FY 2003 PDUFA Performance Report

 

 

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Table of Contents

Commissioner's Report

Executive Summary

Introduction

Overview of PDUFA

REPORT ON FY 2002 and 2003 PDUFA GOALS

Original New Product Applications

Resubmitted New Product Applications

Efficacy Supplements

Manufacturing Supplements

Resubmitted Efficacy Supplements

First Cycle Filing Notification

Procedural and Processing Goals

PDUFA III Management Initiatives

Electronic Applications and Submissions

Appendices:

Appendix A: PDUFA Performance Goals, FY 2002 - FY 2007

Appendix B: List of Approved Applications

Notes

 

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Commissioner's Report

I am pleased to submit the Food and Drug Administration's FY 2003 Performance Report to the President and the Congress for the Prescription Drug User Fee Act (PDUFA). This report marks the eleventh year of PDUFA, and completion of the first year of its most recent reauthorization (PDUFA III). Over the 11 years of PDUFA, the Agency has met or exceeded nearly all of the PDUFA goals, drug approval time has been cut almost in half, and the Agency has maintained its traditionally high standards for safety and effectiveness.

PDUFA I challenged the Agency with goals to speed agency review of new drug applications (NDAs) and biologics licensing applications (BLAs) without compromising safety. PDUFA II added goals to improve the speed of drug development before submission of the NDA or BLA.

PDUFA III expands on those efforts by adding new goals and initiatives to further improve the quality and efficiency of drug development, review, and risk management for newly approved products. The need for these improvements is significant. By some estimates, it costs more than $800 million and takes more than a decade to develop a new drug. After approval, drugs must be safely used and new safety findings can emerge. Adverse drug events result in an estimated 770,000 injuries and deaths each year. Elderly patients, who take more medications and have greater drug sensitivity, are particularly vulnerable to these risks.

PDUFA III initiatives can have a public health impact beyond the earlier market access for safe and effective new drugs. By improving development efficiency and patient safety, these initiatives can also help in controlling health system costs.

Many of the good ideas and process innovations pioneered in the PDUFA program have now been applied and extended to other FDA-regulated products in the FDA's Strategic Plan goal for efficient risk management: to provide timely, high quality and cost-effective processes for the review of new technologies.

Mark B. McClellan, M.D., Ph.D.
Commissioner of Food and Drugs

 

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Executive Summary

This report updates the Agency's review performance on the FY 2002 application submissions and evaluates its performance in reviewing FY 2003 application submissions and meeting other PDUFA performance goals.

In FY 2003 the number of applications and the number of priority applications increased. The total number of applications submitted and filed increased from 105 in FY 2002 to 113 in FY 2003, and the number of priority applications increased from 15 in FY 2002 to 24 in FY 2003. Priority applications comprised over 21% of the total application pool, up from 14% in FY 2002.

With all but two of the original applications submitted during FY 2002 having been reviewed and acted upon by September 30, 2003, we can report that FDA exceeded all the review performance goals for FY 2002. Although only a preliminary performance assessment on applications submitted during FY 2003 is possible at this time, the Agency appears to be exceeding all the review performance goals for FY 2003 submissions. Also in FY 2003, the Agency met or exceeded four of the six "procedural and processing" goals designed to improve its responsiveness to sponsor requests during the early phases of drug development.

In FY 2003 under PDUFA III, FDA began several new initiatives to enhance the effectiveness and efficiency of the entire review process from early development through application review and into post-market risk management. This report describes FDA's accomplishments in FY 2003 toward meeting these new goals and objectives.

 

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Introduction

In 1992, Congress passed the Prescription Drug User Fee Act (PDUFA). PDUFA authorized FDA to collect fees from companies that produce and submit applications for marketing for human drug and biological products. The original PDUFA had a five-year life; it ended in 1997, the same year Congress passed the FDA Modernization Act (FDAMA). FDAMA contained a five-year reauthorization of PDUFA (PDUFA II). PDUFA II ended on September 30, 2002. Last year, Congress passed the Public Health Security and Bioterrorism Preparedness and Response Act of 2002 (the Bioterrorism Act), which extended PDUFA for an additional five years (PDUFA III). Information about PDUFA III, including the text of the amendments and the performance goals and procedures, can be found at http://www.fda.gov/oc/pdufa/PDUFA3.html.

PDUFA requires FDA to submit two annual reports to the President and the 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 2003. This year's report covers FDA's progress meeting the quantifiable PDUFA review goals for FY 2002 and 2003 submissions and the FY 2003 processing and procedural goals. The report also describes FDA progress in accomplishing new initiatives specified in the PDUFA III commitment letter.

PDUFA III also requires that FDA report annually on the Agency's progress in meeting the information-technology commitments of PDUFA III. The section of this report titled "Electronic Applications and Submissions" satisfies that requirement for FY 2003.

 

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Overview of PDUFA

PDUFA has provided FDA with additional revenue to hire more reviewers and support staff and upgrade its information technology systems to speed up the application review process for new drugs and biological products without compromising FDA's traditionally high standards for approval. Under PDUFA, FDA agreed to meet certain performance goals that apply to the review of original and resubmitted new product applications and efficacy and manufacturing supplements to approved applications. FDA also agreed to meet certain procedural and processing goals aimed at speeding-up drug development.

PDUFA II: Speeding up Drug Development

In 1997, Congress passed the Food and Drug Administration Modernization Act (FDAMA) and reauthorized PDUFA (PDFUA II) for five more years. Under PDUFA II, most review goals were shortened and the Agency met or exceeded nearly all of these review goals.

In addition, PDUFA II set new goals intended to improve communication between FDA and 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.

PDUFA III: Refining the Process - From Drug Development through Application Review to Post Market Surveillance

In 2002, Congress passed the Bioterrorism Act, which included an extension of PDUFA (PDUFA III) for an additional five years, FY 2003 through FY 2007. PDUFA III retains the review performance goals and the procedural and processing goals of PDUFA II largely unchanged from their FY 2002 performance levels. PDUFA III establishes several new initiatives to improve application submissions and agency-sponsor interactions during drug development and application review. In addition, it authorizes FDA to expend user-fee funds on certain post-market risk management activities. Detailed information about PDUFA III, including the text of the amendments and the performance goals and procedures can be found at http://www.fda.gov/oc/pdufa/PDUFA3.html.

Trends in NDA/BLA Submissions and Approval Times

PDUFA-enabled improvements in review efficiency and application quality have had an impact on the overall time to marketing approval. FDA tracks a variety of metrics related to the process of human drug review. The time-to-approval statistics are affected by a number of factors including total number of NDA and BLA submissions and the number of newly submitted priority applications, as well as the overall quality of submitted applications and the number of review staff relative to the review workload. These factors can vary from year to year; the charts that follow provide an update on trends in submissions and overall approval times.

 

D

 

Number of Applications and Priority Applications Increased. The total number of applications submitted and filed increased from 105 in FY 2002 to 113 in FY 2003, and the number of priority applications increased from 15 in FY 2002 to 24 in FY 2003. Priority applications comprised over 21% of the total application pool, up from 14% in FY 2002. Priority applications represent significant therapeutic gains.

 

D

Median Time to Approval Decreased in FY 2002. Estimated median approval times for original NDAs and BLAs filed in FY 2001 had increased substantially for both priority applications (15.6 months) and for standard applications (22.1 months), compared to the previous few years. However, preliminary estimates indicate that median approval times for FY 2002 applications have significantly decreased. Based on applications approved by September 30, 2003, under the assumption that 80 percent of all filed applications will ultimately be approved, the estimated median approval times for FY 2002 submissions are 7.5 months for priority applications and 12.8 months for standard applications.

 

D

 

Percentage of First Cycle Approvals Increased in FY 2002. The percentage of applications that could be approved on the first cycle increased in FY 2002. Forty-seven percent of priority applications and thirty-six percent of standard applications were approved on the first review cycle. This is a substantial increase over the previous year, in which fifteen percent of priority applications and nineteen percent of standard applications were approved on the first review cycle. Longer times to marketing approval are generally caused by the need for more than one cycle of review. PDUFA III includes a new initiative to determine the causes of multiple review cycles and to provide earlier feedback on major deficiencies to application sponsors.

 

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Report on FY 2002 and 2003 PDUFA Goals

This report updates the Agency's review performance on the FY 2002 application submissions and evaluates its performance in reviewing FY 2003 application submissions and meeting other PDUFA performance goals. All but two of the original applications submitted during FY 2002 have been reviewed and acted upon, and final performance relative to the goals can now be reported. Only a preliminary performance assessment on applications submitted during FY 2003 is possible at this time. For submission categories with a 10-month review goal, it is too early to measure review performance. For those submission categories with a review goal that is shorter than 10 months, performance on submissions received early in the fiscal year provides an early-indicator of final review performance. Unless otherwise noted, all performance data in this section are as of September 30, 2003.¹

 

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Original New Product Applications

Goal -- Review and act upon complete original NDAs and BLAs

Under PDUFA II, the goal for priority NDAs and BLAs was to review 90 percent in 6 months. The goal for standard NDAs and BLAs over the period progressed from reviewing 90 percent in 12 months as the start of PDUFA II (FY 1998 receipts) to 90 percent in 10 months by the end (FY 2002 receipts). Under PDUFA III, the terminal goals of PDUFA II remain unchanged.

Application Type	Review Time Goal	Performance Level FY 2002 - FY 2007 Submissions
Priority	6 months	90% on time
Standard	10 months	90% on time

Workload

 

Original submissions filed (Priority/Standard):

	FY 99	FY 00	FY 01	FY 02	FY 032
NDAs	121 (30/91)	121 (29/92)	96 (10/86)	96 (12/84)	105 (20/85)
BLAs	6 (1/5)	13 (4/9)	8 (3/5)	9 (3/6)	8 (4/4)
PDUFA Total	127 (31/96)	134 (33/101)	104 (13/91)	105 (15/90)	113 (24/89)
NMEs3	37 (15/22)	30 (16/14)	32 (8/24)	22 (8/14)	25(8/17)

Performance

 

FY 2002 Submissions

FDA met the goal of reviewing and acting upon priority applications within 6 months for all fifteen priority NDAs and BLAs filed in FY 2002. FDA also met the 10?month goal for standard submissions for 87 of the 88 standard submissions reviewed (99% on time). One application failed to meet the 10-month review goal, and two applications were still pending and not overdue as of September 30, 2003.

FY 2002 Submissions			Reviewed and acted upon	Number on time	Percent on time
Priority	6 month goal	All Applications	15	15	100
		NMEs & BLAs	11	11	100
Standard	10 month goal	All Applications	88	87	99*
		NMEs & BLAs	20	19	95

* The final on-time statistic will range from 97% to 99% depending on the final disposition of the two applications that had not been reviewed as of September 30, 2003.

 

FY 2003 Submissions

While it is too early to report final review performance statistics for applications submitted in FY 2003, all priority applications that have been reviewed have met the 6-month review goal, and all standard applications that have been reviewed have met the 10-month review goal. No applications are overdue.

 

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Resubmitted New Product Applications

Goal -- Review and act upon resubmitted NDAs and BLAs.

A resubmission is a firm's response after an FDA action of "approvable," "not approvable," or "complete response" on an application. The applicable performance goal for a resubmission is determined by the year in which the resubmission itself is received, rather than the year in which the original application was submitted. The definitions of Class 1 and Class 2 resubmissions can be found at the end of Appendix A.

Under PDUFA II, the goal for Class 2 resubmissions was to review 90 percent in 6 months. The goals for Class 1 resubmissions over the period progressed from reviewing 90 percent in 6 months at the start of PDUFA II to 90 percent in 2 months by the end (FY 2002 resubmissions). Under PDUFA III, the terminal goals of PDUFA II remain unchanged.

Resubmission Type	Review Time Goal	Performance Level FY 2002 - FY 2007 Resubmissions
Class 1	2 months	90% on time
Class 2	6 months	90% on time

Workload -- Resubmissions received (Class 1/Class 2):

	FY 99	FY 00	FY 01	FY 02	FY 03
of Original NDAs	63 (17/46)	80 (25/55)	62 (25/37)	62 (20/42)	62 (21/41)
of Original BLAs	14 (2/12)	9 (1/8)	16 (6/10)	15 (2/13)	12 (1/11)
PDUFA Total	77 (19/58)	89 (26/63)	78 (31/47)	77 (22/55)	74 (22/52)

 

Performance

 

FY 2002 Submissions

All 22 of the Class 1 resubmissions received in FY 2002 were reviewed and acted upon within 2 months, and all 55 of the Class 2 resubmissions were reviewed and acted upon within 6 months. Review performance on both classes of FY 2002 resubmissions exceeded the 90 percent on-time PDUFA review goals.

FY 2002 Resubmissions		Reviewed and acted upon	Number on time	Percent on time
Class 1	2 months	22	22	100
Class 2	6 months	55	55	100

FY 2003 Submissions

As of September 30, 2003, all 22 of the Class 1 resubmissions received in FY 2003 had been reviewed; 21 (95%) met the 2-month review goal, and 1 was late. Only 25 of the 52 Class 2 resubmissions had been reviewed. Although all of these met the 6-month review goal, with 27 Class 2 resubmissions still pending and not overdue, it is too early to make a final performance determination.

FY 2003 Resubmissions		Reviewed and acted upon	Number on time	Percent on time
Class 1	2 months	22	21	95
Class 2	6 months	25	25	100

 

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Efficacy Supplements

 

Goal -- Review and act upon complete efficacy supplements to NDAs and BLAs

Under PDUFA II, the goal for priority efficacy supplements to NDAs and BLAs was to review 90 percent in 6 months. The goals for standard efficacy supplements over the period progressed from reviewing 90 percent in 12 months at the start of PDUFA II (FY 1998 receipts) to 90 percent in 10 months by the end (FY 2002 receipts). Under PDUFA III, the terminal goals of PDUFA II remain unchanged.

Application Type	Review Time Goal	Performance Level FY 2002 - FY 2007 Submissions
Priority	6 months	90% on time
Standard	10 months	90% on time

Workload -- Efficacy supplements filed (Priority / Standard):

	FY 99	FY 00	FY 01	FY 02	FY 032
to NDAs	135 (15/120)	175 (18/157)	154 (7/147)	159 (31/128)	131 (25/106)
to BLAs	10 (2/8)	12 (2/10)	16 (2/14)	11 (4/7)	14 (2/12)
PDUFA total	145 (17/128)	187 (20/167)	170 (9/161)	170 (35/135)	145 (27/118)

 

Performance

 

FY 2002 Submissions

All 35 of the priority efficacy supplements submitted in FY 2002 were reviewed and acted upon within the 6-month review goal. Of the 135 standard efficacy supplements submitted in FY 2002, 131 were reviewed and acted upon within the 10-month goal. Two were reviewed and missed the goal, and two were pending and overdue as of September 30, 2003. This performance exceeds the FY 2002 goal of 90 percent on time.

FY 2002 Submissions		Reviewed and acted upon	Number on time	Percent on time
Priority	6 months	35	35	100
Standard	10 months	135*	131	97

* Includes 2 pending and overdue on September 30, 2003.

 

FY 2003 Submissions

While it is too early to report final review performance statistics for efficacy supplements submitted in FY 2003, all priority efficacy supplements that have been reviewed have met the 6-month review goal and all standard efficacy supplements that have been reviewed have met the 10-month review goal. No efficacy supplements are late.

FY 2003 Submissions		Reviewed and acted upon	Number on time	Percent on time
Priority	6 months	16	16	100
Standard	10 months	27	27	100

 

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Manufacturing Supplements

 

Goal -- Review and act upon complete manufacturing supplements to NDAs and BLAs

The review performance goals for manufacturing supplements that do not require FDA approval before the changes they specify can be enacted did not change over the five years of PDUFA II. For manufacturing supplements that do require FDA's approval before the changes can be enacted, the goal times decreased from 6 months for FY 1998 submissions to 4 months for FY 2002 submissions. The PDUFA III goals are the same as the FY 2002 goals.

Workload -- Manufacturing supplements filed (Prior Approval / No Prior Approval):

	FY 99	FY 00	FY 01	FY 02	FY 032
to NDAs	1,459 (900/559)	1,438 (684/754)	1,474 (579/895)	1,759 (602/1,157)	1,696 (618/1,078)
to BLAs	477 (259/218)	587 (239/348)	591 (185/406)	717 (228/489)	877 (301/576)
PDUFA total	1,936 (1,159/777)	2,025 (923/1,102)	2,065 (764/1,301)	2,476 (830/1,646)	2,573 (919/1,654)

 

Performance

 

FY 2002 Submissions

Ninety-eight percent of the manufacturing supplements submitted in FY 2002 that did not require prior FDA approval were reviewed within 6 months, and ninety-five percent of the manufacturing supplements submitted in FY 2002 that required prior FDA approval were reviewed within 4 months. Performance on both types of supplements exceeded FY 2002's goal of 90 percent.

FY 2002 Submissions		Reviewed and acted upon	Number on time	Percent on time
Prior approval not required	6 months	1646	1609	98
Prior approval required	4 months	827	785	95

FY 2003 Submissions

As of September 30, 2003, more than 55 percent of the manufacturing supplements that do not require prior approval, and over 67 percent of those that do require prior approval, had been reviewed. Ninety-nine percent of both types of supplements had been reviewed within their respective 6- and 4-month goals. Although it is too early to make a final determination with only 65 percent of the submissions reviewed, performance in both categories is well above the FY 2003 review goals.

FY 2003 Submissions		Reviewed and acted upon	Number on time	Percent on time
Prior approval not required	6 months	916	910	99
Prior approval required	4 months	617	608	99

 

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Resubmitted Efficacy Supplements

Goal -- Review and act upon resubmitted efficacy supplements to NDAs and BLAs

This is a new goal under PDUFA III. For Class 1 resubmissions, the goals progress from reviewing 90 percent of FY 2003 resubmissions in 6 months and 30 percent in 2 months to reviewing 90 percent of FY 2007 resubmissions in 2 months. For Class 2 resubmissions, the goal of reviewing 90 percent in 6 months remains constant over the 5-year period.

Resubmission Type	Review Time Goal	Performance Level
		FY 03	FY 04	FY 05	FY 06	FY 07
Class 1	2 months	30%	50%	70%	80%	90%
	4 months	--	90%	90%	90%	--
	6 months	90%	--	--	--	--
Class 2	6 months	90%	90%	90%	90%	90%

Workload -- Efficacy supplements resubmitted (Class 1 /Class 2):

 

	FY 03
to NDAs	53 (16/37)
to BLAs	3 (1/2)
PDUFA total	56 (17/39)

Performance

 

FY 2003 Efficacy Supplement Resubmissions

As of September 30, 2003, 76 percent of the Class 1 efficacy supplement resubmissions received in FY 2003 and 62 percent of the Class 2 resubmissions had been reviewed. All of the Class 1 resubmissions reviewed met the 2-month review goal, and all of the Class 2 resubmissions met the 6-month goal. No resubmissions were overdue. However, with only 66 percent of all the submissions reviewed, it is too early to make a final performance determination.

FY 2003 Efficacy Supplement Resubmissions	Reviewed and acted upon	Number on time	Percent on time
Class 1: 2 months	13	13	100
Class 1: 6 months	13	13	100
Class 2: 6 months	24	24	100

 

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First Cycle Filing Review Notification

 

Goal -- Report substantive deficiencies (or lack of same) within 14 days after 60 day filing date for original BLAs, NDAs, and Efficacy Supplements

This is a new goal under PDUFA III. FDA is to report substantive deficiencies (or lack of same) identified in the initial filing review to the sponsor by letter, telephone conference, facsimile, secure e-mail, or other expedient means within 14 days of the 60 day filing date. Performance levels progress from 50% on time for FY 2003 submissions to 90 percent for FY 2005 to FY 2007 submissions.

Application Type	Goal	Performance Level
		FY03	FY04	FY05	FY06	FY07
Original NDAs, BLAs, and Efficacy Supplements	74 days	50% on time	70%	90%

Workload and Performance

 

		Applications Submitted	Met Goal	Missed Goal*	Pending Within Goal	% On Time
On-time Goal						50%
CBER	BLAs	8	5	0	3
	Efficacy Supplements	14	13	0	1
CDER	NDAs	105	68	16	21
	Efficacy Supplements**	95	68	14	13
Combined		222	154	30	38	84%

* Includes those that had no filing review notification issued prior to the final action on the submission.

** The First Cycle Filing Review Notification goal applies to original NDAs, BLAs, and efficacy supplements only. It does not apply to labeling supplements that contain clinical data, even though these are counted as efficacy supplements for other PDUFA performance purposes. Therefore, the number of filing review notifications for efficacy supplements is less than the total number of efficacy supplements filed (as shown on p. 12).

 

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Procedural and Processing Goals

This section reports on a number of PDUFA goals related to the IND phase of drug development and some aspects of the infrastructure of drug review. A detailed description of the goals, the annual performance targets, and definitions of terms can be found in Appendix A. This section reports on actions on items that occurred in FY 2003.

Meeting Management:

Meeting Requests: Notify requestor of formal meeting in writing within 14 days of request.

Scheduling Meetings: Schedule meetings within goal date (within 30 days of receipt of request for Type A meetings, 60 days for Type B meetings, and 75 days for Type C meetings). If the requested date for any of these types of meetings is greater than 30, 60, or 75 days, as appropriate, from the date the request is received by the Agency, the meeting date should be within 14 days of the requested date.

Meeting Minutes: Agency prepared minutes, clearly outlining agreements, disagreements, issues for further discussion and action times will be available to sponsor within 30 calendar days of meeting.

			Total	Met Goal	Missed Goal4	Pending Within Goal5	% On Time6
On-time Goal							90%
Meeting Requests		CBER	434	415	9	10
		CDER	1464	1264	182	18
		Combined	1898	1679	191	28	90%
Scheduling Meetings	Type A	CBER	11	10	0	1
		CDER	90	67	23	0
	Type B	CBER	252	205	5	42
		CDER	581	424	150	7
	Type C	CBER	142	112	4	26
		CDER	705	653	51	1
	All	CBER	405	327	9	69
		CDER	1376	1144	224	8
		Combined	1781	1471	233	77	86%
Meeting Minutes		CBER	280	248	11	21
		CDER	1286	805	269	212
		Combined	1566	1053	280	233	79%

Clinical Holds: Respond to sponsor's complete response to a clinical hold within 30 days of receipt

 

 

	Total	Met Goal	Missed Goal4	Pending Within Goal5	% On Time6
On-time Goal					90%
CBER	103	95	4	4
CDER	34	26	7	1
Combined	137	121	11	5	92%

Major Dispute Resolution: Respond to sponsor's appeal of decision within 30 days of receipt

 

	Total	Met Goal	Missed Goal4	Pending Within Goal5	% On Time6
On-time Goal					90%
CBER	0	0	0	0
CDER	20	19	0	1
Combined	20	19	0	1	100%

Special Protocol Question Assessment and Agreement: Respond to sponsor's request for evaluation of protocol design within 45 days of receipt

 

	Total	Met Goal	Missed Goal4	Pending Within Goal5	% On Time6
On-time Goal					90%
CBER	20	18	0	2
CDER	274	223	21	30
Combined	294	241	21	32	92%

 

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PDUFA III Management Initiatives

This section reports on management initiatives detailed in sections VII - XI of the PDUFA III commitment letter. A full description of the goals, the annual performance targets, and definitions of terms can be found in Appendix A. This section reports on accomplishments in FY 2003.

Continuous Marketing Application Pilots:

The first Continuous Marketing Application (CMA) pilot applies to fast track products that have demonstrated significant promise as a therapeutic advance in clinical trials, and will provide an early discipline review of the relevant portions (reviewable units) of the sponsor's NDA/BLA submitted in advance of the complete application. The second CMA pilot applies to fast track drugs or biologics that are intended to treat serious or life threatening diseases, and provides for FDA-sponsor agreement to engage in frequent scientific feedback and interactions during the clinical trial phase of product development.

FY 2003 Accomplishments: Final guidances were published on October 6, 2003 and the pilot programs became effective as of that date. http://www.fda.gov/cber/gdlns/pdufa1.pdf and http://www.fda.gov/cber/gdlns/pdufa2.pdf

First Cycle Review Performance:

Approvals that take more than one review cycle to complete are not in the best interest of the public, the agency, or the company submitting the product application. For applications that are ultimately approved, the causes of multiple review cycles can include deficiencies in sponsors' applications, communication problems during the review process, or difficulty finishing final negotiations on such topics as labeling. Sometimes additional review cycles are necessary to resolve important issues regarding safety, quality, or efficacy; but in other cases the extra cycles could be avoided, saving time and effort. Efforts to improve the review process will include a retrospective analysis of the reasons for multiple cycles, prospective analysis of the quality of submissions, review process and communications between FDA and sponsors during the first cycle, and a formal evaluation of the impact of good review management principles in CDER and CBER when implemented.

FY 2003 Accomplishments: The PDUFA III First Cycle initiative for notification of substantive deficiencies identified during the initial filing review for original NDAs and BLAs was implemented on October 1, 2002. FDA is committed to provide sponsors with notification of deficiencies (or initial lack of deficiencies) prior to the goal date for 50% of submitted applications in FY 2003, 70% of applications in FY 2004, and 90% of applications in FY 2005-2007. FDA is also implementing the PDUFA III First Cycle initiative to develop and publish Good Review Management Principles (GRMP) with provisions for both FDA reviewers and industry sponsors. The draft Good Review Management Principles (GRMP) guidance was published on July 28, 2003 (See http://www.fda.gov/cder/pdufa/default.htm ) and the comment period ended on September 11, 2003. FDA expects to publish the final GRMP guidance in 2004.

Improving FDA Performance Management:

Under the PDUFA III performance management goal, FDA will conduct initiatives that are tar-geted to improve the new drug review process. FDA will award a task order contract to a contrac-tor with the expertise to conduct evaluations and analyses of the new drug review process. The first tasks will include a retrospective evaluation of the first cycle review process and an evalua-tion of the first cycle initiatives under PDUFA III. This contract may also be used for the evaluation of the continuous marketing application pilots and other PDUFA related performance management initiatives.

FY 2003 Accomplishments: FDA published the request for proposals (RFP) on October 21, 2003 and plans to award the task order contract for the First Cycle and CMA evaluations by January 2004. The draft statement of work for the first cycle evaluation was published in the Federal Register for comment on October 21, 2003 as required. ( See http://www.fda.gov/cder/pdufa/default.htm ).

The PDUFA III process review and analysis initiative will focus on implementing a continuous improvement/quality management system for new drug review. FDA plans to award a contract for outside expert consultants for analysis, training, and technical assistance in 2004. FDA also plans to acquire quality system training in 2004 for senior review staff and managers.

Independent Consultants:

This PDUFA III initiative allows a sponsor to request that FDA engage an independent expert consultant during the development period for certain biotechnology products. The consultant would be selected by FDA to assist in the agency's review of the protocol for the clinical studies that would support the claims for the product. This initiative is intended to facilitate product development.

FY 2003 Accomplishments: Draft guidance was published on May 7, 2003 with comments due by August 5, 2003. Final guidance is expected to be published early in CY 2004. The draft guidance is available at: http://www.fda.gov/OHRMS/DOCKETS/98fr/03-11214.html

Risk Management:

The postmarketing initiative to address postmarket risk both before an application is submitted and during the review process will facilitate postmarket risk management by helping FDA better understand any risks and by providing feedback to the sponsors.

FY 2003 Accomplishments: Risk Management public meetings on Good Risk Assessment, Risk Management, and Pharmacovigilance Practices were held on April 9-11, 2003 (http://www.fda.gov/cder/meeting/riskManagement.htm). Three concept papers were published in March 2003. The comment period ended on 5/30/03. FDA expects to publish draft guidances by early CY 2004 and final guidances by September 2004.

In FY 2003, CDER was involved in the review of 32 risk management plans of which 5 were related to NDAs submitted after PDUFA III took effect. CDER also participated in 30 pre-NDA meetings and 11 pre-approval safety conferences. CBER participated in pre-approval safety conferences for 2 vaccines approved after PDUFA III took effect.

 

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Electronic Applications and Submissions

This section reports on goals from the "Electronic Applications and Submissions" section of the PDUFA III commitment letter. These goals relate to the IT initiatives/activities of PDUFA III. A detailed description of the goals, the annual performance targets, and definitions of terms can be found in Appendix A. This section reports on accomplishments in FY 2003.

Centralize the accountability and funding for all PDUFA IT initiatives/activities under the FDA/CIO:

The Agency will centralize the accountability and funding for all PDUFA Information Technology initiatives/activities for CBER, CDER, ORA and OC under the leadership of the FDA CIO. The July 2001 HHS IT 5-year plan states that infrastructure consolidation across the department should be achieved, including standardization. The Agency CIO will be responsible for ensuring that all PDUFA III IT infrastructure and IT investments support the Agency's com-mon IT goals, fit into a common computing environment, and follow good IT management practices (section XII, paragraph a).

FY 2003 Accomplishments: The Agency began several efforts to centralize the accountability and funding for PDUFA III IT initiatives. Specific accomplishments included:

• Implemented PDUFA IT Investment Governance process to review, prioritize, fund, and monitor PDUFA IT investments.
• FDA CIO and PDUFA IT Program Manager managed PDUFA IT funding allocations.
• Implemented Portfolio Management tool for the FY05 budget cycle.

FY 2004 Plans: The Agency will continue to work toward goals of centralization. Specifically, the Agency will integrate the PDUFA IT investment governance process with the Agency IT investment process to ensure alignment and linkage to Agency strategic goals.

Periodically review and evaluate the progress of IT initiatives against project milestones:

The Agency CIO will chair quarterly briefings on PDUFA IT issues to periodically review and evaluate the progress of IT initiatives against project milestones, discuss alternatives when projects are not progressing, and review proposals for new initiatives. On an annual basis, an assessment will be conducted of progress against PDUFA III IT goals and, established program milestones, including appropriate changes to plans. A documented summary of the assessment will be drafted and forwarded to the Commissioner. A version of the study report redacted to remove confidential commercial or security information, or other information exempt from disclosure, will be made available to the public. The project milestones, assessment, and changes will be part of the annual PDUFA III report (section XII, paragraph b).

FY 2003 Accomplishments: This report satisfies this annual requirement. In addition, the Agency reported IT progress to stakeholders at the following meetings:

• PhRMA/BIO semi-annual update (December 2002)
• PhRMA IMPACC introductory meeting (December 2002)
• BIO IT introductory meeting (January 2003)
• PhRMA IMPACC annual meeting (April 2003)
• PhRMA/BIO IT Quarterly update (June 2003)
• PhRMA/BIO semi-annual update (June 2003)

FY 2004 Plans: FDA will continue holding quarterly meetings to report PDUFA III IT progress.

Implement a common solution for the secure exchange of application content:

FDA will implement a common solution in CBER, CDER, ORA and OC for the secure exchange of content including secure e-mail, electronic signatures, and secure submission of, and access to application components (section XII, paragraph c).

FY 2003 Accomplishments: This year, FDA explored SEBiX, the Secure Electronic Biopharmaceutical Information eXchange. The SEBiX objective is to provide a trusted platform for the secure transmission of regulatory data and provider of regulatory data and document management services allowing for the secure exchange of information between Sponsors, business partners, and Regulatory Authorities. FDA participated in the SEBiX proof-of-concept discussions and formed a project team to review the Cost Sharing concept to define FDA requirements and to address regulatory issues. In addition, FDA participated in initial discussions on the SAFE (Secure Access For Everyone) security and trust model as a standard for the biopharmaceutical industry.

FY 2004 Plans: FDA plans to:

• Determine requirements on Cost Sharing model.
• Decide on the level of participation in the development of the SEBiX model and SAFE standard.
• Decision on the level of validation required for electronic signatures on regulatory electronic submissions.
• Design and develop implementation plan for common secure email solution for CDER & CBER.

Deliver a single point of entry for the receipt and processing of all electronic submissions in a highly secure environment:

FDA will deliver a single point of entry for the receipt and processing of all electronic submis-sions in a highly secure environment. This will support CBER, CDER, OC and ORA. The system should automate the current electronic submission processes such as checking the content of electronic submissions for completeness and electronically acknowledging submissions (sec-tion XII, paragraph d).

FY 2003 Accomplishments: This year, the Agency initiated the PDUFA-centric electronic submission target architecture project with the goal of improving the Agency's electronic submission capabilities.

FY 2004 Plans: The Agency will gather electronic submission requirements, define target electronic submission architecture, and develop an implementation plan for CBER and CDER.

Provide a format and review system for the electronic submission of the Common Technical Document (e-CTD):

FDA will provide a specification format for the electronic submission of the Common Technical Document (e-CTD), and provide an electronic review system for this new format that will be used by CBER, CDER and ORA reviewers. Implementation should include training to ensure successful deployment. This project will serve as the foundation for automation of other types of electronic submissions. The review software will be made available to the public (section XII, paragraph e).

FY 2003 Accomplishments: The Agency published Electronic Common Technical Document (eCTD) guidance, released eCTD specification (available on the eCTD web-site http://www.fda.gov/cder/regulatory/ersr/ectd.htm), released the initial production of the e-CTD software, and has received and is reviewing the initial eCTD submissions.

FY 2004 Plans: The Agency will assess the next steps in the development of the e-CTD software.

Conduct an objective analysis and develop a plan for consolidation of PDUFA III IT infrastructure:

Within the first 12 months, FDA will conduct an objective analysis and develop a plan for consolidation of PDUFA III IT infrastructure and desktop management services activities that will access and prioritize the consolidation possibilities among CBER, CDER, ORA and OC to achieve technical efficiencies, target potential savings and realize cost efficiencies. Based upon the results of this analysis, to the extent appropriate, establish common IT infrastructure and architecture components according to specific milestones and dates. A documented summary of analysis will be forwarded to the Commissioner. A version of the study report redacted to re-move confidential commercial or security information, or other information exempt from disclosure, will be made available to the public (section XII, paragraph f).

FY 2003 Accomplishments: Based on the Organizational Assessment of FDA Administrative Services, conducted in 2002, FDA implemented the FDA Office of IT Shared Services, reorganized the Office of the CIO and the OC IT functions, and implemented a consolidated call center for the PDUFA organizations.

FY 2004 Plans: The Agency will continue to implement this plan by developing the following:

• Strategic measures in performance management and change management.
• Integration strategy for consolidating field and Washington-based IT services.
• . Service delivery process in support of and as infrastructure consolidation projects are executed, including integration and coordination with the Enterprise Architecture initiative.

Implement Capability Maturity Model (CMM) and include other industry best practices to ensure quality, efficiency, and cost effectiveness:

FDA will implement Capability Maturity Model (CMM) in CBER, CDER, ORA and OC for PDUFA IT infrastructure and investments, and include other industry best practices to ensure that PDUFA III IT products and projects are of high quality and produced with optimal efficiency and cost effectiveness. This includes the development of project plans and schedules, goals, estimates of required resources, issues and risks/mitigation plans for each PDUFA III IT initiative (section XII, paragraph g).

FY 2003 Accomplishments: In FY 2003, the Agency conducted and completed a project management assessment. The assessment provided FDA with both an understanding of its current FDA IT project management practices as well as its IT investment management procedures. Based on the assessment findings, FDA established the Agency Project Management Office (PMO). The PMO will work with individual projects to address areas in need of attention relevant to project management. The PMO will also work with the IT organizations to ensure that processes are developed correctly, consistently, and rolled out across the organizations. The Agency also established an IT Project Management Steering Committee and Software Development Life-Cycle (SDLC) Working Group to identify and develop a common software development methodology. In addition, FDA initiated a project management training program for over 60 individuals throughout the Agency, and developed a mentoring and coaching program to facilitate the development of project management skills for CBER and CDER.

FY 2004 Plans: The Agency will continue the project management and certification program. FDA will develop the implementation plan for an Agency IT investment governance process to review, prioritize, fund, and monitor all IT investments, and will begin the implementation of a common software development methodology.

Use same software applications where common business needs exist:

Where common business needs exist, CBER, CDER, ORA and OC will use the same software applications, such as eCTD software, and COTS solutions (section XII, paragraph h).

FY 2003 Accomplishments: CDER and CBER co-developed the eCTD software to be used by CBER and CDER. The Agency initiated the Therapeutic Product Integration project to perform the application system and data migration of identified therapeutic products from CBER into the CDER environment. The Therapeutic Integration project will be analyzing CBER and CDER regulatory tracking application systems and identifying consolidation/integration opportunities. The Agency also began the electronic gateway submission project to identify electronic submission requirements throughout the Agency. All of these efforts are part of the Enterprise Architecture initiative that will provide a technical and procedural foundation upon which the FDA can efficiently plan, implement, and field new systems as well as modify existing ones. The architecture will establish common procedures, guidelines, and policies.

FY 2004 Plans: FDA will continue the joint development of the eCTD and electronic submission capabilities. FDA will review and act on the recommendations from the Therapeutic Product Integration project and the Enterprise Architecture initiative that will identify areas for collaboration and integration.

Develop a PDUFA III IT 5-year plan.

Within six months of authorization, a PDUFA III IT 5-year plan will be developed. Progress will be measured against the milestones described in the plan (section XII, paragraph i).

FY 2003 Accomplishments: The plan was completed in March 2003 and was released at the June 2003 PDUFA IT Quarterly meeting.

FY 2004 Plans: The Agency will work with the PDUFA Business Workgroup to update the plan.

 

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APPENDIX A:
PDUFA Performance Goals, FY 2002 - FY 2007

The table below summarizes, by fiscal year, the performance measures set forth in the letters referenced in the Food and Drug Administration Modernization Act of 1997 (PDUFA II) and in the Public Health Security and Bioterrorism Preparedness and Response Act of 2002 (PDUFA III). Goal summaries for the earlier years of PDUFA II can be found in the Appendix of earlier PDUFA Performance Reports. The complete text of the commitment letters is on the Internet at www.fda.gov/oc/pdufa/default.htm.

REVIEW PERFORMANCE GOALS | NEW MOLECULAR ENTITY (NME) PERFORMANCE GOALS | PROCEDURAL AND PROCESSING GOALS | PDUFA III Management Initiatives | Electronic Applications And Submissions | Definitions of Terms:

I. REVIEW PERFORMANCE GOALS

		On-time Performance Level for Fiscal Year of Filing or Receipt
		2002	2003	2004	2005	2006	2007
Review and act on standard original NDAs and PLA/BLAs within 10 months of receipt.7		90% on time
Review and act on priority original NDAs and BLAs within 6 months of receipt.7
Review and act on standard efficacy supplements within 10 months of receipt.7
Review and act on priority efficacy supplements within 6 months of receipt.7
Review and act on all manufacturing supplements within 6 months of receipt and those requiring prior approval within 4 months of receipt.8
Review and act on Class 1 resubmitted original applications within 2 months of receipt.
Review and act on Class 2 resubmitted original applications within 6 months of receipt.7
Review and act on Class 1 resubmitted efficacy supplements within	2 months of receipt.	--	30%	50%	70%	80%	90%
	4 months of receipt		--	90%			--
	6 months of receipt	--	90%	--
Review and act on Class 2 resubmitted efficacy supplements within 6 months of receipt1.7		--	90%
Issue discipline review letters for pre-submitted ÏReviewable UnitsÓ of NDAs/BLAs in 6 months.7		--	--	30%	50%	70%	90%
Report substantive deficiencies (or lack of same) within 14 days after 60 day filing date for original NDAs, BLAs, and efficacy supplements.		--	50%	70%	90%

NEW MOLECULAR ENTITY (NME) PERFORMANCE GOALS

The performance goals for standard and priority original NMEs will be the same as for all of the original NDAs but will be reported separately.

For biological products, for purposes of this performance goal, all original PLA/BLAs will be considered to be NMEs.

PROCEDURAL AND PROCESSING GOALS

Performance Area	Agency Activity	Performance Goal	Performance Level FY 2002- FY 2007
Meeting Management	Meeting Requests -- Notify requestor of formal meeting in writing (date, time, place, and participants)	within 14 days of receipt of request	90% on time
Meeting Management	Scheduling Meetings -- Schedule meetings within goal date or within 14 days of requested date if longer than goal date.	Type A Meetings within 30 days of receipt of request Type B Meetings within 60 days of receipt of request Type C Meetings within 75 days of receipt of request	90% on time
Meeting Management	Meeting Minutes -- Agency prepared minutes, clearly outlining agreements, disagreements, issues for further discussion and action times will be available to sponsor	within 30 calendar days of meeting	90% on time
Clinical Holds	Response to sponsorÌs complete response to a clinical hold	within 30 days of receipt of sponsorÌs response	90% on time
Major Dispute Resolution	Response to sponsorÌs appeal of decision	within 30 days of receipt of sponsorÌs appeal	90% on time
Special Protocol Question Assessment and Agreement	Response to sponsorÌs request for evaluation of protocol design	within 45 days of receipt of protocol and questions	90% on time

IV. PDUFA III Management Initiatives--Performance Level and/or Implementation Timeline (FY)

Not applicable: --
Action due: X

Performance Area	Initiative	Commitment	FY2002	FY2003	FY2004	FY2005	FY2006	FY2007
Continuous Marketing Application	To test whether providing early review of selected applications and additional feedback and advice to sponsors during drug development for selected products can further shorten drug development and review times.	Discipline review team of a Ïreviewable unitÓ for a Fast Track drug or biologic will be completed and a DRL issued within 6 months of the date of the submission	---	---	30%	50%	70%	90%
Independent Consultants for Biotechnology Clinical Trial Protocols	During the development period for a biotechnology product, a sponsor may request that FDA engage an independent expert consultant, selected by FDA, to participate in the AgencyÌs review of the protocol for the clinical studies that are expected to serve as the primary basis for a claim.	If FDA denies request, it must provide a written rationale within 14 days of receipt	---	100%	100%	100%	100%	100%
First Cycle Review Performance Proposal	For original NDA/BLA applications and efficacy supplements, FDA will report substantive deficiencies (or lack of same) identified in the initial filing review to the sponsor by letter, telephone conference, facsimile, secure e-mail, or other expedient means	FDA will provide the sponsor a notification of deficiencies (or lack of same) within 14 calendar days after the 60-day filing date.	---	50%	70%	90%	90%	90%
Improving FDA Performance Management	Two specific initiatives will begin early in PDUFA III and supported from performance management initiative funds 1) evaluation of first cycle review performance, and 2) process review and analysis within the two centers.	In FY 2003, FDA will contract with an outside consultant to conduct a comprehensive process review and analysis within CDER and CBER.	---	X
Risk Management	Pre-NDA/BLA Meeting with Industry: The intent of these discussions will be for FDA to get a better understanding of the safety issues associated with the particular drug/biologic and the proposed risk management plans, and to provide industry with feedback on these proposals so that they can be included in the NDA/BLA submission.	By the end of FY 2004, CDER and CBER will jointly develop final guidance documents that address good risk assessment, risk management, and pharmacovigilance practices.	---		X

V. Electronic Applications And Submissions--Implementation Deadline (FY)

Not applicable: --
Action due: X

Initiatives	FY 2002	FY 2003	FY 2004	FY 2005	FY 2006	FY 2007
The Agency will centralize the accountability and funding for all PDUFA Information Technology initiatives/activities for CBER, CDER, ORA and OC under the leadership of the FDA CIO. The July 2001 HHS IT 5-year plan states that infrastructure consolidation across the department should be achieved, including standardization. The Agency CIO will be responsible for ensuring that all PDUFA III IT infrastructure and IT investments support the AgencyÌs common IT goals, fit into a common computing environment, and follow good IT management practices.	---	X	X	X	X	X
The Agency CIO will chair quarterly briefings on PDUFA IT issues to periodically review and evaluate the progress of IT initiatives against project milestones, discuss alternatives when projects are not progressing, and review proposals for new initiatives. On an annual basis, an assessment will be conducted of progress against PDUFA III IT goals and, established program milestones, including appropriate changes to plans. A documented summary of the assessment will be drafted and forwarded to the Commissioner. A version of the study report redacted to remove confidential commercial or security information, or other information exempt from disclosure, will be made available to the public. The project milestones, assessment and changes will be part of the annual PDUFA III report.	---	X	X	X	X	X
FDA will implement a common solution in CBER, CDER, ORA and OC for the secure exchange of content including secure e-mail, electronic signatures, and secure submission of, and access to application components.	---					X
FDA will deliver a single point of entry for the receipt and processing of all electronic submissions in a highly secure environment. This will support CBER, CDER, OC and ORA. The system should automate the current electronic submission processes such as checking the content of electronic submissions for completeness and electronically acknowledging submissions.	---					X
FDA will provide a specification format for the electronic submission of the Common Technical Document (e-CTD), and provide an electronic review system for this new format that will be used by CBER, CDER and ORA reviewers. Implementation should include training to ensure successful deployment. This project will serve as the foundation for automation of other types of electronic submissions. The review software will be made available to the public.	---					X
Within the first 12 months, FDA will conduct an objective analysis and develop a plan for consolidation of PDUFA III IT infrastructure and desktop management services activities that will access and prioritize the consolidation possibilities among CBER, CDER, ORA and OC to achieve technical efficiencies, target potential savings and realize cost efficiencies. Based upon the results of this analysis, to the extent appropriate, establish common IT infrastructure and architecture components according to specific milestones and dates. A documented summary of analysis will be forwarded to the Commissioner. A version of the study report redacted to remove confidential commercial or security information, or other information exempt from disclosure, will be made available to the public.	---		X
FDA will implement Capability Maturity Model (CMM) in CBER, CDER, ORA and OC for PDUFA IT infrastructure and investments, and include other industry best practices to ensure that PDUFA III IT products and projects are of high quality and produced with optimal efficiency and cost effectiveness. This includes the development of project plans and schedules, goals, estimates of required resources, issues and risks/mitigation plans for each PDUFA III IT initiative.	---					X
Where common business needs exist, CBER, CDER, ORA and OC will use the same software applications, such as eCTD software, and COTS solutions.	---					X
Within six months of authorization, a PDUFA III IT 5-year plan will be developed. Progress will be measured against the milestones described in the plan.	---	X

 Definitions of Terms:

1. The term "review and act on" is understood to mean the issuance of a complete action letter after the complete review of a filed complete application. The action letter, if it is not an approval, will set forth in detail the specific deficiencies and, where appropriate, the actions necessary to place the application in condition for approval.
2. Under PDUFA I and II, receipt of a major amendment to original NDAs and BLAs in the last 3 months extended the goal date by 3 months. Under PDUFA III, this extension also applies to efficacy supplements and Class 2 resubmitted NDAs, BLAs, and efficacy supplements. Receipt of a major amendment to a manufacturing supplement in the last 2 months extends the goal date by 2 months (PDUFA III submissions only).
3. A resubmitted original application is a complete response to an action letter addressing all identified deficiencies.
4. Class 1 resubmitted applications are applications resubmitted after a complete response letter (or a not approvable or approvable letter) that include the following items only (or combinations of these items):
   1. Final printed labeling
   2. Draft labeling
   3. Safety updates submitted in the same format, including tabulations, as the original safety submission with new data and changes highlighted (except when large amounts of new information including important new adverse experiences not previously reported with the product are presented in the resubmission)
   4. Stability updates to support provisional or final dating periods
   5. Commitments to perform Phase 4 studies, including proposals for such studies
   6. Assay validation data
   7. Final release testing on the last 1?2 lots used to support approval
   8. A minor reanalysis of data previously submitted to the application (determined by the agency as fitting the Class 1 category)
   9. Other minor clarifying information (determined by the Agency as fitting the Class 1 category)
   10. Other specific items may be added later as the Agency gains experience with the scheme and will be communicated via guidance documents to industry.
5. Class 2 resubmissions are resubmissions that include any other items, including any item that would require presentation to an advisory committee.
6. A Type A Meeting is a meeting that is necessary for an otherwise stalled drug development program to proceed (a "critical path" meeting).
7. A Type B Meeting is a 1) pre?IND, 2) end of Phase 1 (for Subpart E or Subpart H or similar products) or end of Phase 2/pre?Phase 3, or 3) a pre? NDA/PLA/BLA meeting. Each requestor should usually only request 1 each of these Type B meetings for each potential application (NDA/PLA/BLA) (or combination of closely related products, i.e., same active ingredient but different dosage forms being developed concurrently).
8. A Type C Meeting is any other type of meeting.

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APPENDIX B: List of Approved Applications

 

This appendix updates the detailed review histories of the NDAs and BLAs submitted and approved under PDUFA. It shows approvals of all PDUFA-related submissions that took place in FY 2003 as well as FY 2002 approvals of FY 2002 submissions. Earlier PDUFA approvals were listed in previous performance reports. The following two tables summarize the review histories for all approved applications submitted from FY 1997 through FY 2002. The tables show the average first review, second review, and approval times. Note that times are in months, not all applications required a second review, and some required more than two reviews. The mean total approval times shown in the tables will increase in the future as additional applications are approved.

Approved Priority NDAs/BLAs | Approved Standard NDAs/BLAs | Terms and Coding Used in Tables | FY 2002 Priority NDA and BLA Submissions Approved in FY 2002 (v) and FY 2003 | FY 2002 Standard NDA and BLA Submissions Approved in FY 2002 (v) and FY 2003 | FY 2001 Priority NDA and BLA Submissions Approved in FY 2003 | FY 2001 Standard NDA and BLA Submissions Approved in FY 2003 | FY 2000 and Earlier Priority NDA and BLA Submissions Approved in FY 2003 | FY 2000 and Earlier Standard NDA and BLA Submissions Approved in FY 2003 |

Approved Priority NDAs/BLAs

The remainder of this appendix shows the individual review histories. Approvals are grouped by submission year and priority designation and listed in order of total approval time. Review histories of all other PDUFA submissions approved prior to FY 2003 can be found in the appendices of the earlier PDUFA Performance Reports which are available at www.fda.gov.

Terms and Coding Used in Tables

√ FY 2002 approval of an FY 2002 submission. These were not included in earlier PDUFA performance reports and are included here for completeness.

** Major amendment was received within 3 months of the action due date, which extended the review timeframes by 3 months.

Action Codes: AE = Approvable AP = Approved NA = Not Approvable RL = Complete Response WD = Withdrawn

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Table 1. FY 2002 Priority NDA and BLA Submissions Approved in FY 2002 (√) and FY 2003

	Generic Name	Sponsor	Approval Time (Months)		Review Goal Met
			Total Time	Resubmissions (if necessary)
√	OXALIPLATIN	SANOFI RES	1.5		Y
	NITAZOXANIDE	ROMARK	5.8		Y
	APREPITANT	MERCK	5.9		Y
	ENFUVIRTIDE	ROCHE	5.9		Y
	RIBAVIRIN	ROCHE	6.0		Y
√	ADEFOVIR DIPIVOXIL	GILEAD	6.0		Y
	GEFITINIB	ASTRAZENECA (UK)	9.0		Y**
	LARONIDASE (BLA)	BIOMARIN PHARMACEUTICAL, INC.	9.0	FDA First Action: 6.0 (RL)Sponsor Response: 1.0	Y
				FDA Second Action: 2.0 (AP)	Y

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Table 2. FY 2002 Standard NDA and BLA Submissions Approved in FY 2002 (√) and FY 2003

 

	Generic Name	Sponsor	Approval Time (Months)		Review Goal Met
			Total Time	Resubmissions (if necessary)
	ACYCLOVIR	GLAXOSMITHKLINE	9.0		Y
	AZELAIC ACID	BERLEX	9.1		Y
	ADALIMUMAB (BLA)	ABBOTT LABORATORIES	9.1		Y
	CIPROFLOXACIN	BAYER PHARMS	9.3		Y
	CHLORPHENIRAMINE MALEATE; IBUPROFEN; PSEUDOEPHEDRINE HYDROCHLORIDE	WYETH CONS	9.6		Y
	KETOROLAC TROMETHAMINE	ALLERGAN	9.7		Y
	CIPROFLOXACIN; DEXAMETHASONE	ALCON	9.7		Y
	CHLORHEXIDINE GLUCONATE	BECKLOFF ASSOC	9.8		Y
	PALONOSETRON HYDROCHLORIDE	HELSINN HLTHCARE	9.9		Y
√	EPLERENONE	GD SEARLE LLC	9.9		Y
	EZETIMIBE	MSP SINGAPORE	9.9		Y
√	TIZANIDINE HYDROCHLORIDE	ELAN PHARMS	9.9		Y
	GATIFLOXACIN	ALLERGAN	9.9		Y
	EMTRICITABINE	GILEAD	9.9		Y
	CLOBETASOL PROPIONATE	GALDERMA LABS LP	9.9		Y
	MUPIROCIN	JOHNSON AND JOHNSON	9.9		Y
	BUTENAFINE HYDROCHLORIDE	BERTEK	10.0		Y
	METFORMIN HYDROCHLORIDE; ROSIGLITAZONE MALEATE	SB PHARMCO	10.0		Y
√	IOPROMIDE	BERLEX LABS	10.0		Y
√	LANSOPRAZOLE	TAP PHARM	10.0		Y
	TESTOSTERONE	AUXILIUM A2 INC	10.0		Y
	IBANDRONATE SODIUM	ROCHE	10.0		Y
	METFORMIN HYDROCHLORIDE; GLIPIZIDE	BRISTOL MYERS SQUIBB	10.0		Y
	IBUPROFEN	BANNER PHARMACAPS	10.0		Y
	LEUPROLIDE ACETATE	ATRIX	10.0		Y
	NELFINAVIR MESYLATE	AGOURON	10.0		Y
	OLMESARTAN MEDOXOMIL; HYDROCHLOROTHIAZIDE	SANKYO PHARMA	10.0		Y
	TESTOSTERONE	COLUMBIA LABS	10.0		Y
	MULTIPLE VITAMINS	SABEX 2002	10.0		Y
	CARBIDOPA; LEVODOPA; ENTACAPONE	ORION PHARMS INC	11.5	FDA First Action: 10.0 (AE)Sponsor Response: 0.3	Y
				FDA Second Action: 1.2 (AP)	Y
	BUPROPION HYDROCHLORIDE	SMITHKLINE BEECHAM	12.1	FDA First Action: 9.9 (AE)Sponsor Response: 0.3	Y
				FDA Second Action: 1.8 (AP)	Y
	ARIPIPRAZOLE	OTSUKA PHARM	12.5	FDA First Action: 9.9 (AE)Sponsor Response: 0.7	Y
				FDA Second Action: 1.9 (AP)	Y
	ESCITALOPRAM OXALATE	FOREST LABS	12.7	FDA First Action: 10.0 (AE)Sponsor Response: 0.9	Y
				FDA Second Action: 1.8 (AP)	Y
	ALPRAZOLAM	PHARMA AND UPJOHN FR	12.7	FDA First Action: 10.0 (AE)Sponsor Response: 0.9	Y
				FDA Second Action: 1.9 (AP)	Y
	STAVUDINE	BRISTOL MYERS SQUIBB	12.7		Y**
	LEVETIRACETAM	UCB PHARMA	12.8	FDA First Action: 9.9 (AE)Sponsor Response: 1.2	Y
				FDA Second Action: 1.8 (AP)	Y
	ANTIHEMOPHILIC FACTOR (RECOMBINANT), PLASMA/ALBUMIN FREE METHOD (BLA)	BAXTER HEALTHCARE CORPORATION	13.0		Y**
	ETHINYL ESTRADIOL; LEVONORGESTREL	BARR RES	13.0		Y**
	ATOMOXETINE HYDROCHLORIDE	LILLY	13.5	FDA First Action: 10.0 (AE)Sponsor Response: 1.5	Y
				FDA Second Action: 2.0 (AP)	Y
	BUPIVACAINE HYDROCHLORIDE; LIDOCAINE HYDROCHLORIDE	AMPHASTAR	14.6	FDA First Action: 10.0 (AE)Sponsor Response: 2.7	Y
				FDA Second Action: 1.9 (AP)	Y
	ESTRADIOL ACETATE	GALEN LTD	14.9	FDA First Action: 9.9 (AE)Sponsor Response: 3.1	Y
				FDA Second Action: 1.9 (AP)	Y
	METHYLPHENIDATE HYDROCHLORIDE	MALLINCKRODT	15.8	FDA First Action: 9.9 (AE)Sponsor Response: 4.1	Y
				FDA Second Action: 1.8 (AP)	Y
	PROPRANOLOL HYDROCHLORIDE	RELIANT PHARMS	16.3	FDA First Action: 9.9 (AE)Sponsor Response: 2.9	Y
				FDA Second Action: 3.5 (AP)	Y
	RISPERIDONE	JOHNSON AND JOHNSON	16.4	FDA First Action: 10.0 (AE)Sponsor Response: 4.5	Y
				FDA Second Action: 1.9 (AP)	Y
	PROPAFENONE HYDROCHLORIDE	ABBOTT LABS	17.7	FDA First Action: 10.0 (AE)Sponsor Response: 7.1	Y
				FDA Second Action: 0.6 (AP)	Y
	ZOLMITRIPTAN	ASTRAZENECA PHARMS	19.1	FDA First Action: 9.7 (AE)Sponsor Response: 3.4	Y
				FDA Second Action: 6.0 (AP)	Y
	IMMUNE GLOBULIN INTRAVENOUS (HUMAN), 10% BY CHROMATOGRAPHY PROCESS (BLA)	BAYER CORPORATION	20.3	FDA First Action: 10.0 (RL)Sponsor Response: 1.5	Y
				FDA Second Action: 8.8 (AP)	Y**

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Notes

 1. On June 30, 2003, many of CBER's therapeutic products were transferred to CDER. In this report, however, submissions for these products are all counted under CBER workload and performance through FY 2003.

 2. The count of FY 2003 submissions assumes that all submissions received in the last two months of FY 2003 are filed. When FDA files a submission, it is deemed "complete" by PDUFA definition. FDA makes a filing decision within 60 days of an original application's receipt. All calculations of PDUFA review times are made, however, from the original receipt date of the filed application.

 3. The term "new molecular entity" or "NME" in this report refers exclusively to NMEs that are NDAs. For FDAMA purposes, all BLAs are considered to be equivalent to NMEs; however, workload and performance statistics for BLAs are reported separately. The counts of NMEs in the workload table are of 'discrete,' filed NMEs. CDER often receives multiple submissions for the same new molecular entity, for different dosage forms for example. All are initially designated as NMEs, but, when the first of the multiples is approved, the others are re-designated as non-NMEs. Counts of discrete NMEs in the table have been adjusted to reflect the most recent information. In FY 2003, CDER designated 40 filings as NMEs initially (14 priority, 26 standard). Only 25 of these are 'discrete' (8 priority, 17 standard).

 4. Includes those with late actions and those still pending whose goal date has passed and which have not had actions.

 5. Includes actions that are pending within goal, as well as those whose goal date has passed, but whose action status is deemed incomplete because the database had not been updated to reflect the action in time for this report.

 6. Actions pending within goal were excluded from the calculation.

 7. Receipt of a major amendment in the last 3 months extends the goal date by 3 months. Under PDUFA II (i.e. through FY 2002), this extension applied to original NDAs and BLAs only. Under PDUFA III, it also applies to efficacy supplements and Class 2 resubmitted NDAs, BLAs, and efficacy supplements.

 8. Receipt of a major amendment in the last 2 months extends the goal date by 2 months (PDUFA III submissions only).

 9. This application received tentative approval on 12/12/2002. This date was used to calculated the total approval time. The application received final approval on 12/19/2002.

 10. This application was originally designated a standard NDA designation with 12-month review clock. It was later changed to a Priority application after the application was resubmitted