The FDA upended the entire landscape for makers of sartan-based blood pressure medicines after finding some contained potential carcinogens. Now, the FDA is trying a new tack.
The FDA this month issued a warning letter to an Indian solvent recovery firm whose products may have contributed to some of the tainted drugs. The letter to Lantech Pharmaceuticals says its processing methods left open the chance for cross-contamination of solvents that contained the impurities known as N-Nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA).
“Given that your firm does not maintain logbooks or documentation demonstrating product use or cleaning associated with the use of these tanks, there is a potential for all products manufactured at your facility to contain nitrosamines through mix-ups or cross contamination,” the warning letter says. It follows a March inspection at the facility in Ranastalam.
Lantech, which also makes API intermediates, told the FDA it was suspending its solvent recovery business but would put new processes in place if it starts it up again. That didn’t satisfy the agency, which ordered it to report back on exactly how that would be accomplished.
After discovering the impurities in lots of valsartan, losartan and other angiotensin II receptor blockers last year, the FDA determined the contamination was tied to an approved manufacturing switch that uses certain solvents. The FDA reacted by creating acceptable limits for the impurities. But it did nothing about the solvents, which are regularly recovered and recycled.
The agency was then taken to task in a Citizen Petition from an online pharmacy for not setting limits on the impurities in solvents. New Haven, Connecticut-based Valisure claimed tests it performed found “that the switch in the manufacturing industry to the use of the DMF solvent may be largely responsible” for the appearance of the impurities in the U.S. drug supply.
Valisure, which tests all of the drugs it sells, said it discovered DMF—itself classified as a potential carcinogen—at high levels in more than 20 lots of valsartan, including Aurobindo and Novartis. It said some of those remained on the market.
The Lanetch warning letter is the second recently issued by the FDA as it continues to attack the impurities debacle. In June, it issued a warning letter to an Aurobindo plant in India. While the missive does not specifically say it is addressing Aurobindo’s valsartan manufacturing, the letter makes clear that was what it was aiming at.
The February inspection came just weeks after Aurobindo recalled 80 lots of valsartan because of the detection of NDEA. The letter also talks about Aurobindo’s use of solvents to produce drugs that exceeded the FDA’s acceptable levels for the impurities.