Fifteen months could become the expected review time for new molecular entity and novel biologics license applications, based on a proposed new review model. FDA and industry are considering a review timeline that would automatically add two months to all NME new drug applications and novel BLA application goals with the potential for an additional three-month extension under certain conditions. The new model only would apply to those applications, according to minutes of a Nov. 18 Prescription Drug User Fee Act reauthorization negotiating session with industry. All other NDAs and BLAs would be reviewed under the existing application review system, where the standard review time is 10 months. FDA and industry would receive some of their primary requests under this proposal. It would allow more time to complete reviews in the first cycle and also add a late-cycle meeting between sponsors and the agency to discuss major issues. The new model also would address an industry request for more certainty in the review process. While the existing stated goal is 10 months for all standard applications, FDA’s record of meeting that timeframe is inconsistent. If both sides can agree to the additional review time for NME NDAs and original BLAs, which theoretically require more work, industry could gain the additional consistency in review times that it wants. That is, of course, if the agency actually can finish the reviews within the longer timeframe. The review clock would begin two months later than usual – at the conclusion of application filing and validation activities – to create time for the late-cycle meeting, according to the minutes. The delay would allow the agency to throw out most of the automatic extensions it had been pushing for in previous meetings. Extensions for advisory committees, foreign facility inspections and Risk Evaluation and Mitigation Strategies would not be necessary, the agency said in the minutes. However, the mandatory three-month extension for a major application amendment, no matter when it was submitted, still would be possible. FDA had argued it could not meet the prescribed review goals because applications with a major amendment – as well as those requiring a REMS, foreign inspection and advisory committee meeting – required too much additional work. The agency also said a REMS submission could be considered a major amendment. FDA said applications submitted with a REMS would not trigger an automatic extension, but the agency could take the major-amendment extension if the REMS had to be revised during the review, according to the minutes. The additional two months for all NME NDAs and novel BLAs would push the standard review goal to one year. A major amendment or REMS issue would extend it to 15 months. Interestingly, FDA is asking for more review time as it is near meeting performance goals under the existing PDUFA standards. In fiscal year 2008, the agency reviewed 87% of all standard NMEs and novel BLAs within 10 months, just short of its 90% goal. FDA has more work to do finishing non-novel application reviews on time. Its performance for non-NME or novel BLA applications was 85% in FY08. The new review time of 15 months would still be below the recorded median review time for standard applications, which was 16.2 months in fiscal year 2008. That was the highest since the 20-month median recorded in 2001. The new model also would address only a fraction of all the NDA and BLA applications FDA receives. NMEs accounted for about 22% of all original NDA and BLA applications received from fiscal years 2005 through 2009, according to the FY 2009 PDUFA Performance Report, released in October. In FY 2009, 31 NME applications were received, the most in the five-year span. However, the total of original applications, 147, also was the highest during the period, the agency said in the report. Later Meeting Includes More FDA Officials Under the new model, a late-phase meeting after primary and secondary reviews are finished would be allowed to conduct discussions of application problems as well as advisory committee and risk management plans. It also could cover new data or analysis submissions and whether FDA would review them during the first cycle, according to the minutes. The meeting would include signatory authorities (those who make the final decisions on applications), an industry request during previous meetings. The agency also is willing to give its advisory committee meeting background package to the sponsor 21 business days prior to the scheduled meeting under the new model. Industry had asked in previous meetings to see the documents earlier. If applicable, the late-phase meeting would be scheduled between the receipt of the background package by the sponsor and the AC meeting. The new review timeline would include an additional mid-cycle communication previously offered, where a project manager would give application status updates and talk about any major deficiencies that had been found. The agency previously had offered the mid-cycle meeting, but it was too early for sponsors’ needs. Applications Need More Information Additional expectations also would be placed on industry in the new model. Applications would be expected to be complete at the time of submission and include a complete list of manufacturing facilities so the agency could better plan and conduct pre-approval inspections before advisory committee meetings. Both sides also considered including a complete list of clinical investigation sites in the application so the agency could more easily verify data integrity and protect human subjects, according to the minutes. FDA said comprehensive pre-submission meetings about potential safety issues could help identify risk management needs earlier. Industry representatives said they were looking at best practices for those meetings. More Discussions Of New Model Ahead There was no indication in the minutes that industry had accepted or rejected the new model. Industry representatives appear to have spent much of the hour-long session listening. The new model is the latest move in a long journey toward an upgraded application review system. FDA had argued for more time, while industry wanted additional meetings for sponsors. In an attempt to make more time during the review process for mid-cycle meetings, the agency had at one point proposed a four-phase process that would have allowed FDA to stop the review clock in order to conduct the mid-cycle meeting with the sponsor. That proposal solicited too many questions from both sides and was dropped. The agency then returned to its automatic extensions proposal, which came earlier in the negotiating process. More discussion of the late-phase meeting proposal is scheduled for a future session. If a process resembling the 15-month timetable is enshrined in PDUFA V, however, it may confirm to many in industry that their relationship with the user program is indeed a loveless marriage, in that they are paying more for slower. | 
