FDA Gives Update on Sartan Impurity Probe

The FDA continues to recall angiotensin II receptor blocker (ARB) medications for nitrosamine contamination but, in a statement issued Wednesday morning, offered assurance that it is tackling the manufacturing practices underlying the problem.

“[T]hrough 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,” said Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research.

ARB medications that contain impurities above the published interim acceptable limits continue to be recalled. The most recent was July 15, when a losartan product was pulled for contamination with N-nitroso N-methyl-4-amino butyric acid, or NMBA.

And earlier this month, an Indian company contracted to take solvents out of valsartan active pharmaceutical ingredient for reuse was cited for findings of nitrosodiethylamine (NDEA) impurities in its solvents. The company was placed on import alert and issued a warning from the FDA for “failure to control and monitor procedures to recover solvents to ensure that they meet appropriate standards before reuse.”

“Sartan” recalls started over a year ago with the finding of N-nitrosodimethylamine (NDMA) contamination in valsartan. Since then, certain lots of other ARBs have been affected, including irbesartan (Avapro) and losartan (Cozaar).

In March, a valsartan shortage prompted the FDA to grant approval to a new generic after a fast-track review.

Now, it’s not just ARBs under FDA scrutiny: other drugs with similar manufacturing processes are also being tested for nitrosamine impurities, Woodcock said.

She also noted the agency is working with other countries’ regulators including Health Canada and the European Medicines Agency.

“We share inspectional findings, laboratory testing methods and results, and our assessments of root cause and impact. We are working to incorporate what we have learned about the process risks that caused these impurities into our oversight of drug manufacturing, which includes how we assess applications and changes to applications, as well as enhancing our inspection coverage to evaluate the controls in place to prevent unacceptable levels of nitrosamine,” she said.

Updated lists of affected products and products without impurities remain available online.

“As we continue our assessments and as companies continue to manufacture ARBs without nitrosamine impurities to replenish the U.S. supply, we expect this figure to rise. We know that ARBs can be produced without nitrosamine impurities, and we are working with manufacturers to reach that point,” according to Woodcock.

In the meantime, she emphasized that the FDA’s initial risk estimate — that if 8,000 people took the highest valsartan dose (320 mg) containing NDMA from the recalled batches daily for 4 years, there may be one additional case of cancer over their lifetimes — is a worst-case scenario and that actual risk to patients is probably much lower.

https://www.medpagetoday.com/cardiology/prevention/81843