Sponsors and FDA reviewers will have to adjust to the workload of a drug review shifting earlier in the review cycle as the agency implements Good Review Management Principles, now renamed the "21 Century Review Process."

Speaking at FDC/Windhover's FDA/CMS Summit Dec. 4 in Washington, D.C., Office of New Drugs Director John Jenkins said that with the new streamlined process, the review will start as soon as applications arrive at FDA, with the goal of avoiding a "crisis mentality" as the PDUFA date approaches.

Historically, FDA has done an initial check of the NDA to check that it is sufficient to file, "and then people go off and have many other things that are on their priority lists, and they come back to the application mid to late review cycle," Jenkins said. Now the review will start as soon as they determine if the application is file-able.

"What we're trying to do is make sure that we spread the work throughout the application, which means we have to shift the review work earlier in the cycle."

He said better utilization of the early months will free up time at the end of the review for the activities that have to occur then: "labeling, post-marketing commitments, tying up the loose ends, giving the decision-maker time to review the entire package and write their own reviews and recommendations and decision memos so we have documented in the files why they decided the way they did."

The 21 Century Review Process

GRMPs, FDA's codification of best practices to streamline and improve the drug review process, have been in the works for years, but FDA is finally ready to implement them (¹ Also see "FDA’s Good Review Management Practices To Debut In “Near Future”" - Pink Sheet, 16 September, 2008.). All 17 of CDER's review divisions piloted the process with one application in 2008. FDA has now modified the process to accommodate the lessons learned from the pilot program.

The description of the 21 Century Review Process (not to step on the name of the Good Manufacturing Principles initiative) that Jenkins gave at the FDA/CMS Summit was consistent with earlier presentations of the planning and timeline tools (² Also see "CDER Takes Steps To Meet First-Cycle Review Goals Of GRMP Guidance" - Pink Sheet, 25 June, 2007., p. 13).

But Jenkins stressed a few new, interesting points about the long-awaited program, and identified some key challenges.

Like shifting the workload earlier, he also emphasized that the new system is designed to get higher level review division officials, who often arbitrate on controversial issues and differing conclusions raised in the various subject reviews, involved earlier in the process. "We need to make sure the person who has the authority for signing the application is involved throughout the review process, not just at the end."

Jenkins added that there will also be greater transparency for the sponsor, so firms know where their applications are in the review process. "We want for you guys to have a better understanding of where the review process is for your application, and make earlier communication with you about labeling and post-marketing commitments."

GRMP Kinks: Priority Reviews And REMS

Despite the training and planning already ongoing, adjusting to the new procedures will present practical challenges to FDA staff.

GRMP implementation will ideally keep standard reviews right on schedule - Jenkins said it is the agency's goal to have the primary and secondary level review work completed about two months prior to the PDUFA goal-date, to leave time for labeling discussion and planning of post-marketing study commitments.

But the new process could threaten the six-month priority review timeline (³ Also see "Good Review Principles Implementation Could Threaten Six-Month Priority Review Timeframe" - Pink Sheet, 4 December, 2008.). "We've definitely learned that it's very, very difficult to manage this process with priority applications, and nearly impossible to manage this process for priority applications that need to go to an advisory committee," Jenkins said.

FDA will have some time to roll out the new procedures. The FDA Amendments Act mandates a four-year phase-in, starting in FY 2009 with all new molecular entities and novel biologics. But Jenkins noted FDA has another challenge to work out as it gears up with implementation. It still needs to figure out how to incorporate FDAAA-related activities - such as deciding whether an application needs a Risk Evaluation and Mitigation Strategy - into the process.

Though much of the GRMP process lies in the agency's hands, Jenkins repeated at the conference a point that has become an FDA refrain regarding industry's role in improving the timely review of drug applications: the importance of submitting complete applications (⁴ Also see "Complete Submissions Are Key To Good Review Management Principles – FDA" - Pink Sheet, 21 July, 2008., p. 28).

"You need to learn that you're better off submitting a complete application than submitting an incomplete application and hoping that we'll review your submission during our review clock," he said. "We're not going to do that as much in the future as we have in the past. You must do your part if you want GRMPs and the 21 Century Review Process to be successful."

- Jamie Hammon (j.hammon@elsevier.com)

FDA Says New GRMPs Will Shift Drug Review Workload To Earlier In Cycle

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