This is the accessible text file for GAO report number GAO-12-500 
entitled 'Prescription Drugs: FDA Has Met Most Performance Goals for 
Reviewing Applications' which was released on April 30, 2012. 

This text file was formatted by the U.S. Government Accountability 
Office (GAO) to be accessible to users with visual impairments, as 
part of a longer term project to improve GAO products' accessibility. 
Every attempt has been made to maintain the structural and data 
integrity of the original printed product. Accessibility features, 
such as text descriptions of tables, consecutively numbered footnotes 
placed at the end of the file, and the text of agency comment letters, 
are provided but may not exactly duplicate the presentation or format 
of the printed version. The portable document format (PDF) file is an 
exact electronic replica of the printed version. We welcome your 
feedback. Please E-mail your comments regarding the contents or 
accessibility features of this document to Webmaster@gao.gov. 

This is a work of the U.S. government and is not subject to copyright 
protection in the United States. It may be reproduced and distributed 
in its entirety without further permission from GAO. 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. 

United States Government Accountability Office: 
GAO: 

Report to Congressional Requesters: 

March 2012: 

Prescription Drugs: 

FDA Has Met Most Performance Goals for Reviewing Applications: 

GAO-12-500: 

GAO Highlights: 

Highlights of GAO-12-500, a report to congressional requesters. 

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 communication-
related 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 [hyperlink, http://www.gao.gov/products/GAO-12-500]. For more 
information, contact Marcia Crosse at (202) 512-7114 or 
crossem@gao.gov. 

[End of section] 

Contents: 

Letter: 

Background: 

FDA Met Most Performance Goals for Original NDAs and BLAs While FDA 
Review Time Increased Slightly: 

FDA Met Most Performance Goals for Original Efficacy Supplements While 
FDA Review Time Increased Slightly: 

Stakeholders Noted Issues with the Prescription Drug Review Process 
and FDA Is Taking Steps That May Address Many of Those Issues: 

Concluding Observations: 

Agency Comments: 

Appendix I: FDA NDA and BLA Review Performance for Fiscal Years (FYs) 
2000 through 2011: 

Appendix II: FDA Efficacy Supplement Review Performance for Fiscal 
Years (FYs) 2000 through 2011: 

Appendix III: Full-time Equivalent (FTE) FDA Staff Supporting 
Prescription Drug User Fee Activities, FYs 2000 through 2010: 

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

Appendix V: GAO Contact and Staff Acknowledgments: 

Tables: 

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

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

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

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

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

Table 6: FDA Review Performance for Oncology Drugs Including Those 
Granted Accelerated Approval, FYs 2000 through 2011: 

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

Table 8: FDA Review Performance for Standard Efficacy Supplements, FYs 
2000 through 2011: 

Table 9: Percentages of Closed and Open Efficacy Supplements, FYs 2000 
through 2011: 

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: 

Figure 2: Average FDA Review Time (in Calendar Days) for Priority and 
Standard Original NDAs and BLAs, FYs 2000 through 2010: 

Figure 3: Percentage of Priority and Standard Original NDAs and BLAs 
Receiving FDA First-Cycle Approvals, FYs 2000 through 2010: 

Figure 4: Percentage of Priority and Standard Original Efficacy 
Supplements FDA Reviewed within 6 Months and 10 Months, Respectively, 
FYs 2000 through 2010: 

Figure 5: Average FDA Review Time (in Calendar Days) for Priority and 
Standard Original Efficacy Supplements, FYs 2000 through 2010: 

Figure 6: Percentage of Priority and Standard Original Efficacy 
Supplements Receiving FDA First-Cycle Approvals, FYs 2000 through 2010: 

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: 

[End of section] 

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. 
[Footnote 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.[Footnote 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.[Footnote 3] 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 fees 
collected by FDA—-including application, establishment, and product 
fees—-totaled more than $529 million, including over $172 million in 
application fees.[Footnote 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.[Footnote 5] 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. 

Under each authorization of the prescription drug user fee program, 
FDA committed to performance goals related to the review of drug 
applications.[Footnote 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.[Footnote 7] These 
performance goals, as well as user fee amounts, 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.[Footnote 8] 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 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.[Footnote 9] 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. 

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.[Footnote 10] 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. 

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. 

Background: 

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).[Footnote 11] Prior to submission of an 
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.[Footnote 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.[Footnote 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. 
[Footnote 14] 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. 

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.[Footnote 
15] FDA communicates with sponsors--through telephone conversations, 
letters, or meetings--issues that arise during its review of an 
application that may prevent FDA from approving the application. 
[Footnote 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.[Footnote 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.[Footnote 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.[Footnote 19] 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 being approved). 
[Footnote 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.[Footnote 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.[Footnote 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 resubmissions by 3 months if it receives a major amendment to 
the application from the sponsor within 3 months of the goal date. 
[Footnote 23] 

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

Fiscal year cohorts: Priority NDA, BLA, or efficacy supplement, 
percentage within 6 months; 
Percentage of reviews to be completed within the PDUFA goal time frame: 
2000: 90%; 
2001: 90%; 
2002: 90%; 
2003: 90%; 
2004: 90%; 
2005: 90%; 
2006: 90%; 
2007: 90%; 
2008: 90%; 
2009: 90%; 
2010: 90%; 
2011: 90%. 

Fiscal year cohorts: Standard NDA, BLA, or efficacy supplement, 
percentage within 10 months[A]; 
Percentage of reviews to be completed within the PDUFA goal time frame: 
2000: 50%; 
2001: 70%; 
2002: 90%; 
2003: 90%; 
2004: 90%; 
2005: 90%; 
2006: 90%; 
2007: 90%; 
2008: 90%; 
2009: 90%; 
2010: 90%; 
2011: 90%. 

Fiscal year cohorts: Class 1 NDA or BLA resubmission, percentage 
within 2 months[B]; 
Percentage of reviews to be completed within the PDUFA goal time frame: 
2000: 70%; 
2001: 90%; 
2002: 90%; 
2003: 90%; 
2004: 90%; 
2005: 90%; 
2006: 90%; 
2007: 90%; 
2008: 90%; 
2009: 90%; 
2010: 90%; 
2011: 90%. 

Fiscal year cohorts: Class 2 NDA or BLA resubmission, percentage 
within 6 months; 
Percentage of reviews to be completed within the PDUFA goal time frame: 
2000: 90%; 
2001: 90%; 
2002: 90%; 
2003: 90%; 
2004: 90%; 
2005: 90%; 
2006: 90%; 
2007: 90%; 
2008: 90%; 
2009: 90%; 
2010: 90%; 
2011: 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. 

[End of table] 

FDA Met Most Performance Goals for Original NDAs and BLAs While FDA 
Review Time Increased Slightly: 

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. 

FDA Met Most Performance Goals for Original NDAs and BLAs for FYs 2000 
through 2010: 

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 figure 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.[Footnote 24] 

Figure 1: Percentage of Priority and Standard Original NDAs and BLAs 
FDA Reviewed within 6 Months and 10 Months, Respectively, FYs 2000 
through 2010: 

[Refer to PDF for image: 2 vertical bar graphs] 

Priority submission (6-month goal): 

The horizontal line represents the performance goal to have 90 percent 
of priority NDAs and BLAs reviewed within 6 months for FYs 2000-2010. 

Fiscal year: 2000; 
Percentage: 94.1%. 

Fiscal year: 2001; 
Percentage: 92.9%. 

Fiscal year: 2002; 
Percentage: 100%. 

Fiscal year: 2003; 
Percentage: 100%. 

Fiscal year: 2004; 
Percentage: 100%. 

Fiscal year: 2005; 
Percentage: 96.9%. 

Fiscal year: 2006; 
Percentage: 94.1%. 

Fiscal year: 2007; 
Percentage: 92.9%. 

Fiscal year: 2008; 
Percentage: 77.8%. 

Fiscal year: 2009; 
Percentage: 92.0%. 

Fiscal year: 2010; 
Percentage: 100%. 

Standard submission (10-month goal): 

The horizontal lines represent the phasing in of the performance goal: 

* For FY 2000, the performance goal was to have 50 percent of standard 
NDAs and BLAs reviewed within 10 months. 
* For FY 2001, the performance goal was to have 70 percent of standard 
NDAs and BLAs reviewed within 10 months.
* For FYs 2002-2010, the performance goal was to have 90 percent of 
standard NDAs and BLAs reviewed within 10 months. 

Fiscal year: 2000; 
Percentage: 83.5%. 

Fiscal year: 2001; 
Percentage: 93.1%. 

Fiscal year: 2002; 
Percentage: 98.9%. 

Fiscal year: 2003; 
Percentage: 98.9%. 

Fiscal year: 2004; 
Percentage: 98.0%. 

Fiscal year: 2005; 
Percentage: 98.7%. 

Fiscal year: 2006; 
Percentage: 97.8%. 

Fiscal year: 2007; 
Percentage: 90.1%. 

Fiscal year: 2008; 
Percentage: 87.6%. 

Fiscal year: 2009; 
Percentage: 95.9%. 

Fiscal year: 2010; 
Percentage: 98.8%. 

Source: GAO analysis of FDA data. 

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. 

[End of figure] 

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.[Footnote 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. 

Average FDA Review Time Increased Slightly for Original NDAs and BLAs 
from FY 2000 through FY 2010: 

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 figure 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 taken action was 186 days for priority 
NDAs and BLAs and 308 days for standard NDAs and BLAs.[Footnote 26] 

Figure 2: Average FDA Review Time (in Calendar Days) for Priority and 
Standard Original NDAs and BLAs, FYs 2000 through 2010: 

[Refer to PDF for image: multiple line graph] 

Number of calendar days: 

Fiscal year: 2000; 
Priority: 193; 
Standard: 311. 

Fiscal year: 2001; 
Priority: 201; 
Standard: 315. 

Fiscal year: 2002; 
Priority: 184; 
Standard: 311. 

Fiscal year: 2003; 
Priority: 185; 
Standard: 310. 

Fiscal year: 2004; 
Priority: 183; 
Standard: 310. 

Fiscal year: 2005; 
Priority: 191; 
Standard: 324. 

Fiscal year: 2006; 
Priority: 181; 
Standard: 321. 

Fiscal year: 2007; 
Priority: 198; 
Standard: 338. 

Fiscal year: 2008; 
Priority: 243; 
Standard: 325. 

Fiscal year: 2009; 
Priority: 217; 
Standard: 318. 

Fiscal year: 2010; 
Priority: 207; 
Standard: 315. 

Source: GAO analysis of FDA data. 

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. 

[End of figure] 

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 appendix 
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. 

Percentage of FDA First-Cycle Approvals Generally Increased from FY 
2000 through FY 2010 but Decreased for Priority NDAs and BLAs Since FY 
2007: 

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 figure 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 received a first-cycle action letter had been approved, as had 42 
percent of the standard NDAs and BLAs.[Footnote 27] 

Figure 3: Percentage of Priority and Standard Original NDAs and BLAs 
Receiving FDA First-Cycle Approvals, FYs 2000 through 2010: 

[Refer to PDF for image: multiple line graph] 

Fiscal year: 2000; 
Priority: 44%; 
Standard: 32%. 

Fiscal year: 2001; 
Priority: 14%; 
Standard: 21%. 

Fiscal year: 2002; 
Priority: 47%; 
Standard: 37%. 

Fiscal year: 2003; 
Priority: 52%; 
Standard: 37%. 

Fiscal year: 2004; 
Priority: 59%; 
Standard: 50%. 

Fiscal year: 2005; 
Priority: 66%; 
Standard: 39%. 

Fiscal year: 2006; 
Priority: 68%; 
Standard: 47%. 

Fiscal year: 2007; 
Priority: 68%; 
Standard: 42%. 

Fiscal year: 2008; 
Priority: 56%; 
Standard: 42%. 

Fiscal year: 2009; 
Priority: 52%; 
Standard: 44%. 

Fiscal year: 2010; 
Priority: 50%; 
Standard: 54%. 

Source: GAO analysis of FDA data. 

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. 

[End of figure] 

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 Performance Goals for Original Efficacy Supplements While 
FDA Review Time Increased Slightly: 

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 Performance Goals for Original Efficacy Supplements in 
FYs 2000 through 2010: 

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 figure 
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.[Footnote 28] 

Figure 4: Percentage of Priority and Standard Original Efficacy 
Supplements FDA Reviewed within 6 Months and 10 Months, Respectively, 
FYs 2000 through 2010: 

[Refer to PDF for image: 2 vertical bar graphs] 

Priority submission (6-month goal): 

The horizontal line represents the performance goal to have 90 percent 
of priority efficacy supplements reviewed within 6 months for FYs 2000-
2010. 

Fiscal year: 2000; 
Percentage: 100%. 

Fiscal year: 2001; 
Percentage: 90.0%. 

Fiscal year: 2002; 
Percentage: 94.7%. 

Fiscal year: 2003; 
Percentage: 100%. 

Fiscal year: 2004; 
Percentage: 94.0%. 

Fiscal year: 2005; 
Percentage: 97.6%. 

Fiscal year: 2006; 
Percentage: 97.8%. 

Fiscal year: 2007; 
Percentage: 91.1%. 

Fiscal year: 2008; 
Percentage: 92.1%. 

Fiscal year: 2009; 
Percentage: 85.7%. 

Fiscal year: 2010; 
Percentage: 100%. 

Standard submission (10-month goal): 

The horizontal lines represent the phasing in of the performance goal: 

* For FY 2000, the performance goal was to have 50 percent of standard 
efficacy supplements reviewed within 10 months. 
* For FY 2001, the performance goal was to have 70 percent of standard 
efficacy supplements reviewed within 10 months.
* For FYs 2002-2010, the performance goal was to have 90 percent of 
standard efficacy supplements reviewed within 10 months. 

Fiscal year: 2000; 
Percentage: 91.0%. 

Fiscal year: 2001; 
Percentage: 91.5%. 

Fiscal year: 2002; 
Percentage: 96.2%. 

Fiscal year: 2003; 
Percentage: 97.3%. 

Fiscal year: 2004; 
Percentage: 96.8%. 

Fiscal year: 2005; 
Percentage: 98.3%. 

Fiscal year: 2006; 
Percentage: 98.7%. 

Fiscal year: 2007; 
Percentage: 90.5%. 

Fiscal year: 2008; 
Percentage: 89.2%. 

Fiscal year: 2009; 
Percentage: 96.5%. 

Fiscal year: 2010; 
Percentage: 98.4%. 

Source: GAO analysis of FDA data. 

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. 

[End of figure] 

Average FDA Review Time Generally Increased for Original Efficacy 
Supplements from FYs 2000 through 2010: 

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 
figure 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.[Footnote 29] 

Figure 5: Average FDA Review Time (in Calendar Days) for Priority and 
Standard Original Efficacy Supplements, FYs 2000 through 2010: 

[Refer to PDF for image: multiple line graph] 

Number of calendar days: 

Fiscal year: 2000; 
Priority: 173; 
Standard: 285. 

Fiscal year: 2001; 
Priority: 199; 
Standard: 290. 

Fiscal year: 2002; 
Priority: 176; 
Standard: 287. 

Fiscal year: 2003; 
Priority: 182; 
Standard: 287. 

Fiscal year: 2004; 
Priority: 182; 
Standard: 292. 

Fiscal year: 2005; 
Priority: 179; 
Standard: 285. 

Fiscal year: 2006; 
Priority: 186; 
Standard: 302. 

Fiscal year: 2007; 
Priority: 191; 
Standard: 309. 

Fiscal year: 2008; 
Priority: 194; 
Standard: 316. 

Fiscal year: 2009; 
Priority: 205; 
Standard: 304. 

Fiscal year: 2010; 
Priority: 191; 
Standard: 308. 

Source: GAO analysis of FDA data. 

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. 

[End of figure] 

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 
appendix 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 the sponsor. FDA had issued the complete response letter more 
than 1 year earlier for 168 (86 percent) of these submissions. 

Percentage of FDA First-Cycle Approvals Fluctuated for Priority 
Efficacy Supplements but Generally Increased for Standard Efficacy 
Supplements from FYs 2000 through 2010: 

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 figure 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.[Footnote 30] 

Figure 6: Percentage of Priority and Standard Original Efficacy 
Supplements Receiving FDA First-Cycle Approvals, FYs 2000 through 2010: 

[Refer to PDF for image: multiple line graph] 

Fiscal year: 2000; 
Priority: 76%; 
Standard: 43%. 

Fiscal year: 2001; 
Priority: 60%; 
Standard: 50%. 

Fiscal year: 2002; 
Priority: 47%; 
Standard: 53%. 

Fiscal year: 2003; 
Priority: 70%; 
Standard: 55%. 

Fiscal year: 2004; 
Priority: 72%; 
Standard: 55%. 

Fiscal year: 2005; 
Priority: 64%; 
Standard: 72%. 

Fiscal year: 2006; 
Priority: 80%; 
Standard: 67%. 

Fiscal year: 2007; 
Priority: 58%; 
Standard: 71%. 

Fiscal year: 2008; 
Priority: 63%; 
Standard: 70%. 

Fiscal year: 2009; 
Priority: 62%; 
Standard: 63%. 

Fiscal year: 2010; 
Priority: 63%; 
Standard: 69%. 

Source: GAO analysis of FDA data. 

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. 

[End of figure] 

Stakeholders Noted Issues with the Prescription Drug Review Process 
and FDA Is Taking Steps That May Address Many of Those Issues: 

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 Actions or Requirements That They Believe Can 
Increase Review Times: 

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.[Footnote 31] 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 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.[Footnote 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.[Footnote 33] 

Stakeholders Cite Insufficient Communication between FDA and 
Stakeholders throughout the Review Process: 

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 
midcycle review meetings.[Footnote 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.[Footnote 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. 

Industry Stakeholders Report a Lack of Predictability and Consistency 
in Reviews: 

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 decisions, which they believe would improve the predictability 
of the review process.[Footnote 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. 

Consumer Advocacy Group Stakeholders Suggest That FDA May Provide 
Inadequate Assurance of the Safety and Efficacy of Approved Drugs: 

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 adverse event reporting.[Footnote 37] These 
concerns have also been extensively discussed elsewhere.[Footnote 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.[Footnote 39] 
FDA has also published a report identifying needs that, if addressed, 
would enhance scientific decision making in CDER.[Footnote 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. 

Concluding Observations: 

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 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. 

Agency Comments: 

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 [hyperlink, http://www.gao.gov]. 

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. 

Signed by: 

Marcia Crosse: 
Director, Health Care: 

[End of section] 

Appendix I: FDA NDA and BLA Review Performance for Fiscal Years (FYs) 
2000 through 2011: 

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

Total number of priority NDA and BLA original submissions: All; 
Fiscal year cohorts: 
2000: 34; 
2001: 14; 
2002: 15; 
2003: 23; 
2004: 27; 
2005: 32; 
2006: 34; 
2007: 28; 
2008: 36; 
2009: 25; 
2010: 20; 
2011[A]: 22. 

Total number of priority NDA and BLA original submissions: I.D[B]; 
Fiscal year cohorts: 
2000: 20; 
2001: 12; 
2002: 11; 
2003: 17; 
2004: 20; 
2005: 21; 
2006: 16; 
2007: 16; 
2008: 18; 
2009: 17; 
2010: 11; 
2011[A]: 14. 

Number of submissions that were pending (i.e., not complete for PDUFA 
purposes): All; 
Fiscal year cohorts: 
2000: 0; 
2001: 0; 
2002: 0; 
2003: 0; 
2004: 0; 
2005: 0; 
2006: 0; 
2007: 0; 
2008: 0; 
2009: 0; 
2010: 0; 
2011[A]: 7. 

Number of submissions that were pending (i.e., not complete for PDUFA 
purposes): I.D; 
Fiscal year cohorts: 
2000: 0; 
2001: 0; 
2002: 0; 
2003: 0; 
2004: 0; 
2005: 0; 
2006: 0; 
2007: 0; 
2008: 0; 
2009: 0; 
2010: 0; 
2011[A]: 4. 

Number of submissions that were complete for PDUFA purposes: All; 
Fiscal year cohorts: 
2000: 34; 
2001: 14; 
2002: 15; 
2003: 23; 
2004: 27; 
2005: 32; 
2006: 34; 
2007: 28; 
2008: 36; 
2009: 25; 
2010: 20; 
2011[A]: 15. 

Number of submissions that were complete for PDUFA purposes: I.D; 
Fiscal year cohorts: 
2000: 20; 
2001: 12; 
2002: 11; 
2003: 17; 
2004: 20; 
2005: 21; 
2006: 16; 
2007: 16; 
2008: 18; 
2009: 17; 
2010: 11; 
2011[A]: 10. 

Number of completed submissions reviewed within 6-month goal[C]: All; 
Fiscal year cohorts: 
2000: 32; 
2001: 13; 
2002: 15; 
2003: 23; 
2004: 27; 
2005: 31; 
2006: 32; 
2007: 26; 
2008: 28; 
2009: 23; 
2010: 20; 
2011[A]: 14. 

Number of completed submissions reviewed within 6-month goal[C]: I.D; 
Fiscal year cohorts: 
2000: 19; 
2001: 12; 
2002: 11; 
2003: 17; 
2004: 20; 
2005: 20; 
2006: 15; 
2007: 16; 
2008: 14; 
2009: 15; 
2010: 11; 
2011[A]: 9. 

Percentage of completed submissions reviewed within 6-month goal: All; 
Fiscal year cohorts: 
2000: 94%; 
2001: 93%; 
2002: 100%; 
2003: 100%; 
2004: 100%; 
2005: 97%; 
2006: 94%; 
2007: 93%; 
2008: 78%; 
2009: 92%; 
2010: 100%; 
2011[A]: 93%. 

Percentage of completed submissions reviewed within 6-month goal: I.D; 
Fiscal year cohorts: 
2000: 95%; 
2001: 100%; 
2002: 100%; 
2003: 100%; 
2004: 100%; 
2005: 95%; 
2006: 94%; 
2007: 100%; 
2008: 78%; 
2009: 88%; 
2010: 100%; 
2011[A]: 90%. 

PDUFA goal percentage: All; 
Fiscal year cohorts: 
2000: 90%; 
2001: 90%; 
2002: 90%; 
2003: 90%; 
2004: 90%; 
2005: 90%; 
2006: 90%; 
2007: 90%; 
2008: 90%; 
2009: 90%; 
2010: 90%; 
2011[A]: 90%. 

PDUFA goal percentage: I.D; 
Fiscal year cohorts: 
2000: 90%; 
2001: 90%; 
2002: 90%; 
2003: 90%; 
2004: 90%; 
2005: 90%; 
2006: 90%; 
2007: 90%; 
2008: 90%; 
2009: 90%; 
2010: 90%; 
2011[A]: 90%. 

Met PDUFA goal: All; 
Fiscal year cohorts: 
2000: Yes; 
2001: Yes; 
2002: Yes; 
2003: Yes; 
2004: Yes; 
2005: Yes; 
2006: Yes; 
2007: Yes; 
2008: No; 
2009: Yes; 
2010: Yes; 
2011[A]: Yes. 

Met PDUFA goal: I.D; 
Fiscal year cohorts: 
2000: Yes; 
2001: Yes; 
2002: Yes; 
2003: Yes; 
2004: Yes; 
2005: Yes; 
2006: Yes; 
2007: Yes; 
2008: No; 
2009: No; 
2010: Yes; 
2011[A]: Yes. 

Average FDA review time (in days) for priority original submissions 
that were reviewed within goal[D]: All; 
Fiscal year cohorts: 
2000: 187; 
2001: 193; 
2002: 184; 
2003: 185; 
2004: 183; 
2005: 188; 
2006: 175; 
2007: 193; 
2008: 197; 
2009: 206; 
2010: 207; 
2011[A]: 172. 

Average FDA review time (in days) for priority original submissions 
that were reviewed within goal[D]: I.D; 
Fiscal year cohorts: 
2000: 188; 
2001: 195; 
2002: 186; 
2003: 186; 
2004: 185; 
2005: 197; 
2006: 177; 
2007: 191; 
2008: 201; 
2009: 206; 
2010: 210; 
2011[A]: 171. 

Average FDA review time (in days) for priority original submissions 
that were not reviewed within goal[D]: All; 
Fiscal year cohorts: 
2000: 283; 
2001: 303; 
2002: [Empty]; 
2003: [Empty]; 
2004: [Empty]; 
2005: 254; 
2006: 286; 
2007: 261; 
2008: 405; 
2009: 335; 
2010: [Empty]; 
2011[A]: 382. 

Average FDA review time (in days) for priority original submissions 
that were not reviewed within goal[D]: I.D; 
Fiscal year cohorts: 
2000: 237; 
2001: [Empty]; 
2002: [Empty]; 
2003: [Empty]; 
2004: [Empty]; 
2005: 254; 
2006: 267; 
2007: [Empty]; 
2008: 380; 
2009: 335; 
2010: [Empty]; 
2011[A]: 382. 

Percentage of first-cycle actions that were:[E] 

Approved: All; 
Fiscal year cohorts: 
2000: 44%; 
2001: 14%; 
2002: 47%; 
2003: 52%; 
2004: 59%; 
2005: 66%; 
2006: 68%; 
2007: 68%; 
2008: 56%; 
2009: 52%; 
2010: 50%; 
2011[A]: 93%. 

Approved: I.D; 
Fiscal year cohorts: 
2000: 35%; 
2001: 17%; 
2002: 55%; 
2003: 59%; 
2004: 55%; 
2005: 71%; 
2006: 75%; 
2007: 75%; 
2008: 61%; 
2009: 53%; 
2010: 73%; 
2011[A]: 100. 

Complete response[F]: All; 
Fiscal year cohorts: 
2000: 56%; 
2001: 71%; 
2002: 47%; 
2003: 43%; 
2004: 33%; 
2005: 31%; 
2006: 29%; 
2007: 29%; 
2008: 42%; 
2009: 48%; 
2010: 50%; 
2011[A]: 0. 

Complete response[F]: I.D; 
Fiscal year cohorts: 
2000: 65%; 
2001: 75%; 
2002: 36%; 
2003: 35%; 
2004: 40%; 
2005: 29%; 
2006: 19%; 
2007: 19%; 
2008: 33%; 
2009: 47%; 
2010: 27%; 
2011[A]: 0%. 

Withdrawn: All; 
Fiscal year cohorts: 
2000: 0%; 
2001: 14%; 
2002: 7%; 
2003: 4%; 
2004: 7%; 
2005: 3%; 
2006: 3%; 
2007: 4%; 
2008: 3%; 
2009: 0%; 
2010: 0%; 
2011[A]: 7%. 

Withdrawn: I.D; 
Fiscal year cohorts: 
2000: 0%; 
2001: 8%; 
2002: 9%; 
2003: 6%; 
2004: 5%; 
2005: 0%; 
2006: 6%; 
2007: 6%; 
2008: 6%; 
2009: 0%; 
2010: 0%; 
2011[A]: 0%. 

Percentage of final actions that were:[G] 

Approved: All; 
Fiscal year cohorts: 
2000: 97%; 
2001: 86%; 
2002: 93%; 
2003: 94%; 
2004: 91%; 
2005: 93%; 
2006: 94%; 
2007: 96%; 
2008: 97%; 
2009: 100%; 
2010: 100%; 
2011[A]: 93%. 

Approved: I.D; 
Fiscal year cohorts: 
2000: 94%; 
2001: 92%; 
2002: 91%; 
2003: 92%; 
2004: 93%; 
2005: 95%; 
2006: 87%; 
2007: 94%; 
2008: 94%; 
2009: 100%; 
2010: 100%; 
2011[A]: 100%. 

Withdrawn: All; 
Fiscal year cohorts: 
2000: 3%; 
2001: 14%; 
2002: 7%; 
2003: 6%; 
2004: 9%; 
2005: 7%; 
2006: 6%; 
2007: 4%; 
2008: 3%; 
2009: 0%; 
2010: 0%; 
2011[A]: 7%. 

Withdrawn: I.D; 
Fiscal year cohorts: 
2000: 6%; 
2001: 8%; 
2002: 9%; 
2003: 8%; 
2004: 7%; 
2005: 5%; 
2006: 13%; 
2007: 6%; 
2008: 6%; 
2009: 0%; 
2010: 0%; 
2011[A]: 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 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. [Empty] 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. 

[End of table] 

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

Total number of standard NDA and BLA original submissions: All; 
Fiscal year cohorts: 
2000: 97; 
2001: 87; 
2002: 90; 
2003: 89; 
2004: 101; 
2005: 76; 
2006: 89; 
2007: 91; 
2008: 105; 
2009: 123; 
2010: 84; 
2011[A]: 79. 

Total number of standard NDA and BLA original submissions: I.D[B]; 
Fiscal year cohorts: 
2000: 24; 
2001: 34; 
2002: 21; 
2003: 25; 
2004: 23; 
2005: 22; 
2006: 26; 
2007: 34; 
2008: 32; 
2009: 36; 
2010: 18; 
2011[A]: 24. 

Number of submissions that were pending (i.e., not complete for PDUFA 
purposes): All; 
Fiscal year cohorts: 
2000: 0; 
2001: 0; 
2002: 0; 
2003: 0; 
2004: 0; 
2005: 0; 
2006: 0; 
2007: 0; 
2008: 0; 
2009: 0; 
2010: 0; 
2011[A]: 55. 

Number of submissions that were pending (i.e., not complete for PDUFA 
purposes): I.D; 
Fiscal year cohorts: 
2000: 0; 
2001: 0; 
2002: 0; 
2003: 0; 
2004: 0; 
2005: 0; 
2006: 0; 
2007: 0; 
2008: 0; 
2009: 0; 
2010: 0; 
2011[A]: 19. 

Number of submissions that were complete for PDUFA purposes: All; 
Fiscal year cohorts: 
2000: 97; 
2001: 87; 
2002: 90; 
2003: 89; 
2004: 101; 
2005: 76; 
2006: 89; 
2007: 91; 
2008: 105; 
2009: 123; 
2010: 84; 
2011[A]: 24. 

Number of submissions that were complete for PDUFA purposes: I.D; 
Fiscal year cohorts: 
2000: 24; 
2001: 34; 
2002: 21; 
2003: 25; 
2004: 23; 
2005: 22; 
2006: 26; 
2007: 34; 
2008: 32; 
2009: 36; 
2010: 18; 
2011[A]: 5. 

Number of completed submissions reviewed within 10-month goal[C]: All; 
Fiscal year cohorts: 
2000: 81; 
2001: 81; 
2002: 89; 
2003: 88; 
2004: 99; 
2005: 75; 
2006: 87; 
2007: 82; 
2008: 92; 
2009: 118; 
2010: 83; 
2011[A]: 23. 

Number of completed submissions reviewed within 10-month goal[C]: I.D; 
Fiscal year cohorts: 
2000: 18; 
2001: 30; 
2002: 20; 
2003: 24; 
2004: 23; 
2005: 21; 
2006: 26; 
2007: 30; 
2008: 26; 
2009: 35; 
2010: 18; 
2011[A]: 5. 

Percentage of completed submissions reviewed within 10-month goal: All; 
Fiscal year cohorts: 
2000: 84%; 
2001: 93%; 
2002: 99%; 
2003: 99%; 
2004: 98%; 
2005: 99%; 
2006: 98%; 
2007: 90%; 
2008: 88%; 
2009: 96%; 
2010: 99%; 
2011[A]: 96%. 

Percentage of completed submissions reviewed within 10-month goal: I.D; 
Fiscal year cohorts: 
2000: 75%; 
2001: 88%; 
2002: 95%; 
2003: 96%; 
2004: 100%; 
2005: 95%; 
2006: 100%; 
2007: 88%; 
2008: 81%; 
2009: 97%; 
2010: 100%; 
2011[A]: 100%. 

PDUFA goal percentage[D]: All; 
Fiscal year cohorts: 
2000: 50%; 
2001: 70%; 
2002: 90%; 
2003: 90%; 
2004: 90%; 
2005: 90%; 
2006: 90%; 
2007: 90%; 
2008: 90%; 
2009: 90%; 
2010: 90%; 
2011[A]: 90%. 

PDUFA goal percentage[D]: I.D; 
Fiscal year cohorts: 
2000: 50%; 
2001: 70%; 
2002: 90%; 
2003: 90%; 
2004: 90%; 
2005: 90%; 
2006: 90%; 
2007: 90%; 
2008: 90%; 
2009: 90%; 
2010: 90%; 
2011[A]: 90%. 

Met PDUFA goal: All; 
Fiscal year cohorts: 
2000: Yes; 
2001: Yes; 
2002: Yes; 
2003: Yes; 
2004: Yes; 
2005: Yes; 
2006: Yes; 
2007: Yes; 
2008: No; 
2009: Yes; 
2010: Yes; 
2011[A]: Yes. 

Met PDUFA goal: I.D; 
Fiscal year cohorts: 
2000: Yes; 
2001: Yes; 
2002: Yes; 
2003: Yes; 
2004: Yes; 
2005: Yes; 
2006: Yes; 
2007: No; 
2008: No; 
2009: Yes; 
2010: Yes; 
2011[A]: Yes. 

Average FDA review time (in days) for standard original submissions 
that were reviewed within goal[E]: All; 
Fiscal year cohorts: 
2000: 297; 
2001: 312; 
2002: 310; 
2003: 300; 
2004: 307; 
2005: 322; 
2006: 320; 
2007: 310; 
2008: 307; 
2009: 309; 
2010: 314; 
2011[A]: 306. 

Average FDA review time (in days) for standard original submissions 
that were reviewed within goal[E]: I.D; 
Fiscal year cohorts: 
2000: 297; 
2001: 321; 
2002: 308; 
2003: 306; 
2004: 319; 
2005: 327; 
2006: 332; 
2007: 320; 
2008: 308; 
2009: 306; 
2010: 314; 
2011[A]: 303. 

Average FDA review time (in days) for standard original submissions 
that were not reviewed within goal[E]: All; 
Fiscal year cohorts: 
2000: 386; 
2001: 356; 
2002: 372; 
2003: 1124; 
2004: 354; 
2005: 445; 
2006: 364; 
2007: 599; 
2008: 453; 
2009: 522; 
2010: 405; 
2011[A]: 350. 

Average FDA review time (in days) for standard original submissions 
that were not reviewed within goal[E]: I.D; 
Fiscal year cohorts: 
2000: 411; 
2001: 355; 
2002: 372; 
2003: 1124; 
2004: [Empty]; 
2005: 445; 
2006: [Empty]; 
2007: 477; 
2008: 473; 
2009: 530; 
2010: [Empty]; 
2011[A]: [Empty]. 

Percentage of first-cycle actions that were:[F]: 

Approved: All; 
Fiscal year cohorts: 
2000: 32%; 
2001: 21%; 
2002: 37%; 
2003: 37%; 
2004: 50%; 
2005: 39%; 
2006: 47%; 
2007: 42%; 
2008: 42%; 
2009: 44%; 
2010: 54%; 
2011[A]: 42%. 

Approved: I.D; 
Fiscal year cohorts: 
2000: 8%; 
2001: 21%; 
2002: 33%; 
2003: 40%; 
2004: 35%; 
2005: 18%; 
2006: 31%; 
2007: 41%; 
2008: 25%; 
2009: 36%; 
2010: 50%; 
2011[A]: 20%. 

Complete response[G]: All; 
Fiscal year cohorts: 
2000: 59%; 
2001: 71%; 
2002: 62%; 
2003: 58%; 
2004: 47%; 
2005: 59%; 
2006: 49%; 
2007: 54%; 
2008: 51%; 
2009: 53%; 
2010: 44%; 
2011[A]: 58%. 

Complete response[G]: I.D; 
Fiscal year cohorts: 
2000: 83%; 
2001: 74%; 
2002: 67%; 
2003: 52%; 
2004: 57%; 
2005: 82%; 
2006: 62%; 
2007: 59%; 
2008: 66%; 
2009: 58%; 
2010: 44%; 
2011[A]: 80%. 

Withdrawn: All; 
Fiscal year cohorts: 
2000: 9%; 
2001: 8%; 
2002: 1%; 
2003: 4%; 
2004: 4%; 
2005: 1%; 
2006: 3%; 
2007: 4%; 
2008: 7%; 
2009: 3%; 
2010: 2%; 
2011[A]: 0%. 

Withdrawn: I.D; 
Fiscal year cohorts: 
2000: 8%; 
2001: 6%; 
2002: 0%; 
2003: 8%; 
2004: 9%; 
2005: 0%; 
2006: 8%; 
2007: 0%; 
2008: 9%; 
2009: 6%; 
2010: 6%; 
2011[A]: 0%. 

Percentage of final actions that were:[H] 

Approved: All; 
Fiscal year cohorts: 
2000: 90%; 
2001: 89%; 
2002: 98%; 
2003: 93%; 
2004: 95%; 
2005: 95%; 
2006: 96%; 
2007: 94%; 
2008: 91%; 
2009: 95%; 
2010: 96%; 
2011[A]: 100%. 

Approved: I.D; 
Fiscal year cohorts: 
2000: 90%; 
2001: 91%; 
2002: 94%; 
2003: 89%; 
2004: 87%; 
2005: 90%; 
2006: 89%; 
2007: 100%; 
2008: 85%; 
2009: 92%; 
2010: 92%; 
2011[A]: 100%. 

Withdrawn: All; 
Fiscal year cohorts: 
2000: 10%; 
2001: 11%; 
2002: 2%; 
2003: 7%; 
2004: 5%; 
2005: 5%; 
2006: 4%; 
2007: 6%; 
2008: 9%; 
2009: 5%; 
2010: 4%; 
2011[A]: 0%. 

Withdrawn: I.D; 
Fiscal year cohorts: 
2000: 10%; 
2001: 9%; 
2002: 6%; 
2003: 11%; 
2004: 13%; 
2005: 10%; 
2006: 11%; 
2007: 0%; 
2008: 15%; 
2009: 8%; 
2010: 8%; 
2011[A]: 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. [Empty] 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. 

[End of table] 

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

Priority NDAs and BLAs: 

Percentage of submissions that were closed[A]; 
Fiscal year cohorts: 
2000: 85%; 
2001: 100%; 
2002: 100%; 
2003: 78%; 
2004: 82%; 
2005: 91%; 
2006: 94%; 
2007: 89%; 
2008: 81%; 
2009: 76%; 
2010: 55%; 
2011: 68%. 

Percentage of submissions that were still open[B]; 
Fiscal year cohorts: 
2000: 15%; 
2001: 0%; 
2002: 0%; 
2003: 22%; 
2004: 18%; 
2005: 9%; 
2006: 6%; 
2007: 11%; 
2008: 19%; 
2009: 24%; 
2010: 45%; 
2011: 32%. 

Percentage of submissions that were under FDA review (i.e., pending); 
Fiscal year cohorts: 
2000: 0%; 
2001: 0%; 
2002: 0%; 
2003: 0%; 
2004: 0%; 
2005: 0%; 
2006: 0%; 
2007: 4%; 
2008: 3%; 
2009: 0%; 
2010: 20%; 
2011: 32%. 

Percentage of submissions for which FDA had issued a complete response 
and the sponsor had not resubmitted the application; 
Fiscal year cohorts: 
2000: 15%; 
2001: 0%; 
2002: 0%; 
2003: 22%; 
2004: 18%; 
2005: 9%; 
2006: 6%; 
2007: 7%; 
2008: 17%; 
2009: 24%; 
2010: 25%; 
2011: 0%. 

Standard NDAs and BLAs: 

Percentage of submissions that were closed[A]; 
Fiscal year cohorts: 
2000: 89%; 
2001: 83%; 
2002: 90%; 
2003: 80%; 
2004: 85%; 
2005: 76%; 
2006: 81%; 
2007: 71%; 
2008: 73%; 
2009: 70%; 
2010: 65%; 
2011: 13%. 

Percentage of submissions that were still open[B]; 
Fiscal year cohorts: 
2000: 11%; 
2001: 17%; 
2002: 10%; 
2003: 20%; 
2004: 15%; 
2005: 24%; 
2006: 19%; 
2007: 29%; 
2008: 27%; 
2009: 30%; 
2010: 35%; 
2011: 87%. 

Percentage of submissions that were under FDA review (i.e., pending); 
Fiscal year cohorts: 
2000: 0%; 
2001: 0%; 
2002: 0%; 
2003: 0%; 
2004: 1%; 
2005: 0%; 
2006: 1%; 
2007: 1%; 
2008: 6%; 
2009: 3%; 
2010: 11%; 
2011: 72%. 

Percentage of submissions for which FDA had issued a complete response 
and the sponsor had not resubmitted the application; 
Fiscal year cohorts: 
2000: 11%; 
2001: 17%; 
2002: 10%; 
2003: 20%; 
2004: 14%; 
2005: 24%; 
2006: 18%; 
2007: 27%; 
2008: 21%; 
2009: 27%; 
2010: 24%; 
2011: 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. 

[End of table] 

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

Total number of Class 1 NDA and BLA resubmissions[B]: All; 
Fiscal year cohorts: 
2000: 3%; 
2001: 19%; 
2002: 22%; 
2003: 22%; 
2004: 18%; 
2005: 19%; 
2006: 20%; 
2007: 21%; 
2008: 18%; 
2009: 16%; 
2010: 12%; 
2011[A]: 10%. 

Total number of Class 1 NDA and BLA resubmissions[B]: I.D[C]; 
Fiscal year cohorts: 
2000: 0%; 
2001: 6%; 
2002: 11%; 
2003: 2%; 
2004: 2%; 
2005: 2%; 
2006: 4%; 
2007: 5%; 
2008: 4%; 
2009: 2%; 
2010: 1%; 
2011[A]: 2%. 

Number of resubmissions that were pending (i.e., not complete for 
PDUFA purposes): All; 
Fiscal year cohorts: 
2000: 0%; 
2001: 0%; 
2002: 0%; 
2003: 0%; 
2004: 0%; 
2005: 0%; 
2006: 0%; 
2007: 0%; 
2008: 0%; 
2009: 0%; 
2010: 0%; 
2011[A]: 2%. 

Number of resubmissions that were pending (i.e., not complete for 
PDUFA purposes): I.D; 
Fiscal year cohorts: 
2000: 0%; 
2001: 0%; 
2002: 0%; 
2003: 0%; 
2004: 0%; 
2005: 0%; 
2006: 0%; 
2007: 0%; 
2008: 0%; 
2009: 0%; 
2010: 0%; 
2011[A]: 0%. 

Number of resubmissions that were complete for PDUFA purposes: All; 
Fiscal year cohorts: 
2000: 3%; 
2001: 19%; 
2002: 22%; 
2003: 22%; 
2004: 18%; 
2005: 19%; 
2006: 20%; 
2007: 21%; 
2008: 18%; 
2009: 16%; 
2010: 12%; 
2011[A]: 8%. 

Number of resubmissions that were complete for PDUFA purposes: I.D; 
Fiscal year cohorts: 
2000: 0%; 
2001: 6%; 
2002: 11%; 
2003: 2%; 
2004: 2%; 
2005: 2%; 
2006: 4%; 
2007: 5%; 
2008: 4%; 
2009: 2%; 
2010: 1%; 
2011[A]: 2%. 

Number of completed resubmissions reviewed within 2-month goal: All; 
Fiscal year cohorts: 
2000: 3%; 
2001: 18%; 
2002: 22%; 
2003: 21%; 
2004: 18%; 
2005: 17%; 
2006: 20%; 
2007: 16%; 
2008: 17%; 
2009: 13%; 
2010: 12%; 
2011[A]: 8%. 

Number of completed resubmissions reviewed within 2-month goal: I.D; 
Fiscal year cohorts: 
2000: 0%; 
2001: 6%; 
2002: 11%; 
2003: 2%; 
2004: 2%; 
2005: 2%; 
2006: 4%; 
2007: 5%; 
2008: 4%; 
2009: 2%; 
2010: 1%; 
2011[A]: 2%. 

Percentage of completed resubmissions reviewed within 2-month goal: 
All: 
Fiscal year cohorts: 
2000: 100%; 
2001: 95%; 
2002: 100%; 
2003: 95%; 
2004: 100%; 
2005: 89%; 
2006: 100%; 
2007: 76%; 
2008: 94%; 
2009: 81%; 
2010: 100%; 
2011[A]: 100%. 

Percentage of completed resubmissions reviewed within 2-month goal: 
I.D; 
Fiscal year cohorts: 
2000: [Empty]; 
2001: 100%; 
2002: 100%; 
2003: 100%; 
2004: 100%; 
2005: 100%; 
2006: 100%; 
2007: 100%; 
2008: 100%; 
2009: 100%; 
2010: 100%; 
2011[A]: 100%. 

PDUFA goal percentage: All; 
Fiscal year cohorts: 
2000: 70%[D]; 
2001: 90%; 
2002: 90%; 
2003: 90%; 
2004: 90%; 
2005: 90%; 
2006: 90%; 
2007: 90%; 
2008: 90%; 
2009: 90%; 
2010: 90%; 
2011[A]: 90%. 

PDUFA goal percentage: I.D; 
Fiscal year cohorts: 
2000: 70%; 
2001: 90%; 
2002: 90%; 
2003: 90%; 
2004: 90%; 
2005: 90%; 
2006: 90%; 
2007: 90%; 
2008: 90%; 
2009: 90%; 
2010: 90%; 
2011[A]: 90%. 

Met PDUFA goal: All; 
Fiscal year cohorts: 
2000: Yes; 
2001: Yes; 
2002: Yes; 
2003: Yes; 
2004: Yes; 
2005: No; 
2006: Yes; 
2007: No; 
2008: Yes; 
2009: No; 
2010: Yes; 
2011[A]: Yes. 

Met PDUFA goal: I.D; 
Fiscal year cohorts: 
2000: Yes; 
2001: Yes; 
2002: Yes; 
2003: Yes; 
2004: Yes; 
2005: Yes; 
2006: Yes; 
2007: Yes; 
2008: Yes; 
2009: Yes; 
2010: Yes; 
2011[A]: Yes. 

Total number of Class 2 NDA and BLA resubmissions[B]: All; 
Fiscal year cohorts: 
2000: 2; 
2001: 24; 
2002: 35; 
2003: 44; 
2004: 58; 
2005: 32; 
2006: 38; 
2007: 46; 
2008: 34; 
2009: 52; 
2010: 41; 
2011[A]: 53. 

Total number of Class 2 NDA and BLA resubmissions[B]: I.D; 
Fiscal year cohorts: 
2000: 1; 
2001: 14; 
2002: 16; 
2003: 23; 
2004: 22; 
2005: 11; 
2006: 8; 
2007: 22; 
2008: 14; 
2009: 21; 
2010: 11; 
2011[A]: 17. 

Number of resubmissions that were pending (i.e., not complete for 
PDUFA purposes): All; 
Fiscal year cohorts: 
2000: 0; 
2001: 0; 
2002: 0; 
2003: 0; 
2004: 0; 
2005: 0; 
2006: 0; 
2007: 0; 
2008: 0; 
2009: 0; 
2010: 0; 
2011[A]: 21. 

Number of resubmissions that were pending (i.e., not complete for 
PDUFA purposes): I.D; 
Fiscal year cohorts: 
2000: 0; 
2001: 0; 
2002: 0; 
2003: 0; 
2004: 0; 
2005: 0; 
2006: 0; 
2007: 0; 
2008: 0; 
2009: 0; 
2010: 0; 
2011[A]: 5. 

Number of resubmissions that were complete for PDUFA purposes: All; 
Fiscal year cohorts: 
2000: 2; 
2001: 24; 
2002: 35; 
2003: 44; 
2004: 58; 
2005: 32; 
2006: 38; 
2007: 46; 
2008: 34; 
2009: 52; 
2010: 41; 
2011[A]: 32. 

Number of resubmissions that were complete for PDUFA purposes: I.D; 
Fiscal year cohorts: 
2000: 1; 
2001: 14; 
2002: 16; 
2003: 23; 
2004: 22; 
2005: 11; 
2006: 8; 
2007: 22; 
2008: 14; 
2009: 21; 
2010: 11; 
2011[A]: 12. 

Number of completed resubmissions reviewed 6-month goal[E]: All; 
Fiscal year cohorts: 
2000: 2; 
2001: 24; 
2002: 35; 
2003: 44; 
2004: 57; 
2005: 30; 
2006: 36; 
2007: 43; 
2008: 29; 
2009: 48; 
2010: 39; 
2011[A]: 32. 

Number of completed resubmissions reviewed 6-month goal[E]: I.D; 
Fiscal year cohorts: 
2000: 1; 
2001: 14; 
2002: 16; 
2003: 23; 
2004: 22; 
2005: 10; 
2006: 8; 
2007: 20; 
2008: 11; 
2009: 20; 
2010: 10; 
2011[A]: 12. 

Percentage of completed resubmissions reviewed 6-month goal: All; 
Fiscal year cohorts: 
2000: 100%; 
2001: 100%; 
2002: 100%; 
2003: 100%; 
2004: 98%; 
2005: 97%; 
2006: 95%; 
2007: 93%; 
2008: 85%; 
2009: 92%; 
2010: 95%; 
2011[A]: 100%. 

Percentage of completed resubmissions reviewed 6-month goal: I.D; 
Fiscal year cohorts: 
2000: 100%; 
2001: 100%; 
2002: 100%; 
2003: 100%; 
2004: 100%; 
2005: 91%; 
2006: 100%; 
2007: 91%; 
2008: 79%; 
2009: 95%; 
2010: 91%; 
2011[A]: 100%. 

PDUFA goal percentage: All; 
Fiscal year cohorts: 
2000: 90%; 
2001: 90%; 
2002: 90%; 
2003: 90%; 
2004: 90%; 
2005: 90%; 
2006: 90%; 
2007: 90%; 
2008: 90%; 
2009: 90%; 
2010: 90%; 
2011[A]: 90%. 

PDUFA goal percentage: I.D; 
Fiscal year cohorts: 
2000: 90%; 
2001: 90%; 
2002: 90%; 
2003: 90%; 
2004: 90%; 
2005: 90%; 
2006: 90%; 
2007: 90%; 
2008: 90%; 
2009: 90%; 
2010: 90%; 
2011[A]: 90%. 

Met PDUFA goal: All; 
Fiscal year cohorts: 
2000: Yes; 
2001: Yes; 
2002: Yes; 
2003: Yes; 
2004: Yes; 
2005: Yes; 
2006: Yes; 
2007: Yes; 
2008: No; 
2009: Yes; 
2010: Yes; 
2011[A]: Yes. 

Met PDUFA goal: I.D; 
Fiscal year cohorts: 
2000: Yes; 
2001: Yes; 
2002: Yes; 
2003: Yes; 
2004: Yes; 
2005: Yes; 
2006: Yes; 
2007: Yes; 
2008: No; 
2009: Yes; 
2010: Yes; 
2011[A]: Yes. 

Source: GAO analysis of FDA data. 

Note: Percentages are rounded to the nearest whole number. 

[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. 

[End of table] 

Table 6: FDA Review Performance for Oncology Drugs Including Those 
Granted Accelerated Approval, FYs 2000 through 2011: 

Total number of NDA and BLA original submissions for oncology drugs: 
All; 
Fiscal year cohorts: 
2000: 7; 
2001: 7; 
2002: 6; 
2003: 3; 
2004: 13; 
2005: 10; 
2006: 8; 
2007: 11; 
2008: 8; 
2009: 12; 
2010: 11; 
2011[A]: 15. 

Total number of NDA and BLA original submissions for oncology drugs: 
A.A.[B]; 
Fiscal year cohorts: 
2000: 1; 
2001: 2; 
2002: 2; 
2003: 2; 
2004: 1; 
2005: 3; 
2006: 2; 
2007: 0; 
2008: 1; 
2009: 2; 
2010: 0; 
2011[A]: 1. 

Number of first-cycle approvals[C]: All; 
Fiscal year cohorts: 
2000: 3; 
2001: 4; 
2002: 3; 
2003: 3; 
2004: 8; 
2005: 7; 
2006: 4; 
2007: 6; 
2008: 5; 
2009: 5; 
2010: 6; 
2011[A]: 6. 

Number of first-cycle approvals[C]: A.A.; 
Fiscal year cohorts: 
2000: 1; 
2001: 1; 
2002: 2; 
2003: 2; 
2004: 1; 
2005: 3; 
2006: 2; 
2007: [Empty]; 
2008: 1; 
2009: 2; 
2010: [Empty]; 
2011[A]: 1. 

Number of final approvals[D]: All; 
Fiscal year cohorts: 
2000: 5; 
2001: 5; 
2002: 4; 
2003: 3; 
2004: 8; 
2005: 8; 
2006: 5; 
2007: 7; 
2008: 7; 
2009: 5; 
2010: 9; 
2011[A]: 6. 

Number of final approvals[D]: A.A.; 
Fiscal year cohorts: 
2000: 1;
2001: 2; 
2002: 2; 
2003: 2; 
2004: 1; 
2005: 3; 
2006: 2; 
2007: [Empty]; 
2008: 1; 
2009: 2; 
2010: [Empty]; 
2011[A]: 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). [Empty] 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. [Empty] indicate cohorts for which no submissions met the 
criteria. 

[End of table] 

[End of section] 

Appendix II: FDA Efficacy Supplement Review Performance for Fiscal 
Years (FYs) 2000 through 2011: 

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

Total number of priority efficacy supplements; 
Fiscal year cohorts: 
2000: 21; 
2001: 10; 
2002: 38; 
2003: 37; 
2004: 50; 
2005: 42; 
2006: 45; 
2007: 45; 
2008: 38; 
2009: 42; 
2010: 19; 
2011[A]: 26. 

Number of submissions that were pending (i.e., not complete for PDUFA 
purposes); 
Fiscal year cohorts: 
2000: 0; 
2001: 0; 
2002: 0; 
2003: 0; 
2004: 0; 
2005: 0; 
2006: 0; 
2007: 0; 
2008: 0; 
2009: 0; 
2010: 0; 
2011[A]: 13. 

Number of submissions that were complete for PDUFA purposes; 
Fiscal year cohorts: 
2000: 21; 
2001: 10; 
2002: 38; 
2003: 37; 
2004: 50; 
2005: 42; 
2006: 45; 
2007: 45; 
2008: 38; 
2009: 42; 
2010: 19; 
2011[A]: 13. 

Number of completed submissions reviewed within 6-month goal[B]; 
Fiscal year cohorts: 
2000: 21; 
2001: 9; 
2002: 36; 
2003: 37; 
2004: 47; 
2005: 41; 
2006: 44; 
2007: 41; 
2008: 35; 
2009: 36; 
2010: 19; 
2011[A]: 13. 

Percentage of completed submissions reviewed within 6-month goal; 
Fiscal year cohorts: 
2000: 100%; 
2001: 90%; 
2002: 95%; 
2003: 100%; 
2004: 94%; 
2005: 98%; 
2006: 98%; 
2007: 91%; 
2008: 92%; 
2009: 86%; 
2010: 100%; 
2011[A]: 100%. 

PDUFA goal percentage; 
Fiscal year cohorts: 
2000: 90%; 
2001: 90%; 
2002: 90%; 
2003: 90%; 
2004: 90%; 
2005: 90%; 
2006: 90%; 
2007: 90%; 
2008: 90%; 
2009: 90%; 
2010: 90%; 
2011[A]: 90%. 

Met PDUFA goal; 
Fiscal year cohorts: 
2000: Yes; 
2001: Yes; 
2002: Yes; 
2003: Yes; 
2004: Yes; 
2005: Yes; 
2006: Yes; 
2007: Yes; 
2008: Yes; 
2009: No; 
2010: Yes; 
2011[A]: Yes. 

Average FDA review time (in days) for priority efficacy supplements 
that were reviewed within goal[C]; 
Fiscal year cohorts: 
2000: 173; 
2001: 182; 
2002: 169; 
2003: 182; 
2004: 171; 
2005: 176; 
2006: 182; 
2007: 180; 
2008: 189; 
2009: 182; 
2010: 191; 
2011[A]: 195. 

Average FDA review time (in days) for priority efficacy supplements 
that were not reviewed within goal[C]; 
Fiscal year cohorts: 
2000: [Empty]; 
2001: 347; 
2002: 303; 
2003: [Empty]; 
2004: 356; 
2005: 289; 
2006: 393; 
2007: 309; 
2008: 249; 
2009: 341; 
2010: [Empty]; 
2011[A]: [Empty]. 

Percentage of first-cycle actions that were:[D]: 

Approved; 
Fiscal year cohorts: 
2000: 76%; 
2001: 60%; 
2002: 47%; 
2003: 70%; 
2004: 72%; 
2005: 64%; 
2006: 80%; 
2007: 58%; 
2008: 63%; 
2009: 62%; 
2010: 63%; 
2011[A]: 92%. 

Complete response[E]; 
Fiscal year cohorts: 
2000: 14%; 
2001: 30%; 
2002: 42%; 
2003: 30%; 
2004: 24%; 
2005: 33%; 
2006: 20%; 
2007: 42%; 
2008: 34%; 
2009: 33%; 
2010: 37%; 
2011[A]: 8%. 

Withdrawn; 
Fiscal year cohorts: 
2000: 10%; 
2001: 10%; 
2002: 11%; 
2003: 0%; 
2004: 4%; 
2005: 2%; 
2006: 0%; 
2007: 0%; 
2008: 3%; 
2009: 5%; 
2010: 0%; 
2011[A]: 0%. 

Percentage of final actions that were:[F]: 

Approved; 
Fiscal year cohorts: 
2000: 89%; 
2001: 86%; 
2002: 82%; 
2003: 100%; 
2004: 95%; 
2005: 96%; 
2006: 100%; 
2007: 100%; 
2008: 96%; 
2009: 90%; 
2010: 100%; 
2011[A]: 100%. 

Withdrawn; 
Fiscal year cohorts: 
2000: 11%; 
2001: 14%; 
2002: 18%; 
2003: 0%; 
2004: 5%; 
2005: 4%; 
2006: 0%; 
2007: 0%; 
2008: 4%; 
2009: 10%; 
2010: 0%; 
2011[A]: 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] 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. 

[C] Average review time for the first review cycle for original 
submissions. Resubmissions are subject to different PDUFA goal time 
frames. [Empty] 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. 

[End of table] 

Table 8: FDA Review Performance for Standard Efficacy Supplements, FYs 
2000 through 2011: 

Total number of standard efficacy supplements; 
Fiscal year cohorts: 
2000: 167; 
2001: 164; 
2002: 131; 
2003: 113; 
2004: 156; 
2005: 116; 
2006: 149; 
2007: 147; 
2008[A]: 112; 
2009[A]: 117; 
2010[A]: 128; 
2011[A]: 107. 

Number of submissions that were pending (i.e., not complete for PDUFA 
purposes); 
Fiscal year cohorts: 
2000: 0; 
2001: 0; 
2002: 0; 
2003: 0; 
2004: 0; 
2005: 0; 
2006: 0; 
2007: 0; 
2008[A]: 1; 
2009[A]: 2; 
2010[A]: 1; 
2011[A]: 75. 

Number of submissions that were complete for PDUFA purposes; 
Fiscal year cohorts: 
2000: 167; 
2001: 164; 
2002: 131; 
2003: 113; 
2004: 156; 
2005: 116; 
2006: 149; 
2007: 147; 
2008[A]: 111; 
2009[A]: 115; 
2010[A]: 127; 
2011[A]: 32. 

Number of completed submissions reviewed within 10-month goal[B]; 
Fiscal year cohorts: 
2000: 152; 
2001: 150; 
2002: 126; 
2003: 110; 
2004: 151; 
2005: 114; 
2006: 147; 
2007: 133; 
2008[A]: 99; 
2009[A]: 111; 
2010[A]: 125; 
2011[A]: 32. 

Percentage of completed submissions reviewed within 10-month goal[C]; 
Fiscal year cohorts: 
2000: 91%; 
2001: 91%; 
2002: 96%; 
2003: 97%; 
2004: 97%; 
2005: 98%; 
2006: 99%; 
2007: 90%; 
2008[A]: 89%; 
2009[A]: 97%; 
2010[A]: 98%; 
2011[A]: 100%. 

PDUFA goal percentage[D]; 
Fiscal year cohorts: 
2000: 50%; 
2001: 70%; 
2002: 90%; 
2003: 90%; 
2004: 90%; 
2005: 90%; 
2006: 90%; 
2007: 90%; 
2008[A]: 90%; 
2009[A]: 90%; 
2010[A]: 90%; 
2011[A]: 90%. 

Met PDUFA goal; 
Fiscal year cohorts: 
2000: Yes; 
2001: Yes; 
2002: Yes; 
2003: Yes; 
2004: Yes; 
2005: Yes; 
2006: Yes; 
2007: Yes; 
2008[A]: No; 
2009[A]: Yes; 
2010[A]: Yes; 
2011[A]: Yes. 

Average FDA review time (in days) for standard efficacy supplements 
that were reviewed within goal[E]; 
Fiscal year cohorts: 
2000: 278; 
2001: 278; 
2002: 282; 
2003: 283; 
2004: 287; 
2005: 283; 
2006: 292; 
2007: 290; 
2008[A]: 297; 
2009[A]: 297; 
2010[A]: 306; 
2011[A]: 284. 

Average FDA review time (in days) for standard efficacy supplements 
that were not reviewed within goal[E]; 
Fiscal year cohorts: 
2000: 370; 
2001: 395; 
2002: 394; 
2003: 426; 
2004: 463; 
2005: 397; 
2006: 994; 
2007: 499; 
2008[A]: 470; 
2009[A]: 499; 
2010[A]: 399; 
2011[A]: [Empty]. 

Percentage of first-cycle actions that were:[F] 

Approved; 
Fiscal year cohorts: 
2000: 43%; 
2001: 50%; 
2002: 53%; 
2003: 55%; 
2004: 55%; 
2005: 72%; 
2006: 67%; 
2007: 71%; 
2008[A]: 70%; 
2009[A]: 63%; 
2010[A]: 69%; 
2011[A]: 63%. 

Complete response[G]; 
Fiscal year cohorts: 
2000: 51%; 
2001: 41%; 
2002: 44%; 
2003: 45%; 
2004: 41%; 
2005: 25%; 
2006: 28%; 
2007: 28%; 
2008[A]: 27%; 
2009[A]: 35%; 
2010[A]: 27%; 
2011[A]: 25%. 

Withdrawn; 
Fiscal year cohorts: 
2000: 6%; 
2001: 9%; 
2002: 3%; 
2003: 0%; 
2004: 4%; 
2005: 3%; 
2006: 5%; 
2007: 1%; 
2008[A]: 3%; 
2009[A]: 2%; 
2010[A]: 5%; 
2011[A]: 13%. 

Percentage of final actions that were:[H] 

Approved; 
Fiscal year cohorts: 
2000: 87%; 
2001: 87%; 
2002: 93%; 
2003: 100%; 
2004: 93%; 
2005: 94%; 
2006: 93%; 
2007: 96%; 
2008[A]: 96%; 
2009[A]: 96%; 
2010[A]: 94%; 
2011[A]: 83%. 

Withdrawn; 
Fiscal year cohorts: 
2000: 13%; 
2001: 13%; 
2002: 7%; 
2003: 0%; 
2004: 7%; 
2005: 6%; 
2006: 7%; 
2007: 4%; 
2008[A]: 4%; 
2009[A]: 4%; 
2010[A]: 6%; 
2011[A]: 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. 

[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. 

[End of table] 

Table 9: Percentages of Closed and Open Efficacy Supplements, FYs 2000 
through 2011: 

Priority efficacy supplements: 

Percentage of submissions that were closed[A]; 
Fiscal year cohorts: 
2000: 100%; 
2001: 100%; 
2002: 84%; 
2003: 89%; 
2004: 92%; 
2005: 83%; 
2006: 89%; 
2007: 93%; 
2008: 76%; 
2009: 76%; 
2010: 74%; 
2011: 46%. 

Percentage of submissions that were still open[B]; 
Fiscal year cohorts: 
2000: 0%; 
2001: 0%; 
2002: 16%; 
2003: 11%; 
2004: 8%; 
2005: 17%; 
2006: 11%; 
2007: 7%; 
2008: 24%; 
2009: 24%; 
2010: 26%; 
2011: 54%. 

Percentage of submissions that were under FDA review (i.e., pending); 
Fiscal year cohorts: 
2000: 0%; 
2001: 0%; 
2002: 0%; 
2003: 0%; 
2004: 0%; 
2005: 0%; 
2006: 0%; 
2007: 0%; 
2008: 0%; 
2009: 0%; 
2010: 0%; 
2011: 50%. 

Percentage of submissions for which FDA had issued a complete response 
and the sponsor had not resubmitted the application; 
Fiscal year cohorts: 
2000: 0%; 
2001: 0%; 
2002: 16%; 
2003: 11%; 
2004: 8%; 
2005: 17%; 
2006: 11%; 
2007: 7%; 
2008: 24%; 
2009: 24%; 
2010: 26%; 
2011: 4%. 

Standard efficacy supplements: 

Percentage of submissions that were closed[A]; 
Fiscal year cohorts: 
2000: 83%; 
2001: 89%; 
2002: 84%; 
2003: 86%; 
2004: 75%; 
2005: 91%; 
2006: 82%; 
2007: 88%; 
2008: 83%; 
2009: 80%; 
2010: 82%; 
2011: 22%. 

Percentage of submissions that were still open[B]; 
Fiscal year cohorts: 
2000: 17%; 
2001: 11%; 
2002: 16%; 
2003: 14%; 
2004: 25%; 
2005: 9%; 
2006: 18%; 
2007: 12%; 
2008: 17%; 
2009: 20%; 
2010: 18%; 
2011: 78%. 

Percentage of submissions that were under FDA review (i.e., pending); 
Fiscal year cohorts: 
2000: 0%; 
2001: 0%; 
2002: 0%; 
2003: 0%; 
2004: 0%; 
2005: 0%; 
2006: 0%; 
2007: 0%; 
2008: 1%; 
2009: 2%; 
2010: 1%; 
2011: 70%. 

Percentage of submissions for which FDA had issued a complete response 
and the sponsor had not resubmitted the application; 
Fiscal year cohorts: 
2000: 17%; 
2001: 11%; 
2002: 16%; 
2003: 14%; 
2004: 25%; 
2005: 9%; 
2006: 18%; 
2007: 12%; 
2008: 16%; 
2009: 18%; 
2010: 17%; 
2011: 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. 

[End of table] 

[End of section] 

Appendix III: Full-time Equivalent (FTE) FDA Staff Supporting 
Prescription Drug User Fee Activities, FYs 2000 through 2010: 

Center for Drug Evaluation and Research (CDER): 

FDA centers and offices: Office of the Center Director (OCD); 
Number of FTEs in each fiscal year: 
2000: 44; 
2001: 38; 
2002: 20; 
2003: 19; 
2004: 13; 
2005: 17; 
2006: 19; 
2007: 22; 
2008: 29; 
2009: 38; 
2010: 49. 

FDA centers and offices: Office of Regulatory Policy (ORP)[A]; 
Number of FTEs in each fiscal year: 
2000: N/A; 
2001: 4; 
2002: 23; 
2003: 26; 
2004: 37; 
2005: 33; 
2006: 45; 
2007: 46; 
2008: 47; 
2009: 49; 
2010: 53. 

FDA centers and offices: Office of Executive Programs (OEP)[A,B]; 
Number of FTEs in each fiscal year: 
2000: N/A; 
2001: 3; 
2002: 39; 
2003: 55; 
2004: 58; 
2005: 58; 
2006: 54; 
2007: 53; 
2008: 57; 
2009: 63; 
2010: 70. 

FDA centers and offices: Office of Management (OM); 
Number of FTEs in each fiscal year: 
2000: 65; 
2001: 66; 
2002: 64; 
2003: 57; 
2004: 46; 
2005: 41; 
2006: 43; 
2007: 45; 
2008: 50; 
2009: 62; 
2010: 75. 

FDA centers and offices: Office of Communications (OCOMM)[B]; 
Number of FTEs in each fiscal year: 
2000: 83; 
2001: 87; 
2002: 71; 
2003: 68; 
2004: 72; 
2005: 76; 
2006: 81; 
2007: 53; 
2008: 57; 
2009: 66; 
2010: 72. 

FDA centers and offices: Office of Compliance (OC)[B]; 
Number of FTEs in each fiscal year: 
2000: 27; 
2001: 24; 
2002: 30; 
2003: 31; 
2004: 62; 
2005: 39; 
2006: 47; 
2007: 83; 
2008: 101; 
2009: 173; 
2010: 202. 

FDA centers and offices: Office of Information Technology (OIT/OIM)[C]; 
Number of FTEs in each fiscal year: 
2000: 99; 
2001: 104; 
2002: 95; 
2003: 87; 
2004: 86; 
2005: 78; 
2006: 88; 
2007: 40; 
2008: 38; 
2009: 40; 
2010: 44. 

FDA centers and offices: Office of Translational Sciences (OTS)[D]; 
Number of FTEs in each fiscal year: 
2000: N/A; 
2001: N/A; 
2002: N/A; 
2003: N/A; 
2004: N/A; 
2005: N/A; 
2006: N/A; 
2007: 147; 
2008: 210; 
2009: 286; 
2010: 323. 

FDA centers and offices: Office of New Drugs (OND)[E]; 
Number of FTEs in each fiscal year: 
2000: 705; 
2001: 676; 
2002: 541; 
2003: 593; 
2004: 697; 
2005: 700; 
2006: 725; 
2007: 732; 
2008: 740; 
2009: 858; 
2010: 892. 

FDA centers and offices: Office of Planning and Informatics (OPI)[C]; 
Number of FTEs in each fiscal year: 
2000: N/A; 
2001: N/A; 
2002: N/A; 
2003: N/A; 
2004: N/A; 
2005: N/A; 
2006: N/A; 
2007: 40; 
2008: 48; 
2009: 66; 
2010: 78. 

FDA centers and offices: Office of Counter-Terrorism and Emergency 
Coordination (OCTEC)[E]; 
Number of FTEs in each fiscal year: 
2000: N/A; 
2001: N/A; 
2002: 13; 
2003: 33; 
2004: 43; 
2005: 35; 
2006: 39; 
2007: 23; 
2008: 23; 
2009: 24; 
2010: 12. 

FDA centers and offices: Office of Surveillance & Epidemiology 
(OSE)[D,E]; 
Number of FTEs in each fiscal year: 
2000: N/A; 
2001: N/A; 
2002: 98; 
2003: 99; 
2004: 118; 
2005: 115; 
2006: 136; 
2007: 113; 
2008: 92; 
2009: 134; 
2010: 167. 

FDA centers and offices: Office of Medical Policy (OMP)[B]; 
Number of FTEs in each fiscal year: 
2000: 53; 
2001: 52; 
2002: 54; 
2003: 58; 
2004: 62; 
2005: 47; 
2006: 61; 
2007: 43; 
2008: 46; 
2009: 56; 
2010: 64. 

FDA centers and offices: Office of Pharmaceutical Science (OPS)[D]; 
Number of FTEs in each fiscal year: 
2000: 332; 
2001: 320; 
2002: 302; 
2003: 303; 
2004: 379; 
2005: 394; 
2006: 398; 
2007: 299; 
2008: 308; 
2009: 358; 
2010: 376. 

FDA centers and offices: CDER Total; 
Number of FTEs in each fiscal year: 
2000: 1,408; 
2001: 1,374; 
2002: 1,350; 
2003: 1,429; 
2004: 1,673; 
2005: 1,633; 
2006: 1,736; 
2007: 1,739; 
2008: 1,846; 
2009: 2,273; 
2010: 2,477[F]. 

Center for Biologics Evaluation and Research (CBER): 

FDA centers and offices: Center Director's Office, Office of 
Management (OM), Office of Information Management (OIM) & Office of 
Communication, Outreach and Development (OCOD); 
Number of FTEs in each fiscal year: 
2000: 114; 
2001: 123; 
2002: 124; 
2003: 131; 
2004: 108; 
2005: 106; 
2006: 108; 
2007: 116; 
2008: 128; 
2009: 140; 
2010: 166. 

FDA centers and offices: Office of Blood Research & Review; 
Number of FTEs in each fiscal year: 
2000: 38; 
2001: 46; 
2002: 48; 
2003: 53; 
2004: 50; 
2005: 55; 
2006: 50; 
2007: 56; 
2008: 57; 
2009: 67; 
2010: 69. 

FDA centers and offices: Office of Cellular, Tissue & Gene Therapies; 
Number of FTEs in each fiscal year: 
2000: 0; 
2001: 0; 
2002: 0; 
2003: 54; 
2004: 69; 
2005: 66; 
2006: 69; 
2007: 75; 
2008: 78; 
2009: 82; 
2010: 92. 

FDA centers and offices: Office of Vaccines Research & Review; 
Number of FTEs in each fiscal year: 
2000: 134; 
2001: 136; 
2002: 161; 
2003: 194; 
2004: 201; 
2005: 193; 
2006: 200; 
2007: 217; 
2008: 224; 
2009: 229; 
2010: 238. 

FDA centers and offices: Office of Therapeutics Research & Review; 
Number of FTEs in each fiscal year: 
2000: 157; 
2001: 169; 
2002: 189; 
2003: 141; 
2004: 0; 
2005: 0; 
2006: 0; 
2007: 0; 
2008: 0; 
2009: 0; 
2010: 0. 

FDA centers and offices: Office of Biostatistics & Epidemiology; 
Number of FTEs in each fiscal year: 
2000: 15; 
2001: 17; 
2002: 22; 
2003: 22; 
2004: 14; 
2005: 16; 
2006: 18; 
2007: 24; 
2008: 30; 
2009: 40; 
2010: 45. 

FDA centers and offices: Office of Compliance & Biologics Quality; 
Number of FTEs in each fiscal year: 
2000: 42; 
2001: 42; 
2002: 42; 
2003: 49; 
2004: 36; 
2005: 33; 
2006: 33; 
2007: 34; 
2008: 37; 
2009: 45; 
2010: 44. 

FDA centers and offices: CBER Total; 
Number of FTEs in each fiscal year: 
2000: 500; 
2001: 533; 
2002: 586; 
2003: 644; 
2004: 478; 
2005: 469; 
2006: 478; 
2007: 522; 
2008: 554; 
2009: 603; 
2010: 654. 

FDA centers and offices: Office of Regulatory Affairs (ORA): 

FDA centers and offices: ORA Total; 
Number of FTEs in each fiscal year: 
2000: 180; 
2001: 180; 
2002: 153; 
2003: 147; 
2004: 147; 
2005: 145; 
2006: 142; 
2007: 144; 
2008: 146; 
2009: 194; 
2010: 174. 

FDA centers and offices: Office of the Commissioner (OC): 

FDA centers and offices: OC Total; 
Number of FTEs in each fiscal year: 
2000: 257; 
2001: 253; 
2002: 248; 
2003: 212; 
2004: 206; 
2005: 203; 
2006: 218; 
2007: 168; 
2008: 211; 
2009: 283; 
2010: 282. 

FDA centers and offices: Shared Service (SS)[B,G]: 

FDA centers and offices: SS Total; 
Number of FTEs in each fiscal year: 
2000: N/A; 
2001: N/A; 
2002: N/A; 
2003: N/A; 
2004: 104; 
2005: 90; 
2006: 117; 
2007: 165; 
2008: 168; 
2009: 173; 
2010: 173. 

All Centers and Offices Total; 
Number of FTEs in each fiscal year: 
2000: 2,345; 
2001: 2,340; 
2002: 2,337; 
2003: 2,432; 
2004: 2,608; 
2005: 2,540; 
2006: 2,691; 
2007: 2,738; 
2008: 2,925; 
2009: 3,526; 
2010: 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. 

[End of table] 

[End of section] 

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

Department of Health & Human Services: 
Office of The Secretary: 
Assistant Secretary for Legislation: 
Washington, DC 20201: 

March 16, 2017: 

Marcia Crosse: 
Director, Health Care: 
U.S. Government Accountability Office: 
441 G Street NW: 
Washington, DC 20548: 

Dear Ms. Crosse: 

Attached are comments on the U.S. Government Accountability Office's 
(GAO) draft report entitled, "Prescription Drugs: FDA Has Met Most 
Performance Goals for Reviewing Applications"(GAO-12-500). 

The Department appreciates the opportunity to review this report 
before its publication. 

Sincerely, 

Signed by: 

Jim R. Esquea: 
Assistant Secretary for Legislation: 

Attachment: 

[End of letter] 

General Comments Of The Department Of Health And Human Services (HHS) 
On The Government Accountability Office's (GAO) Draft Report Entitled, 
"Prescription Drugs: FDA Has Met Most Performance Goals For Reviewing 
Applications" (GAO-12-500) 

FDA appreciates the opportunity to comment on GAO's draft report, 
which recognizes FDA's success in meeting its performance goals over 
the last 12 years. GAO's findings reflect what the agency has been 
reporting during the same period and demonstrate that FDA has used the 
additional resources provided by the prescription drug user fee 
program as Congress intended: to assure that the agency conducts 
robust, speedy and efficient reviews of important and cutting-edge 
prescription drug applications so that the American people may have 
access to safe and effective therapies that can improve their health 
and save their lives. 

The last decade has been a defining period for FDA as it has enhanced 
and improved its drug review process and become the world leader in 
efficient and quality drug reviews. FDA's report, FY 2011 Innovative 
Drug Approvals,[Footnote 1] describes the agency's success in 
reviewing and approving state of the art therapies for the American 
people. For example, the report notes that in 2011, FDA approved 35 
innovative drugs, many of them groundbreaking. These drugs offer 
important advances in treatment for hepatitis C, late-stage prostate 
cancer, lupus, drug resistant skin infections, pneumonia, and other 
serious and life-threatening diseases. Almost 70% of these drugs
received FDA approval before that of any other regulatory agency in 
the world, including the European Union's (EU) drug regulatory agency. 
In addition, all but one of these drug approvals met their user fee 
performance target dates, and most received FDA approval within a 
single review cycle. In addition, in recent years, the lengths of FDA 
review times have been demonstrably shorter than those of the EU, with 
the help of the resources and tools collected under the prescription 
drug user fee program. 

In addition to leading the world in first-time drug approvals, FDA 
recognizes its critical role in fostering medical innovation. In 
October 2011, FDA released a report, Driving Biomedical Innovation: 
Initiatives for Improving Products for Patients,[Footnote 2] which 
describes steps that FDA will take to contribute to medical product 
innovation, including building the infrastructure to drive and support 
personalized medicine, expediting the drug development pathway, 
modernizing its systems for data mining, scientific computing, and 
information sharing, and streamlining and reforming FDA regulations to 
promote innovation and access to care. 

FDA has further demonstrated its commitment to strengthening the 
science and performance of the human drug review program through the 
proposed recommendations for the 2012 reauthorization of the 
prescription drug user fee program, which was negotiated with 
regulated industry and forwarded to Congress in January 2012. The 
proposed recommendations include the following enhancements: 

* A new review program for new molecular entity drug applications and 
original biological license applications; 

* a series of initiatives to further advance regulatory science and 
expedite drug development, including: 

- methods for meta-analysis (a technique for combining the findings of 
independent studies to assess the effectiveness of healthcare 
interventions), 

- biomarkers and pharmacogenomics (to understand how genes affect a 
person's response to drugs), 

- use of patient-reported outcomes, 

- development of drugs for rare diseases; 

* enhancing benefit-risk assessment; 

* enhancing and modernizing the FDA drug safety system including: 

- standardizing Risk Evaluation and Mitigation Strategies; 

- using Sentinel (a national, integrated, electronic system for 
monitoring medical product safety) to evaluate drug safety issues; and; 

* requiring electronic submissions and standardization of electronic 
application data to improve the efficiency of human drug reviews. 

FDA strives to meet the challenges of the 21' century in its mission 
to protect the health of the American people by promoting science and 
innovation. The enactment of the prescription drug user fee program 20 
years ago has revolutionized the drug review process and has allowed 
FDA to keep pace with the ever evolving science and technology that it 
must master to achieve its public health mission. The timely and 
seamless reauthorization of this critical program, which expires this 
year on September 30, will allow FDA to sustain and build on its 
significant accomplishments to promote the public health through 
conducting robust and timely drug reviews and advancing regulatory 
science to drive medical innovation. 

Footnotes: 

[1] [hyperlink, 
http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Reports/UCM278
358.pdf]. 

[2] [hyperlink, 
http://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/ucm274333.htm]. 

[End of section] 

Appendix V: GAO Contact and Staff Acknowledgments: 

GAO Contact: 

Marcia Crosse, (202) 512-7114 or crossem@gao.gov: 

Staff Acknowledgments: 

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. 

[End of section] 

Footnotes: 

[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. 

[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. 

[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. 

[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. 

[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. 

[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. 

[10] When we refer to consumer advocacy groups, we are referring to 
groups that advocate on behalf of consumers and patients. 

[11] FDA 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. 

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

[13] FDA 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. 

[14] FDA 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. 

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

[16] For 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. 

[17] FDA 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). 

[18] See 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. 

[19] If 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. 

[20] According 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. 

[21] Prior 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. 

[22] Class 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. 

[23] A 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. 

[24] Approximately 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. 

[25] The 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. 

[26] Approximately 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. 

[27] Approximately 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. 

[28] Approximately 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. 

[29] Approximately 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. 

[30] Approximately 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. 

[31] Both 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. 

[32] In 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). 

[33] We 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, [hyperlink, http://www.gao.gov/products/GAO-08-640] 
(Washington, D.C.: Sept. 30, 2008). 

[34] At 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. 

[35] Investigational new drugs are drugs permitted by FDA to be tested 
in humans but that have not been approved for marketing. 

[36] In 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. 

[37] The 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. 

[38] See GAO, Drug Safety: FDA Has Begun Efforts to Enhance Postmarket 
Safety, but Additional Actions Are Needed, [hyperlink, 
http://www.gao.gov/products/GAO-10-68] (Washington, D.C.: Nov. 9, 
2009); and Drug Safety: Improvement Needed in FDA's Postmarket 
Decision-making and Oversight Process, [hyperlink, 
http://www.gao.gov/products/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). 

[39] See U.S. Department of Health and Human Services, Food and Drug 
Administration, Advancing Regulatory Science at FDA (Silver Spring, 
Md.: August 2011). 

[40] See 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). 

[End of section] 

GAO’s Mission: 

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. 

Obtaining Copies of GAO Reports and Testimony: 

The fastest and easiest way to obtain copies of GAO documents at no 
cost is through GAO’s website [hyperlink, http://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 [hyperlink, http://www.gao.gov] and select “E-
mail Updates.” 

Order by Phone: 

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, [hyperlink, 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: 

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 [hyperlink, http://www.gao.gov]. 

To Report Fraud, Waste, and Abuse in Federal Programs: 

Contact: 
Website: [hyperlink, http://www.gao.gov/fraudnet/fraudnet.htm]; 
E-mail: fraudnet@gao.gov; 
Automated answering system: (800) 424-5454 or (202) 512-7470. 

Congressional Relations: 

Katherine Siggerud, Managing Director, siggerudk@gao.gov, (202) 512-4400
U.S. Government Accountability Office, 441 G Street NW, Room 7125
Washington, DC 20548. 

Public Affairs: 
Chuck Young, Managing Director, youngc1@gao.gov, (202) 512-4800
U.S. Government Accountability Office, 441 G Street NW, Room 7149 
Washington, DC 20548.