Food and Drug Administration
Limited Available Data Indicate That FDA Has Been Meeting Some Goals for Review of Medical Device Applications Gao ID: GAO-05-1042 September 30, 2005The Food and Drug Administration (FDA) reviews applications from manufacturers that wish to market medical devices in the United States. To facilitate 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 from manufacturers and, in return, requires FDA to meet performance goals tied to the agency's review process. These goals are linked to certain actions FDA may take during the application review process. The goals specify lengths of time for taking these actions and the percentage of actions the agency is to take within specified time frames. MDUFMA requires GAO to report on whether FDA is meeting performance goals established by the Secretary of Health and Human Services for fiscal year 2005 and whether FDA is likely to meet the goals established for fiscal year 2006. GAO analyzed data provided by FDA that are based on actions taken on applications FDA received from October 1, 2002, through March 31, 2005. GAO used FDA's performance on applications received in fiscal years 2003 and 2004 as an indicator of the agency's likely performance.
Limited available data indicate that FDA has been meeting some MDUFMA performance goals established for fiscal year 2005. It is uncertain, however, whether FDA will meet all of the goals. FDA met most of the MDUFMA 2005 performance goals for which data were sufficiently complete to measure the agency's performance. As of March 31, 2005, FDA had sufficiently complete data from applications received in fiscal year 2003 to measure performance against 11 of the 20 goals established for fiscal year 2005. FDA met 9 of those 11 goals. For applications received in fiscal year 2004, FDA had sufficiently complete data to measure performance against 10 goals and met 9 of them. When FDA did not have sufficiently complete data to evaluate performance, GAO reviewed preliminary data from applications received in fiscal years 2003, 2004, and 2005. These data suggest that FDA has taken actions tied to many of the fiscal year 2005 goals within specified time frames. These data are preliminary because some applications from each year were pending within the review process and FDA could receive and act on additional applications or amendments to applications. For example, as of March 31, 2005, about half of the applications FDA had received in fiscal year 2005 were pending 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 on applications within required time frames, FDA's performance results could change as the agency completes actions on all applications and amendments for which the performance goals apply. The limited data available on FDA's performance suggest that FDA is likely to meet some fiscal year 2006 performance goals. GAO's analysis of FDA's past performance shows that FDA met most of the MDUFMA 2006 performance goals for which it had sufficiently complete data to evaluate its performance. As of March 31, 2005, FDA has sufficiently complete data from applications received in fiscal year 2003 to measure performance against 14 of 26 goals established for fiscal year 2006. FDA met 12 of those 14 goals. FDA also had sufficiently complete data from applications received in fiscal year 2004 to measure performance against 12 performance goals and met 9 of those 12 goals. GAO also reviewed preliminary data from applications FDA received in fiscal years 2003, 2004, and 2005 and found that FDA took actions tied to many of the fiscal year 2006 goals within specified time frames. Most of these results are preliminary, however, and FDA's performance could change as the agency completes actions for applications received in fiscal years 2003, 2004, and 2005 and receives applications in fiscal year 2006. FDA concurred with GAO's findings.
GAO-05-1042, Food and Drug Administration: Limited Available Data Indicate That FDA Has Been Meeting Some Goals for Review of Medical Device Applications
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Report to Congressional Committees:
United States Government Accountability Office:
GAO:
September 2005:
Food and Drug Administration:
Limited Available Data Indicate That FDA Has Been Meeting Some Goals
for Review of Medical Device Applications:
GAO-05-1042:
GAO Highlights:
Highlights of GAO-05-1042, a report to congressional committees:
Why GAO Did This Study:
The Food and Drug Administration (FDA) reviews applications from
manufacturers that wish to market medical devices in the United States.
To facilitate 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 from
manufacturers and, in return, requires FDA to meet performance goals
tied to the agency‘s review process. These goals are linked to certain
actions FDA may take during the application review process. The goals
specify lengths of time for taking these actions and the percentage of
actions the agency is to take within specified time frames.
MDUFMA requires GAO to report on whether FDA is meeting performance
goals established by the Secretary of Health and Human Services for
fiscal year 2005 and whether FDA is likely to meet the goals
established for fiscal year 2006.
GAO analyzed data provided by FDA that are based on actions taken on
applications FDA received from October 1, 2002, through March 31, 2005.
GAO used FDA‘s performance on applications received in fiscal years
2003 and 2004 as an indicator of the agency‘s likely performance.
What GAO Found:
Limited available data indicate that FDA has been meeting some MDUFMA
performance goals established for fiscal year 2005. It is uncertain,
however, whether FDA will meet all of the goals. FDA met most of the
MDUFMA 2005 performance goals for which data were sufficiently complete
to measure the agency‘s performance. As of March 31, 2005, FDA had
sufficiently complete data from applications received in fiscal year
2003 to measure performance against 11 of the 20 goals established for
fiscal year 2005. FDA met 9 of those 11 goals. For applications
received in fiscal year 2004, FDA had sufficiently complete data to
measure performance against 10 goals and met 9 of them. When FDA did
not have sufficiently complete data to evaluate performance, GAO
reviewed preliminary data from applications received in fiscal years
2003, 2004, and 2005. These data suggest that FDA has taken actions
tied to many of the fiscal year 2005 goals within specified time
frames. These data are preliminary because some applications from each
year were pending within the review process and FDA could receive and
act on additional applications or amendments to applications. For
example, as of March 31, 2005, about half of the applications FDA had
received in fiscal year 2005 were pending 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 on applications within required time frames, FDA‘s performance
results could change as the agency completes actions on all
applications and amendments for which the performance goals apply.
The limited data available on FDA‘s performance suggest that FDA is
likely to meet some fiscal year 2006 performance goals. GAO‘s analysis
of FDA‘s past performance shows that FDA met most of the MDUFMA 2006
performance goals for which it had sufficiently complete data to
evaluate its performance. As of March 31, 2005, FDA has sufficiently
complete data from applications received in fiscal year 2003 to measure
performance against 14 of 26 goals established for fiscal year 2006.
FDA met 12 of those 14 goals. FDA also had sufficiently complete data
from applications received in fiscal year 2004 to measure performance
against 12 performance goals and met 9 of those 12 goals. GAO also
reviewed preliminary data from applications FDA received in fiscal
years 2003, 2004, and 2005 and found that FDA took actions tied to many
of the fiscal year 2006 goals within specified time frames. Most of
these results are preliminary, however, and FDA‘s performance could
change as the agency completes actions for applications received in
fiscal years 2003, 2004, and 2005 and receives applications in fiscal
year 2006.
FDA concurred with GAO‘s findings.
www.gao.gov/cgi-bin/getrpt?GAO-05-1042.
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 or crossem@gao.gov.
[End of section]
Contents:
Letter:
Results in Brief:
Background:
Limited Available Data Indicate That FDA Has Been Meeting Some
Performance Goals Established for Fiscal Year 2005:
Limited Available Data Suggest That FDA is Likely to Meet Some
Performance Goals Established for Fiscal Year 2006:
Agency Comments:
Appendix I: Comments from the Food and Drug Administration:
Appendix II: GAO Contact and Staff Acknowledgments:
Tables:
Table 1: MDUFMA Performance Goals for Fiscal Years 2005 and 2006:
Table 2: Applications Received in Fiscal Years 2003 and 2004 and the
First 6 Months of Fiscal Year 2005 That Were Pending Further Action as
of March 31, 2005:
Figures:
Figure 1: PMA Review Process:
Figure 2: 510(k) Review Process:
Figure 3: BLA Review Process:
Figure 4: FDA's Performance as of March 31, 2005, for Applications
Received in Fiscal Years 2003, 2004, and 2005 as Measured against
MDUFMA Performance Goals Established for Fiscal Year 2005:
Figure 5: FDA's Performance as of March 31, 2005, for Applications
Received in Fiscal Years 2003, 2004, and 2005 as Measured against
MDUFMA Performance Goals Established for Fiscal Year 2006:
Abbreviations:
BLA: biologics license application:
CBER: Center for Biologics Evaluation and Research:
CDRH: Center for Devices and Radiological Health:
FDA: Food and Drug Administration:
GMP: good manufacturing practices:
MDUFMA: Medical Device User Fee and Modernization Act of 2002:
PMA: premarket approval:
United States Government Accountability Office:
Washington, DC 20548:
September 30, 2005:
The Honorable Mike Enzi:
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 that they are safe and
effective for human use. As part of its regulatory responsibilities,
FDA reviews applications from manufacturers that wish to market their
medical devices in the United States, including new devices and devices
that may be substantially equivalent to those already on the market.
When required, FDA also inspects manufacturers' establishments prior to
making a decision. 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 that the
length of time it takes FDA to review applications for marketing
medical devices could delay 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 clearance[Footnote 1] of
applications for marketing medical devices and licensing biological
products.[Footnote 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 of certain medical device and
biological license applications, at least to the extent practicable.
MDUFMA also required the Secretary of Health and Human Services to
develop the specific goals FDA must meet. The Secretary developed
performance goals for fiscal years 2003 through 2007. To help FDA meet
the MDUFMA performance goals, the Secretary also identified several
goal-related activities for FDA to undertake, such as hiring additional
review staff.
MDUFMA performance goals are linked to certain actions FDA may take
during the application review process and specify lengths of time for
taking these actions. Data to measure FDA's performance against the
MDUFMA performance goals are based on the percentages of actions the
agency takes on applications within specified time frames. For example,
one of the performance goals is linked to the time it takes FDA to
review and make a decision about certain applications to market devices
that may be substantially equivalent to devices that are already on the
market. To meet the performance goal established for fiscal year 2005,
FDA must reach a decision about substantial equivalence within 90 days
for 75 percent of such applications received in the fiscal year. In
general, the time frames established by MDUFMA performance goals do not
hold FDA accountable for the time it takes manufacturers to respond to
the agency if the agency determines that substantial additional
information is needed before a decision can be reached.
The number of MDUFMA performance goals that FDA must meet increases
over time, and the percentage of actions taken within the specified
time frame for some goals also increases over time. For fiscal years
2003 and 2004, FDA was to meet the same 2 performance goals for each
year. For fiscal year 2005, FDA was to meet those 2 goals and an
additional 18 performance goals, for a total of 20. For fiscal year
2006, FDA is to meet these 20 goals and an additional 6 performance
goals, for a total of 26. The goals established for fiscal year 2006
are tied to more types of applications than the goals established for
fiscal year 2005. In addition, 16 of the performance goals established
for fiscal year 2006 require that review actions be taken within the
specified time frames on a higher percentage of applications--for
example, on 80 percent rather than 75 percent of the applications--than
was required for similar goals established for fiscal year 2005.
MDUFMA requires us to report on FDA's performance as measured against
these performance goals. Our first report, issued in August,
2004,[Footnote 3] indicated that FDA had limited data that could be
used to measure the agency's performance. As a result, it was uncertain
whether FDA would meet the MDUFMA performance goals for fiscal years
2003, 2004, or 2005. As we reported, FDA's performance data were
preliminary, in part because many of the applications received in
fiscal year 2003 and the first 6 months of fiscal year 2004 were
pending within the review process, that is, awaiting action by FDA or
responses from manufacturers. Because FDA measures its progress in
meeting the MDUFMA performance goals by the percentage of actions the
agency takes within specified time frames, we noted that performance
results could change as FDA completes its actions on these
applications.
This report responds to the MDUFMA requirement that we report on
whether FDA is meeting the MDUFMA performance goals established for
fiscal year 2005 and whether FDA is likely to meet the goals
established for fiscal year 2006.[Footnote 4] To assess FDA's
performance against the 20 MDUFMA performance goals that were
established for fiscal year 2005, we analyzed performance data from
applications the agency received during the first 6 months of fiscal
year 2005. To supplement the data from the first 6 months of fiscal
year 2005, we also compared FDA's actions on applications received in
fiscal years 2003 and 2004 against the 20 MDUFMA performance goals
established for fiscal year 2005, a comparison FDA also conducts. We
used FDA's performance on applications received in fiscal years 2003
and 2004 as an indicator of the agency's experience in meeting the
fiscal year 2005 goals and therefore its likely performance in fiscal
year 2005. Similarly, to determine the likelihood of FDA meeting its
fiscal year 2006 MDUFMA performance goals, we compared performance data
from applications the agency received in fiscal years 2003 and 2004 and
the first 6 months of fiscal year 2005 with the 26 MDUFMA performance
goals that will be effective in fiscal year 2006. In other words, we
analyzed performance data collected by FDA for actions taken on all
applications that were tied to performance goals established for fiscal
years 2005 or 2006 that the agency received from fiscal year 2003
through the first 6 months of fiscal year 2005 (Oct. 1, 2004, through
Mar. 31, 2005).
In conducting our work, we made a distinction between data that were
sufficiently complete to evaluate FDA's performance and preliminary
data that were not sufficiently complete for that purpose. FDA's data
for some MDUFMA performance goals were not complete because
applications were pending within the review process or because
manufacturers can submit additional applications or amendments to their
applications. We defined the data as sufficiently complete to evaluate
performance when we could determine whether FDA would or would not meet
the performance goal. For example, FDA had data on eight of nine
applications tied to one performance goal and took action within the
specified time frame for each of those eight applications. These data
were sufficiently complete to evaluate FDA's performance because the
action was taken within the specified time frame for at least 75
percent of applications--the percentage established for this
performance goal. In contrast, when FDA's data were not sufficiently
complete to evaluate performance, we considered data on FDA's
performance to be preliminary.
To conduct our work and to determine what steps FDA has taken to help
meet its MDUFMA goals, we also reviewed our previous work on FDA's
performance as measured by MDUFMA performance goals, reviewed relevant
documents, and interviewed officials from FDA's Center for Devices and
Radiological Health (CDRH) and Center for Biologics Evaluation and
Research (CBER). In addition, we reviewed FDA's procedures for
verifying the accuracy and consistency of reported performance data. We
determined that the performance data were sufficiently reliable for the
purposes of this report. We conducted our work from May 2005 through
September 2005 in accordance with generally accepted government
auditing standards.
Results in Brief:
The available sufficiently complete data indicate that FDA has been
meeting some MDUFMA performance goals established for fiscal year 2005.
It is uncertain, however, whether FDA will meet all of the goals. Our
analysis shows that FDA met most of the MDUFMA 2005 performance goals
for which there were sufficiently complete data to measure the agency's
performance. These data involve actions taken through March 31, 2005,
on applications that FDA received in fiscal years 2003 and 2004 and
were used to measure the agency's performance against about half of the
performance goals established for fiscal year 2005. As of March 31,
2005, FDA had sufficiently complete data from applications received in
fiscal year 2003 to measure performance against 11 of the 20 goals
established for fiscal year 2005. FDA met 9 of those 11 goals. For
applications received in fiscal year 2004, FDA had sufficiently
complete data to measure performance against 10 goals and met 9 of
them. When FDA did not have sufficiently complete data to evaluate
performance against a MDUFMA performance goal, we reviewed preliminary
data from applications received in fiscal years 2003, 2004, and 2005.
These data suggest that FDA has taken actions tied to most of the
remaining fiscal year 2005 goals within the specified time frames. For
example, FDA had preliminary data from applications received in the
first 6 months of fiscal year 2005 on 11 goals and took actions tied to
these goals within the specified time frames. Because FDA's performance
against the MDUFMA performance goals is based on the percentages of
actions the agency takes on applications within required time frames,
FDA's performance results could change as the agency completes
additional actions on applications that are pending within the review
process or as manufacturers submit additional applications or
amendments to applications.
The limited data available on FDA's performance suggest that FDA is
likely to meet some of the fiscal year 2006 performance goals. Our
analysis of FDA's past performance shows that FDA has been meeting most
of the MDUFMA 2006 performance goals for which it had sufficiently
complete data. As of March 31, 2005, FDA had sufficiently complete data
from applications received in fiscal year 2003 to measure performance
against 14 of 26 goals established for fiscal year 2006. FDA met 12 of
those 14 goals. FDA also had sufficiently complete data from
applications received in fiscal year 2004 to measure performance
against 12 performance goals and met 9 of those 12 goals. We also
reviewed preliminary data about those goals for which FDA did not have
sufficiently complete data to evaluate performance. FDA's preliminary
data from applications received in fiscal years 2003 and 2004 and the
first 6 months of fiscal year 2005 showed that FDA took actions tied to
most of the remaining fiscal year 2006 goals within specified time
frames. For example, FDA had preliminary data from applications
received in fiscal year 2005 for 13 of the 26 goals. FDA took actions
tied to these 13 goals within the established time frames. These
results are preliminary, however, and could change as FDA completes
actions tied to fiscal year 2006 goals for applications received in
fiscal years 2003, 2004, and 2005. FDA's performance could also change
when FDA starts receiving applications in fiscal year 2006.
FDA concurred with our findings.
Background:
Under the Federal Food, Drug, and Cosmetic Act,[Footnote 5] 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 reviewing applications to market medical
devices.[Footnote 6] CDRH reviews applications for the majority of
these devices, such as artificial hearts, dialysis machines, and
radiological devices. CBER reviews applications for devices used in the
testing and manufacture of biological products, including diagnostic
tests intended to screen blood donors (such as for the human
immunodeficiency virus), as well as therapeutic devices used in cell
and gene therapies. FDA also inspects manufacturers' establishments to
assess compliance with good manufacturing practices (GMP). During these
inspections, FDA investigators examine manufacturing facilities,
records of manufacturing processes, and corrective action programs.
Types of Applications Reviewed under MDUFMA Performance Goals:
Nine types of applications for medical devices and biological products
are subject to the MDUFMA performance goals established by the
Secretary of Health and Human Services for fiscal years 2005 or
2006:[Footnote 7]
* Original Premarket Approval (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 to be implanted in
the body for life-supporting purposes).
* Expedited PMAs are used when FDA has granted priority status to an
application to market a medical device because it is intended to treat
or diagnose a life-threatening or irreversibly debilitating disease or
condition and to address an unmet medical need.
* Premarket Reports are applications required for high-risk devices
originally approved for a single use (that is, use on a single patient
during a single procedure) that a manufacturer has reprocessed for
additional use.
* Premarket Notifications, or 510(k)s,[Footnote 8] are applications
used when the intent is to market a type of device that may be
substantially equivalent[Footnote 9] to a legally marketed device that
was not subject to premarket approval.
* 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 a device.
* 180-Day PMA Supplements are also used to supplement approved PMAs or
Premarket Reports. These supplements typically request approval of a
significant change in aspects of a device, such as its design,
specifications, or labeling, when demonstration of reasonable assurance
of safety and effectiveness either does not require new clinical data
or requires only limited clinical data.
* Biologics license applications (BLA) request permission to introduce
and license biological products into interstate commerce. There are two
types of BLAs that are tied to MDUFMA performance goals. Priority BLAs
are for products that would, if approved, involve a significant
improvement in the safety or effectiveness of the treatment, diagnosis,
or prevention of a serious or life-threatening disease. Nonpriority
BLAs are considered standard BLAs.
* BLA Supplements are used to supplement approved BLAs by requesting
approval of a change to a licensed biological product. When the change
has the substantial potential to affect the safety or effectiveness of
the product, FDA approval is required prior to product distribution.
There are MDUFMA performance goals linked to three types of BLA
supplements--BLA manufacturing supplements that require prior approval
and two types of BLA efficacy supplements. Manufacturing supplements
that require prior approval address proposed changes in the manufacture
of the biologic and generally do not require submission of substantive
clinical data. Efficacy supplements include both standard and priority
efficacy supplements and require submission of substantive clinical
data.
* BLA Resubmissions and BLA Efficacy Supplement Resubmissions are used
to respond to a letter from FDA indicating that the information
included in a BLA or BLA Efficacy Supplement was deficient. FDA
classifies these resubmissions into two groups according to the type of
information they provide. For Class 1 resubmissions, the new
information may include matters related to product labeling, safety
updates, and other minor clarifying information. For Class 2
resubmissions, the new information could warrant presentation to an
advisory committee or a reinspection of the manufacturer's device
establishment.
FDA's Medical Device Application Review Processes:
Each of the 2005 and 2006 MDUFMA performance goals are linked to
actions FDA takes under one of three processes for reviewing medical
device applications: the PMA review process, the 510(k) review process,
and the BLA review process.
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,
Expedited PMAs, Premarket Reports, Panel-Track Supplements, and 180-Day
PMA Supplements. After an initial screening of an application and
determination that the review should proceed,[Footnote 10] FDA
multidisciplinary staff conduct a scientific review of the
application.[Footnote 11] (See fig. 1.) If FDA determines that it needs
significant additional information to complete its scientific review,
FDA issues a "major deficiency letter" to the manufacturer identifying
the information that is required. The manufacturer can respond to FDA's
request by submitting an amendment to the original application. FDA
then proceeds with its review of the amended application. FDA can issue
additional major deficiency letters and review additional amendments
until FDA determines that it has sufficient information to make a
decision. As part of its review, FDA may refer applications to an
external advisory committee for evaluation. FDA takes this step 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.[Footnote
12] For applications referred to an advisory committee, the committee
provides input to FDA on the safety and effectiveness of the devices.
Taking the committee's input into consideration, FDA then makes a
decision.
Figure 1: PMA Review Process:
[See PDF for image]
Note: This flow chart presents the typical review process for
applications for which FDA has conducted an initial screening and
determined that the review should proceed.
[End of figure]
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 determines 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 or effectiveness problems,
and decided not to approve the application.
Two of these possible decisions result in issuance of letters
indicating that an application has informational deficiencies--
approvable letters requesting minor corrections or clarifications and
not approvable letters. The manufacturer can respond to these letters
by submitting an amendment to the original application. FDA then
reviews the amendment. FDA can issue additional letters indicating that
information is deficient and review additional amendments until FDA
determines that it has sufficient information to determine whether to
approve or deny the application. For example, if FDA determines that a
manufacturer's amendment to an approvable letter requesting minor
corrections or clarifications does not address all of FDA's questions,
then FDA can issue 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 reviews applications to market a
device that may be substantially equivalent to a legally marketed
device that was not subject to premarket approval (see fig. 2). FDA
staff conduct a scientific review of the application. When a 510(k)
application lacks information necessary for FDA to reach a decision,
the agency may issue an "additional information" letter that indicates
that the information is insufficient. The manufacturer may then submit
additional information. Once FDA has obtained sufficient information
from the manufacturer, FDA may make one of three decisions: FDA may
decide that (1) the device is substantially equivalent and therefore
may be marketed, (2) the device is not substantially equivalent and may
not be marketed, or (3) a 510(k) application was not required because
the product is not regulated as a device or the device is exempt from
the requirements for premarket notification.
Figure 2: 510(k) Review Process:
[See PDF for image]
Note: This flow chart presents the typical review process to determine
whether a 510(k) application is required and, if so, whether a device
is substantially equivalent to a legally marketed device that was not
subject to premarket approval.
[End of figure]
The BLA Review Process:
Under the BLA review process, FDA determines whether to approve
licenses for biological products (see fig. 3). Applications reviewed
under this process include BLAs, BLA Supplements, BLA Resubmissions,
and BLA Supplement Resubmissions. After an initial screening of an
application and determination that the review should proceed, staff
conduct a multidisciplinary scientific review of the application. As
part of its review, FDA may refer applications to an external advisory
committee. After reviewing the application and taking into
consideration any input from an external advisory committee, FDA may
make one of two decisions. FDA may issue (1) an approval letter or (2)
a "complete response" letter, which informs the manufacturer of
deficiencies in the information provided in the application. The
manufacturer can provide the information specified in a "complete
response" letter in a BLA Resubmission or BLA Supplement Resubmission.
Figure 3: BLA Review Process:
[See PDF for image]
Note: This flow chart presents the typical review process for BLA-
related applications for which FDA has conducted an initial screening
and determined that the review should proceed.
[End of figure]
Measuring FDA's Performance under MDUFMA:
The MDUFMA performance goals specify a length of time for taking an
action during the review process, which can include making a decision.
The goals designate a certain percentage of these actions that must
occur within the specified period for FDA to meet the performance
goals. To assess its performance against the MDUFMA performance goals,
FDA measures the time the agency takes to complete certain actions and
make decisions--but not the time it takes a manufacturer to respond to
a letter from FDA.[Footnote 13]
The data for measuring FDA's performance against a specific fiscal
year's MDUFMA performance goals are based on all the applications the
agency received in that year, known as a cohort,[Footnote 14] and are
not complete until all applicable actions have been taken. As a result,
data are preliminary until FDA has completed all actions tied to the
goal for all applications in a cohort--a process that, for PMAs, can
take up to 3 or 4 years. For example, one performance goal established
for fiscal year 2005 is tied to amendments to PMAs that are submitted
in response to major deficiency or not approvable letters. Data on
FDA's performance on this goal will not be complete until after FDA has
issued all major deficiency and not approvable letters it decides to
issue for applications received in fiscal year 2005 and then either (1)
received, reviewed, and acted on all amendments submitted in response
or (2) determined that manufacturers have withdrawn their applications.
For fiscal year 2005, FDA is to meet 20 performance goals and for
fiscal year 2006 FDA is to meet an additional 6 performance goals, for
a total of 26. (See table 1.) The percentage of applications for which
the action must be taken within the specified time frame is higher in
fiscal year 2006 than in fiscal year 2005 for 16 of the performance
goals that are applicable for both years.
Table 1: MDUFMA Performance Goals for Fiscal Years 2005 and 2006:
Type of application: PMAs, Panel-Track Supplements, and Premarket
Reports[A]:
FDA actions, including decisions: Issue a decision letter[B];
Performance goal: Review time: 320 days;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2005 cohort required to meet review time: Not
applicable;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2006 cohort required to meet review time: 80.
FDA actions, including decisions: Issue a first major deficiency
letter;
Performance goal: Review time: 150 days;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2005 cohort required to meet review time: 75;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2006 cohort required to meet review time: 80.
FDA actions, including decisions: Type of application: Issue a decision
letter as a first action on an application[B];
Performance goal: Review time: Type of application: 180 days;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2005 cohort required to meet review time: Type of
application: 75;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2006 cohort required to meet review time: Type of
application: 80.
FDA actions, including decisions: Type of application: Issue a second
or subsequent major deficiency letter;
Performance goal: Review time: Type of application: 120 days;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2005 cohort required to meet review time: Type of
application: 75;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2006 cohort required to meet review time: Type of
application: 80.
FDA actions, including decisions: Type of application: Act on an
amendment containing a complete response to a major deficiency or not
approvable letter;
Performance goal: Review time: Type of application: 180 days;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2005 cohort required to meet review time: Type of
application: 75;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2006 cohort required to meet review time: Type of
application: 80.
FDA actions, including decisions: Type of applicationExpedited PMAs:
Act on an amendment containing a complete response to an approvable
letter pending minor corrections or clarifications;
Performance goal: Review time: Type of applicationExpedited PMAs: 30
days;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2005 cohort required to meet review time: Type of
applicationExpedited PMAs: 90;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2006 cohort required to meet review time: Type of
applicationExpedited PMAs: 90.
Type of application: Expedited PMAs:
FDA actions, including decisions: Issue a decision letter[B];
Performance goal: Review time: 300 days;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2005 cohort required to meet review time: 70;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2006 cohort required to meet review time: 80.
FDA actions, including decisions: Issue a first major deficiency
letter;
Performance goal: Review time: 120 days;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2005 cohort required to meet review time: 70;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2006 cohort required to meet review time: 80.
FDA actions, including decisions: Issue a decision letter as a first
action on an application[B];
Performance goal: Review time: 170 days;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2005 cohort required to meet review time: 70;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2006 cohort required to meet review time: 80.
FDA actions, including decisions: Issue a second or subsequent major
deficiency letter;
Performance goal: Review time: 100 days;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2005 cohort required to meet review time: 70;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2006 cohort required to meet review time: 80.
FDA actions, including decisions: Act on an amendment containing a
complete response to a major deficiency or not approvable letter;
Performance goal: Review time: 170 days;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2005 cohort required to meet review time: 70;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2006 cohort required to meet review time: 80.
FDA actions, including decisions: Act on an amendment containing a
complete response to an approvable letter pending minor corrections or
clarifications;
Performance goal: Review time: 30 days;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2005 cohort required to meet review time: 90;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2006 cohort required to meet review time: 90.
Type of application: 180-Day PMA Supplements:
FDA actions, including decisions: Issue a decision letter[B];
Performance goal: Review time: 180 days;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2005 cohort required to meet review time: 80;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2006 cohort required to meet review time: 80.
FDA actions, including decisions: Type of application: Issue a not
approvable letter as a first action on an application;
Performance goal: Review time: Type of application: 120 days;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2005 cohort required to meet review time: Type of
application: 80;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2006 cohort required to meet review time: Type of
application: 85.
FDA actions, including decisions: Type of application: Issue a decision
letter other than a not approvable letter as a first action on an
application[B];
Performance goal: Review time: Type of application: 180 days;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2005 cohort required to meet review time: Type of
application: 80;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2006 cohort required to meet review time: Type of
application: 85.
FDA actions, including decisions: Type of application510(k)s: Act on an
amendment containing a complete response to a not approvable letter;
Performance goal: Review time: Type of application510(k)s: 160 days;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2005 cohort required to meet review time: Type of
application510(k)s: 80;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2006 cohort required to meet review time: Type of
application510(k)s: 85.
Type of application: 510(k)s:
FDA actions, including decisions: Issue a decision letter[C];
Performance goal: Review time: 90 days;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2005 cohort required to meet review time: 75;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2006 cohort required to meet review time: 75.
FDA actions, including decisions: Issue a first additional information
letter;
Performance goal: Review time: 75 days;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2005 cohort required to meet review time: 70;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2006 cohort required to meet review time: 80.
FDA actions, including decisions: Issue a second or subsequent
additional information letter;
Performance goal: Review time: 60 days;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2005 cohort required to meet review time: 70;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2006 cohort required to meet review time: 80.
Type of application: BLAs:
FDA actions, including decisions: Review and act on a standard original
BLA;
Performance goal: Review time: 10 months;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2005 cohort required to meet review time: Not
applicable;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2006 cohort required to meet review time: 75.
FDA actions, including decisions: Review and act on a priority original
BLA;
Performance goal: Review time: 6 months;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2005 cohort required to meet review time: Not
applicable;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2006 cohort required to meet review time: 75.
Type of application: BLA Supplements:
FDA actions, including decisions: Review and act on a standard BLA
efficacy supplement;
Performance goal: Review time: 10 months;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2005 cohort required to meet review time: Not
applicable;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2006 cohort required to meet review time: 75.
FDA actions, including decisions: Review and act on a priority BLA
efficacy supplement;
Performance goal: Review time: 6 months;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2005 cohort required to meet review time: Not
applicable;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2006 cohort required to meet review time: 75.
FDA actions, including decisions: Review and act on a BLA manufacturing
supplement that requires prior approval;
Performance goal: Review time: 4 months;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2005 cohort required to meet review time: Not
applicable;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2006 cohort required to meet review time: 75.
Type of application: BLA Resubmissions and BLA Efficacy Supplement
Resubmissions:
FDA actions, including decisions: Review and act on a Class 1
resubmission to an original BLA or BLA efficacy supplement;
Performance goal: Review time: 2 months;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2005 cohort required to meet review time: 75;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2006 cohort required to meet review time: 80.
FDA actions, including decisions: FDA actions, including decisions:
Review and act on a Class 2 resubmission to an original BLA or BLA
efficacy supplement;
Performance goal: Review time: 6 months;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2005 cohort required to meet review time: 75;
Performance goal: Percentage of actions taken on applications received
in fiscal year 2006 cohort required to meet review time: 80.
Source: GAO analysis of FDA data.
[A] FDA groups these types of applications when measuring performance
for this goal.
[B] A decision letter for a PMA, Panel-Track Supplement, Premarket
Report, Expedited PMA, or 180-Day PMA Supplement can indicate approval,
approvable pending GMP inspection, approvable pending minor corrections
or clarifications, not approvable, or denial. MDUFMA performance goals
linked to issuance of a decision letter for these applications include
a performance goal that is linked to issuance of a decision letter as a
first action on an application and a performance goal that is linked to
issuance of a decision letter regardless of whether that letter is
issued as a first or later action.
[C] A decision letter for a 510(k) can indicate that the device may be
marketed because it is substantially equivalent to one already on the
market or may not be marketed because it is not substantially
equivalent.
[End of table]
Limited Available Data Indicate That FDA Has Been Meeting Some
Performance Goals Established for Fiscal Year 2005:
The limited data available indicate that FDA has been meeting some
MDUFMA performance goals established for fiscal year 2005. It is
uncertain, however, whether FDA will ultimately meet the fiscal year
2005 performance goals once reviews for all the applications are
complete. We found that FDA met most of the MDUFMA fiscal year 2005
performance goals for which there were sufficiently complete data to
measure the agency's performance. When FDA did not have sufficiently
complete data to evaluate performance against a MDUFMA performance
goal, we reviewed preliminary data and found that FDA took actions tied
to most of these other fiscal year 2005 goals within specified time
frames. Data from the first 6 months of fiscal year 2005 are not
sufficiently complete to evaluate FDA's performance against MDUFMA
performance goals because some applications are pending review and
because manufacturers are likely to submit additional applications and
amendments for review.
Our analysis shows that FDA met most of the MDUFMA 2005 performance
goals for which there were sufficiently complete data to measure
performance (see fig. 4). These data were from applications that FDA
received in fiscal years 2003 and 2004 and were used to measure the
agency's performance against about half of the performance goals
established for fiscal year 2005. As of March 31, 2005, FDA had
sufficiently complete data from applications received in fiscal year
2003 to measure performance against 11 of the 20 goals established for
fiscal year 2005. FDA met 9 of those 11 goals and did not meet 2 of
them. For applications received in fiscal year 2004, FDA had
sufficiently complete data to measure performance against 10 of the 20
goals. It met 9 and did not meet 1 of these goals. For example, one of
FDA's 2005 performance goals requires the agency to issue a first major
deficiency letter within 150 days for 75 percent of PMAs, Panel-Track
Supplements, and Premarket Reports that the agency received during the
fiscal year and found to be incomplete. For applications in the fiscal
year 2003 and 2004 cohorts, respectively, FDA issued 22 of 26 (85
percent) and 23 of 28 (82 percent) first major deficiency letters
within 150 days, thus meeting the goal. FDA had complete data on its
performance against this performance goal from both the fiscal year
2003 and 2004 cohorts--there were no other applications that FDA
received during these years for which a first major deficiency letter
can be issued. Figure 4 also shows that FDA had sufficiently complete
data on applications received in both fiscal years 2003 and 2004 on 2
performance goals established for fiscal year 2005 that are tied to
510(k) applications, the type of MDUFMA-related medical device
application that FDA receives most frequently. These data indicate that
FDA met 1 of the 2 goals with applications received in fiscal year 2003
and met both goals for applications received in fiscal year 2004.
Sufficiently complete data were also available on applications received
in fiscal years 2003 and 2004 to evaluate FDA's performance on 3 of the
2005 performance goals tied to 180-Day PMA Supplements, the type of
MDUFMA-related application that FDA receives second most frequently.
FDA met 2 of these 3 goals on applications received in 2003 and met the
3 goals on applications received in 2004.
Figure 4: FDA's Performance as of March 31, 2005, for Applications
Received in Fiscal Years 2003, 2004, and 2005 as Measured against
MDUFMA Performance Goals Established for Fiscal Year 2005:
[See PDF for image]
Note: FDA's data for some MDUFMA performance goals are not complete
because applications are pending within the review process or because
manufacturers can submit additional applications or amendments to their
applications. We defined the data as sufficiently complete to evaluate
performance when we could determine whether FDA would or would not meet
the performance goal. In contrast, when FDA's data were not
sufficiently complete to evaluate performance, we considered data on
FDA's performance to be preliminary. The performance goals established
for fiscal year 2005 did not include any goals tied to BLAs or BLA
Supplements.
[A] FDA groups these types of applications when measuring performance
for this goal. FDA did not receive any Premarket Reports in fiscal
years 2003 or 2004 or the first 6 months of fiscal year 2005.
[B] A decision letter for a PMA, Panel-Track Supplement, Premarket
Report, Expedited PMA, or 180-Day PMA Supplement can indicate approval,
approvable pending GMP inspection, approvable pending minor corrections
or clarifications, not approvable, or denial.
[C] As of March 31, 2005, FDA had not received any submissions that
required the agency to take the action tied to the performance goal. It
could subsequently receive submissions.
[D] This performance goal had also been established for fiscal years
2003 and 2004 and required 90 percent of actions to be taken within 30
days.
[E] A decision letter for a 510(k) can indicate that the device may be
marketed because it is substantially equivalent to one already on the
market or may not be marketed because it is not substantially
equivalent.
[F] FDA did not receive any submissions that required the agency to
take the action tied to the performance goal. No additional submissions
are possible.
[G] As of March 31, 2005, FDA had received submissions tied to the
performance goal, but had not taken any actions tied to the goal. FDA
could subsequently receive additional submissions.
[End of figure]
As figure 4 shows, FDA's data from applications received in fiscal
years 2003 and 2004 and the first 6 months of fiscal year 2005 are not
sufficiently complete to evaluate the agency's performance against some
fiscal year 2005 goals. The preliminary data available on these goals
suggest that when FDA took actions tied to fiscal year 2005 performance
goals, it generally did so within specified time frames.[Footnote 15]
As of March 31, 2005, FDA had preliminary data from applications
received in fiscal year 2003 on 7 of the 9 performance goals for fiscal
year 2005 for which data were not sufficiently complete to evaluate
performance. FDA took actions tied to 5 of the 7 goals within the
specified time frames. For applications received in fiscal year 2004,
FDA had preliminary data for 7 of the 10 performance goals for which
data were not sufficiently complete, and the agency took actions tied
to these 7 goals within the specified time frames. FDA also had
preliminary performance data from applications received in the first 6
months of fiscal year 2005 for 11 of the 20 goals. FDA took actions
tied to these 11 goals within the specified time frames. These
preliminary results could change as FDA completes its review of pending
applications and additional applications or amendments. For example,
one of FDA's 2005 performance goals for expedited PMAs was to take
action within 170 days for 70 percent of amendments containing complete
responses to a major deficiency or not approvable letter. As of March
31, 2005, FDA had taken action within 170 days on two of two such
amendments (100 percent) to applications in the fiscal year 2003 cohort
and four of five (80 percent) in the fiscal year 2004 cohort and had
received no such amendments for applications in the fiscal year 2005
cohort. These preliminary performance results could change, however, if
manufacturers submit additional amendments to applications in any of
the three cohorts.
Based on the limited data that were available as of March 31, 2005, it
is unclear whether or to what extent FDA will meet the fiscal year 2005
MDUFMA performance goals because the agency's performance could change
as the agency completes its review of applications. For example, some
applications are pending review because FDA has not reached a decision
about the application or because the manufacturer has not responded to
a letter from FDA indicating that the application included insufficient
information for FDA to complete its review. Our analysis shows that as
of March 31, 2005, about half of the applications FDA had received
during the first 6 months of fiscal year 2005--831 of 1,792--were
pending. (See table 2, which also shows the number of pending
applications from the fiscal year 2003 and 2004 cohorts.) The
percentage of pending applications varied by application type. For
example, for the fiscal year 2005 cohort, 22--95.7 percent--of 23 PMAs
and Panel-Track Supplements were pending further action, while 4--33.3
percent--of 12 BLA Supplements were pending.
Table 2: Applications Received in Fiscal Years 2003 and 2004 and the
First 6 Months of Fiscal Year 2005 That Were Pending Further Action as
of March 31, 2005:
Type of application: PMA and Panel-Track Supplements;
Fiscal year 2003: Total number of applications: 50;
Fiscal year 2003: Number (percentage) pending: 5 (10.0%);
Fiscal year 2004: Total number of applications: 48;
Fiscal year 2004: Number (percentage) pending: 13 (27.1%);
First 6 months of fiscal year 2005: Total number of applications: 23;
First 6 months of fiscal year 2005: Number (percentage) pending: 22
(95.7%).
Type of application: Expedited PMAs;
Fiscal year 2003: Total number of applications: 3;
Fiscal year 2003: Number (percentage) pending: 0 (0.0%);
Fiscal year 2004: Total number of applications: 14;
Fiscal year 2004: Number (percentage) pending: 6 (42.9%);
First 6 months of fiscal year 2005: Total number of applications: 3;
First 6 months of fiscal year 2005: Number (percentage) pending: 2
(66.7%).
Type of application: 180-Day PMA Supplements;
Fiscal year 2003: Total number of applications: 206;
Fiscal year 2003: Number (percentage) pending: 0 (0.0%);
Fiscal year 2004: Total number of applications: 106;
Fiscal year 2004: Number (percentage) pending: 0 (0.0%);
First 6 months of fiscal year 2005: Total number of applications: 45;
First 6 months of fiscal year 2005: Number (percentage) pending: 27
(60.0%).
Type of application: 510(k)s;
Fiscal year 2003: Total number of applications: 3,805;
Fiscal year 2003: Number (percentage) pending: 15 (0.4%);
Fiscal year 2004: Total number of applications: 3,432;
Fiscal year 2004: Number (percentage) pending: 165 (4.8%);
First 6 months of fiscal year 2005: Total number of applications:
1,703;
First 6 months of fiscal year 2005: Number (percentage) pending: 770
(45.2%).
Type of application: BLAs;
Fiscal year 2003: Total number of applications: 0;
Fiscal year 2003: Number (percentage) pending: 0 (0.0%);
Fiscal year 2004: Total number of applications: 9;
Fiscal year 2004: Number (percentage) pending: 1 (11.1%);
First 6 months of fiscal year 2005: Total number of applications: 1;
First 6 months of fiscal year 2005: Number (percentage) pending: 1
(100.0%).
Type of application: BLA Supplements;
Fiscal year 2003: Total number of applications: 78;
Fiscal year 2003: Number (percentage) pending: 0 (0.0%);
Fiscal year 2004: Total number of applications: 96;
Fiscal year 2004: Number (percentage) pending: 0 (0.0%);
First 6 months of fiscal year 2005: Total number of applications: 12;
First 6 months of fiscal year 2005: Number (percentage) pending: 4
(33.3%).
Type of application: BLA Resubmissions and BLA Efficacy Supplement
Resubmissions;
Fiscal year 2003: Total number of applications: 2;
Fiscal year 2003: Number (percentage) pending: 0 (0.0%);
Fiscal year 2004: Total number of applications: 5;
Fiscal year 2004: Number (percentage) pending: 0 (0.0%);
First 6 months of fiscal year 2005: Total number of applications: 5;
First 6 months of fiscal year 2005: Number (percentage) pending: 5
(100%).
Type of application: Total;
Fiscal year 2003: Total number of applications: 4,144;
Fiscal year 2003: Number (percentage) pending: 20 (0.5%);
Fiscal year 2004: Total number of applications: 3,710;
Fiscal year 2004: Number (percentage) pending: 185 (5.0%);
First 6 months of fiscal year 2005: Total number of applications:
1,792;
First 6 months of fiscal year 2005: Number (percentage) pending: 831
(46.4%).
Source: GAO analysis of FDA data.
Note: FDA did not receive any Premarket Reports in fiscal years 2003 or
2004 or in the first 6 months of fiscal year 2005.
[End of table]
As previously noted, FDA's preliminary performance results could also
change if manufacturers submit additional applications or amendments,
as is likely. For example, FDA received 1,703 510(k) applications
during the first 6 months of fiscal year 2005, about half the number it
received in each of the 2 preceding full fiscal years (3,805 and 3,432
for fiscal years 2003 and 2004, respectively). These data suggest that
as of March 31, 2005, FDA had received about half of the 510(k)
applications that it may receive in fiscal year 2005. Similarly,
performance results for applications FDA received in fiscal years 2003,
2004, and 2005 could change as manufacturers respond to requests for
additional information or submit amendments to their applications. For
example, as of March 31, 2005, FDA had issued letters requesting
additional information for 659 of the 510(k) applications it received
during the first 6 months of fiscal year 2005. It is likely that FDA
will receive responses to these requests from manufacturers.
Limited Available Data Suggest That FDA is Likely to Meet Some
Performance Goals Established for Fiscal Year 2006:
The limited data available on FDA's performance suggest that FDA is
likely to meet some of its fiscal year 2006 performance goals. Our
analysis of FDA's performance for applications received in fiscal years
2003 and 2004 shows that FDA has been meeting most of the MDUFMA 2006
performance goals for which it had sufficiently complete data. We also
reviewed FDA's preliminary data from applications received in fiscal
years 2003 and 2004 and the first 6 months of fiscal year 2005, and
found that FDA took actions tied to most of the remaining fiscal year
2006 goals within specified time frames. Preliminary performance
results could change as the agency completes actions for applications
received in fiscal years 2003, 2004, and 2005 and FDA's performance
could change as it receives applications in fiscal year 2006. FDA has
taken several steps to help meet the MDUFMA performance goals.
Our analysis of FDA's past performance shows that FDA met most, but not
all, of the MDUFMA 2006 performance goals for which it had sufficiently
complete data. (See fig. 5.) As of March 31, 2005, FDA had sufficiently
complete data from applications received in fiscal year 2003 to measure
performance against 14 of 26 goals established for fiscal year 2006.
FDA met 12 of those 14 goals. FDA also had sufficiently complete data
from applications received in fiscal year 2004 to measure performance
against 12 performance goals and met 9 of those 12 goals. Figure 5 also
shows that FDA had sufficiently complete data from both fiscal years
2003 and 2004 on 2 performance goals established for fiscal year 2006
that are tied to 510(k) applications, the type of MDUFMA-related
medical device application that FDA receives most frequently. These
data indicate that FDA met 1 of the 2 goals for applications received
in both fiscal years 2003 and 2004. Sufficiently complete data were
available for applications received in fiscal years 2003 and 2004 to
evaluate performance on 3 of the 2006 performance goals tied to 180-Day
PMA Supplements, the type of MDUFMA-related application that FDA
receives second most frequently. FDA met 2 of these 3 goals on
applications received in both fiscal years.
Figure 16: FDA's Performance as of March 31, 2005, for Applications
Received in Fiscal Years 2003, 2004, and 2005 as Measured against
MDUFMA Performance Goals Established for Fiscal Year 2006:
Note: FDA's data for some MDUFMA performance goals are not complete
because applications are pending within the review process or because
manufacturers can submit additional applications or amendments to their
applications. We defined the data as sufficiently complete to evaluate
performance when we could determine whether FDA would or would not meet
the performance goal. In contrast, when FDA's data were not
sufficiently complete to evaluate performance, we considered data on
FDA's performance to be preliminary.
[A] FDA groups these types of applications when measuring performance
for this goal. FDA did not receive any Premarket Reports in fiscal
years 2003 or 2004 or the first 6 months of fiscal year 2005.
[B] A decision letter for a PMA, Panel-Track Supplement, Premarket
Report, Expedited PMA, or 180-Day PMA Supplement can indicate approval,
approvable pending GMP inspection, approvable pending minor corrections
or clarifications, not approvable, or denial.
[C] As of March 31, 2005, FDA had not received any submissions that
required the agency to take the action tied to the performance goal. It
could subsequently receive submissions.
[D] A decision letter for a 510(k) can indicate that the device may be
marketed because it is substantially equivalent to one already on the
market or may not be marketed because it is not substantially
equivalent.
[E] FDA did not receive any submissions that required the agency to
take the action tied to the performance goal. No additional submissions
are possible.
[F] As of March 31, 2005, FDA had received submissions tied to the
performance goal, but had not taken any actions tied to the goal. FDA
could subsequently receive additional submissions.
[End of figure]
Figure 5 also shows that preliminary performance data from applications
received in fiscal years 2003 and 2004 and the first 6 months of fiscal
year 2005 indicate that FDA took actions tied to most of the remaining
fiscal year 2006 performance goals within specified time frames. Of 12
performance goals for which data on applications received in fiscal
year 2003 were not sufficiently complete to evaluate performance, FDA
had preliminary data on 7. FDA took actions tied to 5 of these 7 goals
within the specified time frames. Of 14 performance goals for which FDA
did not have sufficiently complete data from applications received in
fiscal year 2004, FDA had preliminary data for 8 and took actions tied
to these 8 goals within the specified time frames. FDA had preliminary
data from applications received in the first 6 months of fiscal year
2005 for 13 of the 26 goals established for fiscal year 2006. FDA took
actions tied to these 13 goals within the established time frames.
These performance results could change as the agency completes actions
for applications received in fiscal years 2003, 2004, and 2005 and
FDA's performance could change as it receives applications in fiscal
year 2006.
In general, when sufficient data indicated that FDA's performance
results for applications received in a fiscal year met the performance
goal established for fiscal year 2005, then the agency also met the
performance goal established for fiscal year 2006, even when the 2006
goal required FDA to take action within specified time frames on a
greater percentage of applications. There were two exceptions that
involved issuing not approvable letters as a first action on 180-Day
PMA Supplements received in fiscal year 2004 and issuing additional
information letters as a first action for 510(k)s received in fiscal
year 2004. In each of these cases, FDA met the performance goal
established for fiscal year 2005, but did not meet the goal established
for fiscal year 2006.
To help meet its MDUFMA performance goals, FDA has taken several steps
consistent with those outlined by the Secretary of Health and Human
Services in his November 2002 letter establishing those goals. For
example, FDA issued additional guidance to manufacturers on topics
related to medical device applications in fiscal year 2004 and 2005. To
help implement MDUFMA, CDRH hired 55 new staff (such as medical
officers, scientists, and engineers) in fiscal year 2004 and 44 new
staff in fiscal year 2005. According to FDA, prior to the enactment of
the Medical Device User Fee Stabilization Act of 2005,[Footnote 16]
there was uncertainty about the continuation of the MDUFMA program, and
as a result, most of these new employees were hired on a temporary
basis. Moreover, CDRH instituted a hiring freeze for MDUFMA-related
positions in May 2005. FDA also said that as a consequence of hiring
fewer personnel than planned to perform tasks associated with the
MDUFMA program, implementation of improvements FDA intended to make was
constrained. For example, fewer new guidance documents were drafted,
fewer existing guidance documents were updated, and the modernization
of data systems proceeded at a slower pace than FDA intended. An FDA
spokesman told us that CDRH may lift its freeze on hiring new staff by
the start of fiscal year 2006.
Agency Comments:
In written comments on a draft of this report, FDA concurred with our
findings. FDA also provided clarifying technical comments, which we
incorporated. FDA's comments are reprinted in appendix I.
We are sending copies of this report to the Secretary of Health and
Human Services and the Acting 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 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 major contributions to this
report are listed in appendix II.
Signed by:
Marcia Crosse:
Director, Health Care:
[End of section]
Appendix I: Comments from the Food and Drug Administration:
DEPARTMENT OF HEALTH & HUMAN SERVICES:
Public Health Service:
Food and Drug Administration:
Rockville MD 20857:
September 26, 2005:
Marcia Crosse:
Director, Health Care:
United States Government Accountability Office:
441 G Street, NW:
Washington, DC 20548:
Dear Ms. Crosse:
FDA found the draft report entitled, "FOOD AND DRUG ADMINISTRATION:
Limited Available Data Indicate that FDA Has Been Meeting Some Goals
for Review of Medical Device Applications (GAO-05-1042) " to be well-
written, well-organized, and accurate in its descriptions of FDA's
medical device review programs, the performance goals we are pursuing
under MDUFMA, and our progress towards achieving those goals. GAO's
findings are fair and accurate, and acknowledge the progress we have
made, the obstacles we have encountered, and the uncertainties that
still exist.
We appreciate the opportunity to review and comment on this draft
report before it is published, as well as the opportunity to work with
your staff in its development.
Sincerely,
Signed by:
Janet Woodcock, M.D.
Deputy Commissioner for Operations:
[End of section]
Appendix II: GAO Contact and Staff Acknowledgments:
GAO Contact:
Marcia Crosse, (202) 512-7119 or crossem@gao.gov:
Acknowledgments:
In addition to the contact named above, James McClyde, Assistant
Director, and Kristen Joan Anderson made key contributions to this
report.
[End of section]
(290452):
FOOTNOTES
[1] The 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.
[2] Pub. L. No. 107-250, sec. 102(a), §§ 737 and 738, 116 Stat. 1588
(to be codified as amended at 21 U.S.C. §§ 379i and 379j).
[3] See GAO, Food and Drug Administration: Data to Measure the
Timeliness of Reviews of Medical Device Applications Are Limited, GAO-
04-1022 (Washington, D.C.: Aug. 30, 2004).
[4] 21 U.S.C. § 379j(g)(1)(B)(i)(II) (2000).
[5] Ch. 675, 52 Stat. 1040 (1938) (codified as amended at 21 U.S.C. §§
301 et seq. (2000)).
[6] In general, an application to market a medical device includes
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.
[7] Some types of applications that involve biologics licenses are
linked to MDUFMA performance goals established for 2006, but not for
2005.
[8] FDA refers to a premarket notification submission as a 510(k)
because the requirement for them is set out in section 510(k) of the
Federal Food, Drug, and Cosmetic Act. 42 U.S.C. § 360(k) (2000).
[9] Substantial 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.
[10] This initial screening is called a filing review.
[11] The 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, and studies that may include
microbiological, toxicological, and engineering tests.
[12] For example, approximately 22 percent of PMAs and Expedited PMAs
were referred to external advisory committees in fiscal years 2002 and
2003. The percentage in fiscal year 2004 was closer to 40 percent. FDA
does not refer 180-Day PMA Supplements to external advisory committees.
[13] If a manufacturer submits an amendment that contains substantial
new information while FDA is reviewing a PMA, Expedited PMA, Premarket
Report, Panel-Track Supplement, or 180-Day PMA Supplement without
having received a request for additional information from FDA, the time
period allowed for the review is extended. There are limits on the
length of time manufacturers have to respond to certain letters
indicating that FDA needs additional information to reach a decision
about a device. For example, as required by FDA regulation,
manufacturers who have submitted PMAs have 180 days to submit
amendments in response 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 who have
submitted 510(k)s have 30 days to respond to first or subsequent
letters requesting additional information and can apply for extensions
of up to 180 days from the date of the first or subsequent letters.
[14] FDA refers to cohorts as "receipt cohorts."
[15] FDA did not have data on a performance goal if the agency had not
received any applications of the type that is tied to that goal or if
the agency had received applications of that type but had not taken any
of the actions tied to the goal as of March 31, 2005.
[16] Pub. L. No. 109-43, § 2(a)(5), 119 Stat. 439, 440.
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