Pictured: Packs of birth control pills/iStock, towfiqu ahamed
At the end of July, Lupin Pharmaceuticals recalled two batches of Tydemy, a birth control drug that the company produces in India, when it was found to have reduced effectiveness. It was the company’s eighth product recall in just 18 months. Lupin was also forced to stop production at one of its Indian plants in 2022 after the FDA issued a warning letter last fall.
Around the same time, another generics manufacturer, Intas Pharmaceuticals, made headlines over a failed FDA inspection at a manufacturing plant in Gujarat, India, leading the company to cease operations there. At a moment when drugs already are in short supply, these disruptions are reducing availability even more, putting entire supply chains at risk and forcing doctors and patients to make difficult, life-changing treatment decisions.
“It’s hard to know” how the issues at Intas and Lupin will influence drug availability in the future, Erin R. Fox, associate chief pharmacy officer of Shared Services at the University of Utah Health and adjunct professor at the University of Utah College of Pharmacy, told BioSpace via email. “The initial stoppages have contributed [and] created shortages, but as time goes by, other suppliers may be able to ramp up, so it really depends on what the other suppliers are able or willing to do.”
In 2020, over 90% of drugs prescribed in the U.S. were generics. Indian companies alone supply 40% of these drugs, The Wall Street Journal reported. Yet, according to a ProPublica investigation into FDA oversight of Indian and Chinese drug factories, only 6% of generic drug manufacturers in these two nations received FDA inspections in 2022.
Now, the FDA is under pressure to balance the demands of a desperate healthcare system with the need to ensure that imported products are safe and effective.
Issues Leading to Lupin’s Recall
Lupin has been the subject of FDA scrutiny since October 2022, receiving several warnings about five of its 12 Indian manufacturing plants within just a few weeks. For example, one of the company’s plants in Pune was cited for 18 violations that month, many pertaining to quality control. In March 2023, a plant in Pithampur received a recommendation for voluntary action from the FDA when an inspection determined that employees were not keeping adequate data records during manufacturing processes. The biggest recent news, however, is Lupin’s voluntary recall after unspecified impurities were found in the oral contraceptive Tydemy.
Lupin distributed the two bad batches of Tydemy in the U.S. between June 2022 and May 2023, totalling over 4,000 boxes. On July 28, the company issued a statement announcing the recall as the FDA warned patients that the drug might not work. So far, no adverse medical effects have been reported due to the ineffective drugs, and affected patients have been urged to continue taking the recalled Tydemy until other medication can be obtained.
In parallel, Intas Pharmaceuticals faced problems of its own, catapulting the oncology field into severe shortages when manufacturing was shut down at one of its factories. In one case, a Sanand facility was discovered to have destroyed records related to current good manufacturing practice by dumping acetic acid on them. In the face of the resulting shortages, some oncology wards have been forced to ration cancer therapy.
Solutions on the Table
Tinglong Dai, a professor at Johns Hopkins Carey Business School, told Biospace by email that the failures of Lupin and Intas highlight a bigger problem with overseas generics manufacturing. “There are definitely broader, industry-specific issues, and these aren’t isolated cases,” he said. “We rely on an incredibly extensive global generic supply chain network that we simply don’t have the resources, capabilities or track record to successfully oversee.”
Fox said that shortages are likely to continue “until we change incentives for companies to improve quality and for hospitals to purchase based on quality.” She pointed to research by Marta Wosińska of the Brookings Institute that proposed a multi-pronged solution to the shortage problem, including a government-run buffer inventory of critical drugs and a program that incentivizes hospitals to prepare for potential drug shortages.
Another approach is to push the FDA to improve its inspection of foreign-made generic drugs. Dai noted that lax adherence to FDA standards—and the consequent recalls and production stoppages—is acutely harming supply at the moment. He suggested that systemic changes, such as providing information about where the drugs they prescribe are manufactured, could allow prescribers to make informed decisions.
During the COVID-19 pandemic, the FDA was unable to complete in-person inspections of Indian facilities, an agency spokesperson told BioSpace. Instead, the agency relied on “alternative inspectional tools” when necessary, including “remote interactive evaluations, record requests, and leveraging information from trusted regulatory partners.” This allowed the agency to maintain oversight on “more than 25% of drug manufacturing facilities in India” since the onset of the pandemic, the spokesperson said, emphasizing that the FDA is now returning to normal inspection operations.
In the short term, however, the messaging around generic drugs should change, Dai said. “Until the FDA can step up its inspection of foreign generic drug manufacturers, it should stop claiming that generic drugs are as safe and effective as brand-name drugs,” he said. “We are living in an extremely dangerous and dire situation, and it is simply a crime if we don’t do something now to fix it.”
Andy Gooding-Call is a freelance science writer based in Northampton, Massachusetts. Reach him at andygoodingcall.com.
