Concerns Mount Over PDUFA Renewal Timetable

Manufacturers and FDA officials are pressing for Congressional action on the latest version of the Prescription Drug User Fee Act (PDUFA VI) and highlighting key provisions in the program designed to accelerate drug development and application review. Congressional staffers have set a goal for finalizing user fee reauthorization measures by June, which would fit the timeframe anticipated by FDA leaders and industry officials eager to avoid disruptions in the program.

The Senate Health, Education, Labor and Pensions (HELP) Committee and the House Energy & Commerce Committee plan to hold hearings in the coming months on PDUFA and similar user fee performance goals for generic drugs, medical devices, and biosimilars. The aim is to reach agreement on funding levels for FDA programs and related policy changes before Congress’ summer recess. Efforts to repeal, revise or replace the Affordable Care Act, however, appear likely to delay consideration of FDA programs.

“We’re not there yet,” observed Theresa Mullin, director of the Office of Strategic Programs in the Center for Drug Evaluation and Research (CDER), at last week’s DIA forum on regulatory submissions, information, and document management in Bethesda, MD. Mullin outlined the need for new processes and resources if FDA is to continue the gains achieved in the drug review process under the current user fee programs.

Sponsors requested nearly 3000 development-phase meetings last year, Mullin pointed out, and with more new scientific discoveries emerging, further modernization of user fee programs are needed for FDA to be able to bring in experts with newly-needed technical specialties. PDUFA VI proposes additional resources to support the breakthrough therapy program, early consultation on biomarker use, and enhanced review of drugs for rare diseases. The review of combination products would gain from clarification of internal procedures for evaluating these therapies, including protocols for human factors studies, plus further guidance on bridging studies and patient-oriented labeling.

CDER and the Center for Biologics Evaluation and Research (CBER) also plan a more systematic approach for incorporating the “Patient’s Voice” into drug development. The aim is to build on the series of public workshops under the current patient-focused drug development program to produce guidances on assessing burden of disease, treatment impacts most important to patients, impact measures, clinical outcome assessments, and endpoints to inform drug development and regulatory decisions.

And with more applications submitted in fully-standardized electronic form, FDA aims to improve the capacity of its staff to assist and analyze new data standards and relevant procedures. A main goal is to further develop and update electronic data standards, while ensuring transparency and security for data submitters.

PDUFA VI also aims to advance the appropriate use of complex adaptive, Bayesian and other novel clinical trial designs, including those where simulation approaches are necessary. FDA supports plans for dedicated meetings and a public workshop to discuss innovative clinical trial designs, which would lead to additional guidance on these study methods. A similar strategy is planned for advancing the use of less common statistical models to advance model-informed drug development.

Another objective is to improve the review and predictability of the biomarker qualification process through staff development, public meetings, guidance development and enhanced communication with sponsors on this process. This approach also will be applied to enhancing the use of real world evidence in evaluating drug safety and effectiveness through pilot studies, methods development plus guidance on how real-world data can support product assessment.