Executive Summary

Shared review memorandum under Office of New Drugs reorg will help eliminate last-minute surprises between disciplines and provide greater consistency between divisions.

The US Food and Drug Administration’s Division of Psychiatry Products has one of the first review teams currently testing out the agency’s proposed new integrated review document as part of the “modernization” of the Office of New Drugs.

“We are early adopters, so we’re going to be piloting this new integrated review process with an application” that is already in house, Division of Psychiatry Products Acting Director Tiffany Farchione said during the Prevision Policy/Friends of Cancer Research Biopharma Congress on 7 October. The division is actively using the shared template with an (unnamed) application under review.

That coordinated review is a major change under the Office of New Drugs “modernization”: A single, shared review document (the “uni-review”) replaces the multiple (and often redundant) memos that the agency has generated in the past. The switch is intended to reduce the level of repetition during the review and make the final document more readable and easier to use.  (Also see “US FDA’s Office Of New Drugs Reorganization Approved, But Not Happening Overnight” – Pink Sheet, 26 Sep, 2019.)

Farchione was among a group of next-generation FDA managers who spoke on a Biopharma Congress panel of “Rising Stars” who applauded the integrated review template as an important change that should enhance the review process – but one that will also require careful, step-by-step rollout.

The current review process can be “siloed,” she acknowledged, with different parts of the review not coming into clear focus until the very end. “I’m hopeful that some of that last-minute panic can be circumvented by having more discussions earlier and seeing some written documentation earlier in the review process.”

“The way that we do our reviews now … you have each discipline doing their own thing and chugging along until it’s time for everyone to turn their reviews over to the cross-discipline team lead. That’s the first time that you get this broad overview of all of the issues all at once.”

Seeing the rationale behind a decision in writing can be surprising: “When you start to read their reviews and how they’ve justified what they’ve been saying, sometimes it brings up some serious questions.”

“That’s a really hard thing to reconcile when you get all the way to the five-yard line,” Farchione said. “Now, all of a sudden, you have to go back and dig through the application and find this information for yourself and do some of your own analyses at the last minute. It can be a) frustrating and b) it upends the whole process at the last minute. Not that it happens all the time, but it happens enough.”

Designed From The Ground Up

The division directors applauded the integrated review template, although they noted the implementation will require some culture change among reviewers who are not used to working within the same document or wish to first clear their opinions with their supervisors. But the gradual rollout of the “uni-review” – including piloted applications – is intended to help smooth out any bumps and inform any needed tweaks to the process.

Division of Bone, Reproductive & Urologic Products Director Hylton Joffe also expressed enthusiasm for the process changes and noted that they were designed “from the ground up,” with input from the reviewers who will actually do the work. “What I like is that they are implementing it in phases,” he added, pointing to the broader, step-by-step process for implementing a new structure in the Office of New Drugs.

Farchione’s enthusiasm for the goals of the “uni-review” were echoed by the dean of FDA’s drug review managers, Center for Drug Evaluation & Research Deputy Director for Clinical Science Robert Temple.

In general, Temple expects the lighter workloads that come with a flatter structure will allow division and office directors to take a more active role in new drug applications. As director of the Office of Drug Evaluation I (and even earlier as a division director), Temple said he rarely saw the results of an application under review until a month before the user fee deadline.

That is not to say that an ODE director did not have any input: Temple pointed out that office directors certainly attend meetings on an application and hear about its progress along the way. “But there wasn’t a lot of input as the thing was being developed.”

Under coordinated review processes, there will be a “systematic attempt to get out a review that’s more comprehensive and reflects all of the views of all the people – including the supervisors who never really got around to it before,” Temple said. “That would be a major change. There should be conversations about these things from the beginning. We are moving toward trying to change that.”

Improved Review Consistency

Ensuring consistency in reviews during and after implementation will remain a priority for FDA and is, in fact, a core goal of the OND reorg overall.

“Different divisions do things very differently now,” Temple acknowledged. “My guess is that is not fun for the people who are receiving the advice. One of the things that [OND Director] Peter Stein and I are very interested in is watching over practices to try and notice whether things are consistent or not.”

In working toward greater consistency, Temple attends meetings on various drug applications to witness how reviewers in different divisions resolve regulatory issues. That can be a tricky balance: “There’s a certain inclination to keep your own territory,” he said.

“We need to, in a friendly and not-too-bossy way, try to discuss these matters with people. I go to a fair amount of other people’s meetings, and so does Peter. I think that’s important.”

What Temple hopes is that lighter workloads will free up time for division and office leadership to attend more internal meetings where they can collaborate on bigger-picture regulatory issues. Going into the reorg, Temple is seeing an increase in the number of issues being brought to the Medical Policy Council for advice. The challenge, he acknowledged, is finding time for review team leadership to attend those meetings.

“The problem for us is to get enough people in the room to hear them and write it up in a way that we learn something,” Temple said. “Even recognizing that you are dealing with an issue that goes beyond an immediate case is not so simple. People tend to want to solve the immediate problem. To know it’s a larger issue and maybe establishes a precedent, or could, is not so easy. It requires attention.”

Joffe said he sees collaboration between divisions already improving, pointing to monthly meetings between division directors and deputies, plus larger meetings with Stein and the OND deputy of operations Khushboo Sharma. “In the past few years, I’ve seen more interaction between divisions, which is great,” he said.

https://pink.pharmaintelligence.informa.com/PS141063/US-FDA-UniReview-R…