Protecting patients is the FDA’s highest priority, and Americans can be confident in the quality of the products the agency approves. The recent Angiotensin II Receptor Blocker (ARB) recalls have deeply concerned patients, the medical community, the agency and international regulatory bodies. The FDA is aware many patients rely on ARB medicines, and we are concerned about the presence of nitrosamine impurities in these drugs. Millions of people benefit from the high-quality products that the FDA regulates, and the U.S. has the most robust drug supply in the world, with strict standards for safety, effectiveness and quality.
Clarifying the risk and scope of exposure
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. 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. Weinitially estimated that if 8,000 people took the highest valsartan dose (320 mg) containing N-Nitrosodimethylamine (NDMA) from the recalled batches daily for four years, there may be one additional case of cancer over the lifetimes of those 8,000 people. In reality, the vast majority of patients exposed to NDMA through ARBs received much smaller amounts of the impurity than this worst-case scenario, and, since not all ARBs are affected, it’s very likely that a patient taking an ARB for four years would not have always received one of the affected products.
One question we have received from many patients and other stakeholders is how big the impact has been – how many patients have been affected? While we know the number of patients taking ARB medicines, we do not know the exact number of patients impacted by these ARB recalls. The reasons for this are nuanced. For example, we understand that health care professionals, out of an abundance of caution, may have replaced their patients’ ARB prescriptions that were not part of the announced recalls. Because patients’ prescription bottles do not always identify lot numbers, it was difficult for patients and pharmacists to determine whether a medicine was part of the recalls. Patients may have returned medication unnecessarily if their supply was not part of a recall, but they were unsure. Therefore, we estimate there were likely more drugs replaced due to recalls than necessary, which means more patients were impacted but not necessarily exposed to an impurity.
Manufacturers only estimate the number of products still in the distribution chain that are subject to recall, but not the number of impacted patients. However, through our ongoing track and trace efforts for prescription drugs in the supply chain, we’re working on ways to improve industry’s ability to track, detect and remove potentially dangerous drugs from the supply chain more rapidly and efficiently. ARB medications that contain impurities above the published interim acceptable limits continue to be recalled, with certain exceptions. However, it’s also important to underscore that there are ARB medicines that remain on the market and have been determined not to contain any nitrosamine impurities. We continue to encourage patients talk to a health care professional if they have questions about their medicine, as the risks of stopping taking an ARB product for treating high blood pressure and heart failure greatly outweighs the potential risk of exposure to trace amounts of nitrosamines.
Enhancing oversight of manufacturing data
As we continue our analysis of this situation to better understand the root causes, we’re learning more about how nitrosamine impurities may have formed and been present in ARBs. Through each step of our investigation, we’ve uncovered new information and taken a number of actions, including regulatory and advisory actions, where appropriate, to prevent the presence of unacceptable levels of these impurities. For example, earlier this month, we issued a warning letter to Lantech Pharmaceuticals Limited in Telangana, India, for current good manufacturing practice violations. Lantech acts as a contract solvent recovery facility for valsartan active pharmaceutical ingredient (API) manufacturing operations. Wh...
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