FDA PREPARING TO OVERRIDE NAPROXEN REJECTION BY OTC ADVISORY COMMITTEE

FDA PREPARING TO OVERRIDE NAPROXEN REJECTION BY OTC ADVISORY COMMITTEE, Office of OTC Drug Evaluation Director Michael Weintraub, MD, indicated in remarks to the Nonprescription Drugs and Arthritis Advisory Committees on Sept. 8. The committees voted 7-4 against approval of Syntex/Procter & Gamble's OTC switch application for naproxen sodium on June 2 ("The Tan Sheet" June 7, p. 1). In reviewing the June meeting, Weintraub suggested that the committees' rejection of the application resulted from three areas of concern: procedures, policies and scientific issues. That breakdown of the reasons behind the advisory committees' rejection vote is important to the naproxen sodium review: FDA can try to focus specifically on the scientific issues related to naproxen while handling policy and procedural matters on a different level. The agency's handling of the naproxen Rx-to-OTC switch could mark a significant precedent. The drug is the first high-profile switch application to be handled by the recently formed OTC drugs office under Weintraub's management and the first to be brought before the Nonprescription Drugs Advisory Committee. The committees' procedural difficulties stemmed from the "NDA day" format of the June 2 meeting, Weintraub suggested. He pointed out that then-Pilot Drug Evaluation Staff Director John Harter, MD, in his introductory memo to the committee, had described the format as "an experiment for these two committees." "Perhaps we were too ambitious or perhaps we weren't clear enough," Weintraub said, "but many of the members of the committees expressed greater comfort with alternative formats. I want to assure you that both the Pilot Drug Evaluation Staff and the Office of OTC Drug Evaluation will take your views into account as we plan future meetings." Policy issues raised by the committee focused primarily on the appropriateness of the various OTC analgesic indications. Weintraub reported that FDA will re-examine its policies in this area, but added that the agency did not believe it would be fair to "change the rules of the game" for Syntex (see story, p. 10). Weintraub addressed the scientific issues raised by the committees by pointing out the various labeling changes to which Syntex had agreed (see following story). "Because FDA requires the sponsor to submit all the data, even from exploratory studies which were never intended to provide definitive effectiveness data, the NDA contains flawed, contradictory data and deficient studies," Weintraub acknowledged. "NDAs are not clean, tidy documents. The job we have . . . is to look over that material very carefully and separate out what is critical for making a regulatory decision. I wanted to make sure you all realize that that is what has happened and will continue to happen." The public update on the status of OTC naproxen appears to allow FDA to dispense with a second formal advisory committee vote on the application while protecting itself from the charge of ignoring expert opinion. Weintraub asked for feedback on his presentation but did not solicit votes on any issue of the naproxon application. Weintraub stressed his desire "to share information with the committee in an open forum." By providing the feedback to you and listening to your reactions today, we hope we will also be supporting and maintaining the advisory committee process as open, interactive and responsive." "We do value and carefully consider all of your input," Weintraub reiterated. However, he reminded the advisory committee members that "the final authority for making a regulatory decision rests with FDA." FDA made it clear at the June meeting that the final decision on the NDA rested with the agency. Following the committees' vote at that meeting, Harter reminded the committees that their "no" vote did "not necessarily mean" that FDA would not approve the application. In preparation for the Sept. 8 meeting, committee members were sent a memorandum from Weintraub previewing the agency's response to the June meeting.