Food and Drug Administration: Data to Measure the Timeliness of  
Reviews
							 
of Medical Device Applications Are Limited (30-AUG-04,		 
GAO-04-1022).							 
                                                                 
FDA reviews applications from manufacturers that wish to market  
medical devices in the United States. To ensure prompt approval  
of new devices and clearance of devices that are substantially	 
equivalent to those legally on the market, the Congress passed	 
the Medical Device User Fee and Modernization Act of 2002	 
(MDUFMA). The act authorizes FDA to collect user fees and, in	 
return, requires FDA to meet performance goals that are tied to  
the agency's review process. The goals set actions FDA may take  
on applications and specify the time that FDA should take in	 
certain phases of the review process. MDUFMA requires GAO to	 
report on FDA's performance against the MDUFMA performance goals 
established for fiscal years 2003 and 2004 and to determine	 
whether FDA is likely to meet the fiscal year 2005 performance	 
goals. MDUFMA also requires GAO to report on the amounts FDA	 
obligated in fiscal year 2002 for medical device compliance	 
activities and inspections of manufacturers after their devices  
are marketed. GAO analyzed data provided by FDA that are based on
actions taken on applications FDA received from October 1, 2002, 
through March 31, 2004. GAO also analyzed data on the amounts FDA
obligated for medical device compliance and inspection activities
for fiscal year 2002.						 
-------------------------Indexing Terms------------------------- 
REPORTNUM:   GAO-04-1022					        
    ACCNO:   A12074						        
  TITLE:     Food and Drug Administration: Data to Measure the	      
Timeliness of Reviews
						 
of Medical Device Applications Are Limited			 
     DATE:   08/30/2004 
  SUBJECT:   Inspection 					 
	     Medical research					 
	     Performance measures				 
	     Reporting requirements				 
	     Research and development				 
	     Safety regulation					 
	     Budget obligations 				 
	     Commodity marketing				 
	     Regulatory agencies				 

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GAO-04-1022

                 United States Government Accountability Office

                     GAO Report to Congressional Committees

August 2004

                                 FOOD AND DRUG
                                 ADMINISTRATION

  Data to Measure the Timeliness of Reviews of Medical Device Applications Are
                                    Limited

                                       a

GAO-04-1022

Highlights of GAO-04-1022, a report to congressional committees

FDA reviews applications from manufacturers that wish to market medical
devices in the United States. To ensure prompt approval of new devices and
clearance of devices that are substantially equivalent to those legally on
the market, the Congress passed the Medical Device User Fee and
Modernization Act of 2002 (MDUFMA). The act authorizes FDA to collect user
fees and, in return, requires FDA to meet performance goals that are tied
to the agency's review process. The goals set actions FDA may take on
applications and specify the time that FDA should take in certain phases
of the review process.

MDUFMA requires GAO to report on FDA's performance against the MDUFMA
performance goals established for fiscal years 2003 and 2004 and to
determine whether FDA is likely to meet the fiscal year 2005 performance
goals. MDUFMA also requires GAO to report on the amounts FDA obligated in
fiscal year 2002 for medical device compliance activities and inspections
of manufacturers after their devices are marketed.

GAO analyzed data provided by FDA that are based on actions taken on
applications FDA received from October 1, 2002, through March 31, 2004.
GAO also analyzed data on the amounts FDA obligated for medical device
compliance and inspection activities for fiscal year 2002.

August 2004

FOOD AND DRUG ADMINISTRATION

Data to Measure the Timeliness of Reviews of Medical Device Applications Are
Limited

FDA had limited data that could be used to measure the agency's
performance against most of the MDUFMA performance goals. Thus, it is
uncertain whether FDA will meet the MDUFMA performance goals for fiscal
years 2003, 2004, and 2005. For fiscal years 2003 and 2004, there were two
performance goals in effect for each year. As of March 31, 2004, only one
application was subject to the action tied to one of the two MDUFMA
performance goals. On this application, FDA completed its review and made
the decision to approve the application within the goal's established time
frame. To determine the likelihood of meeting the 20 MDUFMA performance
goals for fiscal year 2005, FDA is collecting data on its performance
against these goals. GAO found that FDA had performance data for some, but
not all, of the MDUFMA performance goals. From fiscal year 2003
applications, data were available to compare FDA's performance against 17
of the 20 fiscal year 2005 performance goals. FDA took actions tied to 14
of the 17 goals within the goals' established time frames. From fiscal
year 2004 applications, data were available to compare FDA's performance
against 11 of the 20 performance goals. FDA took actions tied to the 11
goals within the goals' established time frames. The results of FDA's
performance against MDUFMA performance goals are preliminary, however,
because 8 percent and 49 percent, respectively, of the applications FDA
accepted in fiscal year 2003 and the first 6 months of fiscal year 2004
were awaiting action by FDA or responses from manufacturers. Because FDA's
performance against the MDUFMA performance goals is based on the
percentages of actions the agency takes within required review times,
FDA's results could change as the agency completes its actions on all
applications for which the goals apply.

FDA obligated about $128 million for postmarket medical device compliance
activities and inspections in fiscal year 2002. FDA obligated about $109
million for compliance activities for outreach coordination, such as
guidance to field staff on reporting problems with medical devices,
laboratory analyses, and research, such as the development of domestic and
international standards to provide reasonable assurance that medical
device products are safe and effective. FDA obligated about $19 million
for inspections of device manufacturers' establishments, including routine
surveillance inspections to determine compliance with medical device
regulations and inspections resulting from device problem reporting or
product recalls.

In commenting on a draft of this report, FDA generally agreed with its
findings.

www.gao.gov/cgi-bin/getrpt?GAO-04-1022.

To view the full product, including the scope and methodology, click on
the link above. For more information, contact Marcia Crosse at (202)
512-7119.

Contents

    Letter                                                                  1 
                                         Results in Brief                   4 
                                            Background                      5 
                        Limited Data to Measure FDA's Performance against  
                                            the MDUFMA                     
                                        Performance Goals                  16 
                          FDA Obligated over $128 Million for Postmarket   
                                          Medical Device                   
                         Compliance Activities and Inspections in Fiscal   23 
                                            Year 2002                      
                                         Agency Comments                   24 
Appendix                                                                
            Appendix I:   Comments from the Food and Drug Administration   

Tables Table 1:

Table 2: Table 3:

Table 4:

MDUFMA Performance Goals for Fiscal Years 2003 and
2004
MDUFMA Performance Goals for Fiscal Year 2005
Status of FDA's Performance for Fiscal Years 2003 and 2004
Compared to MDUFMA Performance Goals That Become
Effective in Fiscal Year 2005
Applications Pending within FDA's Review Process in the
Fiscal Year 2003 Cohort and the First 6 Months of the Fiscal
Year 2004 Cohort

                                     13 14

                                       18

                                       22

Figures	Figure 1: PMA Review Process 8 Figure 2: 510(k) Review Process 11

Contents

Abbreviations

BLA biologics license application
CBER Center for Biologics Evaluation and Research
CDRH Center for Devices and Radiological Health
FDA Food and Drug Administration
FDCA Federal Food, Drug, and Cosmetics Act
GMP good manufacturing practices
HHS Department of Health and Human Services
MDUFMA Medical Device User Fee and Modernization Act of 2002
PMA premarket approval

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. However, because this
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copyright holder may be necessary if you wish to reproduce this material
separately.

A

United States Government Accountability Office Washington, D.C. 20548

August 30, 2004

The Honorable Judd Gregg
Chairman
The Honorable Edward M. Kennedy
Ranking Minority Member
Committee on Health, Education, Labor, and Pensions
United States Senate

The Honorable Joe Barton
Chairman
The Honorable John D. Dingell
Ranking Minority Member
Committee on Energy and Commerce
House of Representatives

The Food and Drug Administration (FDA) is responsible for regulating
medical devices-such as tongue depressors, pacemakers, and artificial
hearts-to provide reasonable assurance of their safety and effectiveness
for human use. As part of its regulatory responsibilities, FDA reviews
applications from manufacturers that wish to have their new medical
devices or devices substantially equivalent to those already on the market
approved for marketing in the United States. When required, FDA inspects
manufacturers' establishments prior to approval. FDA is also responsible
for implementing and enforcing medical device regulations related to
compliance activities, which include the reporting of problems associated
with the safety and effectiveness of devices and inspections of
manufacturers' device establishments after devices reach the market.

Each year FDA receives approximately 10,000 medical device applications.
Members of the Congress, representatives of the medical device industry,
and others have expressed concern about the length of time it takes FDA to
review applications for marketing medical devices, with the consequence
of possibly delaying patients' access to useful, and possibly life-saving,
medical devices.

In October 2002, the Congress passed the Medical Device User Fee and
Modernization Act of 2002 (MDUFMA) to provide FDA with additional

resources to ensure prompt approval or clearance1 of applications for
marketing medical devices and licensing biological products.2 MDUFMA
authorized FDA to collect user fees from manufacturers that submit several
types of applications to FDA for marketing medical devices. In return,
MDUFMA requires FDA to meet performance goals tied to the review process
for medical device and biological applications. MDUFMA also requires the
Secretary of Health and Human Services (HHS) to develop the specific goals
FDA must meet. The Secretary developed performance goals for fiscal years
2003 through 2007. These MDUFMA performance goals are set for certain
actions FDA may take during the application review process and specify
lengths of time for taking these actions. FDA's performance against the
MDUFMA performance goals is based on the percentages of actions the agency
takes on applications within required review times. To help FDA meet the
MDUFMA performance goals, the Secretary of HHS also identified several
goal-related activities for FDA to undertake, such as hiring additional
review staff.

The number of MDUFMA performance goals that FDA must meet increases over
time. For fiscal years 2003 and 2004, FDA must meet the same two
performance goals for each year. For example, one of the performance goals
requires FDA to review a manufacturer's response to the agency's request
for additional information on applications that are approvable with minor
corrections or clarifications,3 and then take the next appropriate action,
such as make a decision to approve the application. To meet the
performance goal, FDA must review and make the decision within 30 days on
90 percent of the applications received for each fiscal year. In fiscal
year 2005, FDA must meet the two goals and an additional 18 performance
goals tied to medical device and biological product applications, for a
total of 20. The 20 performance goals are tied to times for reviews,
decisions, or a combination of both.

MDUFMA requires us to report on FDA's performance as measured against the
fiscal years 2003 and 2004 MDUFMA performance goals and determine

1The term "approval" is generally used for applications for new devices,
while the term "clearance" is used for devices that are substantially
equivalent to those legally on the market.

2Pub. L. No. 107-250, 116 Stat. 1588.

3FDA's request for additional information on such applications is known as
an "approvable" letter.

whether the agency is likely to meet the fiscal year 2005 MDUFMA
performance goals. MDUFMA also requires us to report on the amounts FDA
obligated in fiscal year 2002 for medical device compliance activities and
inspections of manufacturers' device establishments after their devices
are marketed, excluding the amounts that were obligated for inspections
related to the review of medical device applications.

To examine FDA's performance, we analyzed actions taken by FDA on
applications that it received from fiscal year 2003 through the first 6
months of fiscal year 2004 (October 1, 2003, through March 31, 2004). At
the time of our review, performance data through March 31, 2004, were the
most current FDA data available. To assess FDA's performance against the
two MDUFMA performance goals that were established for fiscal years 2003
and 2004, we analyzed performance data for applications received in those
years. To determine the likelihood of FDA meeting its fiscal year 2005
MDUFMA performance goals, we compared performance data that FDA is
collecting on fiscal years 2003 and 2004 applications to the 20 MDUFMA
performance goals that will be effective in fiscal year 2005. We also
reviewed relevant documents and interviewed officials from FDA's Center
for Devices and Radiological Health (CDRH) and Center for Biologics
Evaluation and Research (CBER) about two key FDA medical device
application review processes and the agency's performance as measured
against the MDUFMA performance goals. These two processes are referred to
as (1) the Premarket Approval (PMA) review process, which is used to
review an application for a new medical device or when the risks
associated with the device are considerable, and (2) the 510(k) review
process, which is used to review an application for a type of device that
may be substantially equivalent to one already on the market. In addition,
we reviewed documentation of FDA's procedures for checking the reliability
of MDUFMA performance data and met with FDA officials to discuss their
efforts to verify the accuracy and consistency of their reported
performance data. We determined that the performance data were
sufficiently reliable for the purposes of this report.

To determine the amounts FDA obligated in fiscal year 2002 for medical
device compliance activities and inspections of manufacturers' device
establishments after devices are marketed, we reviewed and analyzed data
from FDA's fiscal year 2004 budget justification and information FDA
provided related to these data. The fiscal year 2004 budget justification
contains FDA's fiscal year 2002 actual obligations for medical device
compliance activities and inspections. To assess the reliability of these
data, we reviewed supporting documentation that FDA provided on the

obligations reported in the agency's fiscal year 2004 budget justification
related to compliance activities and inspections for marketed devices. We
also reviewed FDA's fiscal year 2003 audited financial statement report
that contained information about the reliability of fiscal year 2002
obligations data. The review found no material weaknesses related to our
work. Based on these reviews, we determined that the obligations data were
sufficiently reliable for the purposes of this report. We conducted our
work from January 2004 through August 2004 in accordance with generally
accepted government auditing standards.

Results in Brief	FDA had limited data that could be used to measure the
agency's performance against most of the MDUFMA performance goals. Thus,
it is uncertain whether FDA will meet the goals established for fiscal
years 2003, 2004, and 2005. For example, for fiscal year 2003, the two
performance goals could be applied to 53 applications. However, as of
March 31, 2004, only one application was subject to a review and a
decision tied to one of the two MDUFMA performance goals. On that
application, FDA reviewed the manufacturer's complete response to FDA's
approvable letter and made the decision to approve the application within
the goal's established time frame. For fiscal year 2004, there was no
application subject to the review and decision tied to the two fiscal year
2004 MDUFMA performance goals. FDA had performance data for some, but not
all, of the MDUFMA performance goals that will be effective in fiscal year
2005. For applications received in fiscal year 2003, data were available
to compare FDA's performance against 17 of the 20 performance goals for
fiscal year 2005. FDA took actions on applications tied to 14 of the 17
performance goals within the established time frames. For fiscal year 2004
applications, FDA had performance data for 11 of the 20 performance goals.
FDA took actions on applications tied to the 11 goals within the
established time frames. The results of FDA's performance against MDUFMA
goals are preliminary, however, because many of the applications FDA
received in fiscal year 2003 and the first 6 months of fiscal year 2004
were pending within the review process. Because FDA's performance against
the MDUFMA performance goals is based on the percentages of actions the
agency takes on applications within required review times, FDA's
performance results could change as the agency completes actions on all
applications for which the performance goals apply.

FDA obligated over $128 million for postmarket medical device compliance
activities and inspections in fiscal year 2002. FDA obligated about

$109 million for compliance activities for outreach coordination, such as
guidance to field staff on the reporting of problems with medical devices;
laboratory analyses; and research, such as the development of domestic and
international standards to help provide reasonable assurance that medical
devices are safe and effective. FDA obligated about $19 million for
inspections of manufacturers' device establishments that included routine
surveillance inspections to determine compliance with medical device
regulations and inspections resulting from device problem reporting or
product recalls.

We provided a draft of this report to FDA, which generally agreed with its
findings. FDA believes that it has made a good start in its implementation
of MDUFMA and believes its progress with the MDUFMA performance goals is
consistent with the extensive performance improvements the agency is
expected to achieve each year through 2007.

Background	Under the Federal Food, Drug, and Cosmetic Act (FDCA),4 FDA is
responsible for ensuring that medical devices are reasonably safe and
effective before they go to market (premarket) and that marketed device
products remain safe (postmarket). Two FDA centers, CDRH and CBER, are
responsible for the PMA and clearance of medical device applications.5
CDRH reviews applications for the majority of devices marketed, such as
artificial hearts, dialysis machines, and radiological devices. CBER
reviews applications for devices used in the testing and manufacture of
biological products, such as diagnostic tests intended to screen blood
donors (such as for the human immunodeficiency virus), as well as devices
used in cell and gene therapies.

Each fiscal year, FDA obligates funds for postmarket compliance activities
and inspections related to medical devices and radiological products. FDA
provides field staff with guidance on inspecting manufacturers'
establishments after devices have been marketed, for compliance with the
good manufacturing practices (GMP) requirements, monitoring

4Ch. 675, 52 Stat. 1040 (1938) (codified as amended at 21 U.S.C. S:S: 301
et seq. (2000)).

5In general, medical device applications for PMA that are reviewed by FDA
include information on the device and its components; proposed labeling
for the device; and when applicable, clinical and nonclinical studies that
provide reasonable assurance of the device's safety and effectiveness.

manufacturers' corrections of problems with devices, and removing unsafe
devices from the market. FDA has 21 district offices that support
inspections of manufacturers' establishments. During inspections for
compliance with GMP requirements, FDA investigators examine manufacturer
facilities, records of manufacturing processes, and corrective action
programs.

Types of Applications Reviewed under MDUFMA Performance Goals

MDUFMA identified eight types of applications for medical devices and
biological products that are subject to the performance goals developed by
the Secretary of HHS for fiscal years 2003, 2004, and 2005:

o 	Original PMA applications are generally required when the device is new
or when the risks associated with the device are considerable (as would be
the case if the device is implanted in the body for life-supporting
purposes).

o 	Premarket Notifications, or 510(k)s,6 are applications used when the
intent is to market a type of device that may be considered substantially
equivalent7 to one already on the market and therefore, does not require
PMA.

o 	Premarket Reports are applications required for high-risk devices
originally approved for a single use that a manufacturer has reprocessed
for additional uses.

o 	Panel-Track Supplements are applications used to supplement approved
PMAs or Premarket Reports. These supplements typically request approval of
a significant change in the design or performance of a device, or for a
new purpose for using the device.

o 	Expedited Original PMAs are used when a manufacturer seeks priority
status to market a medical device that is intended to treat or diagnose a
life-threatening or irreversibly debilitating disease or condition or to
address an unmet medical need.

6FDA uses the term 510(k) to refer to a premarket notification submission.

7Substantial equivalence means that a device has (1) the same intended use
and same technological characteristics as a marketed device or (2) the
same intended use and different technological characteristics but is as
safe and effective as the marketed device and does not raise new questions
of safety and effectiveness.

o 	The 180-day PMA Supplements are used to supplement approved PMAs or
premarket reports. The application typically requests approval of a
significant change in aspects of a device, such as its design,
specifications, or labeling.

o 	Biologics license applications (BLAs) 8 Resubmissions (Class 1) are
used to respond to information requested by FDA on a BLA and may include
matters related to product labeling or safety and other minor clarifying
information.

o 	BLA Supplement Resubmissions (Class 2) are used to respond to an FDA
request for information on a BLA regarding the safety and effectiveness of
products or a re-inspection of the manufacturer's device establishment.

FDA's Medical Device Application Review Processes

FDA primarily uses two medical device application review processes; the
PMA review process and the 510(k) review process.9 FDA annually receives
about 50 PMAs and about 4,000 510(k) applications for review through these
processes.

The PMA Review Process	Under the PMA review process, FDA reviews
applications for new devices or those for which risks associated with the
device are considerable. Applications reviewed under this process include
Original PMAs, Premarket Reports, Panel-Track Supplements, Expedited
Original PMAs, and 180-day PMA Supplements. After an initial screening of
an application and determination that the review should proceed, an FDA
multidisciplinary staff conducts a scientific review of the application10
and determines whether it is complete, that is, if it contains sufficient
information to allow the review to continue. (See fig. 1.)

8BLAs are used to request permission to introduce and license biological
products into interstate commerce.

9According to FDA officials, BLA applications go through a review process
that is similar to the PMA review process.

10The scientific review can include reviews of results from clinical
investigations of the device that involve human subjects. FDA also reviews
nonclinical studies of the device, studies that may include
microbiological, toxicological, and engineering tests.

                          Figure 1: PMA Review Process

                                  Source: GAO.

For complete applications, FDA may make one of five decisions. FDA may (1)
issue an order approving the application, which allows the manufacturer to
begin marketing the device; (2) send the manufacturer an approvable letter
pending a GMP inspection, which indicates that FDA should be able to
approve the device after the agency finds that the manufacturer's device
establishment is in compliance with GMP requirements; (3) send the
manufacturer an approvable letter indicating that the agency should be
able to approve the device if the manufacturer can make minor corrections
or clarifications to the application; (4) issue a "not approvable" letter
informing the manufacturer that FDA does not believe that the application
can be approved because the data provided by the manufacturer do not
demonstrate that the device is reasonably safe and effective; or (5) issue
an order denying approval of the application, which informs the
manufacturer that the agency has completed its scientific review,
identified major safety and effectiveness problems, and decided not to
approve the application. FDA may refer complete applications to an
external advisory committee for evaluation when a device is the first of
its kind or when the agency believes it would be useful to have
independent expertise and technical assistance to properly evaluate the
safety and effectiveness of the device.11 For applications referred to an
advisory committee, the committee submits recommendations to FDA on the
safety and effectiveness of the devices. Taking the committee's
recommendations into consideration, FDA then makes its decision.

For incomplete applications, that is, applications for which FDA
determines it needs significant additional information, FDA issues a
"major deficiency letter" to the manufacturer identifying the information
that is required to provide reasonable assurance of the safety and
effectiveness of the device. This request for significant information is
an action referred to as a cycle action. In general, FDA takes cycle
actions when it requests additional information from the manufacturer, or
when it evaluates additional information provided by the manufacturer in
response to an FDA request. The manufacturer responds to FDA's request by
submitting an amendment to the original application. Cycle actions on an
application can occur repeatedly until FDA determines that the
manufacturer has provided what the agency calls a "complete response" to
all of the agency's concerns. Then, FDA may make a decision on the
application.

11According to FDA, approximately 13 percent of the PMAs, Panel-Track
Supplements, and Expedited PMA applications are referred to external
advisory committees.

Manufacturers that receive approvable letters pending minor corrections or
clarifications or not approvable letters can gain final approval by
submitting amendments with complete responses to FDA's concerns. For both
types of decisions, if FDA, as part of a cycle action, determines that the
manufacturer's amendment is a complete response, FDA issues an order
approving the application. If the amendment is not a complete response,
FDA issues another approvable letter pending minor corrections or
clarifications or a not approvable letter.

The 510(k) Review Process	Under the 510(k) review process, FDA decides
whether the application contains sufficient information to determine
whether the device is substantially equivalent to one legally on the
market (see fig. 2). When a 510(k) application lacks information necessary
for FDA to complete its review and make a determination as to whether the
device is substantially equivalent, the agency issues a letter requesting
additional information from the manufacturer. This request for additional
information is a cycle action. The manufacturer may then submit additional
information responding to FDA's concerns. Once FDA has obtained complete
information from the manufacturer, FDA issues a decision letter informing
the manufacturer that the device is substantially equivalent and therefore
may be marketed or the device is not substantially equivalent and may not
be marketed.

                        Figure 2: 510(k) Review Process

                                  Source: GAO.

Measuring FDA's The MDUFMA performance goals specify a length of time for
taking a cycle Performance under action, making a decision, or a
combination of both. The goals designate a MDUFMA certain percentage of
these actions that must occur within the specified

period in order for FDA to meet the performance goals. To measure its

performance against the MDUFMA performance goals, FDA tracks the

time, in calendar days, the agency takes to complete a cycle action or
make

a decision-but not the time it takes a manufacturer to respond to a
request from FDA.12

FDA measures its performance against a specific fiscal year's MDUFMA
performance goals using all the applications it received in that year-
known as a cohort13-regardless of when the final decision is made for each
of the applications in that year's cohort. The agency's performance as
measured against a fiscal year's MDUFMA performance goals is preliminary
until all applications in a cohort are completed -and this can take up to
3 or 4 fiscal years.

The two MDUFMA performance goals that FDA must meet for fiscal years 2003
and 2004 are tied to the same type of cycle action for different types of
applications. One performance goal applies to the cycle action taken on
PMAs, Panel-Track Supplements, and Premarket Reports, and the other
performance goal applies to Expedited PMAs. To meet each performance goal,
FDA must review the completeness of a manufacturer's response to an
approvable letter pending minor corrections or clarifications and make a
decision within 30 days of receiving the manufacturer's amendment. FDA
must meet this time frame on 90 percent of the applications for which it
takes a cycle action (see table 1).

12Except for BLA Resubmissions and BLA Supplement Resubmissions, there are
also limits on the length of time manufacturers have to respond to the
agency's requests for additional information. For example, as required by
FDA regulation, manufacturers submitting amendments to PMAs have 180 days
to respond to major deficiency letters. Manufacturers submitting
amendments to PMAs can also apply for extensions of up to 180 days beyond
the required response time. Manufacturers submitting amendments to 510(k)s
have 30 days to respond to first or subsequent letters requesting
additional information. For amendments to 510(k)s, manufacturers can apply
for extensions of up to 180 days from the date of the first or subsequent
letters.

13FDA refers to cohorts as "receipt cohorts."

        Table 1: MDUFMA Performance Goals for Fiscal Years 2003 and 2004

Performance goal

Percentage of applications received in each fiscal year required to meet
review time

Fiscal year 2003 Fiscal year 2004 Type of application FDA cycle actions
Review time cohort cohort

       PMAs, Panel-Track        Review whether an amendment is a           
Supplements, and Premarket  complete response to an approvable          
                                             letter                        
            Reportsa              pending minor corrections or             
                                         clarifications                    
                                  and make a decision, such as             
                                         approving the                     
                                          application              30 days 90 

Expedited PMAs	Review whether an amendment is a complete response to an
approvable letter pending minor corrections or clarifications and make a
decision, such as approving the application 30 days 90

Source: GAO analysis of HHS and FDA information.

aFDA groups these types of applications together when measuring
performance for this goal.

In fiscal year 2005, 20 MDUFMA performance goals will become effective,
including the 2 performance goals that have been effective since fiscal
year 2003 (see table 2). The 20 performance goals will apply to eight
types of applications identified under MDUFMA and will be tied to other
cycle actions and decisions FDA makes on the applications during the
review process.

Table 2: MDUFMA Performance Goals for Fiscal Year 2005

                                Performance goal

Percentage of applications received in fiscal year 2005 cohort required to
                                                             meet review time

        Type of application FDA cycle actions and decisions Review time

PMAs, Panel-Track Cycle action: Issue first major deficiency letter
Supplements, and Premarket requesting significant information from the
Reportsa manufacturer 150 days

Decision: Issue decision letter (approval,
approvable pending GMP inspection, approvable
pending minor corrections or clarifications, not
approvable, or denial) as a first action on an
application 180 days

Cycle action: Issue second or subsequent major
deficiency letter requesting significant information
from the manufacturer 120 days

Cycle action: Determine whether an amendment contains a complete response
to a major deficiency or not approvable letter 180 days

Cycle action: Review whether an amendment
contains a complete response to an approvable
letter pending minor corrections or clarifications
and make a decision, such as approving the
application 30 days

Expedited PMAs	Decision: Issue decision letter (approval, approvable
pending GMP inspection, approvable pending minor corrections or
clarifications, not approvable, or denial) after taking a cycle action on
an application 300 days

Cycle action: Issue first major deficiency letter
requesting significant information from the
manufacturer 120 days

Decision: Issue decision letter (approval,
approvable pending GMP inspection, not
approvable, approvable pending minor corrections
or clarifications, or denial) as a first action on an
application 170 days 70

           Cycle action: Issue a second or subsequent major             
       deficiency letter requesting significant information             
                                      from the manufacturer  100 days      70 
               Cycle action: Determine whether an amendment             
                    contains a complete response to a major             
                        deficiency or not approvable letter  170 days      70 

(Continued From Previous Page)

                                Performance goal

Percentage of applications received in fiscal year 2005 cohort required to
                                                             meet review time

        Type of application FDA cycle actions and decisions Review time

Cycle action: Review whether an amendment
contains a complete response to an approvable
letter pending minor corrections or clarifications
and make a decision, such as approving the
application 30 days

180-day PMA Supplements	Decision: Issue decision letter (approval,
approvable pending GMP inspection, approvable pending minor corrections or
clarifications, not approvable, or denial) after taking a cycle action on
an application 180 days

Decision: Issue a not approvable letter as a first action on an
application 120 days

Decision: Issue decision letter (approval,
approvable pending GMP inspection, approvable
pending minor corrections or clarifications, or
denial) as a first action on an application 180 days

Cycle action: Determine whether an amendment contains a complete response
to a not approvable letter 160 days

Premarket Notifications    Decision: Issue decision letter (for    
                                           example, a                 
          (510(k)s)        letter for a device that may be marketed   
                           because it                                 
                           is substantially equivalent to one already 
                                             on the                   
                           market, or that may not marketed because   
                           it is not                                  
                                   substantially equivalent)          90 days 

Cycle action: Issue first additional information letter 75 days

Cycle action: Issue second or subsequent
additional information letter 60 days

BLA Resubmissions and BLA  Cycle action: Review and act on a            
                                           Class 1                         
Supplement Resubmissions   resubmission to an original BLA or           
                                             BLA                           
                               supplement (for example, issue a            
                                      letter requesting                    
                                  limited labeling or safety               
                                     information from the                  
                                        manufacturer)             2 months 75 

Cycle action: Review and act on a Class 2
resubmission to an original BLA or BLA
supplement (for example, issue a letter requesting
data on product safety and effectiveness from the
manufacturer) 6 months 75

     Source: GAO analysis of HHS and FDA information as of March 31, 2004.

aFDA groups these types of applications together when measuring
performance for this goal.

Limited Data to Measure FDA's Performance against the MDUFMA Performance
Goals

FDA had limited data that could be used to measure the agency's
performance against most of the MDUFMA performance goals. Thus, it is
uncertain whether FDA will meet the MDUFMA performance goals for fiscal
years 2003, 2004, and 2005. For fiscal year 2003, the two performance
goals could be applied to 53 applications. However, as of March 31, 2004,
only one application was subject to a cycle action tied to one of the two
MDUFMA performance goals. In its review of that application, FDA
determined that the manufacturer provided a complete response to an
approvable letter pending minor corrections or clarifications and made the
decision to approve the application within the goal's time frame. For
fiscal year 2004, there were no applications subject to the cycle action
tied to the two fiscal year 2004 MDUFMA performance goals. In addition,
the likelihood of FDA meeting the fiscal year 2005 MDUFMA performance
goals is uncertain because FDA had performance data for some, but not all,
of the MDUFMA performance goals that will be effective in fiscal year
2005. FDA's performance results could change as the agency completes its
actions on all applications for which the performance goals apply.

Limited Data to Measure FDA's Performance against the MDUFMA Performance
Goals Established for Fiscal Years 2003 and 2004

Limited data exist to measure FDA's performance against the two MDUFMA
performance goals established for fiscal years 2003 and 2004. Our analysis
shows that FDA received 43 PMAs, 7 Panel-Track Supplements, and 3
Expedited PMAs in the fiscal year 2003 cohort.14 As of March 31, 2004, one
application-an Expedited PMA-had been subject to the cycle action tied to
one of the two MDUFMA performance goals for fiscal year 2003.15 In its
review of this application FDA determined that the manufacturer submitted
a complete response to an approvable letter pending minor corrections or
clarifications, and approved the application within 30 days. For PMAs and
Panel-Track Supplements, the same MDUFMA performance goal applied for
fiscal year 2003. However, FDA did not have any applications that required
the issuance of an approvable letter. Similarly, none of the 15 PMAs, 1
Panel-Track Supplement, and 8 Expedited PMA applications from the fiscal
year 2004 cohort required issuance of approvable letters.

14FDA received other types of applications in the fiscal year 2003 and
2004 cohorts, but these types are not connected to the MDUFMA performance
goals established for fiscal years 2003 and 2004. FDA did not receive any
Premarket Report applications, the fourth type of application tied to the
fiscal year 2003 and 2004 MDUFMA performance goals.

15The Expedited PMA is tied to one of the two MDUFMA performance goals.

Many of the applications from the fiscal years 2003 and 2004 cohorts were
pending within the review process for FDA review actions or manufacturers'
responses to FDA. Therefore, FDA's performance results are preliminary. In
the fiscal year 2003 cohort, 21 of the 50 PMAs and Panel-Track Supplements
and 1 of the 3 Expedited PMAs FDA received were pending as of March 31,
2004. Similarly, in the fiscal year 2004 cohort, 13 of the 15 PMAs, 1
Panel-Track Supplement, and all 8 of the Expedited PMAs FDA received were
pending action. Because FDA's performance against the MDUFMA performance
goals is based on the percentages of actions the agency takes on
applications within required review times, FDA's performance results could
change as the agency completes actions on all applications for which the
performance goals apply. Data were not readily available from FDA on the
status of all pending applications within the review process. FDA
anticipates having complete data by the end of fiscal year 2004.

Limited Performance Data to Determine the Likelihood of FDA Meeting the
Fiscal Year 2005 MDUFMA Performance Goals

The likelihood of FDA meeting the MDUFMA performance goals for fiscal year
2005 is uncertain because data to measure the agency's performance are
limited. Specifically, FDA had data that allowed us to compare its
performance against some, but not all, of the 20 MDUFMA performance goals
that will be effective in fiscal year 2005. For example, from the fiscal
year 2003 cohort, data were available to compare FDA's performance against
17 of the 20 performance goals for fiscal year 2005. FDA took actions on
applications tied to 14 of the 17 performance goals within the established
goal time frames. For 7 of the 14 performance goals, FDA's performance was
based on one or two actions on applications. FDA did not take actions
within the established goal time frames on applications tied to 3 of the
17 performance goals. Similarly, from the fiscal year 2004 cohort, FDA had
data for 11 of the 20 MDUFMA performance goals. We found that FDA took
actions on applications tied to each of the 11 performance goals within
the established goal time frames. For 4 of the 11 performance goals, FDA's
performance was based on no more than three actions on applications. (See
table 3.)

Table 3: Status of FDA's Performance for Fiscal Years 2003 and 2004
Compared to MDUFMA Performance Goals That Become Effective in Fiscal Year
2005

        Performance goal Type of application Cycle actions and decisions

Review time

     Percentage of actions required to meet the goal for the fiscal year 2005
                                                                       cohort

Percentage of actions taken on applications within goal's established time frame

Fiscal year 2003 cohort

Fiscal year 2004 cohort

PMAs, Panel-Track Cycle action: Issue first major deficiency 85% 100%
Supplements, and letter requesting significant information
Premarket Reportsa from the manufacturer (22 of 26 cycle (2 of 2 cycle

150 days 75 actions) actions)

Decision: Issue decision letter (approval,
approvable pending GMP inspection,
approvable pending minor corrections or 96% 100%
clarifications, not approvable, or denial)
as a first action on an application 180 days 75 (22 of 23 decisions) (3 of
3 decisions)

           Cycle action: Issue second or                                    b 
      subsequent major deficiency letter                      100%          
      requesting significant information                                    
                                    from                                    
                        the manufacturer 120 days 75  (1 of 1 cycle action) 
      Cycle action: Determine whether an                                    b 
           amendment contains a complete                      89%           
response to a major deficiency or not                                    
                       approvable letter 180 days 75 (8 of 9 cycle actions) 

                Cycle action: Review whether an                      b      b 
                  amendment contains a complete                          
               response to an approvable letter                          
                   pending minor corrections or                          
       clarifications and make a decision, such                          
                   as approving the application     30 days   90         

(Continued From Previous Page)

                                Performance goal

Review time

     Percentage of actions required to meet the goal for the fiscal year 2005
                                                                       cohort

Percentage of actions taken on applications within goal's established time frame

Fiscal year 2003 cohort

Fiscal year 2004 cohort

                Type of application Cycle actions and decisions

Expedited PMAs   Decision: Issue decision letter                         b 
                                         (approval,                         
                  approvable pending GMP                                    
                  inspection,                                               
                           approvable pending minor                         
                                     corrections or                         
                  clarifications, not approvable,                  100%     
                  or denial)                                                
                  after taking a cycle action on an                         
                                                             70   (2 of 2   
                             application            300 days    decisions)  

      Cycle action: Issue first major                      100%          100% 
                           deficiency                           
        letter requesting significant                           
                          information                           
                from the manufacturer             (2 of 2 cycle (4 of 4 cycle 
                                      120 days 70      actions)      actions) 

     Decision: Issue decision letter                               
                          (approval,                               
              approvable pending GMP                               
                         inspection,                               
            approvable pending minor                          100%       100% 
                      corrections or                               
     clarifications, not approvable,                               
                          or denial)                               
             as a first action on an          70                      (1 of 1 
                         application 170 days    (1 of 1 decision)  decision) 

            Cycle action: Issue second or                                 b b 
       subsequent major deficiency letter                                   
requesting additional information from                                   
                         the manufacturer 100 days 70                       
       Cycle action: Determine whether an                                   b 
            amendment contains a complete                     100%          
    response to a major deficiency or not                                   
                        approvable letter 170 days 70 (1 of 1 cycle action) 

           Cycle action: Review whether an                                  b 
             amendment contains a complete                                  
          response to an approvable letter                                  
              pending minor corrections or                    100%          
       clarifications and make a decision,                                  
                                      such                                  
              as approving the application 30 days 90 (1 of 1 cycle action) 

(Continued From Previous Page)

                                Performance goal

Review time

     Percentage of actions required to meet the goal for the fiscal year 2005
                                                                       cohort

Percentage of actions taken on applications within goal's established time frame

Fiscal year 2003 cohort

Fiscal year 2004 cohort

                Type of application Cycle actions and decisions

180-day PMA Decision: Issue decision                         
                      letter (approval,                         
Supplements approvable pending GMP                           
               inspection,                                      
               approvable pending minor                     95%          100% 
                         corrections or                         
                    clarifications, not                         
                 approvable, or denial)                         
                 after taking a cycle               (194 of 205     (15 of 15 
                     action on an                               
                     application         180  80     decisions)    decisions) 
                                        days                    
               Decision: Issue a not                        19%           83% 
               approvable letter                                
               as a first action on an                          
                     application                                
                                                 (6 of 32 cycle (5 of 6 cycle 
                                         120  80                              
                                        days           actions)      actions)

           Decision: Issue decision letter                         
                                (approval,                         
        approvable pending GMP inspection,                     96%       100% 
approvable pending minor corrections or                         
     clarifications, or denial) as a first             (166 of 173    (9 of 9 
                                    action                         
                         on an application 180 days 80 decisions)  decisions) 

    Cycle action: Determine whether                        100%          100% 
                                 an                             
      amendment contains a complete                             
       response to a not approvable             (15 of 15 cycle (1 of 1 cycle 
                             letter                             
                                    160 days 80        actions)      actions) 

510(k)s  Decision: Issue decision                              
                   letter (for                                    
             example, a letter for a                              
                 device that may                                  
             be marketed because it is                        80%         96% 
                         substantially                            
             equivalent to one already                            
                        on the market,                            
           or that may not be marketed            (2,869 of 3,598 (865 of 904 
                            because it                            
              is not substantially             75                             
                   equivalent)         90 days         decisions)  decisions)

    Cycle action: Issue first                           58%               74% 
                   additional                               
           information letter                               
                                         (1,004 of 1,718                      
                                         cycle              (375 of 504 cycle
                              75 days 70           actions)          actions) 
Cycle action: Issue second                           53%               96% 
                           or                               
        subsequent additional                               
           information letter                               
                                          (283 of 530 cycle   (54 of 56 cycle 
                              60 days 70           actions)          actions) 

(Continued From Previous Page)

                                Performance goal

Review time

     Percentage of actions required to meet the goal for the fiscal year 2005
                                                                       cohort

Percentage of actions taken on applications within goal's established time frame

Fiscal year 2003 cohort

Fiscal year 2004 cohort

                Type of application Cycle actions and decisions

BLA Resubmissions  Cycle action: Review and act on a Class             b b 
and BLA Supplement  1 resubmission to an original BLA or                 
     Resubmissions    BLA supplement (for example, issue a                  
                       letter requesting limited labeling or                
                            safety information from the                     
                                   manufacturer)              2 months 75   

       Cycle action: Review and act on a                                    b 
                                   Class                                    
    2 resubmission to an original BLA or                                    
    BLA supplement (for example, issue a                                    
       letter requesting data on product                      100%          
                                  safety                                    
              and effectiveness from the                                    
                           manufacturer) 6 months 75 (2 of 2 cycle actions) 

Source: GAO analysis of FDA data as of March 31, 2004.

aFDA groups these types of applications when measuring performance for
this goal. In both the fiscal year 2003 and 2004 cohorts, FDA did not
receive any Premarket Report applications.

bFDA did not have any applications that required the agency to take the
action tied to the performance goal.

As previously mentioned, many of the applications from the fiscal years
2003 and 2004 cohorts are awaiting actions by FDA or responses from
manufacturers. Our analysis of the applications pending within the review
process shows that of the 4,175 applications received in the fiscal year
2003 cohort, 339, or 8 percent, were pending further action by FDA as of
March 31, 2004. Of the 1,781 applications received in the fiscal year 2004
cohort, 859, or 48 percent, were also pending as of March 31, 2004. The
number of applications pending varied by application type. (See table 4.)
For example, in the fiscal year 2003 cohort, 21-or 42 percent-of the 50
PMAs and Panel-Track Supplements were pending, while 316-or 8 percent-of
the 3,914 510(k)s were pending further action by FDA. As FDA completes its
actions on more applications, its performance results could change.

Table 4: Applications Pending within FDA's Review Process in the Fiscal
Year 2003 Cohort and the First 6 Months of the Fiscal Year 2004 Cohort

                       Fiscal year 2003 Fiscal year 2004

                                          Number                       Number 
                          Total number              Total number              
                                    of (percentage)      of      (percentage)
    Type of application   applications   pending    applications      pending 
    PMA and Panel-Track                     21                   
        Supplements                                              
                                    50    (42%)               16        (88%) 
       Expedited PMAs                             1              
                                     3    (33%)                8       (100%) 
        180-Day PMA                               1              
        Supplements                                              
                                   206     (1%)               42        (64%) 
          510(k)s                          316                   
                                 3,914     (8%)            1,714        (47%) 
BLA Resubmissions and                          0              
            BLA                                                  
         Supplement                                              
       Resubmissions                                             
                                     2     (0%)                1       (100%) 
           Total                           339                   
                                 4,175     (8%)            1,781        (48%) 

Source: GAO analysis of FDA data.

According to FDA officials, in fiscal year 2003, FDA began implementing
activities that are intended to enhance its ability to meet MDUFMA
performance goals that become effective in fiscal year 2005. These
activities, identified in the Secretary of HHS's November 2002 letter
establishing the MDUFMA performance goals, include hiring additional
staff, consulting with experts outside the agency more frequently, and
holding meetings with manufacturers to ensure high-quality applications
are submitted to FDA. For example, in fiscal year 2003, CDRH hired staff
for 67 new positions, such as medical officers, scientists, and engineers,
to improve the timeliness of its device reviews. As of April 2004, CDRH
filled 23 of the 65 positions it plans to fill in fiscal year 2004. CBER
also filled each of the 11 full-time equivalent positions that it received
in fiscal year 2003 and planned to fill 9 full-time equivalent positions
during fiscal year 2004 to improve the timeliness of device reviews as
well as other

activities.16 In addition, to help FDA meet its performance goals, FDA
held about 100 meetings with manufacturers to discuss ways to improve the
quality of applications prior to their submission.

FDA Obligated over $128 Million for Postmarket Medical Device Compliance
Activities and Inspections in Fiscal Year 2002

In fiscal year 2002, FDA obligated about $128 million for postmarket
medical device compliance activities, which include inspections of device
manufacturers' establishments. FDA obligated about $109 million for
compliance activities and about $19 million for inspections. Of the
approximately $109 million, FDA obligated about $99 million for postmarket
compliance activities that encompass outreach coordination, applied
research, and laboratory analyses. Outreach coordination included funds
for guidance to field staff on matters such as the reporting of problems
with medical devices, epidemiology studies, device recalls, and other
activities. Obligations for applied research included funding for
activities such as the development of domestic and international standards
to help provide reasonable assurance that medical devices are safe and
effective. Obligations for laboratory analyses included funding for
activities such as FDA laboratory-based investigations and scientific
training for FDA inspection staff. FDA also obligated an estimated $10
million in rental expenses for office space for FDA staff who conduct
compliance activities.17

In fiscal year 2002, of the $19 million obligated for inspections, FDA
obligated about $17 million for inspections of domestic and foreign
establishments and about $2 million in estimated office space rental
expenses for FDA staff who conduct inspections.18 These inspections
included routine surveillance inspections to determine compliance with
medical device regulations, inspections resulting from the reporting

16CBER did not hire additional staff to work exclusively on device
applications because its staff works with both devices and biologics.
However, biologics account for the majority of CBER's resources.

17FDA does not include rental amounts for each center in its annual budget
justification. Rental expenses are reported as a single amount for all
centers. Therefore, the amounts obligated for rental expenses are
estimated.

18These amounts exclude obligations for inspections of mammography
facilities under the Mammography Quality Standards Act of 1992.
Mammography inspections are not postmarket device establishment
inspections as described in section 704(g)(10)(B) of FDCA.

problems with devices or product recalls, and compliance inspections to
collect evidence for pending enforcement actions.

Agency Comments	In commenting on a draft of this report, FDA generally
agreed with our findings. FDA stated that it believes the agency has made
a good start in its implementation of MDUFMA and FDA believes that its
progress in meeting the MDUFMA performance goals is consistent with the
extensive performance improvements the agency is expect to achieve each
year through 2007. FDA provided technical comments primarily clarifying
aspects of the medical device review process, which we incorporated as
appropriate. FDA's comments are reprinted in appendix I.

We are sending copies of this report to the Secretary of HHS and the
Commissioner of FDA, appropriate congressional committees, and other
interested parties. We will also make copies available to others on
request. In addition, the report is available at no charge on the GAO Web
site at http://www.gao.gov. If you or your staffs have questions about
this report, please contact me at (202) 512-7119 or James McClyde at (202)
512-7152. Darryl Joyce, Donna Bulvin, and Krister Friday also made key
contributions to this report.

Marcia Crosse Director, Health Care-Public Health

and Military Health Care Issues

Appendix I

Comments from the Food and Drug Administration

Appendix I
Comments from the Food and Drug
Administration

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