Approving Animal Drugs through Efficient and Effective Use of Public Resources
Reauthorizations of the Animal Drug User Fee Act of 2008 (ADUFA) and the Animal Generic Drug User Fee Act (AGDUFA) of 2008
ADUFA and the AGDUFA authorize FDA to collect fees for animal drug applications. These fees provide funding for increasing review staff, training and development for staff members, and for refining business processes and developing policies targeted at more efficient review. Both laws require reauthorization during 2013.
Successes of ADUFA I /II and AGDUFA I
During the years of ADUFA I, from fiscal year 2004 to 2008, we eliminated the backlog of applications; reduced review times to statutory timeframes; created a more predictable, streamlined process for reviewing new animal drug applications; and added $43 million and 72 full time staff equivalents (FTEs) to the program over the five years.
We had many accomplishments with ADUFA II, from fiscal year 2009 to 2013 (the current authorization). We reduced the number of second review cycles (i.e. reviews not completed in one cycle) with End-Review Amendments; developed electronic submission capability; added pre-approval foreign inspection goals; increased transparency by participating in ten public workshops; and increased funding to $98 million over five years.
In AGDUFA I (fiscal years 2009 to 2013, the current authorization), we eliminated the backlog of applications; reduced review times; created a more predictable, streamlined process; and added $27 million and 22 FTEs for the program over the five years.
Goals for the Reauthorization of ADUFA and AGDUFA
Our reauthorization goals include:
- Sustaining the fundamentals that drive public health outcomes by supporting the science of drug development, improving the quality of evidence in submitted applications, and promoting a more predictable and efficient review process;
- Focusing performance enhancements on increasing quality and efficiency in the current program and maintaining public confidence;
- Ensuring timely reauthorization;
- Ensuring stakeholders’ participation in the process, and
- Continuing on a sound financial footing.
FDA and regulated industry have agreed on proposed recommendations for the reauthorizations of ADUFA and AGDUFA. The final set of recommendations will be submitted to Congress in January, 2013.
ADUFA III Recommendations
Changes to the performance goals that ADUFA II established to further enhance the process for reviewing animal drug applications include:
Performance Goals highlights. Shorter review times for certain reactivations and resubmissions for microbial food safety hazard characterization and for qualifying prior approval labeling supplements.
Enhancing scientific information exchange. FDA and industry agree on the need to submit information to CVM earlier in the development process to enable the parties to reach agreement at a presubmission conference, or begin review of a protocol. FDA will provide increased flexibility for sponsors to submit scientific data or information concurrent with protocol review. And there will be process improvements for submitting dosage characterization data.
Enhancing chemistry, manufacturing, and controls (CMC). 30-day CBEs (changes being effected) for resubmitted supplements; comparability protocols under investigational new animal drug applications (INADs) and a two-phased CMC technical section review process.
Exploring the feasibility of statutory revisions. Includes expanded use of conditional approval and modifies the current requirement that use of multiple new animal drugs in the same medicated feed be subject to an approved application.
AGDUFA II Recommendations
Performance highlights. Shorter review times for certain reactivations and resubmissions.
Increased communication and transparency with industry. Timely meetings with industry, and question based-review (QbR) for bioequivalence submissions.
Chemistry, manufacturing, and controls (CMC) enhancements. This includes 30-day CBEs for resubmitted supplements, comparability protocols under generic investigational new animal (JINAD) applications, a two-phased CMC technical section review process, and timely foreign pre-approval inspections.
Optimizing Use of Scientific Information for Approval of Safe and Effective Animal Drugs
ONADE identified, developed, and implemented cost-effective enhancements beyond those articulated in the user fee performance goals. Although pre-market evaluation processes for animal drugs are efficient and effective, ONADE recognized the need to be more agile in adapting to an evolving industry – an industry developing new technologies that were not considered when the current review system was established. In response, during FY2012, ONADE identified and began implementing five opportunities for enhancements to enable effective evaluation of innovative technologies.
Define appropriate risk questions for innovative technologies. ONADE formed a senior science advisory team consisting of experts in pharmacology, pharmacokinetics, risk- and decision analysis, veterinary epidemiology, and toxicology. The team is a valuable resource for the review scientists for brainstorming about new approaches in drug evaluation, and for helping tailor drug development based on the specific risks associated with a particular drug. Also, ONADE formed a working group to implement the use of risk-analysis principles in the evaluation of new animal drugs. The group established a current baseline of reviewer knowledge of risk-based decision making. This allows ONADE to identify competencies needed for risk-based review approaches, and to develop risk-based questions to inform safety and effectiveness requirements.
Explore opportunities to facilitate evaluating innovative technologies at Quarterly meetings with industry. Achievements from these meetings included implementing a process through which sponsors can begin working with CVM one to two years earlier in developing innovative new animal drugs. With CVM and industry scientists working on the complex issues specific to innovative technologies during this early phase, we can achieve a shorter time to approval.
Implementing an institutionalized knowledge database to inform future decisions. This March 2012 initiative featured a database that includes a wiki of institutional knowledge of science and policy, thus filling the gap until a policy document or guidance is written.
Developing a research prioritization process to address scientific regulatory questions enabling the evaluation of animal drugs. This included the implementation of a transparent (available on the Internet) tri-annual process for the solicitation and peer review of research proposals from ONADE scientists. The work is to be conducted by CVM’s Office of Research. The research we are prioritizing responds directly to questions regarding drugs or drug classes we are evaluating; the research helps us make more informed decisions in the evaluation process.
Developing a system for tracking research projects pertaining to scientific regulatory questions. In the first quarter of fiscal year 2012, ONADE implemented a new database to capture proposed, active, and completed research projects that involve ONADE staff. This transparent application offers the opportunity for discussion of ideas online.