With the vast majority of drugs and drug ingredients being manufactured outside the U.S., the FDA has had to step up its international oversight and often ban products from plants that don’t meet its standards. But the FDA also has found itself increasingly having to walk a tightrope between drug safety and drug availability.
Because of the nature of the business, with companies in China or India often being a primary source of essential drugs, the FDA sometimes must exempt products and allow imports from plants that it believes have a poor record. Since 2013 the FDA has allowed 8 plants whose products are otherwise banned from the U.S. to go ahead and import some drugs or ingredients to avoid shortages, according to FDA Import Alert records.
There have been exclusions for 6 plants in India, including one operated by Canada’s Apotex and one by Wockhardt, an Indian company that has run into numerous FDA citations. The exempted facilities also include a Teva ($TEVA) plant in Hungary and a plant operated by China’s Zhejiang Hisun Pharmaceutical. The drugmakers have all indicated they take quality seriously and are working closely with the FDA to resolve their issues.
The agency this year found itself having to backtrack in the case of Hisun when it determined there was a shortage of a chemo drug often used to treat AIDS-related Kaposi's sarcoma. The agency in September 2015, banned 15 drugs coming out of the Zhejiang Hisun because of “systemic data manipulation” in the facility. At the time, it excluded tuberculosis treatment capreomycin and 13 others over concerns that shortages might arise. Then in February it updated the order to also exclude daunorubicin HCl, the API used in the injected med DaunoXome because of a "critical drug shortage concern."
In the case of the Teva plant, the FDA last month issued an import alert for all but two products at the Teva facility in Gödöllő: cancer treatment bleomycin and antibiotic amikacin.
The FDA will not address specific cases but has said that when it exempts certain drugs from an import alert due to shortage concerns, it “also often requests the manufacturer to take certain measures to enhance quality oversight for products that are offered for entry into the United States."
But as Bloomberg points out, the FDA leaves that testing up to any drugmaker that buys the exempted ingredients. “There is no transparency,” Erin Fox told Bloomberg. Fox is director of the University of Utah’s Drug Information Service, which tracks drug shortages. “We just have to take FDA’s word that they think it’s OK.”
The FDA learned the hard way that it must sometimes balance the need for demanding companies' GMP compliance and patients having access to needed drugs. It came under intense criticism in Congress some years back, when shortages arose after companies stopped production in some plants to address FDA citations.
It faced a particularly daunting situation in 2013 with the Boehringer Ingelheim Ben Venue plant Bedford, OH, a facility with deep-seated problems that had been responsible for dozens of recalls. But because the sterile injectable drug facility at the time was the only source for so many products, when it came time to lay out its mandates under a consent decree, the FDA allowed it to keep producing about 100 drugs considered "essential for patient care."
Boehringer Ingelheim in 2013 finally decided to simply close the plant, leaving many drugmakers to scramble for production alternatives to keep drugs available. Johnson & Johnson's ($JNJ) Janssen's unit, which had dealt with supply issues for its popular breast cancer treatment Doxil, went so far as to get FDA approval to lease part of the Ben Venue plant and produce the drug there itself until it could arrange for another supplier.
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