FDA's Approvable and Related NDA/BLA Actions

Abstract

This report offers the first comprehensive analysis of FDA approvable actions. During 1998 through 2005, 87 NME drug-product NDAs (NME-NDAs) received at least one approvable action by CDER prior to final approval. The proportion of NME-NDAs receiving at least one approvable action increased from 1998 through 2002 then abruptly fell in 2003 and remained at the lower relative level through 2005. Compared with CDER-approved products never receiving an approvable letter during first NDA review, NDAs issued an approvable letter were associated with longer mean time to first FDA review action: 10.1 versus 8.07 months and with longer mean total review time: 23.1 versus 9.02 months. Compared with CDER-approved products never receiving an approvable letter during first NDA review, drug programs receiving an approvable letter were significantly less likely to have been granted priority review or to have been designated as fast-track. CDER review division was the only analyzed variable independently predicting whether an NME-NDA was ultimately approved following an approvable action. NME-NDAs requiring a new clinical trial following the first review cycle were associated with prolongation of total review time. A total of 19 therapeutic recombinant protein BLAs were issued the CBER-equivalent of an approvable letter prior to approval. There was a strong correlation between the number of review cycles and total review time (R = 0.72). Compared with CBER-approved therapeutic programs not receiving an approvable letter during first BLA review, programs deemed approvable were significantly more likely to have been granted orphan-drug status. Approvable BLAs were associated with significantly longer mean time to first FDA review action: 8.97 versus 7.05 months and with significantly longer mean total review time: 21.3 versus 7.05 months. Issues delaying BLA approvals were qualitatively similar to those delaying NDA approvals. The strategic and tactical implications of these findings are discussed.