Industry wants to place benchmarks in PDUFA that would allow for changes mid-stream, instead of waiting until the end of each five-year cycle.

The idea would give FDA and industry increased flexibility within the Prescription Drug User Fee Act, especially if programs negotiated into the reauthorization do not work out as planned.

It also likely would create additional work for the agency and potentially force it to be constantly on watch for industry challenges to programs and processes it doesn’t like.

Mid-cycle evaluations already are appearing in some new programs where FDA and industry are nearing agreement, including the new application review model. FDA has objected to the idea on at least one occasion, citing legal problems, but has been willing to include them in preliminary agreements.

John Castellani, president and CEO of the Pharmaceutical Research and Manufacturers of America, called for including the mid-cycle assessments under the argument that PDUFA should be about continuous improvement.

No More Stop And Start

Castellani, speaking April 6 during a roundtable discussion at the Food and Drug Law Institute annual meeting, questioned whether PDUFA has to be a “stop-and-start process.”

“If you learn something and it improves the process, it provides more certainty, shouldn’t you stop at some point and say what does it mean? What did I just learn? How can it apply?” he said.

“Or if it slows down the process … creates more uncertainty, and diverts attention from the objective of bringing a safe, effective high-quality medicine to a patient, then what did I learn at that point?”

The comments came in response to a question about whether five years was long enough between PDUFA reauthorizations, particularly whether the time period should be shorter.

Jim Greenwood, CEO of the Biotechnology Industry Organization, compared the question to asking someone if they wanted to go to the dentist more often.

Reauthorizing every five years likely would be better than every six months, Castellani said. But he said there should be times where some items could be reassessed.

“Could you put in that some points in between the five years and say ‘Hey, we learned this, this should be more broadly applicable,’ [or] ‘We learned not to do this, let’s stop it?’” he said. “And that’s one of the things we’re trying to interject in this process.”

Review Model, Sentinel To Be Assessed

Mid-PDUFA assessments already are appearing in the programs being finalized as negotiations for a 2012 reauthorization conclude, despite some FDA objections.

For example, while changes were not made to the PDUFA Workload Adjuster, the formula that helps determine how much user fees increase each year, industry and FDA agreed to conduct a study during PDUFA V that will determine whether changes should be made (see related story, Also see "PDUFA Formula Could Better Incorporate Present Economic Conditions" - Pink Sheet, 18 April, 2011.).

The new application review system, which will become a pilot program under PDUFA V, will include an interim assessment to determine whether the program is working as intended.

Industry asked for the ability to drop the new review model, intended for use only with new molecular entities and novel biologics license applications, if it was not improving review efficiency.

FDA appeared to have reservations about the idea, in part because a program has never been discontinued mid-cycle. The agency said the model would have been part of the congressional record and therefore not easily subject to change. The agency still agreed to decide whether to continue the program throughout PDUFA V after an interim assessment (Also see "PDUFA V: FDA Relaxes Pre-Submission Meeting Requirement" - Pink Sheet, 28 March, 2011.).

User fees also will be used to pay for some projects related to FDA’s Sentinel Initiative, aimed at helping improve the agency's post-marketing surveillance. The agency wanted user fee revenue for the program in part because of a shortage of available appropriations, but industry was not willing to blindly designate money for it.

Industry eventually agreed to provide funding after FDA included two evaluations of Sentinel’s value to safety decision-making during PDUFA V, with the possibility of changing resource allocations (Also see "PDUFA V: Sentinel, Regulatory Science Upgrades Could Gain User Fee Funding" - Pink Sheet, 28 February, 2011.).

A new benefit-risk framework that includes the views of patient advocates and additional reviewer training also would be evaluated as part of the proposal (Also see "PDUFA V Agreement Set In Four Areas, But Broad FDA/Industry Talks Continue" - Pink Sheet, 7 March, 2011.).

Management Evaluations … By Congress

Greenwood also said he wanted more evaluation of FDA managers, including those under the commissioner. He said ultimately management is what can improve FDA operations, rather than program changes.

While commissioners come and go relatively frequently, many upper-tier managers can stay at the agency for much longer. Greenwood said he wanted to use congressional oversight to evaluate those managers, but in a forum not intended to “flog them over some problem.”

“Bring them in in a constructive way and say, 'Let’s talk about a few processes for improvement,' because ultimately they have the purse strings,” he said. “They have leverage that none of us has.”

Some members of Congress already have expressed concerns about the influence of senior management at FDA. In 2008, former Rep. Bart Stupak, D-Mich., suggested no senior manager at FDA become commissioner, even on an interim basis, after Andrew von Eschenbach announced his departure from the top job.

Stupak, who did not run for reelection in 2010 and is now a partner at the law firm Venable LLP, said at the time that the agency's management was too close to industry to bring about meaningful reform (Also see "No FDAer For Commissioner, Interim or Otherwise, Rep. Stupak Urges Obama" - Pink Sheet, 8 December, 2008.).

By Derrick Gingery

PDUFA Needs Mid-Cycle Correction System As Part Of Reauthorization, Industry Says

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