FDA’s new proposed review model would break the process into four distinct phases:
FDA's Proposed Four-Stage Review Cycle |
1. Administrative phase – The agency would validate the application before the review clock starts. 2. Application review phase – Primary and secondary reviews would take place along with the issuing of any discipline review letters. 3. Information sharing phase – The sponsor and the agency discuss how to address issues raised during the initial review. 4. Wrap-up and action phase – Final review activities would be completed. |
Under the proposal the agency would not need some extensions it had previously suggested only because the review clock would be stopped mid-review to address application problems and amendments.
A delay by any other name. This is progress?
The mid-review pause would allow for in-depth discussion between the sponsor and the agency, and appears to be in part a response to an industry request that the review system in the next user fee cycle include a process that makes it easier for sponsors to gain feedback and provide input during an application’s review.
Minutes of an Oct. 12 Prescription Drug User Fee Act negotiation with industry indicated that phase would be used for sponsor meetings with FDA and amendment submissions stemming from reviewers’ issues. The information sharing phase was proposed as a fixed period, although no specific length of time was given.
It would almost certainly be the period where FDA would call its time-out, where the review clock would stop while meetings were conducted.
An application review cycle would begin with the “administrative phase,” where the agency would validate the application before the review clock starts. Primary and secondary reviews would occur in the “application review phase,” along with the issuing of any discipline review letters.
After the sponsor and agency complete the “information sharing phase,” the agency would move to the “wrap-up and action phase,” where final review activities would be completed, including advisory committee meetings, sponsor amendment reviews, risk management agreements, if necessary, and a final decision.
FDA has not determined many details of the new model and minutes called it a “high-level concept.” The agency has not worked out whether the “information sharing phase” would be required for some types of applications that would be considered very likely to be approved or receive a “complete response” letter.
The agency also warned it has not finished refining the concept, so it may not appear superior to the existing review model as it comes into focus. Industry groups at the meeting planned to discuss the new model with their member companies before the next meeting.
The new model is different from any previous compromise FDA has proposed. Agency representatives said in earlier meetings they needed more time than the original PDUFA periods and argued for automatic extensions if advisory committees, foreign facility inspections or certain types of Risk Evaluation and Mitigation Strategies were necessary. The agency also has said any major application amendment should trigger an automatic three-month deadline extension.
Talk about a 90 degree angle!
Under the new review model, the agency would not need three-month extensions for advisory committee meetings or foreign inspections. But it did say a four-month extension still may be needed if complicated REMS was submitted during the review cycle.
Ah – but when during the review cycle should also be a PDUFA reauthorization topic of discussion.
The agency does appear somewhat willing to allow for more Type C meetings in a review cycle, as long as it can control them. “Control” means that the FDA would determine whether a C1 or C2 meeting was appropriate. Industry said sponsors should be allowed to request either classification of meeting, but the agency said it wanted to preserve the standards of what constitutes a Type C meeting. Those standards could be lowered if industry determined the meetings, according to the minutes.
The agency also was concerned the demand for Type C meetings could balloon enough that it would overburden review staff. If the number of meetings eclipsed the 2003 record, the PDUFA workload adjuster, which helps determine annual user fee amounts, would not adequately account for the increase, according to the minutes. If industry accepted the C1 and C2 meetings, the agency said it wanted more resources added early in the PDUFA V cycle to address the workload problem.
Sounds reasonable – but what about a “real time” meeting measurement system to measure if money earmarked results in meetings scheduled?
And what about the issue of so-called “non-binding advice?”
The agency was concerned any provisions allowing non-binding advice would force primary review staff to give advice without supervisory approval or an official record, which could cause an increase in FDA-industry disputes.
Allowing non-binding advice also likely would increase reviewers’ workloads. The agency said some questions that seem simple require input from several reviewers and cannot be answered by one reviewer, according to the minutes.
FDA remained leery about the idea, but was willing to talk about specific parameters where the general scientific discussions that carry no regulatory weight could be allowed, according to the minutes.
Really? Non-binding advice that carries no regulatory weight?
This is progress? This is transparency?
