Associate Director, Global Regulatory Policy and Intelligence, Global Regulatory
Janssen Research and Development United States
This review will identify products or indications that were withdrawn after approval under 21 CFR part 314, subpart H (accelerated approval of new drugs for serious or life-threatening illnesses) or under 21 CFR part 601, subpart E (accelerated approval of biological products)
Accelerated approvals were identified using CDER drugs & biologics approval reports and reviewed at Drugs@FDA for NDA type (NME, NDA/BLA, supplements). Additional information found utilizing FDA advisory committee meeting summaries, Pink Sheet publications and sponsor press releases.
From 1992 to June 2019, there were a total of 198 drugs approved under accelerated approval regulations (21 CRF part 314, subpart H and part 601 subpart E). This included 94 NMEs/new therapeutic biologics, 67 NDA/BLA supplements and 37 non-NME NDAs/BLAs. There have been a total of 12 product or indication withdrawals which included 7 NMEs, 3 NDA/BLA supplements and 2 Non-NME NDAs/BLAs. The majority of accelerated approval withdrawals these have been for oncology indications (N=7).
Accelerated approval is an FDA expedited program that is intended to facilitate and expedite the development and review of drugs and biologics for diseases that are serious or life-threatening. This alternative pathway was added to the regulations in 1992. Confirmatory studies are required after approval to verify the drug’s clinical benefit. A drug approved under the accelerated approval is subject to accelerated withdrawal. FDA may withdraw approval if the confirmatory trial is not conducted or does not show benefit, if there is evidence that the drug is not safe or if the sponsor spreads false or misleading promotional materials. Roughly 6% of all accelerated approvals have been withdrawn. For the majority (n=9) of accelerated approval withdrawals, confirmatory studies were either not done or did not show clinical benefit. Most have been due to confirmatory trials not being completed or not showing clinical benefit. The average time on the market before withdrawal was 8 years (ranging from 10 months to 14 years).