FDA,FY 2002 Performance Report for the Prescription Drug User Fee Act of 1992,PDUFA PDUFA II Outcomes

PDUFA II Outcomes: Continued Success, Unexpected Challenges

In 1997, Congress passed the Food and Drug Administration Modernization Act (FDAMA). Part of FDAMA reauthorized PDUFA (PDFUA II) for five additional years, FY 98 through FY 02. Under PDUFA II, the review goals continued to shorten. For submissions received in FY 2002, the PDUFA II goals called for FDA to review and act on 90 percent of:

Priority new drug and biological product applications and efficacy supplements within 6 months;

Standard new drug and biological product applications and efficacy supplements within 10 months;

Manufacturing supplements within 6 months, and those requiring prior approval within 4 months;

Class 1 resubmissions of original applications within 2 months, and Class 2 resubmissions of original applications within 6 months (Definitions of Class 1 and Class 2 resubmissions can be found at the end of Appendix A.).

In addition, PDUFA II added a new set of goals intended to improve FDA's responsiveness to and communication with application sponsors during the drug development process. These goals specified timeframes for activities such as scheduling meetings and responding to various sponsor submissions such as special protocols and responses to clinical holds. Whereas PDUFA I's intent was to speed up the review process, PDUFA II's intent was to speed up the entire drug development process.

Continued Success. The Agency has met or exceeded nearly all the PDUFA II application review goals every year. The only review goals missed were for priority efficacy supplements submitted in FY 00 and FY 01 where on-time performance fell just short of the 90 percent goal. The Agency has been less successful in meeting the procedural and processing goals, although it has met or exceeded most.

Under PDUFA II, the Agency's review performance continued to accelerate and communication with and responsiveness to sponsor requests during the drug development phase improved. Several important outcomes accrued:

During the early years of PDUFA II, approval times continued to improve. The median time to approval for original priority applications submitted in FY99 was 6 months. For original standard applications submitted that year, the median approval time was 12 months.

More New Molecular Entities (NMEs) were introduced in the U.S. first. Before PDUFA, FDA approved about 40 percent of the NMEs introduced on the world market either first or within 1 year of their introduction in another country. After PDUFA, that percentage nearly doubled providing Americans with more rapid access to safe and effective new drugs.

Unexpected Challenges.

During PDUFA I the number of original applications submitted to the Agency increased at a steady pace each year. During PDUFA II the number of original applications decreased from the levels predicted based on PDUFA I, and more of these applications were either exempt from fees or met the criteria for waiver of fees. As a result, during the last few years of PDUFA II, fee revenue was less than the Agency and Congress had predicted when PDUFA was reauthorized in 1997 while total FDA workload under PDUFA continued to increase. This imbalance between resources and workload resulted in significant stress to the program.

During the last years of PDUFA II:

Median approval times for NDAs and BLAs began to increase. For standard applications submitted in FY 2000, median total approval time increased to 14.8 months. Although it is too soon to make even a preliminary assessment for standard applications submitted in FY 2001, based on the applications approved by September 30, 2002 and the queue of unapproved applications, it appears that the median approval time for the FY 2001 cohort will be even higher. The median approval time for priority applications submitted in FY 2001 is estimated to be 9.8 months based on applications approved by September 30, 2002. This increase in median approval time for priority applications occurred despite a decrease in the number of priority applications submitted to the Agency. Compared with earlier years when more than 30 priority applications were filed annually, only 13 priority applications were filed in FY 2001. Only two of these were approved on the initial review, whereas, in previous years, more than half of the priority NDAs and BLAs were approved on the initial review.

Some FDA stakeholders, and recently the General Accounting Office² (GAO) have expressed concerns about the number of drugs approved under PDUFA that have been withdrawn for safety reasons. However, an analysis of the rate of withdrawal for safety reasons of New Molecular Entities approved prior to PDUFA compared to those approved under the PDUFA program shows no significant difference (2.7% for drugs approved pre-PDUFA and 2.5% for drugs approved under PDUFA³. While FDA's standards for safety have not changed under PDUFA, the total number of drug and biologic products on the U.S. market has increased substantially, and many of these products are being approved first in the U.S. As a result of this heightened awareness, the importance of rigorous post-market surveillance of recently approved products has increased under PDUFA.