Medical Devices
Shortcomings in FDA's Premarket Review, Postmarket Surveillance, and Inspections of Device Manufacturing Establishments
Gao ID: GAO-09-370T June 18, 2009
Americans depend on the Food and Drug Administration (FDA) to provide assurance that medical devices sold in the United States are safe and effective. FDA classifies medical device types into three classes, with class I including those with the lowest risk to patients (such as forceps) and class III including those with the greatest risk (such as pacemakers). FDA's responsibilities include premarket and postmarket oversight--spanning, for example, both premarket review of devices and postmarket surveillance (the collection and analysis of data on marketed devices). These responsibilities apply to all devices marketed in the United States, regardless of whether they are manufactured domestically or overseas. In 2009, GAO added FDA's oversight of medical products, including devices, to its list of high-risk areas warranting attention by Congress and the executive branch. GAO was asked to testify on recent work related to FDA's responsibilities for medical devices, including premarket review, postmarket surveillance, and inspection of manufacturing establishments. This statement is based on a recent GAO report, Medical Devices: FDA Should Take Steps to Ensure That High-Risk Device Types Are Approved through the Most Stringent Premarket Review Process (GAO-09-190, January 15, 2009) and on other GAO reports and testimonies related to FDA oversight.
GAO found that FDA does not review all class III devices through its most stringent premarket review process. Unless exempt by regulation, new devices must clear FDA premarket review through either the 510(k) premarket notification process, which is used to determine if a new device is substantially equivalent to another legally marketed device, or through the more stringent premarket approval (PMA) process, which requires the manufacturer to supply evidence providing reasonable assurance that the device is safe and effective. In 1976, Congress envisioned that FDA would eventually approve all class III devices through the more stringent PMA process, but this process remains incomplete. GAO found that in fiscal years 2003 through 2007, FDA cleared 228 submissions representing 24 types of class III devices through the 510(k) process. GAO recommended in its January 2009 report that FDA expeditiously take steps to issue regulations requiring PMAs for or reclassifying class III device types currently allowed to enter the market via the 510(k) process. In response, in April 2009, FDA required manufacturers to submit information on the safety and effectiveness of these types of devices. However, FDA did not specify a time frame for how quickly it will reclassify them or require PMAs for those device types that remain in class III. FDA also faces challenges in postmarket surveillance of medical devices. In 2008, GAO reported that the number of adverse event reports associated with medical devices increased substantially from 2000 to 2006. Both GAO and FDA, however, have identified shortcomings in FDA's postmarket oversight. For example, in 2006 FDA reported that the agency's ability to understand the risks related to the use of medical devices is limited by the fact that the volume of submitted reports exceeded FDA's ability to consistently enter or review the reports in a routine manner. In 2008, FDA officials told us that while they have a number of strategies to prioritize their reviews of adverse event reports, they still cannot review all the reports they receive. Finally, GAO has found that FDA has not conducted required inspections of manufacturing establishments, another key FDA responsibility for medical devices marketed in the United States. In 2008, GAO reported that FDA has not met a statutory requirement to inspect certain domestic manufacturing establishments every 2 years. Instead, FDA officials estimated that the agency has inspected domestic establishments every 3 years (for class III devices) or 5 years (for class II devices). There is no comparable requirement to inspect foreign establishments, and FDA officials estimate that they have been inspected every 6 years (for class III devices) or 27 years (for class II devices). GAO reported that FDA has taken some steps to address shortcomings related to inspections of foreign establishments, but GAO has not evaluated whether these changes will improve FDA's inspection program. Taken together, these shortcomings in both premarket and postmarket activities raise serious concerns about FDA's regulation of medical devices.
GAO-09-370T, Medical Devices: Shortcomings in FDA's Premarket Review, Postmarket Surveillance, and Inspections of Device Manufacturing Establishments
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Testimony:
Before the Subcommittee on Health, Committee on Energy and Commerce,
House of Representatives:
United States Government Accountability Office:
GAO:
For Release on Delivery:
Expected at 9:30 a.m. EDT:
Thursday, June 18, 2009:
Medical Devices:
Shortcomings in FDA's Premarket Review, Postmarket Surveillance, and
Inspections of Device Manufacturing Establishments:
Statement of Marcia Crosse:
Director, Health Care:
GAO-09-370T:
GAO Highlights:
Highlights of GAO-09-370T, a testimony before the Subcommittee on
Health, Committee on Energy and Commerce, House of Representatives.
Why GAO Did This Study:
Americans depend on the Food and Drug Administration (FDA) to provide
assurance that medical devices sold in the United States are safe and
effective. FDA classifies medical device types into three classes, with
class I including those with the lowest risk to patients (such as
forceps) and class III including those with the greatest risk (such as
pacemakers). FDA‘s responsibilities include premarket and postmarket
oversight”spanning, for example, both premarket review of devices and
postmarket surveillance (the collection and analysis of data on
marketed devices). These responsibilities apply to all devices marketed
in the United States, regardless of whether they are manufactured
domestically or overseas. In 2009, GAO added FDA‘s oversight of medical
products, including devices, to its list of high-risk areas warranting
attention by Congress and the executive branch.
GAO was asked to testify on recent work related to FDA‘s
responsibilities for medical devices, including premarket review,
postmarket surveillance, and inspection of manufacturing
establishments. This statement is based on a recent GAO report, Medical
Devices: FDA Should Take Steps to Ensure That High-Risk Device Types
Are Approved through the Most Stringent Premarket Review Process (GAO-
09-190, January 15, 2009) and on other GAO reports and testimonies
related to FDA oversight.
What GAO Found:
GAO found that FDA does not review all class III devices through its
most stringent premarket review process. Unless exempt by regulation,
new devices must clear FDA premarket review through either the 510(k)
premarket notification process, which is used to determine if a new
device is substantially equivalent to another legally marketed device,
or through the more stringent premarket approval (PMA) process, which
requires the manufacturer to supply evidence providing reasonable
assurance that the device is safe and effective. In 1976, Congress
envisioned that FDA would eventually approve all class III devices
through the more stringent PMA process, but this process remains
incomplete. GAO found that in fiscal years 2003 through 2007, FDA
cleared 228 submissions representing 24 types of class III devices
through the 510(k) process. GAO recommended in its January 2009 report
that FDA expeditiously take steps to issue regulations requiring PMAs
for or reclassifying class III device types currently allowed to enter
the market via the 510(k) process. In response, in April 2009, FDA
required manufacturers to submit information on the safety and
effectiveness of these types of devices. However, FDA did not specify a
time frame for how quickly it will reclassify them or require PMAs for
those device types that remain in class III.
FDA also faces challenges in postmarket surveillance of medical
devices. In 2008, GAO reported that the number of adverse event reports
associated with medical devices increased substantially from 2000 to
2006. Both GAO and FDA, however, have identified shortcomings in FDA‘s
postmarket oversight. For example, in 2006 FDA reported that the agency‘
s ability to understand the risks related to the use of medical devices
is limited by the fact that the volume of submitted reports exceeded
FDA‘s ability to consistently enter or review the reports in a routine
manner. In 2008, FDA officials told us that while they have a number of
strategies to prioritize their reviews of adverse event reports, they
still cannot review all the reports they receive.
Finally, GAO has found that FDA has not conducted required inspections
of manufacturing establishments, another key FDA responsibility for
medical devices marketed in the United States. In 2008, GAO reported
that FDA has not met a statutory requirement to inspect certain
domestic manufacturing establishments every 2 years. Instead, FDA
officials estimated that the agency has inspected domestic
establishments every 3 years (for class III devices) or 5 years (for
class II devices). There is no comparable requirement to inspect
foreign establishments, and FDA officials estimate that they have been
inspected every 6 years (for class III devices) or 27 years (for class
II devices). GAO reported that FDA has taken some steps to address
shortcomings related to inspections of foreign establishments, but GAO
has not evaluated whether these changes will improve FDA‘s inspection
program.
Taken together, these shortcomings in both premarket and postmarket
activities raise serious concerns about FDA's regulation of medical
devices.
View [hyperlink, http://www.gao.gov/products/GAO-09-370T] or key
components. For more information, contact Marcia Crosse at (202) 512-
7114 or crossem@gao.gov.
[End of section]
Mr. Chairman and Members of the Subcommittee:
I am pleased to be here today as you examine issues related to the
regulation of medical devices. Americans depend on the Food and Drug
Administration (FDA), an agency within the Department of Health and
Human Services (HHS) responsible for ensuring that medical devices and
other medical products sold in the United States are safe and
effective.[Footnote 1]
FDA's responsibilities for medical devices begin before a new device is
brought to market and continue after a device's clearance or approval,
and these responsibilities apply to devices marketed in the United
States regardless of whether they are manufactured domestically or
overseas. FDA reviews submissions for thousands of new devices filed
each year to decide whether they should be allowed to be marketed in
the United States and is also responsible for oversight of thousands of
devices already on the market. As part of both premarket and postmarket
oversight, the agency inspects manufacturing establishments to ensure
they are in compliance with the good manufacturing practices specified
in FDA's quality system regulation as well as other statutory and
regulatory requirements.
Recently, concerns have been expressed about FDA's ongoing ability to
fulfill its mission of ensuring the safety and efficacy of medical
products, including drugs, biologics, and devices. Reports issued by
FDA's Science Board in 2007 and the Congressional Research Service in
2008 point out that the demands on the agency have soared in recent
years for a variety of reasons, including the complexity of new
products submitted to FDA for premarket approval and the globalization
of the industries that FDA regulates. The Science Board also found that
FDA's resources had not increased in proportion to the growing demands
placed on it, putting public health at risk. In its fiscal year 2007
and 2008 reports, the HHS Office of Inspector General identified the
oversight of drug and device safety as one of HHS's top management
challenges. In January 2009, we added FDA's oversight of medical
products, including devices, to GAO's list of high-risk areas
warranting attention by Congress and the executive branch.[Footnote 2]
Medical devices range from simple tools like bandages and surgical
clamps to complicated devices like pacemakers. FDA classifies each type
of device into one of three classes--class I, II, or III--based on the
level of risk it poses and the controls necessary to provide reasonable
assurance that it is safe and effective.[Footnote 3] According to FDA,
the risk the type of device poses to the patient or the user is a major
factor in the class it is assigned: class I includes devices with the
lowest risk and class III includes devices with the highest risk.
Examples of types of devices in each class include the following:
* class I: tongue depressors, elastic bandages, reading glasses, and
forceps;
* class II: electrocardiographs, powered bone drills, and mercury
thermometers; and:
* class III: pacemakers and replacement heart valves.
In general, unless exempt under FDA regulations,[Footnote 4] devices
are subject to one of two types of FDA premarket review before they may
be legally marketed in the United States.[Footnote 5]
* Premarket approval (PMA): The manufacturer must provide evidence,
typically including clinical data, providing reasonable assurance that
the new device is safe and effective. The PMA process is the most
stringent type of premarket review. A successful submission results in
FDA approval.
* Premarket notification (510(k)): The manufacturer must demonstrate to
FDA that the new device is substantially equivalent to a legally
marketed device that does not require a PMA.[Footnote 6] A successful
submission results in FDA clearance.
My remarks today will discuss shortcomings we have identified in FDA's
premarket review of medical devices, FDA's postmarket surveillance
activities, and FDA's inspections of manufacturing establishments. My
statement includes findings from our recent report on FDA's premarket
review of medical devices.[Footnote 7] My statement also draws from
several other GAO reports and testimonies on FDA inspections of
domestic and foreign device manufacturing establishments and other
aspects of FDA's oversight of devices that we have issued since 2007,
[Footnote 8] as well as ongoing work we are conducting related to FDA.
For this body of work, we analyzed information from FDA databases;
[Footnote 9] interviewed FDA officials; and reviewed pertinent
statutes, regulations, guidance, and reports. For the report on FDA's
premarket review of devices, we examined the premarket review
processes--the 510(k) premarket notification process or the premarket
approval (PMA) process--FDA used in fiscal years 2003 through 2007 and
reviewed a sample of FDA files related to submissions for new devices.
Our analysis included traditional and abbreviated 510(k) submissions,
original PMA submissions, and submissions for two types of supplemental
PMAs: panel-track PMA supplements (which are supplements requesting
approval for a significant change in design or performance, or a new
use of a device, for which clinical data are generally necessary to
provide reasonable assurance of safety and effectiveness) and 180-day
PMA supplements (which are supplements requesting approval for a
significant change in components, materials, design, specification,
software, color additives, or labeling).[Footnote 10]
To assess FDA's program for inspecting establishments that manufacture
medical devices, we analyzed information from three FDA
databases[Footnote 11] and interviewed officials from FDA's Center for
Devices and Radiological Health and Office of Regulatory Affairs, which
each have responsibilities for managing the medical device inspection
program. We also obtained updated information from FDA on the status of
FDA's programs for third-party inspections in June 2009. Specifically,
we obtained data from FDA on the number of inspections conducted by
accredited third parties since March 11, 2004--the date when FDA first
cleared an accredited organization to conduct inspections.
We conducted our work in accordance with generally accepted government
auditing standards. Those standards require that we plan and perform
the audit to obtain sufficient, appropriate evidence to provide a
reasonable basis for our findings and conclusions based on our audit
objectives. We believe that the evidence obtained provides a reasonable
basis for our findings and conclusions based on our audit objectives.
Background:
FDA's responsibilities related to medical devices include premarket and
postmarket oversight--spanning, for example, both premarket review of
devices and postmarket surveillance (the collection and analysis of
data on marketed devices). As part of both premarket and postmarket
oversight, FDA is responsible for inspecting certain foreign and
domestic establishments to ensure they meet required manufacturing
standards.
Premarket Review:
Relative to the PMA process, the 510(k) premarket review process is
generally:
* Less stringent. For most 510(k) submissions, clinical data are not
required and substantial equivalence will normally be determined based
on comparative device descriptions, including performance data. In
contrast, in order to meet the PMA approval requirement of providing
reasonable assurance that a new device is safe and effective, most
original PMAs and some PMA supplements require clinical data.
* Faster. FDA generally makes decisions on 510(k) submissions faster
than it makes decisions on PMA submissions. FDA's fiscal year 2009 goal
is to review and decide on 90 percent of 510(k) submissions within 90
days and 98 percent of them within 150 days. The comparable goal for
PMAs is to review and decide upon 60 percent of original PMA
submissions in 180 days and 90 percent of them within 295 days.
[Footnote 12]
* Less expensive. The estimated cost to FDA for reviewing submissions
is substantially lower for 510(k) submissions than for PMA submissions.
For fiscal year 2005, for example, according to FDA the estimated
average cost for the agency to review a 510(k) submission was about
$18,200, while the estimate for a PMA submission was about $870,000.
For the applicant, the standard fee provided to FDA at the time of
submission is also significantly lower for a 510(k) submission than for
a PMA submission. In fiscal year 2009, for example, the standard fee
for 510(k) submissions is $3,693, while the standard fee for original
PMA submissions is $200,725.
In general, class I and II device types subject to premarket review are
required to obtain FDA clearance through the 510(k) process, and class
III device types are required to obtain FDA approval through the more
stringent PMA process. With the enactment of the Medical Device
Amendments of 1976, Congress imposed requirements under which all class
III devices would be approved through the PMA process before being
marketed in the United States.[Footnote 13] However, certain types of
class III devices that were in commercial distribution in the United
States before May 28, 1976[Footnote 14] (called preamendment device
types) and those determined to be substantially equivalent to them may
be cleared through the less stringent 510(k) process until FDA
publishes regulations requiring them to go through the PMA process or
reclassifies them into a lower class.[Footnote 15] Prior to 1990, FDA
issued regulations requiring some class III device types to go through
the PMA process but many class III device types continued to be
reviewed through the 510(k) process.[Footnote 16] The Safe Medical
Devices Act of 1990 required FDA (1) to reexamine the preamendment
class III device types for which PMAs were not yet required to
determine if they should be reclassified to class I or II or remain in
class III and (2) to establish a schedule to promulgate regulations
requiring those preamendment device types that remain in class III to
obtain FDA approval through the PMA process.[Footnote 17] Accordingly,
all class III devices are eventually to be reviewed through the PMA
process.
Postmarket Surveillance:
In addition to its responsibilities for premarket review of devices,
FDA's postmarket activities to help ensure that devices already on the
market remain safe and effective include collecting and analyzing
reports of device-related adverse events and reviewing annual reports
required from manufacturers.[Footnote 18] FDA's reporting framework for
device-related adverse events includes both mandatory and voluntary
components. Under FDA's Medical Device Reporting regulation,
* manufacturers are required to report device-related deaths, serious
injuries, and certain malfunctions to FDA and:
* user facilities, such as hospitals and nursing homes, are required to
report device-related deaths to FDA and to the device manufacturer and
to report serious injuries to the manufacturer (or, if the manufacturer
is unknown, to FDA).
[End of section]
Manufacturers and user facilities, as well as health professionals and
consumers, may also voluntarily report less serious device-related
events to FDA. FDA maintains databases that include both mandatory and
voluntary reports of device-related adverse events, which agency
officials can search to conduct research on trends or emerging problems
with device safety. FDA scientists review these reports, request follow-
up investigations, and determine whether further action is needed to
ensure patient safety. Such action may include product recalls, public
health advisories to notify health care providers and the public of
potential device-related health and safety concerns, or requiring a
manufacturer to change the instructions in its device labeling.
Inspections of Device Manufacturing Establishments:
Finally, as part of both premarket and postmarket oversight of medical
devices, FDA is responsible for inspecting certain foreign and domestic
establishments to ensure they meet required manufacturing
standards.[Footnote 19] Such inspections are FDA's primary means of
assuring that the safety and effectiveness of devices are not
jeopardized by poor manufacturing practices. Requirements governing
domestic and foreign inspections differ. Specifically, FDA is required
to inspect domestic establishments that manufacture class II or III
devices every 2 years.[Footnote 20] There is no comparable requirement
to inspect foreign establishments.
In 2002, in response to concerns about FDA's ability to meet its
responsibilities for inspecting device manufacturing establishments,
Congress included certain provisions in the Medical Device User Fee and
Modernization Act of 2002 (MDUFMA).[Footnote 21] These provisions were
designed to (1) increase the number of inspected device manufacturing
establishments and (2) help device manufacturers meet the inspection
requirements of both the United States and foreign countries in a
single inspection. Specifically, MDUFMA required FDA to accredit third-
party organizations to conduct inspections of certain foreign and
domestic establishments. In response, FDA implemented its Accredited
Persons Inspection Program, which permits certain establishments to
voluntarily request inspections from third-party organizations to meet
inspectional requirements. Additionally, in September 2006, in
partnership with Health Canada,[Footnote 22] FDA established another
program for inspection by accredited third parties--the Pilot Multi-
purpose Audit Program--that allows accredited organizations to conduct
a single inspection to meet the regulatory requirements of both
countries.
FDA Has Not Ensured That All Class III Devices Are Approved through the
Most Stringent Premarket Review Process:
Although Congress envisioned that all class III devices would
eventually be approved through the more stringent PMA process, we found
that this was not always the case. In January 2009, we reported that in
fiscal years 2003 through 2007, FDA reviewed all submissions for class
I and II devices through the 510(k) process, and reviewed submissions
for some types of class III devices through the 510(k) process and
others through the PMA process.[Footnote 23]
* FDA reviewed all 13,199 submissions for class I and class II devices
through the 510(k) process, clearing 11,935 (90 percent) of these
submissions.
* FDA also reviewed 342 submissions for class III devices through the
510(k) process, clearing 228 (67 percent) of these submissions.
* In addition, the agency reviewed 217 original PMA submissions and 784
supplemental PMA submissions for class III devices and approved 78
percent and 85 percent, respectively, of these submissions.
[End of section]
Table 1 summarizes the FDA review decisions, by class of device, in
fiscal years 2003 through 2007 for 510(k) and PMA submissions.
Table 1: FDA 510(k) and PMA Decisions by Class, Fiscal Years 2003
through 2007:
Submission type: 510(k);
Device class: Class I;
Determined substantially equivalent or approved (percentage of row):
1,265 (84);
Determined not substantially equivalent or denied (percentage of row):
40 (3);
Other decision[A](percentage of row): 204 (14);
Total (percentage of row): 1,509 (100).
Submission type: 510(k);
Device class: Class II;
Determined substantially equivalent or approved (percentage of row):
10,670 (91);
Determined not substantially equivalent or denied (percentage of row):
373 (3);
Other decision[A](percentage of row): 647 (6);
Total (percentage of row): 11,690 (100).
Submission type: 510(k);
Device class: Class III;
Determined substantially equivalent or approved (percentage of row):
228 (67);
Determined not substantially equivalent or denied (percentage of row):
100 (29);
Other decision[A] (percentage of row): 14 (4);
Total (percentage of row): 342 (100).
Submission type: 510(k);
Device class: Other[B];
Determined substantially equivalent or approved (percentage of row):
476 (33);
Determined not substantially equivalent or denied (percentage of row):
27 (2);
Other decision[A](percentage of row): 955 (66);
Total (percentage of row): 1,458 (100).
Submission type: PMA; Original;
Device class: Class III;
Determined substantially equivalent or approved (percentage of row):
170 (78);
Determined not substantially equivalent or denied (percentage of row):
[Empty][C];
Other decision[A](percentage of row): 47 (22)[C];
Total (percentage of row): 217 (100).
Submission type: PMA; Supplemental[D];
Device class: Class III;
Determined substantially equivalent or approved (percentage of row):
664 (85);
Determined not substantially equivalent or denied (percentage of row):
[Empty][C];
Other decision[A](percentage of row): 120 (15)[C];
Total (percentage of row): 784 (100).
Source: GAO analysis of FDA data.
Notes: Data represent 14,999 traditional and abbreviated 510(k)
submissions, 217 original PMA submissions, and 784 supplemental PMA
submissions for which FDA made review decisions in fiscal years 2003
through 2007. Percentages may not sum to 100 because of rounding.
[A] Other decisions include submissions that were withdrawn, were
exempted by regulation, were not responsive to FDA's requests within a
specified time frame, were forwarded to another FDA center (e.g., drugs
or biologics), were duplicates, or were for products determined not to
be devices.
[B] Other device class includes submissions for which a device class
was not recorded in FDA's 510(k) database.
[C] According to FDA data, all PMA decisions during fiscal years 2003
through 2007 were approved or withdrawn. FDA did not deny approval of
any PMA submissions during this period. According to FDA officials,
when a PMA was seriously deficient, FDA issued a "not approvable"
letter under 21 C.F.R. § 814.44(f) and placed the submission on hold. A
company may withdraw a submission voluntarily. FDA also considers
submissions to be withdrawn voluntarily if the applicant is unable to
provide the information necessary to support approval within 180 days.
[D] Supplemental PMA submissions include 180-day (user-fee) and panel-
track PMA supplements. The numbers in this row do not include other
types of PMA supplements.
[End of table]
With respect to class III devices, in fiscal years 2003 through 2007,
FDA reviewed submissions for some types of class III devices through
the 510(k) process, and other types of class III devices through the
PMA process. Specifically, FDA reviewed 342 submissions for new class
III devices through the 510(k) process, determining 228 (67 percent) of
these submissions to be substantially equivalent to a legally marketed
device.[Footnote 24] During the same time period, FDA reviewed 217
original PMA submissions and 784 supplemental PMA submissions for class
III devices and approved 78 percent and 85 percent of them,
respectively. (See figure 1.)
Figure 1: Class III Device Submissions with FDA Review Decisions in
Fiscal Years 2003 through 2007, by FDA Review Process and Review
Decision:
[Refer to PDF for image: vertical bar graph]
FDA review process: 510(k);
Number of submissions cleared/approved (percentage): 228 (67%);
Number of submissions not cleared/not approved: 114;
Total number of submissions: 342.
FDA review process: Original PMA;
Number of submissions cleared/approved (percentage): 170 (78%);
Number of submissions not cleared/not approved: 47;
Total number of submissions: 217.
FDA review process: Supplemental PMA;
Number of submissions cleared/approved (percentage): 664 (85%);
Number of submissions not cleared/not approved: 120;
Total number of submissions: 784.
Source: GAO analysis of FDA data.
Notes: Figure represents FDA review decisions made between October 1,
2002, and September 30, 2007, for class III device submissions reviewed
through the 510(k) and PMA processes. 510(k) includes traditional and
abbreviated 510(k) submissions; supplemental PMA includes panel-track
supplements and 180-day (user-fee) supplements.
Not cleared/not approved includes (1) for 510(k) submissions, those
submissions FDA found to be not substantially equivalent or withdrawn
and (2) for PMA submissions, those submissions that were withdrawn.
According to FDA data, all PMA decisions during fiscal years 2003
through 2007 were approved or withdrawn. FDA did not deny approval of
any PMA submissions during this period. According to FDA officials,
when a PMA is seriously deficient, FDA issues a "not approvable" letter
and places the submission on hold. An applicant may then withdraw a
submission voluntarily. FDA also considers submissions to be withdrawn
voluntarily if the applicant is unable to provide the information
necessary to support approval within 180 days.
[End of figure]
The 228 class III device submissions FDA cleared through the 510(k)
process in fiscal years 2003 through 2007 were for devices such as
artificial hip joints, implantable blood access devices, and automated
external defibrillators. Class III 510(k) submissions were more likely
than other 510(k) submissions to be for device types that were
implantable; were life sustaining; or pose a significant risk to the
health, safety, or welfare of a patient. Of the 228 510(k) submissions
for class III devices that FDA cleared in fiscal years 2003 through
2007, FDA's databases flagged 66 percent as being for device types that
are implantable, life sustaining, or of significant risk. This compares
to no 510(k) submissions for class I devices and 25 percent of 510(k)
submissions for class II devices.
Although the Medical Device Amendments of 1976 imposed requirements
under which all class III devices would be approved through the PMA
process, and the Safe Medical Devices Act of 1990 required that FDA
either reclassify or establish a schedule for requiring PMAs for class
III device types, this process remains incomplete. The 228 class III
device submissions cleared by FDA through the 510(k) process in fiscal
years 2003 through 2007 represented 24 separate types of class III
devices. As of October 2008, 4 of these device types had been
reclassified to class II, but 20 device types could still be cleared
through the 510(k) process. FDA officials said that the agency is
committed to issuing regulations either reclassifying or requiring PMAs
for the class III devices currently allowed to receive clearance for
marketing via the 510(k) process, but did not provide a time frame for
doing so.
We recommended that the Secretary of Health and Human Services direct
the FDA Commissioner to expeditiously take steps to issue regulations
for each class III device type currently allowed to enter the market
through the 510(k) process. These steps should include issuing
regulations to (1) reclassify each device type into class I or class
II, or require it to remain in class III, and (2) for those device
types remaining in class III, require approval for marketing through
the PMA process. In commenting on a draft of our report, HHS agreed
with our recommendation, noting that since 1994 (when FDA announced its
strategy to implement provisions of the Safe Medical Devices Act of
1990) FDA has called for PMAs or reclassified the majority of class III
devices that did not require PMAs at that time. The department's
comments, however, did not specify time frames in which FDA will
address the remaining class III device types allowed to enter the
market via the 510(k) process, stating instead that the agency is
considering its legal and procedural options for completing this task
as expeditiously as possible, consistent with available resources and
competing time frames. Given that more than 3 decades have passed since
Congress envisioned that all class III devices would eventually be
required to undergo premarket review through the more stringent PMA
process, we believe it is imperative that FDA take immediate steps to
address the remaining class III device types that may still enter the
market through the less stringent 510(k) process by requiring PMAs for
or reclassifying them.
In April 2009, FDA took what it termed "the first step towards
completing the review of Class III device types predating the 1976 law,
as was recommended by the U.S. Government Accountability Office (GAO)
in a January 2009 report to Congress." Specifically, FDA announced that
it was requiring manufacturers of 25 types of class III medical devices
marketed prior to 1976 to submit safety and effectiveness information
to the agency by August 7, 2009, so that it may evaluate the risk level
for each device type. In the Federal Register notice announcing the
requirement,[Footnote 25] FDA stated that once the safety and
effectiveness information was submitted, the agency would be able to
determine which device types would be required to undergo the agency's
most stringent premarket review process. FDA's requirement that
manufacturers submit safety and effectiveness information is an
essential initial step toward implementing our recommendation and fully
implementing the law. However, FDA did not specify a time frame for how
quickly it will review the submitted information, determine whether to
reclassify the device types, and require PMAs for those that remain in
class III.
It should be noted, however, that while the PMA process is more
stringent than the 510(k) process, FDA can approve a device through the
PMA process without clinical data demonstrating the safety and
effectiveness of the device. For example, in our review of FDA's
approval of PMAs for certain temporomandibular joint (jaw) implants,
FDA managers overruled their review staff to approve one of the
devices, despite the review staff's concern over the sufficiency of the
clinical data.[Footnote 26] The review decision stated that either good
engineering data or good clinical data--not necessarily both--were
acceptable to approve a device and accepted the engineering data as a
basis for approving an implanted device for which the review staff had
determined that the clinical data were inadequate.
FDA Faces Challenges in Postmarket Surveillance:
In our recent high-risk report, we noted that FDA's monitoring of
postmarket safety of approved products, including medical devices, has
been questioned by numerous groups.[Footnote 27] In 2008, we reported
that the number of adverse event reports associated with all devices
increased substantially from about 77,000 reports in 2000 to about
320,000 reports in 2006.[Footnote 28] FDA's review and analysis of
these reports provides information about trends such as infection
outbreaks or common user errors caused by inadequate instructions and
may result in actions such as device recalls. During fiscal year 2006,
FDA initiated 651 recall actions involving 1,550 medical devices. This
included 21 recall actions in which FDA determined that it was likely
that the use of the medical device would cause serious health problems
or death.
We and FDA have identified shortcomings in FDA's postmarket
surveillances. In 2006, FDA reported that the agency's Center for
Devices and Radiological Health's ability to understand the risks of
adverse events related to the use of medical devices--whether used in
the in the home of a patient, in a hospital, in a laboratory, or in the
office of a private practitioner--is limited both by a lack of
informative, validated adverse event reports and by a lack of quality
epidemiologic information.[Footnote 29] FDA specifically reported:
* One major constraint is the lack of objective data about device use
and device-related problems.
* Underreporting of adverse events continues to be a problem.
* FDA's medical device reporting system is a passive system--that is,
the reports are entered as reported by manufacturers, facilities,
practitioners, or patients--and, as a result, some reports are
incomplete or difficult to understand.
* The volume of submitted reports exceeded the center's ability to
consistently enter or review the data in a routine manner.
In its 2006 report, FDA identified areas for improvement in postmarket
problem assessment for the center. In 2008, FDA officials told us that
while they have a number of strategies to prioritize their reviews,
they still cannot review all the reports they receive.
We have also found shortcomings in FDA's monitoring of manufacturers'
compliance with requirements following device approval. In 2007, we
found that manufacturers do not always submit their required annual
reports in a timely manner. For example, FDA was missing five annual
reports from the manufacturer of one device we were examining, but it
was not until we requested these reports that FDA contacted the
manufacturer to obtain the missing information.[Footnote 30] Without
these annual reports, FDA cannot adequately monitor manufacturers'
compliance with postmarket requirements.
FDA Has Not Conducted Required Inspections of Manufacturing
Establishments:
Our work has also identified challenges faced by FDA in terms of
inspecting establishments that manufacture medical devices. In January
2008, we testified that FDA has not met a statutory requirement to
inspect certain domestic manufacturing establishments every 2 years.
[Footnote 31] FDA officials estimated that the agency has inspected
these establishments every 3 years (for establishments manufacturing
class III devices) or every 5 years (for establishments manufacturing
class II devices). There is no comparable requirement to inspect
foreign establishments, and agency officials estimate that these
establishments have been inspected every 6 years (for class III
devices) or 27 years (for class II devices).
We also testified that FDA faces additional challenges in managing its
inspections of foreign device establishments. We found that two
databases that provide FDA with information about foreign device
establishments and the products they manufacture for the U.S. market
contain inaccuracies that create disparate estimates of establishments
subject to FDA inspection.[Footnote 32] Although comparing information
from these two databases could help FDA determine the number of foreign
establishments marketing devices in the United States, these databases
cannot exchange information and any comparisons must be done manually.
Moreover, inspections of foreign device manufacturing establishments
pose unique challenges to FDA, such as difficulties in finding
translation services and in extending trips if the inspections uncover
problems. FDA has taken some steps to address shortcomings related to
inspections of foreign establishments, including changes to its
registration database to improve the accuracy of the count of
establishments and initiatives to address unique challenges related to
inspections of foreign manufacturers, but we have not evaluated whether
these changes will improve FDA's inspection program.
In addition, FDA's accredited third-party inspection programs may be
unable to quickly help FDA fulfill its responsibilities. In January
2007, we reported on the status of the Accredited Persons Inspection
Program, citing, among other things, concerns regarding its
implementation and potential incentives and disincentives that may
influence manufacturers' participation.[Footnote 33] We found that
several factors may influence manufacturers' interest in voluntarily
requesting an inspection by an accredited organization. According to
FDA and representatives of affected entities, there are potential
incentives and disincentives to requesting an inspection, as well as
reasons for deferring participation in the program. Potential
incentives include the opportunity to reduce the number of inspections
conducted to meet FDA and other countries' requirements and to control
the scheduling of the inspection. Potential disincentives include
bearing the cost for the inspection and uncertainty about the potential
consequences of making a commitment to having an inspection to assess
compliance with FDA requirements in the near future. Some manufacturers
might be deferring participation. For example, manufacturers that
already contract with a specific accredited organization to conduct
inspections to meet the requirements of other countries might defer
participation until FDA has cleared that organization to conduct
independent inspections. In both our January 2008 and May 2008
testimonies, we reported that few inspections of device manufacturing
establishments had been conducted through FDA's two accredited third-
party inspection programs.[Footnote 34] As of June 12, 2009, FDA
reported that a total of 21 inspections--8 inspections of domestic
establishments and 13 inspections of foreign establishments--had been
conducted under these programs. The small number of inspections
completed by accredited third-party organizations raises questions
about the practicality and effectiveness of these programs to quickly
help FDA increase the number of establishments inspected.
Taken together, these shortcomings in both premarket and postmarket
activities raise serious concerns about FDA's regulation of medical
devices.
Mr. Chairman, this completes my prepared statement. I would be happy to
respond to any questions you or the other members of the subcommittee
may have at this time.
Contacts and Acknowledgments:
For further information about this statement, please contact Marcia
Crosse, at (202) 512-7114 or crossem@gao.gov. Contact points for our
Offices of Congressional Relations and Public Affairs may be found on
the last page of this statement. Kim Yamane and Geraldine Redican-
Bigott, Assistant Directors; Susannah Bloch; Matt Byer; Sean DeBlieck;
Helen Desaulniers; and Julian Klazkin made key contributions to this
report.
[End of section]
Related GAO Products:
High-Risk Series: An Update. [hyperlink,
http://www.gao.gov/products/GAO-09-271]. Washington, D.C.: January
2009.
Medical Devices: FDA Should Take Steps to Ensure That High-Risk Device
Types Are Approved through the Most Stringent Premarket Review Process.
[hyperlink, http://www.gao.gov/products/GAO-09-190]. Washington, D.C.:
January 15, 2009.
Health-Care-Associated Infections in Hospitals: Number Associated with
Medical Devices Unknown, but Experts Report Provider Practices as a
Significant Factor. [hyperlink,
http://www.gao.gov/products/GAO-08-1091R]. Washington, D.C.: September
26, 2008.
Medical Devices: FDA Faces Challenges in Conducting Inspections of
Foreign Manufacturing Establishments. [hyperlink,
http://www.gao.gov/products/GAO-08-780T]. Washington, D.C.: May 14,
2008.
Reprocessed Single-Use Medical Devices: FDA Oversight Has Increased,
and Available Information Does Not Indicate That Use Presents an
Elevated Health Risk. [hyperlink,
http://www.gao.gov/products/GAO-08-147]. Washington, D.C.: January 31,
2008.
Medical Devices: Challenges for FDA in Conducting Manufacturer
Inspections.[hyperlink, http://www.gao.gov/products/GAO-08-428T].
Washington, D.C.: January 29, 2008.
Medical Devices: FDA's Approval of Four Temporomandibular Joint
Implants. [hyperlink, http://www.gao.gov/products/GAO-07-996].
Washington, D.C.: September 17, 2007.
Food and Drug Administration: Methodologies for Identifying and
Allocating Costs of Reviewing Medical Device Applications Are
Consistent with Federal Cost Accounting Standards, and Staffing Levels
for Reviews Have Generally Increased in Recent Years. [hyperlink,
http://www.gao.gov/products/GAO-07-882R]. Washington, D.C.: June 25,
2007.
Medical Devices: Status of FDA's Program for Inspections by Accredited
Organizations. [hyperlink, http://www.gao.gov/products/GAO-07-157].
Washington, D.C.: January 5, 2007.
[End of section]
Footnotes:
[1] Generally, medical devices include items used for the diagnosis,
cure, mitigation, treatment, or prevention of a disease. See 21 U.S.C.
§ 321(h). Throughout this statement, the term device refers to a
medical device that is not being regulated as a drug or a biological
product.
[2] See GAO, High-Risk Series: An Update, [hyperlink,
http://www.gao.gov/products/GAO-09-271] (Washington, D.C.: Jan. 2009).
[3] Throughout this statement, we refer to type of device or device
type to indicate a generic category of device, which has a particular
intended use (for example, a scalpel is intended to cut tissue) and
which may include a variety of models made by different manufacturers.
FDA's classifications of device types are codified in parts 862 through
892 of title 21 of the Code of Federal Regulations. Class I devices are
those for which compliance with general controls, such as good
manufacturing practices specified in FDA's quality system regulation,
are sufficient to provide reasonable assurance of their safety and
effectiveness. Class II devices are subject to general controls and may
also be subject to special controls, such as postmarket surveillance.
For class II devices intended to support or sustain human life, FDA
must examine, identify, and describe the special controls necessary to
provide assurance of their safety and effectiveness. Class III devices
are those (1) for which insufficient information exists to determine
whether general and special controls are sufficient to provide
reasonable assurance of their safety and effectiveness and (2) that
support or sustain human life or are of substantial importance in
preventing impairment of human health, or that present a potential
unreasonable risk of illness or injury. See 21 U.S.C. § 360c.
[4] Under federal regulations, many types of devices are exempt from
FDA premarket review. Although FDA does not track the number of devices
that are actually sold or marketed in the United States, manufacturers
are required to register with FDA and provide a list of devices
intended for commercial distribution, including device types that are
exempt from premarket review. See 21 U.S.C. § 360(j)(2)(A); 21 C.F.R. §
807.21 (2008). About 67 percent of the more than 50,000 separate
devices that manufacturers listed with FDA during fiscal years 2003
through 2007 were exempt from premarket review. Of the exempt devices
that manufacturers listed with FDA, about 95 percent were class I
devices, for example reading glasses and forceps. About 5 percent were
class II devices, for example wheeled stretchers and mercury
thermometers.
[5] A small percentage of devices enter the market by other means, such
as through the humanitarian device exemption process that allows market
entry, without adherence to certain requirements, for devices
benefiting patients with rare diseases or conditions. See 21 U.S.C. §
360j(m), 21 C.F.R. pt. 814, subpart H (2008).
[6] Substantial equivalence or substantially equivalent means that the
device has the same intended use as another legally marketed device and
the same technological characteristics, or different technological
characteristics and submitted information demonstrates that the device
is as safe and effective as the legally marketed device and does not
raise different questions of safety or effectiveness. See 21 U.S.C. §
360c(i)(1)(A).
[7] See GAO, Medical Devices: FDA Should Take Steps to Ensure That High-
Risk Device Types Are Approved through the Most Stringent Premarket
Review Process, [hyperlink, http://www.gao.gov/products/GAO-09-190]
(Washington, D.C.: Jan. 15, 2009).
[8] See "Related GAO Products" at the end of this testimony.
[9] The databases we used included FDA's 510(k) and premarket approval
(PMA) databases, Device Nomenclature Management System, Device
Registration and Listing System (DRLS), Field Accomplishments and
Compliance Tracking System (FACTS), and Operational and Administrative
System for Import Support (OASIS).
[10] Our analysis did not include certain types of device submissions,
for example, special 510(k) submissions, which are requests for
clearance of minor modifications to devices that have already been
cleared through the 510(k) process.
[11] The FDA databases we used were DRLS, FACTS, and OASIS.
[12] FDA's goals for original PMAs included panel-track PMA
supplements.
[13] See Pub. L. No. 94-295, 90 Stat. 539, 552-53 (codified at 21
U.S.C. § 360e).
[14] May 28, 1976, is the date of enactment of the Medical Device
Amendments of 1976, which established the three device classes. Pub. L.
No. 94-295, 90 Stat. 539.
[15] Based on new information respecting a device, FDA may, upon its
initiative or upon petition of an interested person, by regulation
change the classification of a device from class III to (1) class II if
it determines that special controls would provide reasonable assurance
of the safety and effectiveness of the device and that general controls
alone would not provide reasonable assurance of the safety and
effectiveness of the device or (2) class I if FDA determines that
general controls alone would provide reasonable assurance of the safety
and effectiveness of the device. 21 U.S.C. § 360c(e).
[16] In August 1988, GAO reported that FDA had called for premarket
approval applications for only 9 of approximately 150 types of
preamendment class III device types. See GAO, Medical Devices: FDA's
510(k) Operations Could Be Improved, [hyperlink,
http://www.gao.gov/products/GAO/PEMD-88-14] (Washington, D.C.: Aug. 17,
1988).
[17] Pub. L. No. 101-629, § 4(b), 104 Stat. 4511, 4515-17 (codified at
21 U.S.C. § 360c(i)).
[18] FDA approves some devices conditionally, meaning that as a
condition of approval, manufacturers must comply with specific terms
specified by FDA, such as conducting postmarket surveillance studies.
Manufacturers report to FDA on their compliance with these conditions
through annual reports.
[19] FDA regulations define an establishment as a place of business
under one management at one general physical location at which a device
is manufactured, assembled, or otherwise processed. 21 C.F.R. §
807.3(c) (2007). Device manufacturers may have more than one
establishment. We use the term manufacture to refer to activities
including manufacturing, preparing, and processing devices.
[20] 21 U.S.C. § 360(h). There is no statutory requirement for
inspection of class I device manufacturing establishments, and FDA does
not routinely inspect them. However, FDA periodically inspects
establishments manufacturing surgeon's gloves and patient examination
gloves, which are both class I devices, due to ongoing problems with
leakage. FDA also periodically inspects manufacturers of randomly
selected class I devices.
[21] See Pub. L. No. 107-250, § 201, 116 Stat. 1588, 1602-09 (2002)
(codified as amended at 21 U.S.C. § 374(g)).
[22] Health Canada is the governmental entity that regulates medical
devices marketed in Canada.
[23] See [hyperlink, http://www.gao.gov/products/GAO-09-190].
[24] Consumer advocates have raised questions regarding 510(k)
clearance of devices that may utilize new technologies that are
different than those in the marketed devices to which they are
compared. In our review of a representative sample of 510(k)
submissions for which FDA reached a review decision of substantially
equivalent or not substantially equivalent in fiscal years 2005 through
2007, we found that FDA determined 23 percent of cleared class III
device submissions had new technological characteristics. This compares
to 14 percent of cleared class II submissions.
[25] See 74 Fed. Reg. 16214 (Apr. 9, 2009).
[26] See GAO, Medical Devices: FDA's Approval of Four Temporomandibular
Joint Implants, [hyperlink, http://www.gao.gov/products/GAO-07-996]
(Washington, D.C.: Sept. 17, 2007).
[27] See [hyperlink, http://www.gao.gov/products/GAO-09-271], 18.
[28] FDA officials told us that the vast majority of reports involve a
device malfunction that has the potential to cause a death or serious
injury if the malfunction were to recur, even though there was no death
or serious injury in the reported event. See GAO, Reprocessed Single-
Use Medical Devices: FDA Oversight Has Increased, and Available
Information Does Not Indicate That Use Presents an Elevated Health
Risk, GAO-08-147 (Washington, D.C.: Jan. 31, 2008).
[29] See Food and Drug Administration, Ensuring the Safety of Marketed
Medical Devices, CDRH's Medical Device Postmarket Safety Program (Jan.
18, 2006).
[30] [hyperlink, http://www.gao.gov/products/GAO-07-996].
[31] See GAO, Medical Devices: Challenges for FDA in Conducting
Manufacturer Inspections, [hyperlink,
http://www.gao.gov/products/GAO-08-428T] (Washington, D.C.: Jan. 29,
2008).
[32] These two databases are DRLS and OASIS.
[33] See GAO, Medical Devices: Status of FDA's Program for Inspections
by Accredited Organizations, [hyperlink,
http://www.gao.gov/products/GAO-07-157] (Washington, D.C.: Jan. 5,
2007).
[34] See [hyperlink, http://www.gao.gov/products/GAO-08-428T] and GAO,
Medical Devices: FDA Faces Challenges in Conducting Inspections of
Foreign Manufacturing Establishments, [hyperlink,
http://www.gao.gov/products/GAO-08-780T] (Washington, D.C.: May 14,
2008).
[End of section]
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