India’s Aurobindo Pharma has been one of the culprits found manufacturing the high blood pressure medicine valsartan with high levels of impurities that carry a risk of cancer. Now the FDA has savaged it in a warning letter for missteps that paved the pathway to the mess.
The highly redacted warning letter for a plant in Srikakulam District does not specifically say it is addressing Aurobindo’s valsartan manufacturing but the letter makes clear that is exactly what is at issue.
The inspection of the plant in February came just weeks after Aurobindo recalled 80 lots of valsartan because of the detection of N-nitrosodiethylamine (NDEA) one of the impurities. The letter also talks about Aurobindo’s use of solvents to produce drugs that exceeded the FDA’s acceptable levels for the impurities.
The FDA last year determined that the suspected carcinogens NDMA, NDEA and NMBA, can form through specific and commonly used manufacturing processes that involve using certain solvents. The discovery has led to a global recall of hundreds of lots and millions of bottles of the commonly prescribed blood pressure meds valsartan, losartan and Irbesartan.
Aurobindo blames the problem on ingredients it bought from a contractor and poor cleaning procedures, but the FDA says the company did not do enough to get to the root cause. It also did not initially let the FDA know about some changes in its processes and of other impurities it uncovered.
“Your Quality Unit failed to report to FDA these impurities, which were also above your internal reporting threshold limit of no more than (b)(4)%. You updated the information in your Drug Master File (DMF) only after FDA investigators communicated during the inspection that you should be reporting all observed impurities above the reporting threshold.”
The FDA ordered the company to do a risk assessment for all the API and intermediates manufactured at the facility to check for the potential presence of the impurities.
Aurobindo is one of a number of companies whose products have been found tainted. In April, Teva and Torrent recalled more than 350 lots of tainted Losartan. Some products are now in short supply, leading the FDA to establish acceptable levels for the impurities and to tell consumers to take their meds regardless of the recalls. It says the risk from heart problems is greater than the risk of getting cancer from the impurities.