FINAL

PERFORMANCE REPORT

Prescription Drug User Fee

Act of 1992

Fiscal Year 1997 Report to Congress

COMMISSIONER'S REPORT   The Prescription Drug User Fee Act of 1992 is now history, but it has left a legacy of success that goes far beyond its literal intent. By working together to meet the Act's increasingly stringent performance goals, the industry and the Agency have forged a partnership that is bringing the benefits of effective new products to the market at an unprecedented pace without compromising safety. Again this year, the Agency has exceeded all the review performance goals, but as the following pages show, the true gains are in the outcomes that matter to the health care community and patients. The five years of PDUFA have produced:  More applications for new products  Higher rates of approval  Faster review times and total approval times PDUFA has demonstrated that the Agency and the industry, by combining their resources and working together, can achieve the levels of performance the American people deserve. I commend everyone who has contributed to this remarkable effort.   Michael A. Friedman, M. D. Lead Deputy Commissioner of Food and Drugs

TABLE OF CONTENTS Outcomes Report on FY 1997 PDUFA Goals NDAs, PLAs, and ELAs Resubmitted NDAs, PLAs, and ELAs Efficacy Supplements Manufacturing Supplements Notes Appendices: Appendix A: Purpose Appendix B: PDUFA Performance Goals, FY 1993 - FY 1997 Appendix C: List of Approved Applications

OUTCOMES As the original Prescription Drug User Fee Act (PDUFA) expires, the successes reported last year have been confirmed and surpassed. PDUFA has resulted in more and better applications that can be filed immediately, reviewed more quickly, and approved more quickly. New products get on the market faster, and the American consumer and the pharmacuetical industry benefit. The cumulative effects of additional human and financial resources, the use of project management methodology to guide the review process and monitor the increasing workload, the elimination of the backlogs, and the increased emphasis on timeliness as a performance measure, have significantly improved Agency and industry performance, predictability, and accountability. More Applications Filed: Over the five years of PDUFA, submissions of original NDAs, PLAs, and ELAs have increased from 96 in FY 93 to 144 in FY 97. This equates to a 50 percent increase in new application workload. Over the same period, the number of efficacy supplements received each year has increased from 100 to 158 (a 58 percent increase) and manufacturing supplements have increased from 1,248 to 1,597 (up 28 percent). Fewer Applications Refused: The "Refuse to File" rate is a key measure of submission quality. Only two of the 144 NDAs, PLAs, and ELAs submitted in FY 97 were refused. This initial Agency ruling -- the fate of more than a third of all original submissions at the start of PDUFA -- is now approaching the vanishing point. In marked contrast with the situation a few years ago, nearly all applications now go directly into the review process.

More Approvals on First Review: Of the NDAs and PLAs submitted in FY 96 and reviewed, 44 percent were approved on the first review. This is a major increase over initial approval rates for the previous years. Only 33 percent of the FY 95 submissions were approved on initial review, and that was an improvement over the rates of 21 percent and 28 percent for FY 94 and FY 93 submissions respectively. This high initial approval rate is another measure of submission quality and a key factor in achieving timely approvals. Over the five years of PDUFA, the median time to approval for those NDAs and PLAs that were approved on first review was 11.8 months. By contrast, those that required two or more review cycles took a median of 20.3 months to approve. Increasing Approval Rates: Another indication of improved submission quality is the increase in the percentage of submissions that are ultimately approved. As of September 30, 1997, 65 percent of the FY 96 original NDA and PLA submissions (74) had been approved and another 13 percent (15) had received an initial "approvable" decision. The final approval rate for the FY 96 submissions should reach 85 percent. The approval rates for both the FY 95 and FY 94 submissions currently stand at 81 percent and should also reach 85 percent. For the years immediately preceding PDUFA, less than 60 percent of the original submissions were approved.1 Quicker Approval Times: The ultimate approval times for applications submitted during the PDUFA years continue to decline. If 85 percent of the FY 96 submissions are approved, the median approval time will be 12 months.2 This improves on the 15 month median of the FY 95 submissions, the 19 to 20 month medians of the FY 93 and FY 94 submissions, and the 23 month median typical of the early 1990s.1

REPORT ON FY 1997 PDUFA GOALS Twenty-nine goals constitute the management framework for PDUFA (see Appendix B). Twenty-two of the goals have been reported in previous years' performance reports; seven goals remain for FY 97. Six of the FY 97 goals specify review performance targets for the submissions received subject to PDUFA during FY 97. The seventh goal relates to the FY 97 staffing level and will be addressed in the Financial Report in February 1998. The review goals define submission categories (e.g., Efficacy Supplements), review time targets for those categories (e.g., within 12 months), and levels of achievement (e.g., 70 percent of reviews on-time). For the first four PDUFA years, both the submission categories and the review time targets remained unchanged, but the achievement levels changed, increasing from 55 percent in FY 93 to 80 percent in FY 96. For FY 97, while achievement levels continued to increase to the 90 percent level, within submission categories some of the review time targets changed. This report updates the performance on the FY 96 submissions and evaluates the Agency's performance on the FY 97 submissions to date. Nearly all of the FY 96 submissions have been reviewed and, while some performance statistics are still open, final performance relative to the goals can now be reported. Only a preliminary performance assessment on FY 97 submissions is possible at this time. For submission categories with a 12-month review goal, it is too early to measure review performance. For those submission categories with a 6-month review goal, performance on those received in the first half of the year provides an early-indicator of final review performance.

Original NDAs, PLAs, and ELAs

Goal -- Review and act upon complete NDAs, PLAs, and ELAs FY 94-96: Within 12 months of submission date3 FY 97: Priority applications within 6 months of submission date, standard  applications within 12 months3 Submission Year FY 94 FY 95 FY 96 FY 97 On-time Goal (%) 55 70 80 90   Workload -- Original submissions filed: FY 93 FY 94 FY 95 FY 96 FY 974 NDAs 81 90 106 105 120* PLAs+ELAs 7+8 4+4 12+7 9+6 16+8** PDUFA Total 96 98 125 120 144 * Includes 24 priority NDAs (6-month goal) ** Includes 3 priority PLAs and 1 priority ELA (6-month goal) Performance FY 96 submissions: Combined CDER/CBER on-time performance is currently 96 percent which exceeds FY 96 on-time goal of 80 percent Could reach 100 percent if 3 pending submissions are reviewed within time frame FY 97 submissions: As of September 30, 1997, 19 FY 97 submissions had been reviewed, all on-time  Combined CDER/CBER early-indicator performance for 11 priority (6-month goal) submissions received during the first six months of FY 97 is 100 percent on-time Final review performance assessment will occur on December 31, 1998

Resubmitted NDAs, PLAs, and ELAs

Goal -- Review and act upon resubmitted5 NDAs, PLAs, and ELAs within 6 months of resubmission date: Submission Year FY 94 FY 95 FY 96 FY 97 On-time Goal 55 70 80 90   Workload -- Resubmissions received: FY 93 FY 94 FY 95 FY 96 FY 97 of Original NDAs 2 24 58 89 85 of Original PLAs, ELAs 1 13 11 19 14 PDUFA Total 3 37 69 108 99   Performance FY 96 resubmissions: Combined CDER/CBER on-time performance is 99 percent which exceeds FY 96 goal of 80 percent Combined CDER/CBER performance improves over FY 95 on-time rate of 96 percent FY 97 resubmissions: As of September 30, 1997, 71 FY 97 resubmissions had been reviewed, 70 on-time Combined CDER/CBER early-indicator performance for 39 resubmissions received through first 6 months is 97 percent on-time Final performance assessment will occur on March 31, 1998

Efficacy Supplements

Goal -- Review and act upon complete efficacy supplements to NDAs and PLAs FY 94-96: Within 12 months of submission date FY 97: Priority supplements and supplements without clinical data within 6 months of submission date, others within 12 months Submission Year FY 94 FY 95 FY 96 FY 97 On-time Goal (%) 55 70 80 90   Workload -- Efficacy supplements filed: FY 93 FY 94 FY 95 FY 96 FY 974 to NDAs 92 86 77 105 144* to PLAs 8 6 10 8 14* PDUFA Total 100 92 87 113 158 * Includes 10 priority NDA supplements and 15 w/o clinical data (6-month goal) ** Includes 3 priority PLA supplements (6-month goal)   Performance FY 96 Submissions: Combined CDER/CBER on-time performance is 96 percent which exceeds FY 96 on-time goal of 80 percent Combined CDER/CBER performance improves over FY 95 on-time rate of 93 percent FY 97 Submissions: As of September 30, 1997, 41 FY 97 efficacy supplements had been reviewed, all on-time Combined CDER/CBER early-indicator performance for 19 efficacy supplements with 6-month goals received during the first six months of FY 97 is 95 percent on-time Final review performance assessment will occur on September 30, 1998

Manufacturing Supplements

Goal -- Review and act upon complete manufacturing supplements to NDAs and PLAs FY 94-96: Within 6 months of submission date FY 97: Priority supplements and supplements without clinical data within 6 months of submission date, others within 12 months Submission Year FY 94 FY 95  FY 96  FY 97 On-time Goal (%) 55 70 80 90   Workload -- Manufacturing supplements filed: FY 93 FY 94 FY 95 FY 96 FY 974 to NDAs 1,045 871 1,249 1,218 1,258* to PLAs, ELAs 202 186 273 261 338** PDUFA Total 1,247 1,057 1,522 1,479 1,596 * Includes 2 NDA supplements with clinical data (12 month goal) ** Includes 5 PLA/ELA supplements with clinical data (12 month goal)   Performance FY 96 Submissions Combined CDER/CBER on-time performance is 96 percent which exceeds FY 96 on-time goal of 80 percent Proportion of submissions reviewed on-time improves over FY 95 on-time rate of 89 percent FY 97 Submissions As of September 30, 1997, 1,039 FY 97 manufacturing supplements had been reviewed, 1,027 on-time Combined CDER/CBER early-indicator performance for 806 manufacturing supplements with 6-month goals received during the first six months of FY 97 is 98 percent on-time Final review performance assessment will occur on September 30, 1998

1. Source: United States General Accounting Office, FDA Drug Approval: Review Time Has Decreased in Recent Years (GAO/PEMD-96-1), October 1995.

2. Although the last approvals for FY 96 submissions (as well as for earlier years) have not yet occurred, the median statistic can be computed from approvals to date and estimates of the percent of submissions that will ultimately be approved.

3. The PDUFA agreements allow for one 3-month extension of the review time if there is a major amendment to an original NDA, PLA, or ELA submission in the 3-month period before the original due date. This extension is not allowed for efficacy supplements, manufacturing supplements, or resubmissions.

4. The count of FY 97 submissions assumes that all submissions received in the last two months of FY 97 are filed. When FDA files a submission, it is deemed "complete" by PDUFA definition. FDA determines the "fileability" of an application within 60 days of its original receipt. All calculations of PDUFA review times are made, however, from the original receipt date of the filed application.

5. A resubmission is a firm's response after an FDA action of "approvable" or "not approvable" on an application. The applicable performance goal for a resubmission is determined by the year in which the resubmission itself is received, rather than its original application's year. This explains the relatively low number of resubmissions in the early PDUFA years.