The Food and Drug Administration (FDA) recently announced an opportunity for public comment on the statement of work for an assessment of the Program for Enhanced Review Transparency and Communication for New Molecular Entity (NME) New Drug Applications (NDAs) and Original Biologics License Applications (BLAs) (the Program). The Program is part of the FDA performance commitments under the fifth authorization of the Prescription Drug User Fee Act (PDUFA), which, allows FDA to collect user fees for the review of human drug and biologics applications for fiscal years (FYs) 2013–2017.
The Program will be evaluated by an independent contractor in an interim and final assessment. As part of the FDA performance commitment, FDA is providing a period of 30 days for public comment on the statement of work before letting the contract for the assessment. Comments are due by August 6, 2012: Docket No. FDA–2012–N–0603.
Background
The timely review of the safety and effectiveness of new drugs and biologics is central to FDA’s mission to protect and promote the public health. Before the enactment of PDUFA in 1992, FDA’s drug review process was relatively slow and not very predictable compared to other countries.
As a result of concerns expressed by industry, patients, and other stakeholders at the time, Congress enacted PDUFA, which provided the added funds through user fees that enabled FDA to hire additional reviewers and support staff and upgrade its information technology systems. In return for these additional resources, FDA agreed to certain review performance goals, such as completing reviews of NDAs and BLAs and taking regulatory actions on them in predictable timeframes. These changes revolutionized the drug approval process in the United States and enabled FDA to speed the application review process for new drugs and biologics without compromising the Agency’s high standards for demonstration of safety, efficacy, and quality of new drugs and biologics prior to approval.
PDUFA provides FDA with a source of stable, consistent funding that has made possible our efforts to focus on promoting innovative therapies and helping to bring to market critical products for patients. When PDUFA was originally authorized in 1992, it had a 5-year term. The PDUFA program has been reauthorized every 5 years, with the most recent reauthorization occurring in 2012 for FYs 2013–2017.
As directed by Congress in preparing for reauthorization of PDUFA for a new 5-year period, FDA conducted negotiations with regulated industry and conducted regular consultations with public stakeholders, including patient advocates, consumer advocates, and health care professionals between July 2010 and May 2011. Following these discussions, related public meetings, and Agency requests for public comment, FDA transmitted proposed PDUFA V recommendations to Congress for FYs 2013–2017 on January 13, 2012. FDA’s proposed PDUFA V recommendations included an FDA commitment to implement a new review program for NME NDAs and original BLAs to enhance review transparency and communication between FDA and applicants on these complex applications.
II. PDUFA V NME NDA and Original BLA Review Program
FDA’s existing review performance goals for priority and standard applications, 6 and 10 months respectively, were established more than 15 years ago. Since that time, additional requirements in the drug review process and scientific advances in drug development have made those goals increasingly challenging to meet, particularly for more complex applications like NME NDAs and original BLAs that generally are discussed in an FDA advisory committee meeting. FDA further recognizes that increasing communication between the Agency and applicants during FDA’s review has the potential to increase efficiency in the review process.
To promote greater transparency and improve communication between the FDA review team and the applicant, FDA has proposed a new review model for NME NDAs and original BLAs in PDUFA V. The Program provides opportunities for increased communication by building in mid-cycle communications and late-cycle meetings between FDA and applicants.
To accommodate this increased interaction during regulatory review and to address the need for additional time to review these complex applications, FDA’s review clock will begin after the 60-day administrative filing review period for applications reviewed under the Program. The Program will apply to all NME NDAs and original BLAs received from October 1, 2012, through September 30, 2017.
The goal of the Program is to improve the efficiency and effectiveness of the first-cycle review process by increasing communication with sponsors before application submission to improve the quality and completeness of submissions, and by increasing communications during application review. This will provide sponsors with opportunities to clarify previous submissions and provide additional data and analyses that are readily available, potentially avoiding the need for an additional review cycle when FDA’s concerns about an application can be promptly resolved, but without compromising FDA’s traditional high standards for approval.
An efficient and effective review process that allows for timely responses to FDA questions can help ensure timely patient access to safe, effective, and high quality new drugs and biologics. To understand the Program’s effect on the review of these applications, interim and final assessments by an independent contractor are key components of the Program. The performance commitments state that the statement of work for this effort will be published for public comment before beginning the assessment. Because the assessment needs to commence at the beginning of PDUFA V on October 1, 2012, FDA must publish the statement of work for public comment in advance of that reauthorization to be able to begin the assessment on October 1, 2012.
Key Objectives
The primary objective of this evaluation task order is to determine the impact of the Program on the efficiency and effectiveness of review of NME NDAs and original BLAs. For an application that otherwise meets FDA’s high standards for approval, an optimal review allows for resolution of all issues (e.g., negotiation of labeling, risk evaluation and mitigation strategies (REMS) and postmarketing requirements and/or commitments) that must precede the issuance of an approval action letter on or before the original PDUFA goal date. Subsequent review cycles are sometimes necessary for applications that contain outstanding deficiencies or require additional discussions between FDA and the applicant. This represents an inefficient use of resources if resolution of these issues could have been achieved prior to the first cycle PDUFA goal date.
The Program builds in specific opportunities for communication between FDA and the applicant regarding the content of a complete application prior to submission and any deficiencies identified during application review while also building in additional time during review to address any deficiencies that can be resolved prior to the first cycle PDUFA goal date. Despite these modifications to the review process, the first review cycle alone may be unable to accommodate substantial application deficiencies or a delay in an applicant’s response to an The primary objective of this evaluation task order is to determine the impact of the Program on the efficiency and effectiveness of review of NME NDAs and original BLAs.
For an application that otherwise meets FDA’s high standards for approval, an optimal review allows for resolution of all issues (e.g., negotiation of labeling, risk evaluation and mitigation strategies (REMS) and postmarketing requirements and/or commitments) that must precede the issuance of an approval action letter on or before the original PDUFA goal date. Subsequent review cycles are sometimes necessary for applications that contain outstanding deficiencies or require additional discussions between FDA and the applicant. This represents an inefficient use of resources if resolution of these issues could have been achieved prior to the first cycle PDUFA goal date.
The Program builds in specific opportunities for communication between FDA and the applicant regarding the content of a complete application prior to submission and any deficiencies identified during application review while also building in additional time during review to address any deficiencies that can be resolved prior to the first cycle PDUFA goal date. Despite these modifications to the review process, the first review cycle alone may be unable to accommodate substantial application deficiencies or a delay in an applicant’s response to an information request that could address the identified deficiencies. Therefore, it will be important for the program assessment to examine attributes beyond those of the Program in assessing the review performance for these applications.
Because the features of the Program occur throughout the review cycle, the assessment shall be performed while these applications are under FDA review and finalized soon after the review is completed. This prospective analysis will examine the set of metrics described in the PDUFA V commitment letter in addition to the attributes of the applications and the review process that factored into the timing of the regulatory outcome of the application. Key Objectives of the Assessment include:
- Using information from FDA’s corporate databases, construct and analyze a baseline data set of NME NDAs and original BLAs received and acted on prior to implementation of the Program. This set of applications shall be used to assess the impact on the key evaluation measures for applications reviewed under the Program.
- Using information from FDA’s corporate databases as well as other databases (e.g., database or other tracking mechanism developed by contractor) for applications reviewed under the Program, collect and analyze data on all NME NDA and original BLAs reviewed under the Program.
- Determine the nature of relationships between attributes of the Program and the timing of the regulatory outcome in the first review cycle
- Determine the nature of relationships between other attributes of the review process and applications that are reviewed under the Program and the timing of the regulatory outcome in the first review cycle.
- Collect and analyze applicant and FDA review staff feedback on applications reviewed under the Program, including any best practices, key concerns, or challenges with regard to the enhanced communication and review of these applications.