FDA is seeking ‘root cause’ of drug recalls

Blood pressure medicine tested for impurities

In July, drug companies began recalling dozens of lots of the blood pressure and heart medications called valsartan, losartan and irbesartan after testing found the drugs had trace amounts of cancer-causing impurities.

The Food and Drug Administration is investigating the underlying causes of the tainted drugs. Although the federal agency’s inquiry isn’t complete, inspections at factories in China and India revealed a history of problems before carcinogens in the drugs were ever discovered.

Here are answers to common questions about the recalls, the medications and what the FDA is doing.

Which drugs are affected by the recalls?

Valsartan, losartan and irbesartan are commonly prescribed blood pressure medications that are part of a large class of drugs called angiotensin II receptor blockers, or ARBs, which work by blocking the effects of a hormone that narrows blood vessels.

ARBs and another class of drugs called angiotensin converting-enzyme inhibitors, or ACE inhibitors, are often the first drugs doctors recommend to lower a patient’s blood pressure.

Though companies recalled specific lots of the three medications – alone or with other drugs – many of these commonly prescribed drugs are not part of the recall.

Consumers can check the FDA’s website for a full list of recalled drugs. No contaminants have been found in Novartis’ Diovan, the brand-drug version of valsartan, the FDA said.

Throughout the recalls, doctors said stopping a medication without a replacement drug could cause a patient more harm than continuing the drug.

Why were the drugs recalled?

The FDA traced the drug impurities to factories in China and India that make and supply valsartan ingredients to generic drug companies worldwide.

Testing showed the factories made valsartan that contained N-nitrosodimethylamine, or NDMA, a possibly cancer-causing substance. In September, the FDA said testing revealed a second

contaminant, NDEA, in certain valsartan drugs.

Inspection reports revealed problems at both factories.

How many patients have been affected?

It’s unclear how many people on valsartan and the other blood pressure drugs have been affected by the recall. About 103 million U.S. adults had high blood pressure in 2017, the American College of Cardiology, the American Heart Association and other groups said in a report.

The groups based the number on new, more aggressive guidelines for treating hypertension. They estimated that 36 percent of adults should be treated with medication.

Which factories made the tainted drugs?

The source of the bulk of blood pressure drug recalls is the Zhejiang Huahai Pharmaceutical factory in Linhai, China.

FDA inspectors found equipment had fraying gaskets, rusted screws and missing pieces and discovered workers repeatedly failed to investigate testing anomalies in drug batches.

Still, factory operations continued until testing in June revealed unacceptable levels of NDMA. The FDA announced a recall in July, and testing found NDEA in valsartan batches.

At a Hetero Labs plant in Jadcherla, India, workers were found shredding documents before inspectors were scheduled to arrive in 2016, per the FDA. The FDA warned the drugmaker that it failed to investigate discrepancies in drug batches and didn’t regularly clean equipment to prevent contamination.

The FDA issued an import alert to the Zhejiang factory, preventing its drugs from being shipped to the USA. It did not issue an alert against Hetero.

What’s the FDA doing to address the problem?

Factories that make drugs abroad are subject to inspection by the FDA. They are required to inform regulators about changes in how they make the drug ingredients.

The FDA will make public results of its root-cause investigation, according to Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, who said last month that all “sartan” medications are being tested for impurities.

“We still don’t understand the complete root cause of this problem,” Woodcock said. “I would think these recalls would start dropping off now.”

The FDA’s probe is unfolding during the partial government shutdown, and Commissioner Scott Gottlieb said Tuesday that the agency is “focused on preserving the function of our programs for as long as we can.”

About 103 million U.S. adults had high blood pressure in 2017, the American College of Cardiology and others groups said in a report.

Food and Drug Administration Commissioner Scott Gottlieb, foreground, says the agency is trying to keep its programs running during the government shutdown. The FDA is investigating the discovery of possibly cancer-causing contaminants in blood pressure medications that came from factories in China and India.