FDA Commissioner Testifies for PDUFA Reauthorization

Last week, FDA Commissioner Margaret A. Hamburg testified before the House Committee on Energy and Commerce, Subcommittee on Health to support the fifth authorization of the Prescription Drug User Fee Act (PDUFA), also known as PDUFA V. She also outlined a series of recommendations, sent to Congress in January 2012, to include in PDUFA V.

The current authorization for PDUFA, PDUFA IV, expires on Sept. 30, 2012, and Hamburg testified that fees collected under PDUFA constitute an important part of the agency’s funding. Of the nearly $932 million obligated in support of the process for the review of human drug applications in fiscal year (FY) 2010, PDUFA fees funded 62% and the rest were through appropriations. Three fees are collected under PDUFA: application fees for new drug applications (NDAs) and biologics license applications (BLAs), product fees, and establishment fees.

In making the case for PDUFA reauthorization, Hamburg highlighted the review performance of FDA. Of the 35 innovative drugs approved in FY 2011, 24, or 70%, were approved by FDA before any other regulatory agency in the world, including the European Medicines Agency. Of 57 novel drugs approved by both FDA and the EU between 2006 and 2010, 43, or 75%, were approved first in the United States. Preliminary data show that in 2011, over half of all new active drug substances were first launched in the US.

Hamburg also provided a list of recommendations to enhance PDUFA V, which were gained through a series of meetings with the industry, the public, and other stakeholders. These recommendations were sent to Congress on Jan. 13, 2012. These recommendations or “enhancements” to PDUFA V focused on improving communication between FDA and sponsor companies during development, improving regulatory science and innovation at FDA, and expediting drug development.

To increase communication and improve efficiency in the review process, FDA agreed to an enhancement to FDA’s review program for new molecular entity NDAs and original BLAs to include presubmission meetings, mid-cycle communications, and late-cycle meetings between FDA and sponsors for these applications. To accommodate this increased interaction during regulatory review, as agreed to with industry, FDA’s review clock would begin after the 60-day administrative filing review period for this subset of applications.

Five enhancements focus on regulatory science and expediting drug development. These enhancements include:

• Establishing drug-development communication and training staff in FDA for improving communication between FDA and sponsors during development

• Developing methods for meta analysis in premarket and postmarket clinical evaluations

• Improving the agency’s clinical, clinical pharmacology, and statistical capacity to address submissions using biomarkers or pharmacogenomic markers

• Improving FDA’s clinical and statistical capacity to address submissions involving patient-reported outcomes and other endpoint-assessment tools, including providing consultation during the early stages of drug development

• Facilitating rare disease drug development by FDA issuing relevant guidance, increasing the agency’s outreach efforts to the rare-disease patient community, and providing specialized training in rare-disease drug development for sponsors and FDA staff.

Other PDUFA V enhancements include:

• Expanding implementation of FDA’s benefit–risk framework in the drug-review process, including holding public workshops to discuss the application of frameworks for considering benefits and risks that are most appropriate for the regulatory setting.

• Standardizing risk evaluation and mitigation strategies (REMS) by initiating a public process to explore strategies and initiate projects to standardize REMS with the goal of reducing burden on practitioners, patients, and others in the healthcare setting. Additionally, FDA will conduct public workshops and develop guidance on methods for assessing the effectiveness of REMS and the impact on patient access and burden on the healthcare system.
• Using user-fee funds to conduct a series of activities to determine the feasibility of using the Sentinel (i.e., a national electronic system for FDA to track the safety of drugs, biologics, and medical devices) to evaluate drug-safety issues that may require regulatory action, such as labeling changes, postmarketing requirements, or postmarketing commitments.
• Requiring a phased-in requirement for standardized, fully electronic submissions during PDUFA V for all marketing and investigational applications. Through partnership with open-standards development organizations, the agency would also conduct a public process to develop standardized terminology for clinical and nonclinical data submitted in marketing and investigational applications.

The cost of the agreed upon PDUFA V enhancements translates to an overall increase in fees of approximately 6%.