PRESCRIPTION 

DRUGS

FDA Has Met Most 

Performance Goals for 

Reviewing 

Applications

Report to Congressional Requesters

March 2012

GAO-12-500

United States Government Accountability Office

GAO
United States Government Accountability Office

Highlights of GAO-12-500, a report to 

congressional requesters

March 2012

PRESCRIPTION DRUGS

FDA Has Met Most Performance Goals for Reviewing 

Applications 

Why GAO Did This Study

The Food and Drug Administration 

(FDA) within the Department of Health 

and Human Services (HHS) is 

responsible for overseeing the safety 

and efficacy of drugs and biologics 

sold in the United States. New drugs 

and biologics must be reviewed by 

FDA before they can be marketed, and 

the Prescription Drug User Fee Act 

(PDUFA) authorizes FDA to collect 

user fees from the pharmaceutical 

industry to support its review of 

prescription drug applications, 

including new drug applications (NDA), 

biologic license applications (BLA), and 

efficacy supplements that propose 

changes to the way approved drugs 

and biologics are marketed or used. 

Under each authorization of PDUFA 

since 1992, FDA committed to 

performance goals for its drug and 

biologic reviews. 

In preparation for the next PDUFA 

reauthorization, GAO was asked to

examine FDA’s drug and biologic 

review processes. In this report, we 

(1) examine trends in FDA’s NDA and 

BLA review performance for fiscal 

years (FY) 2000 through 2010, 

(2) examine trends in FDA’s efficacy 

supplement review performance for 

FYs 2000 through 2010, and 

(3) describe issues stakeholders have 

raised about the drug and biologic 

review processes and steps FDA is 

taking that may address these issues. 

To do this work, GAO examined FDA 

drug and biologic review data, 

reviewed FDA user fee data, 

interviewed FDA officials, and 

interviewed two industry groups and 

five consumer advocacy groups. All of 

the stakeholder groups participated in 

at least half of the meetings held by 

FDA to discuss the reauthorization of 

the prescription drug user fee program.

What GAO Found

FDA met most performance goals for priority and standard NDAs and BLAs 

received from FY 2000 through FY 2010. FDA meets its performance goals by 

completing its review and issuing an action letter—such as an approval or a 

response detailing deficiencies that are preventing the application from being 

approved—for a specified percentage of applications within a designated period 

of time. FDA designates NDAs and BLAs as either priority—if the product would 

provide significant therapeutic benefits when compared to available drugs—or 

standard. FDA met the performance goals for both priority and standard NDAs 

and BLAs for 10 of the 11 fiscal years GAO examined; FDA did not meet either of

the goals for FY 2008. Although FDA had not yet issued an action letter for all of 

the applications it received in FY 2011 and results are therefore preliminary, FDA 

was meeting the goals for both priority and standard NDAs and BLAs on which it 

had taken action. Meanwhile, FDA review time for NDAs and BLAs—the time

elapsed between FDA’s receipt of an application and issuance of an action 

letter—increased slightly from FY 2000 through FY 2010. In addition, the 

percentage of NDAs and BLAs receiving an approval letter at the end of the first 

review cycle generally increased, although that percentage has decreased for 

priority NDAs and BLAs since FY 2007. 

FDA met most of its performance goals for efficacy supplements from FY 2000 

through FY 2010. Specifically, FDA met the performance goals for both priority 

and standard efficacy supplements for 10 of the 11 fiscal years GAO examined. 

FDA review time generally increased during the analysis period for both priority 

and standard efficacy supplements. The percentage of priority efficacy 

supplements receiving an approval letter at the end of the first review cycle 

fluctuated from FY 2000 through FY 2010, ranging between 47 percent and

80 percent during this time. The results for standard efficacy supplements 

showed a steadier increase with the percentage of first-cycle approval letters

rising from 43 percent for FY 2000 applications to 69 percent for FY 2010 

applications. 

The industry groups and consumer advocacy groups we interviewed noted a 

number of perceived issues related to FDA’s review of drug and biologic 

applications. The most commonly mentioned issues raised by industry and 

consumer advocacy stakeholder groups were actions or requirements that can 

increase review times (such as taking more than one cycle to approve 

applications) and insufficient communication between FDA and stakeholders 

throughout the review process. Industry stakeholders also noted a perceived lack 

of predictability and consistency in reviews. Consumer advocacy group 

stakeholders noted issues related to inadequate assurance of the safety and 

effectiveness of approved drugs. FDA is taking steps that may address many of 

these issues, including issuing new guidance, establishing new communicationrelated performance goals, training staff, and enhancing scientific decision 

making. 

In commenting on a draft of this report, HHS generally agreed with GAO’s 

findings and noted that they reflect what the agency reported for the same time 

period. HHS also called attention to activities FDA has undertaken to improve the 

prescription drug review process.

View GAO-12-500. For more information, 

contact Marcia Crosse at (202) 512-7114 or 

crossem@gao.gov.
Page i GAO-12-500 Prescription Drug Performance Goals

Letter 1 

Background 4

FDA Met Most Performance Goals for Original NDAs and BLAs 

While FDA Review Time Increased Slightly 8

FDA Met Most Performance Goals for Original Efficacy 

Supplements While FDA Review Time Increased Slightly 15

Stakeholders Noted Issues with the Prescription Drug Review 

Process and FDA Is Taking Steps That May Address Many of 

Those Issues 20

Concluding Observations 26

Agency Comments 27

Appendix I FDA NDA and BLA Review Performance for Fiscal Years (FYs) 

2000 through 2011 29

Appendix II FDA Efficacy Supplement Review Performance for Fiscal Years 

(FYs) 2000 through 2011 36

Appendix III Full-time Equivalent (FTE) FDA Staff Supporting Prescription Drug 

User Fee Activities, FYs 2000 through 2010 41

Appendix IV Comments from the Department of Health and Human Services 43

Appendix V GAO Contact and Staff Acknowledgments 46

Tables

Table 1: FDA’s NDA, BLA and Efficacy Supplement Performance 

Goals, FYs 2000 through 2011 Cohorts 8

Table 2: FDA Review Performance for Priority Original NDAs and 

BLAs Including Innovative Drugs, FYs 2000 through 2011 29

Table 3: FDA Review Performance for Standard Original NDAs and 

BLAs Including Innovative Drugs, FYs 2000 through 2011 31

Contents
Page ii GAO-12-500 Prescription Drug Performance Goals

Table 4: Percentages of Closed and Open NDAs and BLAs, FYs 

2000 through 2011 33

Table 5: FDA Review Performance for NDA and BLA 

Resubmissions Including Innovative Drugs, FYs 2000 

through 2011 34

Table 6: FDA Review Performance for Oncology Drugs Including 

Those Granted Accelerated Approval, FYs 2000 through 

2011 35

Table 7: FDA Review Performance for Priority Efficacy 

Supplements, FYs 2000 through 2011 36

Table 8: FDA Review Performance for Standard Efficacy 

Supplements, FYs 2000 through 2011 38

Table 9: Percentages of Closed and Open Efficacy Supplements, 

FYs 2000 through 2011 40

Figures

Figure 1: Percentage of Priority and Standard Original NDAs and 

BLAs FDA Reviewed within 6 Months and 10 Months, 

Respectively, FYs 2000 through 2010 10

Figure 2: Average FDA Review Time (in Calendar Days) for Priority 

and Standard Original NDAs and BLAs, FYs 2000 through 

2010 12

Figure 3: Percentage of Priority and Standard Original NDAs and 

BLAs Receiving FDA First-Cycle Approvals, FYs 2000 

through 2010 14

Figure 4: Percentage of Priority and Standard Original Efficacy 

Supplements FDA Reviewed within 6 Months and 10 

Months, Respectively, FYs 2000 through 2010 16

Figure 5: Average FDA Review Time (in Calendar Days) for Priority 

and Standard Original Efficacy Supplements, FYs 2000 

through 2010 18

Figure 6: Percentage of Priority and Standard Original Efficacy 

Supplements Receiving FDA First-Cycle Approvals, FYs 

2000 through 2010 20
Page iii GAO-12-500 Prescription Drug Performance Goals

Abbreviations

BLA biologic license application

CBER Center for Biologics Evaluation and Research

CDER Center for Drug Evaluation and Research

FDA Food and Drug Administration

FDAAA Food and Drug Administration Amendments Act of 2007

FTE full-time equivalent

FY fiscal year

HHS Department of Health and Human Services

NDA new drug application

NME new molecular entity

PDUFA Prescription Drug User Fee Act

REMS Risk Evaluation and Mitigation Strategy

This is a work of the U.S. government and is not subject to copyright protection in the 

United States. The published product may be reproduced and distributed in its entirety 

without further permission from GAO. However, because this work may contain 

copyrighted images or other material, permission from the copyright holder may be 

necessary if you wish to reproduce this material separately.
Page 1 GAO-12-500 Prescription Drug Performance Goals

United States Government Accountability Office

Washington, DC 20548

March 30, 2012

The Honorable Richard Burr

Ranking Member

Subcommittee on Children and Families

Committee on Health, Education, Labor, and Pensions

United States Senate

The Honorable Tom Coburn

Ranking Member

Permanent Subcommittee on Investigations

Committee on Homeland Security and Governmental Affairs

United States Senate

The Food and Drug Administration (FDA) within the Department of Health 

and Human Services (HHS) is responsible for overseeing the safety and 

efficacy of drugs and biological products sold in the United States.1 In 

1992, Congress passed the Prescription Drug User Fee Act (PDUFA) to 

provide additional resources for FDA to support the process of reviewing 

applications for new drugs.2 PDUFA authorized FDA to collect user fees 

from the pharmaceutical and biotechnology industries to supplement its 

annual appropriation for salaries and expenses; these user fees include 

application fees, annual establishment registration fees, and annual 

product fees. The prescription drug user fee program has been 

reauthorized every 5 years since 1992, most recently as part of the Food 

and Drug Administration Amendments Act of 2007 (FDAAA), which 

authorizes FDA to collect user fees for fiscal years (FY) 2008 through 

2012.3

 

1

Biological products—which include vaccines, blood products, and proteins—are derived 

from living sources such as humans, animals, and microorganisms, while drugs are 

chemically synthesized. Unless otherwise indicated, throughout this report we use the 

term “drug” to refer to both chemically synthesized drugs and therapeutic biological 

products.

User fees have become a larger part of FDA’s funding for drug 

review processes, rising from 26.1 percent of costs in FY 1993—the first 

year FDA collected user fees for drugs—to 61.5 percent in FY 2010, the 

most recent year for which data are available. In FY 2010, PDUFA user 

2

Pub. L. No. 102-571, tit. I, 106 Stat. 4491 (1992).

3

Pub. L. No. 110-85, tit. I, 121 Stat. 823 (2007). Fees are collected and available for 

obligation only to the extent and in the amount provided in advance in appropriations acts.

 
 

Page 2 GAO-12-500 Prescription Drug Performance Goals

fees collected by FDA—including application, establishment, and product 

fees—totaled more than $529 million, including over $172 million in 

application fees.4

Application fees are collected for a variety of drug and biologic application 

types, including new drug applications (NDA), biologic license 

applications (BLA), and efficacy supplements to approved NDAs and 

BLAs; the amount of the user fee varies for different types of 

applications.5

Under each authorization of the prescription drug user fee program, FDA 

committed to performance goals related to the review of drug 

applications.

An NDA is an application to market a new drug—either an 

innovative drug or a variation of a previously marketed drug. A BLA is an 

application to market a new biologic. FDA categorizes innovative drugs 

that have not previously been marketed in any dosage or form as new 

molecular entities (NMEs); FDA also considers nearly all BLAs to be 

innovative drugs. An efficacy supplement to an NDA or BLA is submitted 

to propose changes to the way an approved drug is marketed or used, 

such as adding or modifying an indication or claim, revising the dose or 

dose regimen, providing for a new route of administration, or changing the 

marketing status from prescription to over-the-counter use.

6 FDA meets its performance goals by completing its review 

and issuing an action letter (i.e., an approval, denial, or complete 

response) for a specified percentage of applications within a designated 

period of time.7

 

4

For the remainder of this report, we use the term “user fees” to refer to user fees 

submitted with drug applications such as NDAs, BLAs, and efficacy supplements.

These performance goals, as well as user fee amounts, 

5

For applications submitted in FY 2012, the fee for the review of an application (e.g., an 

NDA or BLA) that requires clinical data is $1,841,500. The user fee for applications that do 

not require clinical data is half this amount ($920,750), as is the fee for efficacy 

supplements requiring clinical data. Some applications—such as those for orphan 

designated products to treat rare diseases or conditions—are exempt from user fees. In 

addition, abbreviated new drug applications, which are applications for the approval of 

generic drugs, are not subject to user fees.

6

See Pub. L. No. 110-85, § 101(c), 121 Stat. 823, 825 (2007). The performance goals are 

identified in letters sent by the Secretary of Health and Human Services to the Chairman 

of the Senate Committee on Health, Education, Labor, and Pensions and the Chairman of 

the House Committee on Energy and Commerce, and are published on FDA’s website. 

Each fiscal year, FDA is required to submit a report on its progress in achieving those 

goals and future plans for meeting them. See 21 U.S.C. § 379h-2(a). 

7

A complete response letter describes any deficiencies that must be corrected in order for

an application to be approved.
 

Page 3 GAO-12-500 Prescription Drug Performance Goals

are negotiated between FDA and industry stakeholders and submitted to 

congressional committees prior to each reauthorization. FDA’s authority 

to collect user fees for drugs expires on October 1, 2012, and the 

prescription drug user fee program will need to be reauthorized in order 

for FDA to continue to collect user fees. In preparation for the 

reauthorization of the prescription drug user fee program, you requested 

that we examine FDA’s prescription drug review process. In this report, 

we (1) examine trends in FDA’s NDA and BLA review performance for 

FYs 2000 through 2010, (2) examine trends in FDA’s efficacy supplement 

review performance for FYs 2000 through 2010, and (3) describe the 

issues stakeholders have raised about the prescription drug review 

processes and steps FDA is taking that may address these issues. We 

provide additional details on FDA’s NDA and BLA review performance in 

appendix I and efficacy supplement review performance in appendix II. 

You also asked us to provide information on the number of full-time 

equivalent (FTE) staff involved in the prescription drug review process; 

this information is provided in appendix III.

To determine the trends in FDA’s review performance for NDAs, BLAs, 

and efficacy supplements to approved NDAs and BLAs for FYs 2000 

through 2010, we examined data obtained from FDA on the review 

process for all such applications submitted to FDA in those years. 

Additionally, we reviewed data on FY 2011 applications in order to 

provide preliminary performance results for that year. FDA had not yet 

completed its first review for a majority of the FY 2011 applications at the 

time we received FDA’s data; as these reviews are completed, the 

preliminary results are likely to change.8

 

8

Specifically, FDA had completed its first review for only 39 percent of original NDAs and 

BLAs and 34 percent of original efficacy supplements for FY 2011 at the time we received 

FDA’s data, which include reviews by CBER and CDER through November 30, 2011.

We reviewed the data for 

reasonableness and consistency, including screening for missing data, 

outliers, and obvious errors. We also interviewed FDA officials about 

steps they take to ensure data reliability. We determined that these data 

were sufficiently reliable for our purposes. Our analyses focused on the 

proportion of drug applications in each fiscal year for which FDA met or 

did not meet the applicable performance goal(s); the FDA review time 

(i.e., the time counted toward user fee performance goals, from the date 

of receipt of an application to the date FDA issued an action letter to end 

the first review cycle); the time to final decision (i.e., the total time 

between submission of an application and the sponsor’s withdrawal of the 
 

Page 4 GAO-12-500 Prescription Drug Performance Goals

application or FDA’s issuance of an approval or denial action letter in the 

last completed review cycle); and the percentage of first-cycle decisions 

that were approvals.9

To describe the issues stakeholders have raised about the drug review 

processes and what steps FDA is taking that may address these issues, 

we interviewed two industry groups representing drug manufacturers and 

five consumer advocacy groups.

We also reviewed user fee data from FDA’s annual 

PDUFA financial reports to Congress for FYs 1993 through 2010 and 

interviewed FDA staff regarding drug review processes and the data we 

received from FDA.

10

We conducted this performance audit from October 2011 through March 

2012 in accordance with generally accepted government auditing 

standards. Those standards require that we plan and perform the audit to 

obtain sufficient, appropriate evidence to provide a reasonable basis for 

our findings and conclusions based on our audit objectives. We believe 

that the evidence obtained provides a reasonable basis for our findings 

and conclusions based on our audit objectives.

All of these groups have participated in 

at least half of the meetings held by FDA to discuss the reauthorization of 

the prescription drug user fee program. We performed content analyses 

of the interviews to determine the most pressing issues based on how 

often each issue was raised. To describe steps FDA is taking that may

address some of these issues, we examined publicly available FDA 

documents, including the draft agreement between FDA and industry on 

the user fees and performance goals for FYs 2013 through 2017.

Drug applications—including NDAs, BLAs, and efficacy supplements—

are reviewed primarily by FDA’s Center for Drug Evaluation and 

Research (CDER), with a smaller proportion reviewed by the Center for 

Biologics Evaluation and Research (CBER).11

 

9

The first review cycle begins when FDA receives an application from a sponsor and ends 

when FDA issues an action letter. If FDA does not approve the application during the first 

review cycle, a new review cycle begins if the sponsor resubmits the application to FDA. 

Prior to submission of an 

10When we refer to consumer advocacy groups, we are referring to groups that advocate 

on behalf of consumers and patients. 

11FDA also reviews other types of drug applications that are beyond the scope of our 

work, such as manufacturing supplements that describe changes to production processes, 

equipment, or facilities used to produce an approved drug.

Background 
 

Page 5 GAO-12-500 Prescription Drug Performance Goals

application, sponsors may choose to seek accelerated approval status if 

the drug is intended to treat a serious or life-threatening illness (such as 

cancer) and has the potential to provide meaningful therapeutic benefit to 

patients over existing treatments.12 Sponsors of a drug with accelerated 

approval status may be granted approval on the basis of clinical trials 

conducted using a surrogate endpoint—such as a laboratory 

measurement or physical sign—as an indirect or substitute measurement 

for a clinically meaningful outcome such as survival.13 According to FDA, 

the agency generally also speeds its review of drug applications with 

accelerated approval status by granting them priority review, although 

priority review can also be granted to an application without accelerated 

approval status.14

The review process involves evaluating scientific and clinical data in the 

application submitted by a sponsor to determine whether the drug meets 

statutory and regulatory standards for safety and effectiveness, 

manufacturing and controls, and labeling. For example, sponsors must 

demonstrate “substantial evidence” of effectiveness for the claimed 

indications of the drug in order for FDA to approve the drug.

FDA grants priority review for applications that it 

expects, if approved, would provide significant therapeutic benefits, 

compared to available drugs, in the treatment, diagnosis, or prevention of 

a disease. Applications for which there are no perceived significant 

therapeutic benefits beyond those for available drugs are granted 

standard review.

15

 

12See 21 C.F.R. §§ 314.500-314.560, 601.40-601.46.

FDA 

communicates with sponsors—through telephone conversations, letters, 

or meetings—issues that arise during its review of an application that may 

13FDA may require that a drug granted accelerated approval undergo postmarketing 

studies to verify the drug’s clinical benefit. Additionally, if FDA concludes that a drug can 

be safely used only if distribution or use is restricted, FDA will require postmarketing 

restrictions, such as restricting distribution to certain facilities or physicians with special 

training or experience. FDA may withdraw approval of a drug granted accelerated 

approval if postmarketing studies fail to verify clinical benefit or the sponsor fails to adhere 

to the postmarketing restrictions, or for other reasons.

14FDA assesses all applications for priority review eligibility; the sponsor does not need to 

request priority review. If priority review is granted, the sponsor is notified within 60 days 

of the start of the review period.

15See 21 U.S.C. § 355(d); 42 U.S.C. § 262(j).
 

Page 6 GAO-12-500 Prescription Drug Performance Goals

prevent FDA from approving the application.16 In response, sponsors can 

submit additional information to FDA in the form of amendments to the 

application. Certain applications are also subject to review by an 

independent advisory committee.17 FDA convenes advisory committees 

to provide independent expertise and technical assistance to help the 

agency make decisions about drug products. Additionally, FDA might 

require the sponsor to submit a Risk Evaluation and Mitigation Strategy 

(REMS) for the drug under review to ensure that the benefits of the drug 

outweigh its risks.18

FDA review time for an original application is calculated as the time 

elapsed from the date FDA receives the application and associated user 

fee to the date it issues an action letter; it is calculated using only the first 

review cycle and therefore does not include any time that may elapse 

while FDA is waiting for a sponsor to respond to FDA’s first-cycle action 

letter or any review time that elapses during subsequent review cycles.19

 

16For example, FDA issues a letter to sponsors to inform them of filing review issues that 

were identified during FDA’s initial review of an application. Additionally, approximately 

midway through its review of an application, FDA provides feedback to sponsors on the 

general progress and status of the application.

In order to close the review cycle for NDAs, BLAs, and efficacy 

supplements, FDA must complete its review and issue an approval letter, 

a denial letter, or a “complete response” letter (i.e., a letter delineating 

any problems FDA identified in the application that prevented it from 

17FDA convenes an advisory committee meeting for all applications for NMEs and original 

BLAs, unless an adequate justification is documented explaining the decision to not hold a 

meeting. For other applications, an advisory committee may be convened if (1) the clinical 

trial design used novel clinical or surrogate endpoints, (2) the application raises significant 

issues regarding the safety or effectiveness of the drug, or (3) the application raises 

significant public health questions on the role of the drug in the diagnosis, cure, mitigation, 

treatment, or prevention of a disease. See 21 U.S.C. § 355(n), (s).

18See 21 U.S.C. § 355-1; 42 U.S.C. § 262(a)(2)(D). Examples of elements that may be 

required as part of a REMS include medication guides, patient package inserts, 

communication plans to health care providers, prescriber or pharmacy certification, and 

restrictions on distribution.

19If the user fee is not paid within 5 days of receipt of the application, FDA will suspend 

the review. The review clock is reset to start the first review cycle on the date that the user 

fee is received.
 

Page 7 GAO-12-500 Prescription Drug Performance Goals

being approved).20 The review cycle will also be closed if the application 

is withdrawn by the sponsor. The date on which one of these actions

occurs is used to determine whether the review was completed within the 

PDUFA goal time frame.21 If FDA issues a complete response letter, the 

sponsor may choose to submit a revised application to FDA. These are 

known as resubmissions and their review is covered under the user fee 

paid with the original submission. Resubmissions are classified as 

Class 1 or Class 2 according to the complexity of the information they 

contain, with Class 2 being the most complex.22

Although the prescription drug performance goals have continued to 

evolve with each reauthorization of the prescription drug user fee 

program, the goals for NDAs, BLAs, and efficacy supplements have 

remained fairly stable for recent cohorts—a cohort being comprised of all 

the submissions of a certain type filed in the same fiscal year (see 

table 1). For standard NDAs, BLAs, and efficacy supplements, the current 

goal was phased in until it reached the current level (90 percent of 

reviews completed within 10 months) in FY 2002. Similarly, the goal for

Class 1 NDA and BLA resubmissions was phased in, reaching its current 

level of 90 percent of reviews completed within 2 months in FY 2001.

FDA can extend the review time frame for NDAs, BLAs, or Class 2 

 

20According to FDA officials, FDA rarely issues a denial letter. If FDA issues a complete 

response letter to conclude its review of an application, FDA provides the sponsor an 

opportunity to meet with reviewing officials to discuss what further steps need to be taken 

by the sponsor before the application can be approved. FDA may consider a sponsor’s 

failure to take action within 1 year after the issuance of a complete response letter to be a 

request by the sponsor to withdraw the application, unless the sponsor has requested an 

extension of time to resubmit the application. 

21Prior to August 2008, FDA also issued “approvable” and “not approvable” letters. 

Historically an approvable letter was issued when FDA determined that an application 

could be approved if the sponsor submitted additional information or agreed to certain 

conditions, while a not approvable letter indicated that FDA was not able to approve an 

application due to major deficiencies. Beginning in August 2008, FDA started issuing 

complete response letters in lieu of approvable and not approvable letters.

22Class 1 resubmissions contain only certain information such as draft or final printed 

labeling, safety or stability updates, or other minor clarifying information. Class 2 

resubmissions are those containing any information not specified in the definition of 

Class 1 resubmission, including any item that would require presentation to an advisory 

committee. 
 

Page 8 GAO-12-500 Prescription Drug Performance Goals

resubmissions by 3 months if it receives a major amendment to the 

application from the sponsor within 3 months of the goal date.23

Table 1: FDA’s NDA, BLA and Efficacy Supplement Performance Goals, FYs 2000 through 2011 Cohorts

Percentage of reviews to be completed within the PDUFA goal time frame

Fiscal year cohorts 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011

Priority NDA, BLA, or efficacy supplement, 

percentage within 6 months 90 90 90 90 90 90 90 90 90 90 90 90

Standard NDA, BLA, or efficacy 

supplement, percentage within 

10 months 50 a 70 90 90 90 90 90 90 90 90 90 90

Class 1 NDA or BLA resubmission, 

percentage within 2 months 70 b 90 90 90 90 90 90 90 90 90 90 90

Class 2 NDA or BLA resubmission, 

percentage within 6 months 90 90 90 90 90 90 90 90 90 90 90 90

Source: GAO analysis of FDA data.

Note: A review cohort includes all the drug submissions relating to a particular performance goal that 

were submitted in a given fiscal year. For example, all NDAs received by FDA from October 1, 2010, 

to September 30, 2011, make up the NDA review cohort for FY 2011.

a

For FYs 2000 and 2001, FDA also had a goal to complete 90 percent of these reviews within 

12 months.

b

For FY 2000, FDA also had a goal to complete 90 percent of these reviews within 4 months.

FDA met most of its performance goals for priority and standard original 

NDA and BLA submissions for the FYs 2000 through 2010 cohorts. 

However, the average FDA review time increased slightly during this 

period for both priority and standard NDAs and BLAs. The percentage of 

FDA first-cycle approvals for both priority and standard NDAs and BLAs 

generally increased from FY 2000 through FY 2010; however, the 

percentage of first-cycle approvals has decreased for priority NDAs and 

BLAs since FY 2007.

 

23A major amendment is one that contains one or both of the following: (1) a substantial 

amount of new data or new information not previously submitted to, or reviewed by, FDA 

(e.g., a major new clinical safety or efficacy study report); or (2) a new analysis or major 

reanalysis of studies previously submitted for the pending application. A major 

amendment can be solicited or unsolicited. Prior to FY 2003, FDA did not extend the 

review time frame for efficacy supplements. Amendments cannot be submitted for Class 1 

resubmissions.

FDA Met Most 

Performance Goals 

for Original NDAs and 

BLAs While FDA 

Review Time 

Increased Slightly
 

Page 9 GAO-12-500 Prescription Drug Performance Goals

FDA met most of its performance goals for priority and standard original 

NDA and BLA submissions during our analysis period by issuing the 

proportion of action letters specified in the performance goals within the 

goal time frames. Specifically, for priority original NDAs and BLAs, FDA 

met the performance goals for 10 of the 11 completed cohorts we 

examined (see fig. 1). FDA also met the performance goals for 10 of the 

11 completed standard NDA and BLA cohorts we examined. However, 

FDA did not meet the goals (i.e., issue the specified proportion of action 

letters within the goal time frames) for priority or standard NDAs and 

BLAs in the FY 2008 cohort. FDA and industry stakeholders we 

interviewed suggested that the reason FDA did not meet the goals for this 

cohort was that extra time was required for implementation of REMS 

requirements, which were introduced as part of the implementation of 

FDAAA. Although the FY 2011 cohort was still incomplete at the time we 

received FDA’s data, FDA was meeting the goals for both priority and 

standard original NDAs and BLAs on which it had taken action.24

 

24Approximately 32 percent of priority original NDAs and BLAs and 70 percent of standard 

original NDAs and BLAs received in FY 2011 were still under review at the time we 

received FDA’s data, which include reviews by CBER and CDER through November 30, 

2011. As a result, it was too soon to tell what the final results for this cohort would be. The 

percentage of priority and standard original drug submissions reviewed within 6 months 

and 10 months, respectively, may increase or decrease as those reviews are completed. 

FDA Met Most 

Performance Goals for 

Original NDAs and BLAs 

for FYs 2000 through 2010
 

Page 10 GAO-12-500 Prescription Drug Performance Goals

Figure 1: Percentage of Priority and Standard Original NDAs and BLAs FDA Reviewed within 6 Months and 10 Months, 

Respectively, FYs 2000 through 2010

Notes: A review cohort includes all of the drug submissions relating to a particular performance goal 

that were submitted in a given fiscal year. Only original NDAs and BLAs that had received an action 

letter from FDA at the time we received FDA’s data were included in this analysis; the data include 

reviews by CBER and CDER through November 30, 2011. The review cycle for original submissions 

starts when FDA receives a submission and ends when FDA issues an action letter or the sponsor 

withdraws the submission.

Priority and standard designations are associated with different lengths of time allotted (6 and 

10 months, respectively) for FDA to complete its review of original drug submissions and issue an 

action letter. If FDA completed its review of a priority submission in 6 months or less, it met the 

priority goal time frame. If FDA completed its review of a standard submission in 10 months or less, it 

met the standard goal time frame. Our calculations include extensions of the goal time frame, where 

applicable. Goal time frames can be extended by 3 months if the sponsor submits a major 

amendment to the application within 3 months of the goal date.

For FYs 2000 and 2001, FDA also had a goal to complete 90 percent of standard reviews within 

12 months.
 

Page 11 GAO-12-500 Prescription Drug Performance Goals

For the subset of priority NDAs and BLAs that were for innovative drugs, 

FDA met the performance goals for 9 of the 11 completed cohorts—all 

cohorts except FYs 2008 and 2009. For the subset of standard NDAs and 

BLAs that were for innovative drugs, FDA also met the performance goals 

for 9 of the 11 completed cohorts—all cohorts except FYs 2007 and 2008. 

For the incomplete FY 2011 cohort, FDA was meeting the goals for the 

subsets of both priority and standard NDAs and BLAs that were for 

innovative drugs.

If FDA issues a complete response letter to the sponsor noting 

deficiencies with the original submission, the sponsor can resubmit the 

application with the deficiencies addressed. For Class I NDA and BLA 

resubmissions, FDA met the performance goals for 8 of the 11 completed 

cohorts we examined.25 For Class 2 NDA and BLA resubmissions, FDA 

met the performance goals for 10 of the 11 completed cohorts we 

examined. Although the FY 2011 cohort was still incomplete at the time 

we received FDA’s data, FDA was meeting the goals for both the Class 1 

resubmissions and the Class 2 resubmissions on which it had taken 

action.

Overall, average FDA review time—the time elapsed from when FDA 

received a submission until it issued an action letter—increased slightly 

from FY 2000 through FY 2010 for both priority and standard NDAs and 

BLAs. There was a larger increase in average review time for both types 

of applications beginning in FY 2006. However, average review time 

began decreasing after FY 2007 for standard applications and after 

FY 2008 for priority applications, bringing the review times back near the 

FY 2000 levels (see fig. 2). As mentioned previously, FDA and industry 

stakeholder groups noted the implementation of REMS requirements as a 

contributing factor to increased review times for the FY 2008 cohort. 

Although the FY 2011 cohort was still incomplete at the time we received 

FDA’s data, average FDA review time for applications on which FDA had 

 

25The performance we report for FDA’s review of resubmissions may not match the 

performance reported in FDA’s annual PDUFA performance reports because our analysis 

was limited to resubmissions made in FYs 2000 through 2011 for original NDAs and BLAs 

that were also submitted in FYs 2000 through 2011. Resubmissions made in FYs 2000 

through 2011 for original NDAs and BLAs submitted prior to FY 2000 were not captured 

by our analysis.

Average FDA Review Time 

Increased Slightly for 

Original NDAs and BLAs 

from FY 2000 through 

FY 2010
 

Page 12 GAO-12-500 Prescription Drug Performance Goals

taken action was 186 days for priority NDAs and BLAs and 308 days for 

standard NDAs and BLAs.26

Figure 2: Average FDA Review Time (in Calendar Days) for Priority and Standard 

Original NDAs and BLAs, FYs 2000 through 2010

Note: A review cohort includes all of the drug submissions relating to a particular performance goal 

that were submitted in a given fiscal year. Only original NDAs and BLAs that had received an action 

letter from FDA at the time we received FDA’s data were included in this analysis; the data include 

reviews by CBER and CDER through November 30, 2011. The review cycle for original submissions 

starts when FDA receives a submission and ends when FDA issues an action letter or the sponsor 

withdraws the submission. Priority and standard designations are associated with different lengths of 

time allotted (6 and 10 months, respectively) for FDA to complete its review of original drug 

submissions and issue an action letter.

 

26Approximately 32 percent of priority original NDAs and BLAs and 70 percent of standard 

original NDAs and BLAs received in FY 2011 were still under review at the time we 

received FDA’s data, which include reviews by CBER and CDER through November 30, 

2011. As a result, it was too soon to tell what the final results for this cohort would be. The 

average FDA review time for this cohort may increase or decrease as those reviews are 

completed.
 

Page 13 GAO-12-500 Prescription Drug Performance Goals

Trends in average FDA review time for the subset of NDAs and BLAs that 

were for innovative drugs were similar to trends for all priority or standard 

NDAs and BLAs. For the subset of priority NDAs and BLAs that were for 

innovative drugs, average FDA review times were sometimes longer and 

sometimes shorter than those for all priority NDAs and BLAs; review 

times for the subset of standard NDAs and BLAs that were for innovative 

drugs were generally slightly longer than review times for all standard 

NDAs and BLAs.

We were unable to calculate the average time to final decision for original 

NDAs and BLAs—that is, the average time elapsed between submission 

of an application and the sponsor’s withdrawal of the application or FDA’s 

issuance of an approval or denial action letter in the last completed 

review cycle. Time to final decision includes FDA review time as well as 

time that elapsed between review cycles while FDA was waiting for the 

sponsor to resubmit the application. We were unable to complete this 

calculation because most cohorts were still open for these purposes 

(i.e., fewer than 90 percent of submissions had received a final action 

such as approval, denial, or withdrawal). Specifically, for priority NDAs 

and BLAs, only four cohorts (FYs 2001, 2002, 2005, and 2006) had at 

least 90 percent of submissions closed, and for standard NDAs and 

BLAs, only one cohort (FY 2002) had at least 90 percent of submissions 

closed. (See app. I, table 4 for details.) As a result, there were too few 

completed cohorts available to calculate the time to final decision in a 

meaningful way. FDA may opt to consider an application withdrawn (and 

thus closed) if the sponsor fails to resubmit the application within 1 year 

after FDA issues a complete response letter. When we examined the 

open applications using this criterion, we identified 194 open NDAs and 

BLAs in FYs 2000 through 2010 for which FDA had issued a complete 

response letter in the most recent review cycle but had not yet received a 

resubmission from the sponsor. FDA had issued the complete response 

letter more than 1 year earlier for 162 (84 percent) of these applications.

The percentage of priority NDAs and BLAs receiving an approval letter at 

the end of the first review cycle exhibited a sharp 1-year decline from 

FY 2000 to FY 2001, then increased substantially from FY 2001 through 

FY 2007, before decreasing again from FY 2007 through FY 2010 (see 

fig. 3). The percentage of first-cycle approvals for standard NDAs and 

BLAs showed a similar 1-year decline from FY 2000 to FY 2001, then 

varied somewhat but generally increased from FY 2002 through FY 2010. 

Although review of the FY 2011 cohort was incomplete at the time we 

received FDA’s data, 93 percent of the priority NDAs and BLAs that had 

Percentage of FDA 

First-Cycle Approvals 

Generally Increased from 

FY 2000 through FY 2010 

but Decreased for Priority 

NDAs and BLAs Since 

FY 2007
 

Page 14 GAO-12-500 Prescription Drug Performance Goals

received a first-cycle action letter had been approved, as had 42 percent 

of the standard NDAs and BLAs.27

Figure 3: Percentage of Priority and Standard Original NDAs and BLAs Receiving 

FDA First-Cycle Approvals, FYs 2000 through 2010

Note: A review cohort includes all of the drug submissions relating to a particular performance goal 

that were submitted in a given fiscal year. Only original NDAs and BLAs that had received an action 

letter from FDA at the time we received FDA’s data were included in this analysis; the data include 

reviews by CBER and CDER through November 30, 2011. The review cycle for original submissions 

starts when FDA receives a submission and ends when FDA issues an action letter or the sponsor 

withdraws the submission. Priority and standard designations are associated with different lengths of 

time allotted (6 and 10 months, respectively) for FDA to complete its review of original drug 

submissions and issue an action letter.

 

27Approximately 32 percent of priority original NDAs and BLAs and 70 percent of standard 

original NDAs and BLAs received in FY 2011 were still under review at the time we 

received FDA’s data, which include reviews by CBER and CDER through November 30, 

2011. As a result, it was too soon to tell what the final results for this cohort would be. The 

percentage of first-cycle approvals for this cohort may increase or decrease as those 

reviews are completed.
 

Page 15 GAO-12-500 Prescription Drug Performance Goals

Trends for FYs 2000 through 2010 in the percentage of first-cycle 

approvals were similar for the subset of NDAs and BLAs that were for 

innovative drugs when compared to trends for all priority or standard 

NDAs and BLAs. For the subset of priority NDAs and BLAs for innovative 

drugs, the percentage of first-cycle approvals was generally higher than 

for all priority NDAs and BLAs. For standard submissions, the percentage 

of first-cycle approvals for innovative drugs was generally lower than for 

all standard NDAs and BLAs; for some cohorts (e.g., FYs 2000, 2004–

2006, and 2008) this difference was substantial.

FDA met most of its performance goals for priority and standard original 

efficacy supplements to approved NDAs and BLAs for the FYs 2000 

through 2010 cohorts. However, the average FDA review time generally 

increased during this period for both priority and standard efficacy 

supplements. The percentage of FDA first-cycle approvals fluctuated for 

priority efficacy supplements but generally increased for standard efficacy 

supplements for the FYs 2000 through 2010 cohorts.

FDA met most of its performance goals for efficacy supplements to 

approved NDAs and BLAs during our analysis period. Specifically, FDA 

met the performance goals for both priority and standard efficacy 

supplements for 10 of the 11 completed cohorts we examined (see fig. 4). 

Although the FY 2011 cohort was still incomplete at the time we received 

FDA’s data, based on efficacy supplements on which it had taken action, 

FDA was meeting the goal for both priority and standard efficacy 

supplements.28

 

28Approximately 50 percent of priority and 70 percent of standard efficacy supplements 

received in FY 2011 were still under review at the time we received FDA’s data, which 

include reviews by CBER and CDER through November 30, 2011. As a result, it was too 

soon to tell what the final results for this cohort would be. The percentage of priority and 

standard efficacy supplements reviewed within 6 and 10 months, respectively, may 

increase or decrease as those reviews are completed. 

FDA Met Most 

Performance Goals 

for Original Efficacy 

Supplements While 

FDA Review Time 

Increased Slightly

FDA Met Most 

Performance Goals for 

Original Efficacy 

Supplements in FYs 2000 

through 2010
 

Page 16 GAO-12-500 Prescription Drug Performance Goals

Figure 4: Percentage of Priority and Standard Original Efficacy Supplements FDA Reviewed within 6 Months and 10 Months, 

Respectively, FYs 2000 through 2010

Notes: A review cohort includes all of the efficacy supplement submissions relating to a particular 

performance goal that were submitted in a given fiscal year. Only original efficacy supplements that 

had received an action letter from FDA at the time we received FDA’s data were included in this 

analysis; the data include reviews by CBER and CDER through November 30, 2011. The review 

cycle for efficacy supplements starts when FDA receives a submission and ends when FDA issues an 

action letter or the sponsor withdraws the submission.

Priority and standard designations are associated with different lengths of time allotted (6 and 

10 months, respectively) for FDA to complete its review of original efficacy supplement submissions 

and issue an action letter. If FDA completed its review of a priority submission in 6 months or less, it 

met the priority goal time frame. If FDA completed its review of a standard submission in 10 months 

or less, it met the standard goal time frame. Our calculations include extensions of the goal time 

frame, where applicable. Goal time frames can be extended by 3 months if the sponsor submits a 

major amendment to the application within 3 months of the goal date. Prior to FY 2003, FDA did not 

extend the goal time frame for efficacy supplement submissions.

For FYs 2000 through 2001, FDA also had a goal to complete 90 percent of standard reviews within 

12 months.
 

Page 17 GAO-12-500 Prescription Drug Performance Goals

Average FDA review time generally increased during our analysis period 

for both priority and standard efficacy supplements. Specifically, average 

FDA review time for priority efficacy supplements increased from 

173 days in the FY 2000 cohort to a peak of 205 days in the FY 2009 

cohort and then fell in the FY 2010 cohort to 191 days (see fig. 5). For 

standard efficacy supplements, average FDA review time rose from 

285 days in the FY 2000 cohort to a peak of 316 days in the FY 2008 

cohort and then fell in the FY 2010 cohort to 308 days. Although the 

FY 2011 cohort was still incomplete at the time we received FDA’s data, 

average FDA review time for efficacy supplements on which FDA had 

taken action was 195 days for priority submissions and 284 days for 

standard submissions.29

 

29Approximately 50 percent of priority and 70 percent of standard efficacy supplements 

received in FY 2011 were still under review at the time we received FDA’s data, which 

include reviews by CBER and CDER through November 30, 2011. As a result, it was too 

soon to tell what the final results for this cohort would be. The average FDA review time 

for this cohort may increase or decrease as those reviews are completed.

Average FDA Review Time 

Generally Increased for 

Original Efficacy 

Supplements from 

FYs 2000 through 2010
 

Page 18 GAO-12-500 Prescription Drug Performance Goals

Figure 5: Average FDA Review Time (in Calendar Days) for Priority and Standard 

Original Efficacy Supplements, FYs 2000 through 2010

Note: A review cohort includes all of the efficacy supplement submissions relating to a particular 

performance goal that were submitted in a given fiscal year. Only original efficacy supplements that 

had received an action letter from FDA at the time we received FDA’s data were included in this 

analysis; the data include reviews by CBER and CDER through November 30, 2011. The review 

cycle for efficacy supplements starts when FDA receives a submission and ends when FDA issues an 

action letter or the sponsor withdraws the submission. Priority and standard designations are 

associated with different lengths of time allotted (6 and 10 months, respectively) for FDA to complete 

its review of original efficacy supplement submissions and issue an action letter.

As with NDA and BLA submissions, we were unable to calculate the 

average time to final decision for efficacy supplements in any meaningful 

way because there were too few completed cohorts. Specifically, for 

priority efficacy supplements, only four cohorts (FYs 2000, 2001, 2004, 

and 2007) had at least 90 percent of submissions closed, and for 

standard efficacy supplements, only one cohort (FY 2005) had at least 90 

percent of submissions closed. (See app. II, table 9 for details.) FDA may 

opt to consider an application withdrawn (and thus closed) if the sponsor 

fails to resubmit the application within 1 year after FDA issues a complete 

response letter. When we examined the open applications using this 

criterion, we identified 196 open efficacy supplements in FYs 2000 

through 2010 for which FDA had issued a complete response letter in the 

most recent review cycle but had not yet received a resubmission from 
 

Page 19 GAO-12-500 Prescription Drug Performance Goals

the sponsor. FDA had issued the complete response letter more than 

1 year earlier for 168 (86 percent) of these submissions.

The percentage of priority efficacy supplements receiving an approval 

decision at the end of the first review cycle fluctuated for FYs 2000 

through 2010, ranging between 47 percent and 80 percent during this 

time (see fig. 6). The results for standard efficacy supplements showed a 

steadier increase than for priority submissions. Specifically, the 

percentage of first-cycle approvals rose from 43 percent in the FY 2000 

cohort to 69 percent in the FY 2010 cohort. Although the FY 2011 cohort 

was still incomplete at the time we received FDA’s data, 63 percent of 

first-cycle action letters for standard submissions and 92 percent of 

first-cycle action letters for priority submissions issued by that time were 

approvals.30

 

30Approximately 50 percent of priority and 70 percent of standard efficacy supplements 

received in FY 2011 were still under review at the time we received FDA’s data, which 

include reviews by CBER and CDER through November 30, 2011. As a result, it was too 

soon to tell what the final results for this cohort would be. The percentage of first-cycle 

approvals for this cohort may increase or decrease as those reviews are completed.

Percentage of FDA 

First-Cycle Approvals 

Fluctuated for Priority 

Efficacy Supplements but 

Generally Increased for 

Standard Efficacy 

Supplements from 

FYs 2000 through 2010
 

Page 20 GAO-12-500 Prescription Drug Performance Goals

Figure 6: Percentage of Priority and Standard Original Efficacy Supplements 

Receiving FDA First-Cycle Approvals, FYs 2000 through 2010

Note: A review cohort includes all of the efficacy supplement submissions relating to a particular 

performance goal that were submitted in a given fiscal year. Only original efficacy supplements that 

had received an action letter from FDA at the time we received FDA’s data were included in this 

analysis; the data include reviews by CBER and CDER through November 30, 2011. The review 

cycle for efficacy supplements starts when FDA receives a submission and ends when FDA issues an 

action letter or the sponsor withdraws the submission. Priority and standard designations are 

associated with different lengths of time allotted (6 and 10 months, respectively) for FDA to complete 

its review of original efficacy supplement submissions and issue an action letter.

The industry groups and consumer advocacy groups we interviewed 

noted a number of issues related to FDA’s review of prescription drug 

applications. The most commonly mentioned issues raised by industry 

and consumer advocacy stakeholder groups were actions or 

requirements that stakeholders believe can increase review times and 

insufficient communication between FDA and stakeholders throughout the 

review process. Industry stakeholders also noted a lack of predictability 

and consistency in reviews. Consumer advocacy group stakeholders 

noted issues related to inadequate assurance of the safety and efficacy of 

approved drugs. FDA is taking steps that may address many of these 

issues. 

Stakeholders Noted 

Issues with the 

Prescription Drug 

Review Process and 

FDA Is Taking Steps 

That May Address 

Many of Those Issues
 

Page 21 GAO-12-500 Prescription Drug Performance Goals

Most of the seven stakeholder groups we interviewed told us that there 

are actions and requirements that can lengthen FDA’s review process. 

For example, four of the five consumer advocacy group stakeholders 

noted that FDA does not require sponsors to submit electronic 

applications; three of these stakeholders noted that requiring electronic 

applications could make the review process faster. Additionally, the two 

industry stakeholders told us that they believe FDA should approve more 

applications during the first review cycle. We found that an average of 

44 percent of all original NDAs and BLAs submitted in FYs 2000 through 

2010 were approved during the first review cycle, while 75 percent were 

ultimately approved.

In addition, the two industry stakeholders that we interviewed raised 

requirements that can make review times longer, but the consumer 

advocacy group stakeholders did not agree with these points. For 

example, both industry stakeholders noted that working out the 

implementation of REMS requirements introduced in FDAAA slowed 

FDA’s review process. One industry stakeholder stated that discussions 

about REMS often happened late in the review process, resulting in an 

increase in review times; another noted that REMS requirements have 

not been standardized, contributing to longer review times. In contrast, 

one consumer advocacy group stakeholder that we interviewed 

suggested that standardized REMS requirements or a “one size fits all” 

approach would not be meaningful as a risk management strategy. The 

industry and consumer advocacy group stakeholders also disagreed on 

another issue that can potentially lengthen the review process—FDA’s 

process for using outside scientific expertise for the review of

applications.31

 

31Both industry stakeholders stated that FDA’s ability to consult with advisory committees 

is inefficient in part due to the associated rules, including the conflict-of-interest provisions 

in FDAAA and transparency provisions in the Federal Advisory Committee Act. FDAAA 

placed a cap on the number of conflict-of-interest waivers that FDA can grant annually, 

and although one stakeholder did not think the number of waivers FDA grants each year 

approaches this cap, the stakeholder suggested that the very existence of a cap could 

discourage FDA from granting waivers. See 21 U.S.C. § 379d-1(c). The Federal Advisory 

Committee Act places a particular emphasis on open meetings, chartering, and public 

involvement. See 5 U.S.C. app. 2, §§ 9, 10.

The two industry stakeholders we interviewed stated that 

the rules surrounding consultation with an advisory committee—

particularly those related to conflicts of interest—can extend the time it 

takes FDA to complete the review process. In contrast, two of the 

consumer advocacy group stakeholders we interviewed specifically stated 

Stakeholders Noted 

Actions or Requirements 

That They Believe Can 

Increase Review Times
 

Page 22 GAO-12-500 Prescription Drug Performance Goals

that FDA should be concerned with issues of conflict of interest in 

advisory committees used during the drug review process.

FDA has taken or plans to take several steps that may address issues 

stakeholders noted can lengthen the review process, including issuing 

new guidance, commissioning and issuing assessments of the review 

process, training staff, and establishing programs aimed at helping 

sponsors. For example, according to the draft agreement with industry for 

the upcoming prescription drug user fee program reauthorization, FDA 

would issue guidance on the standards and format for submitting 

electronic applications and would begin tracking and reporting on the 

number of electronic applications received.32 In addition, according to the 

draft agreement, FDA would publish both an interim and a final 

assessment of the review process for innovative drugs and then hold 

public meetings for stakeholders to present their views on the success of 

the program, including its effect on the efficiency and effectiveness of 

first-cycle reviews. FDA would also provide training to staff on reviewing 

applications containing complex scientific issues, which may improve 

FDA’s ability to grant first-cycle approvals where appropriate. In addition, 

FDA would issue guidance on assessing the effectiveness of REMS for a 

particular drug and would hold public meetings to explore strategies to 

standardize REMS, where appropriate. However, we did not identify any 

examples of steps FDA has taken to address industry stakeholder issues 

with leveraging outside expertise during the drug review process in any of 

the recently released strategy, assessment, and guidance documents we 

reviewed.33

 

32In February 2012, FDA issued draft guidance on providing applications in electronic 

format. See U.S. Department of Health and Human Services, Food and Drug 

Administration, Draft Guidance for Industry on Providing Regulatory Submissions in 

Electronic Format—Standardized Study Data (Silver Spring, Md.: February 2012).

33We considered documents published in 2010 or later to be recently released. In a 

previous study, GAO found that while FDA faced barriers to recruiting advisory committee 

candidates without conflicts of interest, the agency may be able to mitigate these barriers 

by expanding its outreach efforts. See GAO, FDA Advisory Committees: Process for 

Recruiting Members and Evaluating Potential Conflicts of Interest, GAO-08-640

(Washington, D.C.: Sept. 30, 2008).
 

Page 23 GAO-12-500 Prescription Drug Performance Goals

Most of the two industry and five consumer advocacy group stakeholders 

that we interviewed told us that there is insufficient communication 

between FDA and stakeholders throughout the review process. For 

example, both of the industry stakeholders noted that FDA does not 

clearly communicate the regulatory standards that it uses to evaluate 

applications. In particular, the industry stakeholders noted that the 

regulatory guidance documents issued by FDA are often out of date or 

the necessary documents have not yet been developed. Additionally, both 

industry stakeholders and two consumer advocacy group stakeholders 

noted that after sponsors submit their applications, insufficient 

communication from FDA prevents sponsors from learning about 

deficiencies in their applications early in FDA’s review process. According 

to these four stakeholders, if FDA communicated these deficiencies 

earlier in the process, sponsors would have more time to address them; 

this would increase the likelihood of first-cycle approvals. Finally, three 

consumer advocacy group stakeholders also noted that FDA does not 

sufficiently seek patient input during reviews. One stakeholder noted that 

it is important for FDA to incorporate patient perspectives into its reviews 

of drugs because patients might weigh the benefits and risks of a certain 

drug differently than FDA reviewers.

FDA has taken or plans to take several steps that may address 

stakeholders’ issues with the frequency and quality of its communications 

with stakeholders, including conducting a review of its regulations, 

establishing new review programs and communication-related 

performance goals, providing additional staff training, and increasing its 

efforts to incorporate patient input into the review process. FDA is in the 

process of reviewing its regulations to identify burdensome, unclear, 

obsolete, ineffective, or inefficient regulations and is soliciting stakeholder 

input on additional rules that could be improved. In addition, according to 

the draft agreement with industry, FDA would establish a review model 

with enhanced communication requirements for innovative drugs, 

including requirements to hold pre- and late-cycle submission meetings 

with sponsors as well as to update sponsors following FDA’s internal 

Stakeholders Cite 

Insufficient 

Communication between 

FDA and Stakeholders 

throughout the Review 

Process
 

Page 24 GAO-12-500 Prescription Drug Performance Goals

midcycle review meetings.34 Additionally, under the draft user fee 

agreement, FDA would inform sponsors of the planned review timeline 

and any substantive review issues identified thus far within 74 days of 

receipt for 90 percent of original NDAs, BLAs, and efficacy supplements. 

FDA would also issue guidance, develop a dedicated drug development 

training staff, and provide training on communication for all CDER staff 

involved in the review of investigational new drugs.35 Finally, FDA would 

increase its utilization of patient representatives as consultants to provide 

patient views early in the product development process and to ensure 

those perspectives are considered in regulatory discussions. More 

specifically, FDA would expect to start with a selected set of disease 

areas and meet with the relevant patient advocacy groups and other 

interested stakeholders to determine how to incorporate patient 

perspectives into FDA’s decision making.

The two industry stakeholders that we interviewed also told us that there 

is a lack of predictability and consistency in FDA’s reviews of drug 

applications. For example, both stakeholders noted that there is 

sometimes inconsistent application of criteria across review divisions or 

offices. Further, both industry stakeholders we interviewed noted that 

FDA lacks a structured benefit-risk framework to refer to when making 

 

34At the presubmission meeting, FDA and the sponsor will agree on the content of a 

complete application, including preliminary discussions on the need for REMS; the 

agreement and discussion will be summarized at the end of the meeting and will be 

reflected in the FDA meeting minutes. Following the internal midcycle review meeting, 

FDA will call the sponsor with an update on the status of the review of its application; this 

update will include any significant issues identified to date; any information requests; 

information regarding safety concerns and preliminary thoughts regarding risk 

management; proposed dates for the late-cycle meeting; updates regarding plans for any 

potential advisory committee meetings; and other projected milestone dates for the 

remainder of the review cycle. At the late-cycle meeting, potential topics for discussion 

include major deficiencies identified to date; issues to be discussed at any planned 

advisory committee meetings; current assessment of the need for a REMS or other risk 

management actions; information requests from the review team to the sponsor; and 

additional data or analyses the sponsor may wish to submit.

35Investigational new drugs are drugs permitted by FDA to be tested in humans but that 

have not been approved for marketing.

Industry Stakeholders 

Report a Lack of 

Predictability and 

Consistency in Reviews
 

Page 25 GAO-12-500 Prescription Drug Performance Goals

decisions, which they believe would improve the predictability of the 

review process.36

FDA has taken or plans to take steps that may address stakeholders’ 

issues with the predictability and consistency of its reviews of drug 

applications. For example, FDA plans to provide training related to the 

development, review, and approval of drugs for rare diseases, which may 

help to improve the consistency of FDA’s review of those drugs. In 

addition, FDA has appointed a Deputy Commissioner for Medical 

Products to oversee and manage CBER, CDER, and the Center for 

Devices and Radiological Health (CDRH) in an attempt to improve 

integration and consistency between the centers. Furthermore, FDA has 

agreed to create a 5-year plan to develop and implement a structured 

benefit-risk framework in the review process. FDA will also revise its 

internal guidance to incorporate a structured benefit-risk framework and 

then train its review staff on these revisions.

Three of the five consumer advocacy group stakeholders that we spoke 

with raised issues about whether FDA is adequately ensuring the safety 

and efficacy of the drugs it approves for marketing. All three of these 

stakeholders told us that FDA should place greater priority on safety and 

efficacy over review speed. In addition, three stakeholders told us that 

FDA does not gather enough data on long-term drug safety and efficacy 

through methods such as postmarket surveillance. One stakeholder 

suggested that FDA should more effectively utilize its Sentinel System for 

 

36In mentioning a structured benefit-risk framework, industry stakeholders were referring 

to an established process for weighing the potential benefits of a new drug against the 

potential risks it poses.

Consumer Advocacy 

Group Stakeholders 

Suggest That FDA May 

Provide Inadequate 

Assurance of the Safety 

and Efficacy of Approved 

Drugs
 

Page 26 GAO-12-500 Prescription Drug Performance Goals

adverse event reporting.37 These concerns have also been extensively 

discussed elsewhere.38

FDA has taken or plans to take steps that may address stakeholders’ 

issues with the safety and efficacy of approved drugs, including 

publishing a regulatory science strategic plan. This document describes 

various plans FDA has for emphasizing safety and efficacy, such as 

developing assessment tools for novel therapies, assuring safe and 

effective medical innovation, and integrating complex data (including 

postmarket data) to allow for better analyses.39 FDA has also published a 

report identifying needs that, if addressed, would enhance scientific 

decision making in CDER.40 Some of the needs identified included 

improving access to postmarket data sources and exploring the feasibility 

of different postmarket analyses; improving risk assessment and 

management strategies to reinforce the safe use of drugs; and developing 

and improving predictive models of safety and efficacy in humans. Finally, 

in the draft agreement with industry, FDA has committed to conducting 

both an interim and a final assessment of the strengths, limitations, and 

appropriate use of the Sentinel System for helping FDA determine the 

regulatory actions necessary to manage safety issues.

FDA met most of the performance goals for the agency to review and 

issue action letters for original NDA and BLA submissions, Class 1 and 

Class 2 resubmissions, and original efficacy supplements for the 

 

37The Sentinel System is a national electronic system FDA has been developing that will 

draw on existing automated health care data from multiple sources—such as electronic 

health record systems, administrative and insurance claims databases, and registries—to 

monitor the safety of medical products continuously and in real time.

38See GAO, Drug Safety: FDA Has Begun Efforts to Enhance Postmarket Safety, but 

Additional Actions Are Needed, GAO-10-68 (Washington, D.C.: Nov. 9, 2009); and Drug 

Safety: Improvement Needed in FDA’s Postmarket Decision-making and Oversight 

Process, GAO-06-402 (Washington, D.C.: Mar. 31, 2006). Also see Institute of Medicine 

of the National Academies, The Future of Drug Safety: Promoting and Protecting the 

Health of the Public (Washington, D.C.: 2007).

39See U.S. Department of Health and Human Services, Food and Drug Administration, 

Advancing Regulatory Science at FDA (Silver Spring, Md.: August 2011).

40See U.S. Department of Health and Human Services, Food and Drug Administration, 

The CDER Science Prioritization and Review Committee (SPaRC): Identifying CDER’s 

Science and Research Needs Report (Silver Spring, Md.: July 2011).

Concluding 

Observations 
 

Page 27 GAO-12-500 Prescription Drug Performance Goals

FYs 2000 through 2010 cohorts. FDA review times increased slightly for 

original NDAs, BLAs, and efficacy supplements during this period while 

changes in the percentage of first-cycle approvals varied by application 

type. While FDA has met most of the performance goals we examined, 

stakeholders we spoke with point to a number of issues that the agency 

could consider to improve the drug review process; FDA is taking or has 

agreed to take steps that may address these issues, such as issuing new 

guidance, establishing new communication-related performance goals, 

training staff, and enhancing scientific decision making. It is important for 

the agency to continue monitoring these efforts in order to increase the 

efficiency and effectiveness of the review process and thereby help 

ensure that safe and effective drugs are reaching the market in a timely 

manner.

HHS reviewed a draft of this report and provided written comments, which 

are reprinted in appendix IV. HHS generally agreed with our findings and 

noted that they reflect what the agency reported for the same time period. 

HHS also called attention to activities FDA has undertaken to improve the 

prescription drug review process. It highlighted FDA’s performance in 

approving innovative drugs in FY 2011. HHS also noted steps FDA will 

take to contribute to medical product innovation including expediting the 

drug development pathway and streamlining and reforming FDA 

regulations. Finally, HHS discussed enhancements to the drug review 

program that were included in the proposed recommendations for the 

2012 reauthorization of the prescription drug user fee program, such as 

establishing a new review program for innovative drugs, enhancing 

benefit-risk assessment, and requiring electronic submissions and 

standardization of electronic application data to improve efficiency. HHS 

also provided technical comments, which we incorporated as appropriate.

As agreed with your office, unless you publicly announce the contents of 

this report earlier, we plan no further distribution until 30 days from the 

report date. At that time, we will send copies of this report to the 

Secretary of Health and Human Services, the Commissioner of the Food 

and Drug Administration, and other interested parties. In addition, the 

report will be available at no charge on the GAO website at 

http://www.gao.gov. 

Agency Comments
 

Page 28 GAO-12-500 Prescription Drug Performance Goals

If you or your staff have any questions about this report, please contact 

me at (202) 512-7114 or crossem@gao.gov. Contact points for our 

Offices of Congressional Relations and Public Affairs may be found on 

the last page of this report. GAO staff who made key contributions to this 

report are listed in appendix V.

Marcia Crosse

Director, Health Care
Appendix I: FDA NDA and BLA Review 

Performance for Fiscal Years (FYs) 2000 

through 2011

Page 29 GAO-12-500 Prescription Drug Performance Goals

Table 2: FDA Review Performance for Priority Original NDAs and BLAs Including Innovative Drugs, FYs 2000 through 2011

Fiscal year cohorts

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011

Total number of 

a

priority NDA All 

and BLA original submissions

34 14 15 23 27 32 34 28 36 25 20 22

I.D 20 b 12 11 17 20 21 16 16 18 17 11 14

Number of submissions that 

were pending (i.e., not complete 

for PDUFA purposes)

All 0 0 0 0 0 0 0 0 0 0 0 7 

I.D 0 0 0 0 0 0 0 0 0 0 0 4 

Number of submissions that 

were complete for PDUFA 

purposes

All 34 14 15 23 27 32 34 28 36 25 20 15

I.D 20 12 11 17 20 21 16 16 18 17 11 10

Number of completed 

submissions reviewed 

within 6-month goal

All 

c

32 13 15 23 27 31 32 26 28 23 20 14

I.D 19 12 11 17 20 20 15 16 14 15 11 9 

Percentage of completed 

submissions reviewed 

within 6-month goal

All 94 93 100 100 100 97 94 93 78 92 100 93 

I.D 95 100 100 100 100 95 94 100 78 88 100 90

PDUFA goal percentage All 90 90 90 90 90 90 90 90 90 90 90 90

I.D 90 90 90 90 90 90 90 90 90 90 90 90

Met PDUFA goal All Yes Yes Yes Yes Yes Yes Yes Yes No Yes Yes Yes

I.D Yes Yes Yes Yes Yes Yes Yes Yes No No Yes Yes

Average FDA review time 

(in days) for priority original 

submissions that were reviewed 

within goal

All 

d

187 193 184 185 183 188 175 193 197 206 207 172

I.D 188 195 186 186 185 197 177 191 201 206 210 171

Average FDA review time 

(in days) for priority original 

submissions that were not 

reviewed within goal

All 

d

283 303 — — — 254 286 261 405 335 — 382

I.D 237 — — — — 254 267 — 380 335 — 382

Percentage of first-cycle actions that were:e

Approved All 44 14 47 52 59 66 68 68 56 52 50 93

I.D 35 17 55 59 55 71 75 75 61 53 73 100

Complete response All f 56 71 47 43 33 31 29 29 42 48 50 0 

I.D 65 75 36 35 40 29 19 19 33 47 27 0 

Withdrawn All 0 14 7 4 7 3 3 4 3 0 0 7 

I.D 0 8 9 6 5 0 6 6 6 0 0 0 

Percentage of final actions that were:g

Approved All 97 86 93 94 91 93 94 96 97 100 100 93

I.D 94 92 91 92 93 95 87 94 94 100 100 100

Withdrawn All 3 14 7 6 9 7 6 4 3 0 0 7 

I.D 6 8 9 8 7 5 13 6 6 0 0 0 

Source: GAO analysis of FDA data.

Appendix I: FDA NDA and BLA Review 

Performance for Fiscal Years (FYs) 2000 

through 2011
Appendix I: FDA NDA and BLA Review 

Performance for Fiscal Years (FYs) 2000 

through 2011

Page 30 GAO-12-500 Prescription Drug Performance Goals

Note: Percentages are rounded to the nearest whole number and may not add to 100 due to 

rounding.

a

For the FY 2011 priority NDA/BLA original submission cohort, 7 out of 22 submissions (32 percent) 

were still under review at the time we received FDA’s data, which include reviews by CBER and 

CDER through November 30, 2011. Therefore, values indicated for FY 2011 in the table above may 

change as these reviews are completed.

b

“I.D.” stands for innovative drugs, a subset of all priority original NDAs and BLAs that includes nearly 

all BLAs and those NDAs designated as new molecular entities (NMEs).

c

Our calculations include extensions of the PDUFA goal time frame, where applicable. PDUFA goal 

time frames can be extended by 3 months if the sponsor submits a major amendment to the 

application within 3 months of the goal date. For priority NDA/BLA original submissions in FYs 2000 

through 2011, 62 out of 311 submissions (20 percent) received PDUFA goal extensions. The 

percentage was slightly higher for innovative drugs in these cohorts, with 24 percent receiving 

PDUFA goal extensions.

d

Average review time for the first review cycle for original submissions. Resubmissions are subject to 

different PDUFA goal time frames. Dashes (—) indicate cohorts for which no submissions met the 

criteria.

e

Includes only those submissions that had received a first-cycle FDA action letter at the time we 

received FDA’s data, which include reviews by CBER and CDER through November 30, 2011.

f

Prior to August 2008, FDA also issued “approvable” and “not approvable” letters, which served the 

same purpose as the complete response letters currently used. We grouped these three types of 

letters together in our analysis.

g

Includes only those submissions that had received a final FDA action letter (i.e., approval) in their 

last completed review cycle or were withdrawn by the sponsor at the time we received FDA’s data, 

which include reviews by CBER and CDER through November 30, 2011.
Appendix I: FDA NDA and BLA Review 

Performance for Fiscal Years (FYs) 2000 

through 2011

Page 31 GAO-12-500 Prescription Drug Performance Goals

Table 3: FDA Review Performance for Standard Original NDAs and BLAs Including Innovative Drugs, FYs 2000 through 2011

Fiscal year cohorts

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011

Total number of 

a

standard NDA All 

and BLA original submissions

97 87 90 89 101 76 89 91 105 123 84 79

I.D 24 b 34 21 25 23 22 26 34 32 36 18 24

Number of submissions that

were pending (i.e., not complete 

for PDUFA purposes)

All 0 0 0 0 0 0 0 0 0 0 0 55

I.D 0 0 0 0 0 0 0 0 0 0 0 19

Number of submissions that 

were complete for PDUFA 

purposes

All 97 87 90 89 101 76 89 91 105 123 84 24

I.D 24 34 21 25 23 22 26 34 32 36 18 5 

Number of completed 

submissions reviewed 

within 10-month goal

All 

c

81 81 89 88 99 75 87 82 92 118 83 23

I.D 18 30 20 24 23 21 26 30 26 35 18 5 

Percentage of completed 

submissions reviewed 

within 10-month goal

All 84 93 99 99 98 99 98 90 88 96 99 96

I.D 75 88 95 96 100 95 100 88 81 97 100 100

PDUFA goal percentage All d 50 70 90 90 90 90 90 90 90 90 90 90

I.D 50 70 90 90 90 90 90 90 90 90 90 90

Met PDUFA goal All Yes Yes Yes Yes Yes Yes Yes Yes No Yes Yes Yes

I.D Yes Yes Yes Yes Yes Yes Yes No No Yes Yes Yes

Average FDA review time 

(in days) for standard original 

submissions that were reviewed 

within goal

All 

e

297 312 310 300 307 322 320 310 307 309 314 306

I.D 297 321 308 306 319 327 332 320 308 306 314 303

Average FDA review time 

(in days) for standard original 

submissions that were not

reviewed within goal

All 

e

386 356 372 1124 354 445 364 599 453 522 405 350

I.D 411 355 372 1124 — 445 — 477 473 530 — — 

Percentage of first-cycle actions that were:f

Approved All 32 21 37 37 50 39 47 42 42 44 54 42

I.D 8 21 33 40 35 18 31 41 25 36 50 20

Complete response All g 59 71 62 58 47 59 49 54 51 53 44 58

I.D 83 74 67 52 57 82 62 59 66 58 44 80

Withdrawn All 9 8 1 4 4 1 3 4 7 3 2 0 

I.D 8 6 0 8 9 0 8 0 9 6 6 0 
Appendix I: FDA NDA and BLA Review 

Performance for Fiscal Years (FYs) 2000 

through 2011

Page 32 GAO-12-500 Prescription Drug Performance Goals

Fiscal year cohorts

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011

Percentage of 

a

final actions that were:h

Approved All 90 89 98 93 95 95 96 94 91 95 96 100

I.D 90 91 94 89 87 90 89 100 85 92 92 100

Withdrawn All 10 11 2 7 5 5 4 6 9 5 4 0 

I.D 10 9 6 11 13 10 11 0 15 8 8 0 

Source: GAO analysis of FDA data.

Note: Percentages are rounded to the nearest whole number and may not add to 100 due to 

rounding.

a

For the FY 2011 standard NDA/BLA original submission cohort, 55 out of 79 submissions 

(70 percent) were still under review at the time we received FDA’s data, which include reviews by 

CBER and CDER through November 30, 2011. As a result, it was too soon to tell what the final 

results for this cohort would be. Therefore, values indicated for FY 2011 in the table above may 

change as these reviews are completed.

b

“I.D.” stands for innovative drugs, a subset of all priority original NDAs and BLAs that includes nearly 

all BLAs and those NDAs designated as new molecular entities (NMEs).

c

Our calculations include extensions of the PDUFA goal time frame, where applicable. PDUFA goal 

time frames can be extended for 3 months if the sponsor submits a major amendment to the 

application within 3 months of the goal date. For standard NDA/BLA original submissions from 

FYs 2000 through 2011, 168 out of 1,110 submissions (15 percent) received PDUFA goal extensions. 

The percentage was higher for innovative drugs in these cohorts, with 22 percent receiving PDUFA 

goal extensions.

d

In FYs 2000 and 2001, standard original submissions were also subject to a 12-month goal time 

frame that is not shown in our analysis.

e

Average review time for the first review cycle for original submissions. Resubmissions are subject to 

different PDUFA goal time frames. Dashes (—) indicate cohorts for which no submissions met the 

criteria.

f

Includes only those submissions that had received a first-cycle FDA action letter at the time we 

received FDA’s data, which include reviews by CBER and CDER through November 30, 2011.

g

Prior to August 2008, FDA also issued “approvable” and “not approvable” letters, which served the 

same purpose as the complete response letters currently used. We grouped these three types of 

letters together in our analysis.

h

Includes only those submissions that had received a final FDA action letter (i.e., approval) in their 

last completed review cycle or were withdrawn by the sponsor at the time we received FDA’s data, 

which include reviews by CBER and CDER through November 30, 2011.
Appendix I: FDA NDA and BLA Review 

Performance for Fiscal Years (FYs) 2000 

through 2011

Page 33 GAO-12-500 Prescription Drug Performance Goals

Table 4: Percentages of Closed and Open NDAs and BLAs, FYs 2000 through 2011

Fiscal year cohorts

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011

Priority NDAs and BLAs

 Percentage of submissions that

 were closed 85 a 100 100 78 82 91 94 89 81 76 55 68

 Percentage of submissions that

 were still open 15 b 0 0 22 18 9 6 11 19 24 45 32

Percentage of submissions 

that were under FDA review 

(i.e., pending) 0 0 0 0 0 0 0 4 3 0 20 32

Percentage of submissions for 

which FDA had issued a complete 

response and the sponsor had not 

resubmitted the application 15 0 0 22 18 9 6 7 17 24 25 0 

Standard NDAs and BLAs

 Percentage of submissions that

 were closed 89 a 83 90 80 85 76 81 71 73 70 65 13

 Percentage of submissions that

 were still open 11 b 17 10 20 15 24 19 29 27 30 35 87

Percentage of submissions that 

were under FDA review 

(i.e., pending) 0 0 0 0 1 0 1 1 6 3 11 72

Percentage of submissions for 

which FDA had issued a complete 

response and the sponsor had not 

resubmitted the application 11 17 10 20 14 24 18 27 21 27 24 15

Source: GAO analysis of FDA data.

Note: Percentages are rounded to the nearest whole number.

a

We defined a submission as closed if it was approved or withdrawn in the last completed review 

cycle. Although denial is an action available to FDA officials to close the review of an application, no 

NDAs or BLAs were denied for FYs 2000 through 2011.

b

We defined a submission as open if the most recent review cycle was still underway (i.e., pending) or 

if FDA had issued a complete response letter in the most recent review cycle and the sponsor still 

had the option of resubmitting the application under the original user fee. Submissions that have 

received a complete response letter are considered complete for purposes of determining whether 

FDA met the PDUFA performance goals, but the review is not closed. Prior to August 2008, FDA also 

issued “approvable” and “not approvable” letters, which served the same purpose as the complete 

response letters currently used. We grouped these three types of letters together in our analysis.
Appendix I: FDA NDA and BLA Review 

Performance for Fiscal Years (FYs) 2000 

through 2011

Page 34 GAO-12-500 Prescription Drug Performance Goals

Table 5: FDA Review Performance for NDA and BLA Resubmissions Including Innovative Drugs, FYs 2000 through 2011

Fiscal year cohorts

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011

Total number of 

a

Class 1 NDA and 

BLA resubmissions

All b 3 19 22 22 18 19 20 21 18 16 12 10 

I.D 0 c 6 11 2 2 2 4 5 4 2 1 2 

Number of resubmissions that 

were pending (i.e., not complete 

for PDUFA purposes)

All 0 0 0 0 0 0 0 0 0 0 0 2 

I.D 0 0 0 0 0 0 0 0 0 0 0 0 

Number of resubmissions that 

were complete for PDUFA 

purposes

All 3 19 22 22 18 19 20 21 18 16 12 8 

I.D 0 6 11 2 2 2 4 5 4 2 1 2 

Number of completed 

resubmissions reviewed 

within 2-month goal

All 3 18 22 21 18 17 20 16 17 13 12 8 

I.D 0 6 11 2 2 2 4 5 4 2 1 2 

Percentage of completed 

resubmissions reviewed 

within 2-month goal

All 100 95 100 95 100 89 100 76 94 81 100 100

I.D — 100 100 100 100 100 100 100 100 100 100 100

PDUFA goal percentage All 70 90 d 90 90 90 90 90 90 90 90 90 90

I.D 70 90 90 90 90 90 90 90 90 90 90 90

Met PDUFA goal All Yes Yes Yes Yes Yes No Yes No Yes No Yes Yes

I.D Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes

Total number of Class 2 NDA 

and BLA resubmissions

All b 2 24 35 44 58 32 38 46 34 52 41 53

I.D 1 14 16 23 22 11 8 22 14 21 11 17

Number of resubmissions that 

were pending (i.e., not complete 

for PDUFA purposes)

All 0 0 0 0 0 0 0 0 0 0 0 21

I.D 0 0 0 0 0 0 0 0 0 0 0 5 

Number of resubmissions that 

were complete for PDUFA 

purposes

All 2 24 35 44 58 32 38 46 34 52 41 32

I.D 1 14 16 23 22 11 8 22 14 21 11 12

Number of completed 

resubmissions reviewed

6-month goal

All 

e

2 24 35 44 57 30 36 43 29 48 39 32

I.D 1 14 16 23 22 10 8 20 11 20 10 12

Percentage of completed 

resubmissions reviewed

6-month goal

All 100 100 100 100 98 97 95 93 85 92 95 100

I.D 100 100 100 100 100 91 100 91 79 95 91 100

PDUFA goal percentage All 90 90 90 90 90 90 90 90 90 90 90 90

I.D 90 90 90 90 90 90 90 90 90 90 90 90

Met PDUFA goal All Yes Yes Yes Yes Yes Yes Yes Yes No Yes Yes Yes

I.D Yes Yes Yes Yes Yes Yes Yes Yes No Yes Yes Yes

Source: GAO analysis of FDA data.

Note: Percentages are rounded to the nearest whole number.
Appendix I: FDA NDA and BLA Review 

Performance for Fiscal Years (FYs) 2000 

through 2011

Page 35 GAO-12-500 Prescription Drug Performance Goals

a

The FY 2011 cohort was not complete at the time we received FDA’s data, which include reviews by 

CBER and CDER through November 30, 2011. Therefore, values indicated for FY 2011 in the table 

above may change as these reviews are completed.

b

Our analysis was limited to resubmissions made in FYs 2000 through 2011 for original NDAs and 

BLAs that were also submitted in FYs 2000 through 2011. Resubmissions made in FYs 2000 through 

2011 for original NDAs and BLAs submitted prior to FY 2000 were not captured by our analysis.

c

“I.D.” stands for innovative drugs, a subset of all priority original NDAs and BLAs that includes nearly 

all BLAs and those NDAs designated as new molecular entities (NMEs).

d

In FY 2000, Class 1 resubmissions were also subject to a 4-month goal time frame which is not 

shown in our analysis.

e

Our calculations include extensions of the PDUFA goal time frame, where applicable. PDUFA goal 

time frames for Class 2 resubmissions can be extended for 3 months if the sponsor submits a major 

amendment to the resubmission within 3 months of the goal date. For Class 2 NDA/BLA 

resubmissions in these cohorts, 45 out of 463 submissions (9.7 percent) received goal extensions.

Table 6: FDA Review Performance for Oncology Drugs Including Those Granted Accelerated Approval, FYs 2000 through 

2011

Fiscal year cohorts

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011

Total number of NDA and BLA 

original submissions for 

oncology drugs

a

All 7 7 6 3 13 10 8 11 8 12 11 15

A.A. 1 b 2 2 2 1 3 2 0 1 2 0 1 

Number of first-cycle approvals All c 3 4 3 3 8 7 4 6 5 5 6 6 

A.A. 1 1 2 2 1 3 2 — 1 2 — 1 

Number of final approvals All d 5 5 4 3 8 8 5 7 7 5 9 6 

A.A. 1 2 2 2 1 3 2 — 1 2 — 1 

Source: GAO analysis of FDA data.

a

For the FY 2011 cohort, 55 out of 79 standard NDA and BLA submissions (70 percent) and 7 out of 

22 priority submissions (32 percent) were still under review at the time we received FDA’s data, which 

include reviews by CBER and CDER through November 30, 2011. Therefore, values indicated for 

FY 2011 in the table above may change as these reviews are completed.

b

“A.A.” designates the subset of oncology drug submissions granted accelerated approval status.

c

Includes only those submissions that had received a first-cycle FDA approval letter at the time we 

received FDA’s data, which include reviews by CBER and CDER through November 30, 2011. 

Includes tentative approvals (one each in FYs 2005, 2007, and 2009). Dashes (—) indicate cohorts 

for which no submissions met the criteria.

d

Includes only those submissions that had received an approval letter in their last completed review 

cycle at the time we received FDA’s data, which include reviews by CBER and CDER through 

November 30, 2011. Dashes (—) indicate cohorts for which no submissions met the criteria.
Appendix II: FDA Efficacy Supplement Review 

Performance for Fiscal Years (FYs) 2000 

through 2011

Page 36 GAO-12-500 Prescription Drug Performance Goals

Table 7: FDA Review Performance for Priority Efficacy Supplements, FYs 2000 through 2011

Fiscal year cohorts

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011

Total number of 

a

priority

21

efficacy 

supplements 10 38 37 50 42 45 45 38 42 19 26

 Number of submissions that were

 pending (i.e., not complete for

 PDUFA purposes) 0 0 0 0 0 0 0 0 0 0 0 13

 Number of submissions that were

 complete for PDUFA purposes 21 10 38 37 50 42 45 45 38 42 19 13

Number of completed 

submissions reviewed within 

6-month goal 21 b 9 36 37 47 41 44 41 35 36 19 13

Percentage of completed 

submissions reviewed within 

6-month goal 100 90 95 100 94 98 98 91 92 86 100 100

 PDUFA goal percentage 90 90 90 90 90 90 90 90 90 90 90 90

Met PDUFA goal Yes Yes Yes Yes Yes Yes Yes Yes Yes No Yes Yes

Average FDA review time (in days) for 

priority efficacy supplements that 

were reviewed within goal 173 c 182 169 182 171 176 182 180 189 182 191 195

Average FDA review time (in days) for 

priority efficacy supplements that 

were not reviewed within goal ─ c 347 303 ─ 356 289 393 309 249 341 ─ ─

Percentage of first-cycle actions that were:d

Approved 76 60 47 70 72 64 80 58 63 62 63 92

Complete response 14 e 30 42 30 24 33 20 42 34 33 37 8 

Withdrawn 10 10 11 0 4 2 0 0 3 5 0 0 

Percentage of final actions that were:f

Approved 89 86 82 100 95 96 100 100 96 90 100 100

Withdrawn 11 14 18 0 5 4 0 0 4 10 0 0 

Source: GAO analysis of FDA data.

Note: Percentages are rounded to the nearest whole number and may not add to 100 due to 

rounding.

a

For the FY 2011 priority efficacy supplement cohort, 13 out of 26 submissions (50 percent) were still 

under review at the time we received FDA’s data, which include reviews by CBER and CDER through 

November 30, 2011. As a result, it was too soon to tell what the final results for this cohort would be. 

Therefore, values indicated for FY 2011 in the table above may change as these reviews are 

completed.

b

Appendix II: FDA Efficacy Supplement 

Review Performance for Fiscal Years (FYs) 

2000 through 2011

Our calculations include extensions of the PDUFA goal time frame, where applicable. PDUFA goal 

time frames can be extended for 3 months if the sponsor submits a major amendment to the 

application within 3 months of the goal date. For priority efficacy supplements in FYs 2000 through 

2011, 24 out of 400 submissions (6 percent) received PDUFA goal extensions.
Appendix II: FDA Efficacy Supplement Review 

Performance for Fiscal Years (FYs) 2000 

through 2011

Page 37 GAO-12-500 Prescription Drug Performance Goals

c

Average review time for the first review cycle for original submissions. Resubmissions are subject to 

different PDUFA goal time frames. Dashes (—) indicate cohorts for which no submissions met the 

criteria.

d

Includes only those submissions that had received a first-cycle FDA action letter at the time we 

received FDA’s data, which include reviews by CBER and CDER through November 30, 2011.

e

Prior to August 2008, FDA also issued “approvable” and “not approvable” letters, which served the 

same purpose as the complete response letters currently used. We grouped these three types of 

letters together in our analysis.

f

Includes only those submissions that had received a final FDA approval letter in their last completed 

review cycle or were withdrawn by the sponsor at the time we received FDA’s data, which include 

reviews by CBER and CDER through November 30, 2011.
Appendix II: FDA Efficacy Supplement Review 

Performance for Fiscal Years (FYs) 2000 

through 2011

Page 38 GAO-12-500 Prescription Drug Performance Goals

Table 8: FDA Review Performance for Standard Efficacy Supplements, FYs 2000 through 2011 

Fiscal year cohorts

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 a 2010 a 2011 a

Total number of 

a

standard

167

efficacy 

supplements 164 131 113 156 116 149 147 112 117 128 107

 Number of submissions that were

 pending (i.e., not complete for

 PDUFA purposes) 0 0 0 0 0 0 0 0 1 2 1 75

 Number of submissions that were

 complete for PDUFA purposes 167 164 131 113 156 116 149 147 111 115 127 32

Number of completed 

submissions reviewed within 

10-month goal 152 b 150 126 110 151 114 147 133 99 111 125 32

Percentage of completed 

submissions reviewed within 

10-month goal 91 c 91 96 97 97 98 99 90 89 97 98 100

 PDUFA goal percentage 50 d 70 90 90 90 90 90 90 90 90 90 90

Met PDUFA goal Yes Yes Yes Yes Yes Yes Yes Yes No Yes Yes Yes

Average FDA review time 

(in days) for standard efficacy 

supplements that were reviewed 

within goal 278 e 278 282 283 287 283 292 290 297 297 306 284

Average FDA review time 

(in days) for standard efficacy 

supplements that were not

reviewed within goal 370 e 395 394 426 463 397 994 499 470 499 399 ─

Percentage of first-cycle actions that were:f

Approved 43 50 53 55 55 72 67 71 70 63 69 63

Complete response 51 g 41 44 45 41 25 28 28 27 35 27 25

Withdrawn 6 9 3 0 4 3 5 1 3 2 5 13

Percentage of final actions that were:h

Approved 87 87 93 100 93 94 93 96 96 96 94 83

Withdrawn 13 13 7 0 7 6 7 4 4 4 6 17

Source: GAO analysis of FDA data.

Note: Percentages are rounded to the nearest whole number and may not add to 100 due to 

rounding.

a

For the FYs 2008 through 2011 standard efficacy supplement cohorts, certain submissions were still 

under review at the time we received FDA’s data, which include reviews by CBER and CDER through 

November 30, 2011. For FY 2008, 1 out of 112 submissions (less than 1 percent) was still under 

review. For FY 2009, 2 out of 117 submissions (approximately 2 percent) were still under review. For 

FY 2010, 1 out of 128 submissions (less than 1 percent) was still under review. For FY 2011, 75 out 

of 107 submissions (70 percent) were still under review. As a result, it was too soon to tell what the 

final results for this cohort would be. Therefore, values indicated for these cohorts in the table above 

may change as these reviews are completed.
Appendix II: FDA Efficacy Supplement Review 

Performance for Fiscal Years (FYs) 2000 

through 2011

Page 39 GAO-12-500 Prescription Drug Performance Goals

b

Our calculations include extensions of the PDUFA goal time frame, where applicable. PDUFA goal 

time frames can be extended for 3 months if the sponsor submits a major amendment to the 

application within 3 months of the goal date. For standard efficacy supplements in FYs 2000 through 

2011, 90 out of 1,528 submissions (6 percent) received PDUFA goal extensions.

c

FYs 2008 through 2011 calculations exclude submissions for which FDA had not yet issued an 

action letter.

d

In FYs 2000 and 2001, standard efficacy supplement submissions were also subject to a 12-month 

goal time frame that is not shown in our analysis.

e

Average review time for the first review cycle for original submissions. Resubmissions are subject to 

different PDUFA goal time frames.

f

Includes only those submissions that had received a first-cycle FDA action letter at the time we 

received FDA’s data, which include reviews by CBER and CDER through November 30, 2011.

g

Prior to August 2008, FDA also issued “approvable” and “not approvable” letters, which served the 

same purpose as the complete response letters currently used. We grouped these three types of 

letters together in our analysis.

h

Includes only those submissions that had received a final FDA approval letter in their last completed 

review cycle or were withdrawn by the sponsor at the time we received FDA’s data, which include 

reviews by CBER and CDER through November 30, 2011.
Appendix II: FDA Efficacy Supplement Review 

Performance for Fiscal Years (FYs) 2000 

through 2011

Page 40 GAO-12-500 Prescription Drug Performance Goals

Table 9: Percentages of Closed and Open Efficacy Supplements, FYs 2000 through 2011

Fiscal year cohorts

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011

Priority efficacy supplements

 Percentage of submissions that were

 closed 100 a 100 84 89 92 83 89 93 76 76 74 46

 Percentage of submissions that were

 still open 0 b 0 16 11 8 17 11 7 24 24 26 54

Percentage of submissions that were 

under FDA review (i.e., pending) 0 0 0 0 0 0 0 0 0 0 0 50

Percentage of submissions for which 

FDA had issued a complete 

response and the sponsor had not 

resubmitted the application 0 0 16 11 8 17 11 7 24 24 26 4 

Standard efficacy supplements

 Percentage of submissions that were 

 closed 83 a 89 84 86 75 91 82 88 83 80 82 22

 Percentage of submissions that were

 still open 17 b 11 16 14 25 9 18 12 17 20 18 78

Percentage of submissions that were 

under FDA review (i.e., pending) 0 0 0 0 0 0 0 0 1 2 1 70

Percentage of submissions for which 

FDA had issued a complete 

response and the sponsor had not 

resubmitted the application 17 11 16 14 25 9 18 12 16 18 17 7 

Source: GAO analysis of FDA data.

Note: Percentages may not add to totals due to rounding.

a

We defined a submission as closed if it was approved or withdrawn in the last completed review 

cycle. Although denial is an action available to FDA officials to close the review of a submission, no 

efficacy supplements were denied in FYs 2000 through 2011.

b

We defined a submission as open if the most recent review cycle was still underway (i.e., pending) or 

if FDA issued a complete response letter in the most recent review cycle (i.e., the sponsor still had 

the option of resubmitting the application under the original user fee). Submissions that have received 

a complete response letter are considered complete for purposes of determining whether FDA met 

the PDUFA performance goals, but the review is not closed. Prior to August 2008, FDA also issued 

“approvable” and “not approvable” letters, which served the same purpose as the complete response 

letters currently used. We grouped these three types of letters together in our analysis.
Appendix III: Full-time Equivalent (FTE) FDA 

Staff Supporting Prescription Drug User Fee 

Activities, FYs 2000 through 2010

Page 41 GAO-12-500 Prescription Drug Performance Goals

Number of FTEs in each fiscal year

FDA centers and offices 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

Center for Drug Evaluation and Research (CDER)

 Office of the Center Director (OCD) 44 38 20 19 13 17 19 22 29 38 49

 Office of Regulatory Policy (ORP) N/A a 4 23 26 37 33 45 46 47 49 53

 Office of Executive Programs (OEP) N/A a,b 3 39 55 58 58 54 53 57 63 70

 Office of Management (OM) 65 66 64 57 46 41 43 45 50 62 75

 Office of Communications (OCOMM) 83 b 87 71 68 72 76 81 53 57 66 72

 Office of Compliance (OC) 27 b 24 30 31 62 39 47 83 101 173 202

 Office of Information Technology (OIT/OIM) 99 c 104 95 87 86 78 88 40 38 40 44

 Office of Translational Sciences (OTS) N/A d N/A N/A N/A N/A N/A N/A 147 210 286 323

 Office of New Drugs (OND) 705 e 676 541 593 697 700 725 732 740 858 892

 Office of Planning and Informatics (OPI) N/A c N/A N/A N/A N/A N/A N/A 40 48 66 78

 Office of Counter-Terrorism and Emergency 

 Coordination (OCTEC) N/A e N/A 13 33 43 35 39 23 23 24 12

 Office of Surveillance & Epidemiology

 (OSE) N/A d,e N/A 98 99 118 115 136 113 92 134 167

 Office of Medical Policy (OMP) 53 b 52 54 58 62 47 61 43 46 56 64

 Office of Pharmaceutical Science (OPS) 332 d 320 302 303 379 394 398 299 308 358 376

CDER Total 1,408 1,374 1,350 1,429 1,673 1,633 1,736 1,739 1,846 2,273 2,477

Center for Biologics Evaluation and Research (CBER)

f

 Center Director’s Office, Office of

 Management (OM), Office of Information

 Management (OIM) & Office of

 Communication, Outreach and Development

 (OCOD) 114 123 124 131 108 106 108 116 128 140 166

 Office of Blood Research & Review 38 46 48 53 50 55 50 56 57 67 69

 Office of Cellular, Tissue & Gene Therapies 0 0 0 54 69 66 69 75 78 82 92

 Office of Vaccines Research & Review 134 136 161 194 201 193 200 217 224 229 238

 Office of Therapeutics Research & Review 157 169 189 141 0 0 0 0 0 0 0 

 Office of Biostatistics & Epidemiology 15 17 22 22 14 16 18 24 30 40 45

 Office of Compliance & Biologics Quality 42 42 42 49 36 33 33 34 37 45 44

CBER Total 500 533 586 644 478 469 478 522 554 603 654

Appendix III: Full-time Equivalent (FTE) 

FDA Staff Supporting Prescription Drug User 

Fee Activities, FYs 2000 through 2010
Appendix III: Full-time Equivalent (FTE) FDA 

Staff Supporting Prescription Drug User Fee 

Activities, FYs 2000 through 2010

Page 42 GAO-12-500 Prescription Drug Performance Goals

Number of FTEs in each fiscal year

FDA centers and offices 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

Office of Regulatory Affairs (ORA)

ORA Total 180 180 153 147 147 145 142 144 146 194 174

Office of the Commissioner (OC)

OC Total 257 253 248 212 206 203 218 168 211 283 282

Shared Service (SS)b,g

SS Total N/A N/A N/A N/A 104 90 117 165 168 173 173

All Centers and Offices Total 2,345 2,340 2,337 2,432 2,608 2,540 2,691 2,738 2,925 3,526 3,760

Source: GAO analysis of FDA data.

Note: One FTE represents 40 hours of work per week conducted by a federal government employee 

over the course of 1 year. FTEs do not include contractors and therefore provide a partial measure of 

staffing resources.

a

ORP and OEP were created in FY 2001.

b

In FY 2007, Medical Library staff were transferred from OCOMM to SS, Division of Training staff 

were transferred from OCOMM to OEP, and the Division of Scientific Investigations was transferred 

from OMP to OC.

c

OPI was created in FY 2007 through transfers from OIT; other OIT staff were realigned to OIM.

d

OTS was created in FY 2007 through transfers from OSE and OPS.

e

OCTEC and OSE were created in FY 2002 through transfers from OND.

f

CDER total in FY 2010 includes Commissioner’s Fellows.

g

SS FTEs were not separated from the center FTEs until FY 2004.
Appendix IV: Comments from the Department 

of Health and Human Services

Page 43 GAO-12-500 Prescription Drug Performance Goals

Appendix IV: Comments from the 

Department of Health and Human Services
Appendix IV: Comments from the Department 

of Health and Human Services

Page 44 GAO-12-500 Prescription Drug Performance Goals
Appendix IV: Comments from the Department 

of Health and Human Services

Page 45 GAO-12-500 Prescription Drug Performance Goals
Appendix V: GAO Contact and Staff 

Acknowledgments

Page 46 GAO-12-500 Prescription Drug Performance Goals

Marcia Crosse, (202) 512-7114 or crossem@gao.gov

In addition to the contact named above, Robert Copeland, Assistant 

Director; Carolyn Fitzgerald; Cathleen Hamann; Karen Howard; Hannah 

Marston Minter; Lisa Motley; Aubrey Naffis; and Rachel Schulman made 

key contributions to this report.

Appendix V: GAO Contact and Staff 

Acknowledgments 

GAO Contact

Staff 

Acknowledgments 

(291008)
The Government Accountability Office, the audit, evaluation, and 

investigative arm of Congress, exists to support Congress in meeting its 

constitutional responsibilities and to help improve the performance and 

accountability of the federal government for the American people. GAO 

examines the use of public funds; evaluates federal programs and 

policies; and provides analyses, recommendations, and other assistance 

to help Congress make informed oversight, policy, and funding decisions. 

GAO’s commitment to good government is reflected in its core values of 

accountability, integrity, and reliability.

The fastest and easiest way to obtain copies of GAO documents at no 

cost is through GAO’s website (www.gao.gov). Each weekday afternoon, 

GAO posts on its website newly released reports, testimony, and 

correspondence. To have GAO e-mail you a list of newly posted products, 

go to www.gao.gov and select “E-mail Updates.”

The price of each GAO publication reflects GAO’s actual cost of 

production and distribution and depends on the number of pages in the 

publication and whether the publication is printed in color or black and 

white. Pricing and ordering information is posted on GAO’s website, 

http://www.gao.gov/ordering.htm. 

Place orders by calling (202) 512-6000, toll free (866) 801-7077, or 

TDD (202) 512-2537. 

Orders may be paid for using American Express, Discover Card, 

MasterCard, Visa, check, or money order. Call for additional information.

Connect with GAO on Facebook, Flickr, Twitter, and YouTube. 

Subscribe to our RSS Feeds or E-mail Updates. Listen to our Podcasts. 

Visit GAO on the web at www.gao.gov. 

Contact:

Website: www.gao.gov/fraudnet/fraudnet.htm

E-mail: fraudnet@gao.gov

Automated answering system: (800) 424-5454 or (202) 512-7470

Katherine Siggerud, Managing Director, siggerudk@gao.gov, (202) 512-

4400, U.S. Government Accountability Office, 441 G Street NW, Room 

7125, Washington, DC 20548

Chuck Young, Managing Director, youngc1@gao.gov, (202) 512-4800

U.S. Government Accountability Office, 441 G Street NW, Room 7149 

Washington, DC 20548

GAO’s Mission

Obtaining Copies of 

GAO Reports and 

Testimony 

Order by Phone

Connect with GAO

To Report Fraud, 

Waste, and Abuse in 

Federal Programs

Congressional 

Relations 

Public Affairs

Please Print on Recycled Paper.