofi and Sandoz both participated in another major recall in 2019 due to NDMA-contaminated drugs that forced the heartburn medication Zantac and its generics to be pulled from the market. The independent testing laboratory Valisure, located in New Haven, discovered NDMA in the drug and alerted authorities. Ranitidine, the active ingredient in Zantac, was found to produce NDMA over time or when stored at high temperatures.

Zantac was not the last company to recall NDMA or other chemicals that fall under the category of nitrosamines. Last year, the widely used diabetes drug metformin was recalled for NDMA contamination, and Pfizer Inc. voluntarily re-recalled all of its smoking cessation pill Chantix last month after it was found to contain a nitrosamine.

In 2018, Hetero supplied the active ingredient to some of the pharmaceutical firms that had to pull their products because they contained NDMA and other similar chemicals. While the recalls began that same year, authorities and industry continued to uncover additional contamination from chemicals similar to NDMA in the blood pressure tablets valsartan, losartand, and irbesardan; the result was a series of recall cases that lasted almost two years as tainted drugs were identified. The NDMA was probably formed as part of the manufacturing process for the active ingredients, though drug makers and regulators didnt detect the problem for many years.

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