FDA defends oversight amid questions of safety of generic drugs made in India and China
Confronted with questions about the safety and effectiveness of generic drugs made overseas, the Food and Drug Administration this week pulled back the curtain on how it scores drug quality based on the agency’s inspections.
The agency released its State of Pharmaceutical Quality report that includes average scores of drug factory inspections by location, type of drug and other categories. The agency also defended its track record in blog posts and interviews this week as a newly-released book documents problems with some overseas generic drug manufacturers.
“I think, ironically, the quality of the drug supply has never been higher,” says Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research. “
The FDA faces an enormous challenge policing a global pharmaceutical supply chain in which at least 80 percent of drug ingredients and 40 percent of finished drugs sold in the USA are made or handled at thousands of factories overseas.
In 2012, Congress directed the agency to prioritizes inspections of domestic and overseas inspections based on a drug factory’s safety risk as measured by factors such as compliance, drug recalls and inherent risk of the type of drug the factory makes.
‘We found a lot of bad things’
The FDA’s report released this week includes average “site inspection scores” over the past decade at drug factories worldwide. Factories in Europe had the highest average drug quality score of 7.9 on a 10-point rating scale, followed by U.S. factories at 7.7.
Factories in India and China – two countries with the most drug factories outside the U.S. – had average scores of 7, below the world average of 7.2
FDA officials say the lower scores in India and China reflect more robust inspections that have uncovered problems. The agency sought to get more inspectors overseas, both those who are stationed abroad and increasingly those assigned to a U.S.-based unit that travels overseas to inspect factories.
“Not surprisingly, when we started that intensity of inspection overseas, we found a lot of bad things,” Woodcock says. “The rate looks alarming perhaps because it’s higher in India and China. But a lot of those firms are on import alert,” which prohibits those factories from shipping drugs to the U.S.
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Woodcock says that the FDA has had “decades of intensive inspection” that have compelled manufacturing improvements in Europe and the U.S. By contrast, factories in India and China have had a much shorter track record of agency inspections.
But others question whether overseas drug factories – particularly those that make lower-cost generic drugs that account for 90 percent of drugs dispensed at U.S. pharmacies – are cutting corners to reduce costs.
‘They shred documents’
Dinesh Thakur is a former executive of India-based Ranbaxy, a generic drug manufacturer that pled guilty to drug safety charges in 2013 and paid $500 million in criminal fines and civil settlements. Ranbaxy shipped batches of adulterated drugs, had incomplete testing records and inadequate program to assess drug quality, according to the Justice Department.
Arun Sawhney, incoming managing director of Ranbaxy Laboratories Ltd., speaks during a news conference in New Delhi, India, on Thursday, Aug. 12, 2010. Ranbaxy Laboratories Ltd., India's largest drugmaker, said Atul Sobti resigned as chief executive officer and managing director. Photographer: Prashanth Vishwanathan/Bloomberg *** Local Caption *** Arun Sawhney ORG XMIT: 103134194 [Via MerlinFTP Drop] (Photo: Prashanth Vishwanathan, Bloomberg)
Thakur noticed problems at Ranbaxy, quit his executive post and reported the company to the FDA. He became a whistleblower under the federal False Claims Act, which allows citizens to bring federal civil cases on behalf of the federal government.
The former Ranbaxy executive says he believes that FDA inspectors detect only a fraction of problematic practices at overseas factories.
“The FDA will point to their data and say we are catching these guys who are doing this type of nonsense,” Thakur says. “My experience on the ground tells me we are able to catch 20 to 30 percent of the issues out there.”
Thakur says the FDA largely halted unannounced inspections of overseas plants. Because plant managers know when the FDA will arrive, it gives them time to prepare by cleaning a lab or training staff on what to tell inspectors during site visits, he says.
In her newly-released books “Bottle of Lies,” journalist Katherine Eban documented problems with Ranbaxy and other generic drug manufacturing overseas.
She agrees with Thakur’s assessment that overseas drugmakers have time to “stage” a factory for inspections.
“These plants get two months advanced notice and they clean up,” Eban says. “They fabricate documents. They shred documents and they move unauthorized equipment out of these plants in advance of these visits (inspections).”
Since July, two factories in China and India were linked to a series of recalls of the commonly-prescribed blood pressure drugs losartan and valsartan after testing revealed the drugs were tainted with suspected carcinogens.
Both factories had a series of problems documented by FDA inspectors before the tainted blood pressure drugs were discovered. In 2016, employees at the Hetero Labs plant in Jadcherla, India were found shredding documents before inspectors were scheduled to arrive.
FDA officials say they still conduct surprise inspections if they are responding to a drug safety issue or a whistleblower complaint. However, in some cases, FDA gives the targeted factory a limited same-day notification of the impending inspection, says Alonza Cruse, director of the FDA’s Office of Pharmaceutical Quality Operations.
While Congress holds public hearings on drug affordability, Thakur says he would like to see policymakers focus more attention on the long-term effects of tainted drugs made overseas.
“We really don’t have any way to study the long-term effects of bad quality drugs,” Thakur says.
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