Stopped in their Tracks

That FDA has apparently been issuing more refusal to file decisions, particularly to big pharma, is "yet another possible indication that [the agency] is getting still tougher with its approval process," Pharmalot's Ed Silverman says. "Among big drug-makers receiving an RTF [refusal to file notice] in the last two years were Pfizer, Novartis, Roche and Merck, as well as Gilead Sciences, one of the largest biotechs," Silverman adds. Howard Liang, managing director of biotechnology at investment firm Leerink Swann, tells Pharmalot that these RTFs could "be related to the recent FDA implementation of good review practices in an initiative … under which reviewers are expected to frontload the review and identify showstoppers early." In reviewing 28 RTFs issued to pharma, Liang tells Silverman he found three common problem-areas that may have led to FDA's refusal to file — "deficiencies" in clinical data; problems with chemistry, manufacturing, and controls; and electronic file errors.