Purpose Commissioner's Report Report on FY 1996 PDUFA Goals Discussion of Performance in FY 1996 Notes Appendices: Appendix A: PDUFA Performance Goals, FY 1993 - FY 1997 Appendix B: Approval History of FY 93, FY 94, and FY 95 Submissions   This report was prepared by FDA's Office of Planning and Evaluation in collaboration with the Center for Biologics Evaluation and Research (CBER) and the Center for Drug Evaluation and Research (CDER). The report is also available in PDF format. For information on obtaining additional copies contact: Office of Planning and Evaluation (HFP-1) Food and Drug Administration 5600 Fishers Lane Rockville, Maryland 20857-001 Phone: 301-443-4230 FAX: 301-443-3955

PURPOSE

The Prescription Drug User Fee Act of 1992 (PDUFA), Public Law 102-571, authorized revenues from fees paid by the pharmaceutical industry to expedite review by the Food and Drug Administration (FDA) of human drug applications. These revenues were directed by section 102(3) of this Act toward accomplishment of goals identified in the letters of September 14 and 21, 1992 from the Commissioner of Food and Drugs to the Chairman of the Energy and Commerce Committee of the House of Representatives and the Chairman of the Labor and Human Resources Committee of the Senate (as set forth at 138 Congressional Record H9099-H9100: daily edition of September 22, 1992). Section 104 of the Act requires FDA to submit two annual reports to Congress for each fiscal year during which fees are collected: 1) a performance report due within 60 days of the end of the fiscal year, and 2) a financial report due within 120 days of the end of the fiscal year. This document fulfills the first of these requirements for Fiscal Year 1996. It reports on progress toward four FY 96 submission review goals, and updates performance on the FY 95 submission goals.

COMMISSIONER'S REPORT   On-Time Review Performance FY95 Submissions Goal Actual Original NDAs/ PLAs/ElAs 70% 95% Efficacy Supplements 70% 93% Manufacturing Supplements 70% 89% Resubmissions 70% 96%

Four years ago, Congress enacted the Prescription Drug User Fee Act of 1992 which set increasingly stringent annual review goals for FDA and provided the resources to meet those goals. It is now clear that PDUFA has produced much more than its stated objectives. It is having a dramatic effect on the number of new products reaching the market and the speed with which they get there. Again this year, the Agency has exceeded all the performance goals. The table to the left summarizes that performance, and the body of this report provides the details. What I want to emphasize, however, are the more profound and important results that are beginning to emerge. Just as the Agency has improved under PDUFA, so has the industry. Sponsors are submitting more new product applications to the Agency, and the quality of these submissions is greatly improved. As a result, more review decisions are positive, and record proportions of submissions are proceeding to approval. PDUFA is a success. The Agency and the industry have forged a working relationship based on a commitment to excellence which is producing measurable benefits for the American consumer. David A. Kessler, M.D. Commissioner of Food and Drugs

REPORT ON FY 1996 PDUFA GOALS

Twenty-nine performance-based goals constitute the management framework for PDUFA. These goals, listed by fiscal year in Appendix A, span the five-year term of the statute. Collectively, they direct management efforts toward three broad priorities: eliminating overdue backlogs, building excellence into the review process, and achieving measurable, high performance. Eighteen of the goals have been reported in previous years' performance reports. Four goals remain for FY 96 and seven for FY 97. The FY 96 goals specify review performance targets for the submissions received subject to PDUFA during FY 96. Final review performance results on submissions received during a fiscal year cannot be determined fully at the end of that fiscal year. The review goals for original NDAs, PLAs, and ELAs and for efficacy supplements specify a 12-month review period. For most FY 96 submissions, the 12-month review period obviously has not yet occurred. In contrast, nearly all of the FY 95 submissions have been reviewed, and Agency performance on those submissions can now be evaluated. This report uses the FY 90 and FY 91 submissions as a pre-PDUFA baseline for evaluating longer term changes. The baseline omits FY 92 because some PDUFA measures extend into the last month of FY 92, and the processing of most FY 92 submissions benefited from post-PDUFA process improvements. Some CBER pre-PDUFA comparisons are not possible due to the imprecise distinction between an original biologic application and its resubmission before PDUFA.

Goal 1

Review and act upon complete NDA, PLA and ELA submissions within 12 months of submission date: FY 94 Submissions: 55 percent on-time FY 95 Submissions: 70 percent on-time FY 96 Submissions: 80 percent on-time Original NDAs, PLAs, and ELAs Filed: FY932 FY94 FY95 FY963 NDAs 81 90 106 116 PLA 7+8 4+5 12+7 9+6 PDUFA Total 96 99 125 131 Performance on FY 95 submissions: Combined CDER/CBER on-time performance is currently 95 percent. Could reach 99 percent if 5 pending submissions are reviewed within time frame Performance exceeds FY95's 70 percent goal Proportion of submissions reviewed on-time more than doubles the pre-PDUFA performance level of 42 percent Only one submission has failed to meet the performance goal -- an NDA that was three days late Performance on FY 96 submissions: On-time review performance will exceed the PDUFA standard of 80 percent based on year-to-year performance trends Final review performance assessment will occur on December 31, 1997 As of October 1, 1996, 16 percent of applications had been acted upon (all within goal)

Goal 2

Review and act upon efficacy supplements4 to NDAs and PLAs within 12 months of submission date: FY 94 Submissions: 55 percent on-time FY 95 Submissions: 70 percent on-time FY 96 Submissions: 80 percent on-time Efficacy Supplements Filed: FY932 FY94 FY95 FY963 to NDAs 92 86 77 101 to PLAs 8 6 10 8 PDUFA Total 100 92 87 109 Performance on FY 95 submissions: Combined CDER/CBER on-time performance is 93 percent Performance exceeds FY95's 70 percent goal Proportion of submissions reviewed within a 12-month time frame nearly triples the pre-PDUFA performance level of 33 percent Combined CDER/CBER performance improves over FY93's 42 percent on-time rate (no goal in effect) and FY94's 77 percent rate Performance on FY 96 submissions: On-time review performance will exceed the PDUFA performance standard of 80 percent based on year-to-year performance trends Final review performance assessment will occur on September 30, 1997 As of October 1, 1996, 20 percent of submissions had been acted upon (all within goal)

Goal 3

Review and act upon manufacturing supplements to NDAs, PLAs and ELAs within 6 months of submission date: FY 94 Submissions: 55 percent on-time FY 95 Submissions: 70 percent on-time FY 96 Submissions: 80 percent on-time Manufacturing Supplements Filed: FY932 FY94 FY95 FY963 to NDAs 1,045 872 1,251 1,232 to PLAs, ELAs 203 186 268 262 PDUFA Total 1,248 1,058 1,519 1,494 Performance on FY 95 submissions: Combined CDER/CBER on-time performance is 89 percent Performance exceeds FY 95's 70 percent goal Combined CDER/CBER performance improves over FY 93's 51 percent on-time rate (no goal in effect) and FY 94's 69 percent rate Performance on FY 96 submissions: FY96 bars in charts depict on-time performance on supplements received during first half of FY 96. Since review goal is 6 months, this is an early indicator of final FY 96 performance Combined CDER/CBER on-time performance through first 6 months is 96 percent Final on-time performance projected to exceed FY 96's 80 percent goal Combined CDER/CBER projected performance improves over FY95's 89 percent on-time rate Final review performance assessment will occur on March 31, 1997

Goal 4

Review and act upon resubmitted NDAs, PLAs and ELAs within 6 months of resubmission date: FY 94 Submissions: 55 percent on-time FY 95 Submissions: 70 percent on-time FY 96 Submissions: 80 percent on-time Resubmissions Received: FY93 FY94 FY95 FY96 of Original NDAs 2 24 58 89 of Original PLAs 1 13 11 18 PDUFA Total 3 37 71 106 Performance on FY 95 resubmissions: Combined CDER/CBER on-time performance is 96 percent Performance exceeds FY 95's 70 percent goal Combined CDER/CBER performance improves over FY 94's 81 percent on-time rate Performance on FY 96 resubmissions: FY96 bars in charts depict on-time performance on resubmissions received during first half of FY 96. Since review goal is 6 months, this is an early indicator of final FY 96 performance Combined CDER/CBER on-time performance through first 6 months is 98 percent Final on-time performance projected to exceed FY 96's 80 percent goal Combined CDER/CBER projected performance improves over FY95's 89 percent on-time rate Final review performance assessment will occur on March 31, 1997

DISCUSSION OF PERFORMANCE DURING FY96

As the fourth year of PDUFA ends, its success is apparent. 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, are resulting in significantly improved Agency and industry performance, predictability, and accountability. In FY 96, FDA approved a record 131 NDAs and PLAs -- a substantial increase over the 84 in FY 95 and the 67 in FY 94. The record number of approvals is but one sign of an improved working relationship between sponsors and the Agency. PDUFA has resulted in better applications which can be accepted immediately and reviewed more quickly. Ultimately, new products get on the market faster. These changes can be documented by empirical evidence. Better Initial Submissions: A key measure of submission quality is the "Refuse to File" rate. As of October 1, 1996, only 6 NDAs/PLAs/ELAs submitted in FY 96 had been refused. These numbers compare with nine RTFs total for the FY 95 submissions, and are much lower than the 25 RTFs for the FY 94 submissions and 34 for FY 93. Because so few initial submissions are refused, more applications are going directly into the review process. Higher Rates of Positive First Actions: The proportion of first reviews that result in positive (i.e., "Approved" or "Approvable") decisions is another measure of submission quality and another key factor in achieving timely approvals. For original NDAs, PLAs, and ELAs submitted in FY 95, this measure rose to a 67 percent rate which is a substantial increase over the 48 percent rate experienced only one year ago (FY 94). As a result, comparatively few eventually approved applications go through time-consuming major revisions in response to "Not Approvable" decisions by FDA. Faster Action on Resubmissions: Sponsor response times to initial decisions (other than "Approved") and Agency decisions following the resubmissions continue to accelerate. In response to initial FDA decisions on FY 95 submissions, sponsors resubmitted NDA and PLA applications to the Agency in an average of 1.2 months. The Agency reviewed these resubmissions and issued action letters in an average of 2.2 months after resubmission. For FY 95 submissions, total elapsed time from initial decision to approval averaged 3.4 months which is less than half the 8.4 months experienced on resubmissions of FY 94 applications. Further details on resubmission performance are provided in Appendix B. Increasing Approval Rates: Another indication of improved submission quality is the increase in the percentage of submissions that are ultimately approved. For the years immediately preceding PDUFA, roughly 56 percent of the original submissions were approved. To date, 55 percent of the FY 95 submissions (65 NDAs and PLAs) have been approved and another 18 percent (20) are "approvable" or "pending" following an initial "approvable" decision. The final approval rate for the FY 95 submissions will approach 80 percent. The final approval rates for the FY 94 and FY 93 submissions are also high by historical standards and should reach 75 percent. Quicker Approval Times: The ultimate approval times for applications submitted during the PDUFA years continue to decline from the 23 month median typical of the early 1990's.7 Submission Year FY93 FY94 FY95 Median Months to Approval 19.0 18.5 15.0 Progress on Priority Applications: Beginning with the FY 97 submissions, 90 percent of the priority NDAs, PLAs, and ELAs must be reviewed and acted upon within six months. Even though there was no separate goal for priority applications submitted prior to FY 97, some progress is already evident. In the first half of FY 96, FDA received 18 priority applications. Ten of these (56 percent) were reviewed within 6 months. This is an improvement over the 33 percent rate for priority applications received in FY 95 and the 37 percent rate for FY 94's receipts, but it is still well below the 90 percent goal that is in effect for the FY 97 submissions.Notes:

1. 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 month 10, 11, or 12 of the first review cycle. A submission that was received in late FY 95 that received such a major amendment could have as its PDUFA review goal a date in December 1996. This extension is not allowed for efficacy supplements, manufacturing supplements, or resubmissions.

2. FY 93 was a 13-month fiscal year including September 1992. Calculations of annual changes in workload extrapolate counts downward to a 12-month year.

3. The count of FY 96 submissions assumes that all submissions received in the last two months of FY 96 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.

4. The term "supplement" applies to both drug and biologic submissions. It includes the former term of "amendments" to biologic submissions.

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.

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

7. The calculation of the ultimate median approval times for the PDUFA years is based upon final approval rates of 75 % for FY 93 and FY 94 submissions and 80 % for FY 95. Although the last approvals for these submission years have not yet occurred the median statistic can be computed from approvals to date.