FDA expects an analysis of the "root causes" of multi-cycle product reviews to begin in fiscal year 2004, Office of New Drugs Director John Jenkins, MD, said June 24 during the Biotechnology Industry Organization annual meeting in Washington, D.C.

"We plan to start this in fiscal year '04," Jenkins said. "There will be annual reports to the agency...and then a final report at the end" of the current Prescription Drug User Fee Act program in fiscal 2007.

The "root causes" analysis, in concert with the "74-day filing review issues letter" and good review management principles guidance, are parts of Commissioner McClellan's "first cycle review" initiative (¹ [A#00650050012], p. 15).

FDA will issue a "statement of work" for the multi-cycle review analysis contract "soon" that will be available for public comment, with the expectation that "we're going to try to get on board in the next six months or so," Jenkins said.

The agency is seeking a consultant with an intimate knowledge of both drug development and the FDA review process under PDUFA, Jenkins explained.

"We're going to be looking for contractors or consultants who obviously have the ability to do this type of analytic work and study. But...we don't want just any consultant, so we're weighing factors in the contract to make sure that these people have to understand drug development and have a working knowledge of FDA regulations and the PDUFA review process so we don't have to spend the first year training them on [how] we do review of drugs."

The "root cause" analysis will use the fiscal 2002 review performance as a baseline to compare against a prospective analysis of current product reviews, Jenkins explained.

The consultant will be "reviewing the FDA files, working with sponsors to try to find out what went well, what didn't go so well, why did there end up being a second review cycle."

In "real time," the consultant also will be "interacting with the agency and with the sponsor to understand how the process is moving forward, where are the communication difficulties, where are the things that are working well."

"One of our challenges is going to be to make sure that we get good data from this project in an ongoing way on a global basis because we don't want the contractor to be influencing how we actually manage the review of a particular application. That would be a bias introduced into the study," Jenkins acknowledged.

"We would want the contractor to be providing us feedback in real time by providing yearly reports [so] that we can implement changes in a systematic way across the program without biasing the result of each individual application."

"We're going to be looking at all first-cycle reviews of NME NDAs and BLAs during PDUFA III. We'll be assessing the impact of the [good review management principles] guidance and the effectiveness of training."

FDA expects that "74-day letters" will also increase first-cycle approvals. The letters, in which the agency identifies potential issues after initial review of an application, are mandated under PDUFA III.

In the first six months of the fiscal year, FDA received 62 NDAs and issued 38 of the new letters, 18 of which cited application flaws. The agency has issued 74-day letters for 64% of NDAs, above the 50% goal for the year (² Also see "FDA Has “Issues” With NDAs; Half Of 74-Day Letters Note Application Flaws" - Pink Sheet, 21 April, 2003., p. 37).

While FDA is on track with the 74-day letter program, the agency is behind in releasing the Good Review Management Practices guidance, Jenkins said.

"The draft guidance has been pretty much completed. It's within the final clearance process within FDA. I hope it will be published soon, within the next several weeks or so for public comment." The goal is to "have a draft guidance out well before the end of September."

However, "we have a target to publish the final guidance by the end of September. That's not going to happen." FDA has had an internal draft since last fall (³ Also see "FDA Emphasizing Written Communication With Sponsors On Pending NDAs" - Pink Sheet, 14 October, 2002., p. 16).

"I think we'll be okay, because the draft guidance will go a long way towards helping FDA and sponsors understand good review management principles, and we will be developing a training program for our staff that will be implemented in the fall."

The draft "does not focus on scientific review issues. This will address our expectations with FDA staff and sponsors about how to efficiently manage the process for first-cycle review of applications."

In addition to the multi-cycle review contract, FDA is also drafting a contract for a consultant to assess the two continuous marketing application pilot programs, which are slated to begin Oct. 1 (⁴ [A#00650240014], p. 21).

Jenkins suggested that the pilot programs could help FDA meet the commissioner's goal of reducing the median time for product review by 10% (see ⁵ Also see "McKesson Splits CEO Into Operations & Strategy: Hammergren & Mahoney" - Pink Sheet, 28 June, 1999. ).

"We're currently in the process of putting out the statement of work to find contractors to do this actual contract," Jenkins said. "We'll be getting a preliminary report in time to help inform decisions about the PDUFA IV program."

The consultant will "be looking at the value, the cost and the impact on drug development in the review process" of the pilot programs, Jenkins explained.

"These are essentially experiments to see how do these things work. Do they actually add value to the drug development and review process and how much do they cost?"

"I think a lot of us think that these initiatives add value, but we also need to know how much value do they add and how much do they cost, so that we can all do kind of a cost-benefit analysis at the end of this."

The analysis will help FDA "decide are we going to expand this to other products? Are we going to limit it to fast-track products or is it too costly or not productive enough that we want to not go forward with it in the future?"

"This is going to be a two-sided analysis," Jenkins said. "They're not going to just be looking at what FDA does, they're also going to be looking at how the sponsors interact with the programs, which I think is a very important component."

"This really represents the first systematic assessment by FDA or by anyone that I'm aware of of the cost and the impact of the various actions to speed the development and review of new drugs."

FDA Multi-Cycle Product Review Analysis To Begin In Fiscal 2004

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