The safety of generic drugs is questioned by the recall of valsartan

Faced with questions about the safety and efficacy of foreign-made generic drugs, the Food and Drug Administration drew this week's curtain on how it assesses the quality of drugs based on drug inspections. agency.

The agency released its report on the state of pharmaceutical quality, which includes the average number of drug factory inspections by location, type of drug and other categories. The agency has also defended its record in blog posts and interviews this week as a recently published book that documents problems with some generic drug companies overseas.

"Ironically, the quality of the drug supply has never been greater," says Janet Woodcock, Director of the FDA Center for Drug Evaluation and Research. "

The FDA is facing a daunting challenge to control a global pharmaceutical supply chain in which at least 80% of the ingredients and 40% of the finished drugs sold in the United States are manufactured or processed in thousands of years. factories abroad.

In 2012, Congress asked the agency to prioritize national and international inspections based on the safety risks of a drug plant, as measured by factors such as compliance, recalls of drugs and the inherent risk of the type of drug manufactured by the factory.

"We found a lot of bad things"

The FDA report released this week includes the average "site inspection scores" recorded over the last decade in drug factories around the world. Factories in Europe had the highest average score for drug quality (7.9 on a 10-point scoring scale), followed by US plants (7.7).

Factories in India and China – two countries with the largest number of drug factories outside the United States – had average scores of 7, a score below the world average of 7.2.

According to FDA officials, the lowest scores in India and China reflect more robust inspections that have revealed problems. The agency has sought to have more inspectors abroad, whether they are posted or more and more assigned to a US-based unit that travels abroad to inspect factories.

"Not surprisingly, when we started this intensity of inspection abroad, we found a lot of problems," said Woodcock. "The rate seems alarming maybe because it's higher in India and China, but many of these companies are on import alert", which prohibits these factories from shipping drugs in the United States.

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Woodcock says the FDA has had "decades of intensive inspection" that have forced manufacturing improvements in Europe and the United States. By contrast, factories in India and China had a much shorter history of agency inspections.

But still others are wondering whether overseas drug factories – especially those that manufacture lower-cost generic drugs, which account for 90% of the drugs dispensed in US pharmacies – are saving money to reduce their costs.

"They are shredding documents"

Dinesh Thakur is a former executive of Ranbaxy, a generic drug manufacturer based in India, who pleaded guilty to drug safety charges in 2013 and paid $ 500 million in criminal fines and civil settlements. According to the Department of Justice, Ranbaxy shipped adulterated drug lots, had incomplete test records and an inadequate program to assess the quality of the drugs.

Arun Sawhney, the new managing director of Ranbaxy Laboratories Ltd., speaks at a press conference in New Delhi, India, on Thursday, August 12, 2010. Ranbaxy Laboratories Ltd., the world's largest drug maker India, announced the resignation of its director general. General manager. Photographer: Prashanth Vishwanathan / Bloomberg *** Local Legend *** Arun Sawhney ORG XMIT: 103134194 [Via MerlinFTP Drop] (Photo: Prashanth Vishwanathan, Bloomberg)

Thakur noticed problems at Ranbaxy, left his management position and reported the company to the FDA. He has become a whistleblower under the Federal False Statements Act, which allows citizens to bring federal civil actions on behalf of the federal government.

The former Ranbaxy executive stated that he thought FDA inspectors were only detecting a tiny portion of the problematic practices in factories overseas.

"The FDA will refer to their data and say that we catch those guys doing this kind of nonsense," says Thakur. "My experience in the field has taught me that we are able to solve 20 to 30 percent of the problems."

Thakur says the FDA has largely stopped unannounced factory inspections abroad. Because plant managers know when the FDA is going to arrive, it gives them time to prepare by cleaning up a lab or training staff to tell inspectors during site visits, he says.

Journalist Katherine Eban, in her new books "Bottle of Lies," has described issues related to Ranbaxy and the manufacture of other generic drugs abroad.

She shares Thakur's view that drug companies abroad have the time to organize a "factory" for inspections.

"These plants are given two months' notice and they clean up," says Eban. "They are making documents, shredding documents and moving unauthorized material from these factories before visits (inspections)."

Since July, two factories in China and India have been associated with a series of recalls of commonly prescribed antihypertensive drugs, losartan and valsartan, after tests revealed that the drugs were contaminated with suspected carcinogens.

FDA inspectors documented a series of problems in both plants prior to the discovery of the contaminated blood pressure medications. In 2016, employees of the Hetero Labs factory in Jadcherla, India were found shredding documents before the expected arrival of the inspectors.