Drugs Approved With Manufacturing Issues: Kaiser
A lengthy Kaiser Health News online story details instances in which FDA has approved branded drugs for marketing despite manufacturing issues raised by agency inspectors. The story says the pressure on the agency to get innovative drugs to market quickly is considerable, because they offer new treatments for desperate patients and because the medicines are highly profitable.
According to Kaiser, “FDA has repeatedly found a way to approve brand-name drugs despite safety concerns at manufacturing facilities that had prompted inspectors to push to reject those drugs’ approval. This happened in 2018 with drugs for cancer, migraines, HIV, and a rare disease, and 10 other times in recent years, federal records show. In such cases, how those issues were discussed, negotiated, and ultimately resolved is not public record.”
Although the report faults FDA for at times resolving manufacturing issues without a follow-up inspection, it quotes CDER director Janet Woodcock that an inspector’s recommendation to withhold approval can be “dealt with” without a follow-up. She said the agency can’t comment on specifics, and Kaiser notes that companies are reluctant to discuss the cases because details of the resolution are protected as a corporate trade secret. “That doesn’t mean there’s anything wrong with the drug,” Woodcock told the news service.
In contrast, industry and agency experts said, if FDA finds problems in preapproval inspections for generic drugs, it is likely to deny approval and delay the drug’s launch until the next year’s review cycle. Kaiser reports that just 12% of generics were approved the first time their sponsors submitted applications from 2015 through 2017. In 2018, it says, 95% of novel drugs were approved on the first try, according to FDA data.
Woodcock reportedly said the agency has “the same standards for all drugs,” but emphasized that many manufacturing issues are “somewhat subjective.” For new branded drugs, she said, FDA will “work very closely with the company to … bring the manufacturing up to snuff.” Kaiser says the manufacturer submits written responses and commits to resolve quality concerns, but the details are kept confidential.
Kaiser concludes that problems with drugs can take years to discover, and then only after patients are injured. So health researchers say that more caution is warranted. “They’re doing so few of these inspections pre-market,” said Diana Zuckerman, president of the nonprofit National Center for Health Research. “The least they can do is listen to the ones they’re doing.”