The FDA has spent more than a year tracking down the factors and players that led to a global recall of high blood pressure medicines tainted with a suspected carcinogen. Now, the FDA has called out India’s Torrent Pharmaceuticals as one of the main culprits in the mess.
The agency not only issued a warning letter to India’s Torrent, it publicly named the company in an update on its investigation, saying the drugmaker “has been one subject of an ongoing global investigation into nitrosamine impurities in angiotensin II receptor blockers (ARBs) such as valsartan, losartan and irbesartan.”
The FDA update pointed out the warning letter found manufacturing violations at Torrent’s Taluka-Kadi, Indrad, Gujarat facility in India that contributed to the production of tainted valsartan, losartan and irbesartan.
Torrent last week acknowledged the warning letter without saying it had anything to do with the FDA investigation of the problem of unsafe levels of the probable carcinogen NDMA in its drugs. In its statement (PDF), Torrent said it was committed to quality standards and is working with the FDA to resolve the issues.
The warning letter says the plant didn’t follow its own written procedures for production and process control and failed to carefully investigate batch discrepancies. “In addition, multiple batches of Losartan Potassium were recalled for unacceptable amounts of nitrosamine impurities,” the warning letter says.
The FDA in May signaled its focus on Torrent when it released a Form 483 for the plant that found over two years ending in March of this year, 340 finished product batches tested out of spec. The plant simply retested then reversed those findings in nearly three-quarters of those cases, often on grounds the FDA said were without merit. The retests were then reported for the record. With stability testing, it happened 61% of the time.
Torrent is just one of the companies whose "sartan" blood pressure drugs were found to have been made with APIs containing unacceptable levels of the suspected carcinogen. While other drugmakers like Sandoz and Teva have also recalled products, the numbers from Torrent have been much larger. It had 17 reported recalls totaling more than 2.1 million bottles of losartan potassium tablets and losartan potassium/hydrochlorothiazide tablets.
In recent weeks, the FDA’s focus on tainted meds has shifted to Zantac and generic ranitidine-based antacids. It has discovered that the suspected cancer-causing impurity NDMA also shows up during their manufacture. Drugmakers are in the midst of clearing pharmacy shelves of those over-the-counter products after the agency reported NDMA levels in them exceed acceptable levels.