Contents of FDA refuse-to-file letters for NDAs and efficacy supplements and their public disclosure by applicants

FDA occasionally issues refuse-to-file (RTF) letters explaining why new drug applications and efficacy supplements are not yet ready for full agency review. To offer more insight into the grounds for this response and to gauge how often applicants publicly disclose such action, researchers examined the 103 such communications sent out from 2008 through 2017. The regulator cited 644 unique reasons for refusing to review those applications, 84.5% of which were due to scientific flaws—especially those related to drug safety/efficacy and drug quality. The other 15.5% of refusals were based on application organization deficiencies or legal issues. Sponsors seeking product approvals or efficacy supplements publicly disclosed the receipt of just 16% of the RTF letters issued during the study period, and they shared only 5% of the refusal reasons listed in them. “We found that FDA refuses to file applications for substantive reasons related to quality, safety, and efficacy of drugs, and disclosure of FDA’s refusal reasons is incomplete,” the study authors write. “Greater transparency of such reasons could help applicants avoid RTF letters and thereby facilitate timelier patient access to new therapies.”