Anatomy of an FDA Drug Recall: The 17α-Hydroxyprogesterone Accelerated Approval and Withdrawal Processes

This review examines the processes by which drug approval decisions are made in the U.S., the caveats that accompany them, and follow-up reports that determine whether a drug should remain on the market, with specific reference to 17α-hydroxyprogesterone caproate (17-OHPC).

Preterm birth (PTB) is the leading cause of perinatal morbidity and mortality worldwide. Efforts to date to prevent this serious pregnancy-related complication have been largely unsuccessful. On February 3, 2011, based on a single randomized controlled trial, the U.S. FDA approved the use of 17-OHPC to prevent spontaneous PTB (sPTB) in high-risk patients under their Accelerated Approval Program. This was the first time the FDA had approved a medication for sPTB prevention and the first approval of a drug specifically for use in pregnancy in more than 15 years. The drug was widely used and quickly became the standard of care for high risk patients. However, on April 5, 2023, the FDA withdrew approval for 17-OHPC based on the results of subsequent studies and meta-analyses showing lack of efficacy; there were no major safety concerns.

The FDA has been heavily criticized for its approach to this situation. Here, we present a detailed review of the circumstances and argue that both decisions—the 2011 approval of 17-OHPC to prevent recurrent sPTB and its subsequent withdrawal in 2023—were appropriate and in accordance with the guidelines of the FDA’s Accelerated Approval Program. Our conclusion is that the FDA made the difficult, yet correct case-use decision.