Drospirenone/Ethinyl Estradiol/Levomefolate Calcium

Lupin got its start back in 1968 as an Indian vitamin manufacturer, thanks to 5,000 rupees founder Desh Bandhu Gupta borrowed from his wife. From vitamin maker to pharmaceutical specialist and now contract manufacturer, India’s Lupin is embarking on a new phase of its corporate journey. Lupin on Monday unveiled its new subsidiary, Lupin Manufacturing Solutions, which is poised to work on the development, production and sale of active pharmaceutical ingredients. The company is now starting to build out its contract development and manufacturing operations business, Lupin explained in a press release. At the same time, Lupin announced Abdelaziz Toumi will take the reins as CEO of the newly formed unit. Toumi’s track record includes stints at Bayer, Merck, Catalent, Lonza and KBI Biopharma. He will be based in Switzerland and spend a considerable amount of time in India, Lupin said. “We are delighted to welcome Abdel to our team,” Lupin’s managing director, Nilesh Gupta, said in a statement. “He brings a wealth of knowledge and experience in the API CDMO space and will be instrumental in establishing LMS as a trusted and preferred partner for our global customers.” Lupin got its start back in 1968 as an Indian vitamin manufacturer, thanks to 5,000 rupees founder Desh Bandhu Gupta borrowed from his wife. The company’s first manufacturing plant churned out iron and folic acid tablets for India’s government as part of a countrywide program aimed at improving maternal and childhood health. Soon after, Lupin started producing drugs for tuberculosis, according to its website. Meanwhile, Lupin has made headlines in recent years courtesy of recalls and FDA citations. That said, the company recently cleared an FDA inspection of its plant in Nagpur, India, with zero observations. Prior to that, Lupin revealed it had signed a license and supply agreement with Thailand’s OLIC to market Fuji Pharma’s pregnancy prevention drug Nextstellis in Vietnam and the Philippines. And, last summer, Lupin became the first company to score approval in the U.S. for its generic version of Boehringer Ingelheim’s blockbuster chronic obstructive pulmonary disease treatment Spiriva HandiHaler. The approval marked the first in the U.S. for a dry powder inhaler from India, Lupin’s CEO, Vinita Gupta, said at the time. Lupin’s manufacturing footprint spans 15 facilities across India, the U.S., Brazil and Mexico, with the company claiming its “pe-eminence as a leader in formulations and APIs.” Nevertheless, the company has run into production shortfalls before. Last summer, the company recalled two batches of birth control pills on the fact that they may not have been effective at preventing pregnancy. At the time, Lupin said testing on one of the lots of Tydemy tablets found low levels of ascorbic acid and high levels of a “known impurity.” Prior to that, Lupin in Nov. of 2022 received another in a series of Form 483 citations from the FDA, with the regulatory wrist slap focusing on the company’s API plant in Manideep, India.  Editor's note: This story has been updated with additional information on Lupin's manufacturing. 

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.