Months after the latest losartan recall and more than a year after drug companies first started pulling bulk lots of angiotensin II receptor blockers (ARB) from pharmacy shelves, the FDA has issued a statement updating the American public on the scope of the situation.
In the Aug. 28 memo, penned by Center for Drug Evaluation and Research Director Janet Woodcock, MD, the FDA acknowledged the recent slew of ARB recalls have “deeply concerned patients, the medical community, the agency and international regulatory bodies.”
Since last summer, common BP and heart failure drugs such as valsartan, losartan and irbesartan have come under fire for containing carcinogenic impurities.
“As part of our efforts to be transparent regarding impurities in ARBs, we want to make sure patients have a full understanding of how these impurities may affect them,” Woodcock wrote. “Notably, we would like to stress that the actual risk to patients is likely much lower than our estimates, which reflect a scientific assessment of the highest possible exposure.”
She explained the FDA initially estimated if 8,000 people took the highest dose—320 mg—of N-Nitrosodimethylamine (NDMA)-tainted valsartan each day for four years, there might be one additional case of cancer over the lifetimes of those 8,000 people. One in 8,000 works out to a risk of just 0.01%, but in reality Woodcock said the risk patients face is likely much smaller, with the agency’s predictions representing a worst-case scenario.
She said the FDA is aware of how many patients in the U.S. take ARB medications, but for “nuanced” reasons the agency hasn’t been able to pin down how many of those patients have been affected by recalls. Since it can be difficult to identify which specific lot numbers and medications were recalled, Woodcock said worried patients might have replaced their prescriptions even if it wasn’t necessary. That means more patients were impacted—but not necessarily exposed—to an impurity.
The FDA has reportedly been working to ID the root causes of the nitrosamine impurities, and with that knowledge they’ve been evaluating non-ARB medications that share similar manufacturing processes.
“We have known that certain drug manufacturing processes pose a risk for forming genotoxic impurities, and this is an issue the FDA and other regulators have been working on for a number of years—well before the nitrosamine impurities were discovered in ARBs last summer,” Woodcock wrote.
Some of those regulators include the European Medicines Agency and Health Canada, which work with the FDA and other regulatory agencies to share inspectional findings, lab test results and research. The collaborations have resulted in plans to enhance inspection coverage of API sites in the U.S. to include stricter evaluation of impurity controls, especially if the manufacturing process in question could potentially form nitrosamine or when recycled raw materials are used.
According to Woodcock’s statement, the FDA has been conducting unannounced, for-cause inspections of various API manufacturers over the past year. Woodcock did note the FDA has identified 43 ARB medications without any nitrosamine impurities, proving the drugs can be produced safely.
“As we work to safeguard the quality of our medicines, the American public can expect that we will act quickly to address any issue as soon as we find out about it to prevent as much harm to patients as possible,” she wrote. “We’re also committed to communicating as transparently as possible. Ultimately, our goal is to be certain that no ARBs with unacceptable impurity levels reach patients.”