FDA Investigating How a Potential Carcinogen Found its Way in Heart Drugs

After learning an ingredient used to make a widely prescribed heart drug contained a substance linked to cancer, the Food and Drug Administration is now testing all drugs in that class for traces of the toxic material.

The probe into angiotensin II receptor blockers is part of a widening investigation into a mystery over an impurity known as NDMA, which was found last month in generic valsartan blood pressure pills made by Zhejiang Huahai Pharmaceutical. NDMA, which is considered a possible carcinogen by the Environmental Protection Agency, is an organic chemical once used to make rocket fuel and is an unintended by-product of certain chemical reactions.

The finding caused widespread concern and product recalls by several manufacturers as the FDA and regulators from other countries scrambled to determine how the substance found its way into the medicine. The FDA issued a statement saying it believes the problem occurred “through a specific sequence of steps in the manufacturing process,” but the agency is “still not 100 percent sure this is the root cause.”

Numerous companies either manufacture or repackage these drugs, which are regularly used to combat high blood pressure and heart failure. As of now, they noted that more than half of all valsartan medicines that are on the market are being recalled.

The episode underscores ongoing concerns about the quality of the pharmaceutical supply chain emanating from countries such as China and India that are large ingredients manufacturers, but have a history of inconsistent — some say inadequate — government oversight. A 2016 report by the U.S. Government Accountability Office found the FDA was struggling to assess its overseas inspection efforts.

Mindful of such concerns, the FDA statement took pains to explain the steps taken by the agency to respond to the NDMA problem. These included alerts issued to patients and health care providers on the agency web site; analysis by FDA staff at its St. Louis laboratory; communicating with regulators in Canada, Europe, and Japan; and inspecting Zhejiang Huahai facilities in China.

At the same time, the FDA reiterated an earlier alert that attempted to put the risk into context.

The agency estimated that if 8,000 people took the highest valsartan dose of 320 mg in a pill containing NDMA daily for four years — which is the amount of time the FDA believes the affected pill had been on the U.S. market — there may be one additional case of cancer over their lifetimes beyond the average cancer rate among Americans.

“This estimate represented the highest possible level of NDMA exposure. It was a measure of the risk under the most extreme circumstances. Most patients who were exposed to the impurity through the use of valsartan received less exposure than this worst-case scenario,” Gottlieb and Woodcock wrote in a bid to reassure the public about the likelihood of the risk of developing cancer.

Meanwhile, they added that they plan to use what they learn from this scare to “inform assessments of product applications being submitted and currently reviewed by the FDA. We will disseminate that information to manufacturers of all drugs and to the scientific community and re-evaluate our existing guidance to manufacturers.”