Medical Devices: Challenges for FDA in Conducting Manufacturer
Inspections (29-JAN-08, GAO-08-428T).
As part of the Food and Drug Administration's (FDA) oversight of
the safety and effectiveness of medical devices marketed in the
United States, it inspects domestic and foreign establishments
where these devices are manufactured. To help FDA address
shortcomings in its inspection program, the Medical Device User
Fee and Modernization Act of 2002 required FDA to accredit third
parties to inspect certain establishments. In response, FDA has
implemented two such voluntary programs. GAO previously reported
on the status of one of these programs, citing concerns regarding
its implementation and factors that may influence manufacturers'
participation. (Medical Devices: Status of FDA's Program for
Inspections by Accredited Organizations, GAO-07-157, January
2007.) This statement (1) assesses FDA's management of
inspections of establishments--particularly those in foreign
countries--manufacturing devices for the U.S. market, and (2)
provides the status of FDA's programs for third-party inspections
of medical device manufacturing establishments. GAO interviewed
FDA officials; reviewed pertinent statutes, regulations,
guidance, and reports; and analyzed information from FDA
databases. GAO also updated its previous work on FDA's programs
for inspections by accredited third parties.
-------------------------Indexing Terms-------------------------
REPORTNUM: GAO-08-428T
ACCNO: A80232
TITLE: Medical Devices: Challenges for FDA in Conducting
Manufacturer Inspections
DATE: 01/29/2008
SUBJECT: Certification and accreditation
Eligibility determinations
Evaluation criteria
Inspection
Institution accreditation
Manufacturing industry
Medical equipment
Program evaluation
Quality control
Schedule slippages
Voluntary compliance
FDA Inspection By Accredited Persons
Program
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GAO-08-428T
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United States Government Accountability Office:
GAO:
Testimony:
Before the Subcommittee on Oversight and Investigations, Committee on
Energy and Commerce, House of Representatives:
For Release on Delivery:
Expected at 10:00 a.m. EST:
Tuesday, January 29, 2008:
Medical Devices:
Challenges for FDA in Conducting Manufacturer Inspections:
Statement of Marcia Crosse
Director, Health Care:
GAO-08-428T:
GAO Highlights:
Highlights of GAO-08-428T, a testimony before the Subcommittee on
Oversight and Investigations, Committee on Energy and Commerce, House
of Representatives.
Why GAO Did This Study:
As part of the Food and Drug Administration�s (FDA) oversight of the
safety and effectiveness of medical devices marketed in the United
States, it inspects domestic and foreign establishments where these
devices are manufactured. To help FDA address shortcomings in its
inspection program, the Medical Device User Fee and Modernization Act
of 2002 required FDA to accredit third parties to inspect certain
establishments. In response, FDA has implemented two such voluntary
programs. GAO previously reported on the status of one of these
programs, citing concerns regarding its implementation and factors that
may influence manufacturers� participation. (Medical Devices: Status of
FDA�s Program for Inspections by Accredited Organizations, GAO-07-157,
January 2007.)
This statement (1) assesses FDA�s management of inspections of
establishments�particularly those in foreign countries�manufacturing
devices for the U.S. market, and (2) provides the status of FDA�s
programs for third-party inspections of medical device manufacturing
establishments. GAO interviewed FDA officials; reviewed pertinent
statutes, regulations, guidance, and reports; and analyzed information
from FDA databases. GAO also updated its previous work on FDA�s
programs for inspections by accredited third parties.
What GAO Found:
FDA has not met the statutory requirement to inspect certain domestic
establishments manufacturing medical devices every 2 years, and the
agency faces challenges inspecting foreign establishments. FDA
primarily inspected establishments located in the United States. The
agency has not met the biennial inspection requirement for domestic
establishments manufacturing medical devices that FDA has classified as
high risk, such as pacemakers, or medium risk, such as hearing aids.
FDA officials estimated that the agency has inspected these
establishments every 3 years (for high risk devices) or 5 years (for
medium risk devices). There is no comparable requirement to inspect
foreign establishments, and agency officials estimate that these
establishments have been inspected every 6 years (for high risk
devices) or 27 years (for medium risk devices). FDA faces challenges in
managing its inspections of foreign medical device establishments. Two
databases that provide FDA with information about foreign medical
device establishments and the products they manufacture for the U.S.
market contain inaccuracies that create disparate estimates of
establishments subject to FDA inspection. Although comparing
information from these two databases could help FDA determine the
number of foreign establishments marketing medical devices in the
United States, these databases cannot exchange information and any
comparisons must be done manually. Finally, inspections of foreign
medical device manufacturing establishments pose unique challenges to
FDA in human resources and logistics.
Few inspections of medical device manufacturing establishments have
been conducted through FDA�s two accredited third-party inspection
programs�the Accredited Persons Inspection Program and the Pilot Multi-
purpose Audit Program (PMAP). From March 11, 2004�the date when FDA
first cleared an accredited organization to conduct independent
inspections�through January 11, 2008, five inspections have been
conducted by accredited organizations through FDA�s Accredited Persons
Inspection Program. An incentive to participation in the program is the
opportunity to reduce the number of inspections conducted to meet FDA
and other countries� requirements. Disincentives include bearing the
cost for the inspection, particularly when the consequences of an
inspection that otherwise might not occur in the near future could
involve regulatory action. The Food and Drug Administration Amendments
Act of 2007 made several changes to program eligibility requirements
that could result in increased participation by manufacturers. PMAP was
established on September 7, 2006, and as of January 11, 2008, two
inspections had been conducted by an accredited organization through
this program, which is more limited than the Accredited Persons
Inspection Program. The small number of inspections completed to date
by accredited third-party organizations raises questions about the
practicality and effectiveness of establishing similar programs that
rely on third parties to quickly help FDA fulfill its responsibilities.
To view the full product, including the scope and methodology, click on
[hyperlink, http://www.GAO-08-428T]. For more information, contact
Marcia Crosse at (202) 512-7114 or [email protected].
[End of section]
Mr. Chairman and Members of the Subcommittee:
I am pleased to be here today as you examine how the Food and Drug
Administration (FDA) has been meeting its regulatory responsibilities.
One area of FDA responsibility is the regulation of medical
devices[Footnote 1]--such as hearing aids and pacemakers--marketed in
the United States, whether manufactured in domestic or foreign
establishments.[Footnote 2] FDA classifies medical devices into one of
three classes based on degree of potential risk and level of control
needed to reasonably ensure safety and effectiveness.[Footnote 3]
Inspection of establishments is FDA's primary means of assuring that
the safety and effectiveness of medical 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 (medium risk) or III
(high risk) medical devices every 2 years.[Footnote 4] There is no
comparable requirement to inspect foreign establishments.
The Medical Device User Fee and Modernization Act of 2002 (MDUFMA)
addressed concerns about FDA's ability to meet its responsibilities for
inspecting medical device manufacturing establishments.[Footnote 5]
MDUFMA included provisions designed to (1) increase the number of
inspected medical device manufacturing establishments and (2) help
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 domestic and foreign establishments.[Footnote 6]
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. In
January 2007, we reported on the status of this program citing, among
other things, concerns regarding its implementation and potential
incentives and disincentives that may influence manufacturers'
participation.[Footnote 7] Additionally, in partnership with Health
Canada,[Footnote 8] FDA has established another program for inspection
by accredited third parties--the Pilot Multi-purpose Audit Program
(PMAP)--that allows accredited organizations to conduct a single
inspection to meet the regulatory requirements of both countries. A
report by the House of Representatives Committee on Energy and Commerce
that accompanied MDUFMA stated that inspections by accredited third
parties would permit FDA to focus the agency's inspection resources on
manufacturers that have greater problems and devices that present
higher risks.[Footnote 9]
In addition to the questions about medical devices that led to the
creation of FDA's third-party inspection program, questions have also
been raised about how FDA is meeting its regulatory responsibilities in
other program areas, such as drugs. In November 2007, we testified on
our preliminary findings regarding FDA's program for inspecting foreign
drug manufacturers.[Footnote 10] Our findings suggested that FDA
conducted infrequent inspections; had weaknesses in its data systems,
including conflicting information on the number of foreign
establishments; and faced challenges unique to foreign inspections,
including those involving human resource issues. (See app. I for a
summary of that testimony. We plan to issue a final report at a later
date.) Also in November 2007, a subcommittee of the FDA Science
Board[Footnote 11] issued a report that identified growing demands on
FDA, including the globalization of the industries that FDA regulates.
The report found that disparities between FDA's responsibilities and
its available resources--including human resources--have resulted in
serious weaknesses that jeopardize the agency's ability to meet current
and emerging regulatory responsibilities.[Footnote 12] The
subcommittee's report noted that these weaknesses include inadequate
inspections of manufacturers. It also emphasized that FDA's information
technology infrastructure is obsolete and unstable; provides an
insufficient basis to access, integrate, and analyze data; and is
subject to frequent system failures.
Third-party organizations have been identified as one mechanism that
could help FDA address shortcomings in inspection programs, beyond the
programs for medical devices. The federal Interagency Working Group on
Import Safety recently suggested that the use of third-party
organizations could provide FDA with information to help the agency
target its inspection resources to those products of greatest
risk.[Footnote 13] In addition, we recommended that FDA consider
developing a third-party inspection program to help it meet its
responsibilities for inspecting foreign firms importing seafood to the
United States.[Footnote 14]
Given the recent questions regarding FDA's inspection programs and
suggestions that third-party organizations could supplement FDA's
resources, you asked for information on FDA's management of its medical
device inspection program. My remarks will focus on (1) our assessment
of FDA's program for inspecting establishments that manufacture medical
devices for the U.S. market, particularly those located in foreign
countries and (2) the status of FDA's programs for third-party
inspections of medical device manufacturing establishments. Today, in a
separate statement, we are also discussing the federal oversight of
food safety as a high-risk area and ways in which FDA can better
leverage its resources.[Footnote 15] These and other recent testimonies
on drug safety and food safety offer some observations on FDA's
inspection program capacity.
To address these issues, we interviewed officials from FDA's Center for
Devices and Radiological Health (CDRH) and Office of Regulatory Affairs
(ORA), which each have responsibilities for managing the medical device
inspection program.[Footnote 16] We reviewed pertinent statutes and
regulations, as well as agency documents that provide guidance on FDA's
inspection requirements and programs for inspections by accredited
third parties. To assess FDA's program for inspecting establishments
that manufacture medical devices, we obtained information from FDA's
Device Registration and Listing System (DRLS), as of September 19,
2007; Field Accomplishments and Compliance Tracking System (FACTS) for
fiscal year 2002 through fiscal year 2007; and Operational and
Administrative System for Import Support (OASIS) for fiscal year 2007.
We assessed the reliability of these data by (1) reviewing existing
information about the data and the databases that produced them, (2)
interviewing agency officials knowledgeable about the data, and (3)
performing electronic testing of data elements from DRLS and FACTS. We
found the data in the FACTS database sufficiently reliable for our
purposes. We also found that DRLS was sufficiently reliable, to the
extent that it accurately reflects information provided by domestic and
foreign establishments that register to market medical devices in the
United States. However, we determined that these data do not
necessarily reflect the number of establishments that manufacture
medical devices for the U.S. market. In addition, we found that OASIS
is likely to overestimate the number of foreign establishments whose
medical devices have been imported into the United States, due to
uncorrected errors in the data. Therefore, we present information from
both DRLS and OASIS to illustrate the variability in information that
FDA's databases provide to agency officials on this topic. These data
represent the best information available and are what FDA relies on to
manage its domestic and foreign medical device inspection activities.
To examine the status of FDA's programs for third-party inspections, we
received FDA data on the number of inspections conducted by accredited
third parties from March 11, 2004--the date when FDA first cleared an
accredited organization to conduct inspections--through January 11,
2008. This updates the data we obtained for our January 2007 report for
which data collection ended on October 31, 2006. We also obtained
information from FDA about other critical aspects of their programs for
inspections by accredited third parties, such as the number of
accredited organizations. To gain perspective on recent changes to
FDA's programs for inspections by accredited third parties, we
contacted representatives of the same 13 affected entities we
interviewed for our January 2007 report on this topic.[Footnote 17] We
received responses from 2 of 4 accredited organizations, 2 of 3
organizations that represent medical device manufacturers, and 1 of 6
manufacturers. We received technical comments on a draft of this
statement from FDA, which we incorporated, as appropriate. We conducted
this performance audit from December 2007 to January 2008, 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.
In summary, we found that FDA has not met the requirement to inspect
domestic establishments manufacturing class II or III medical devices
every 2 years and faces challenges in inspecting foreign
establishments. FDA primarily inspected domestic establishments. FDA
officials estimated that the agency has inspected domestic class II
manufacturers every 5 years and domestic class III manufacturers every
3 years. There is no comparable requirement to conduct foreign
inspections and FDA has conducted relatively few. Officials estimated
the agency has inspected foreign class II manufacturers every 27 years
and foreign class III manufacturers every 6 years. In addition, FDA
faces challenges in managing its foreign medical device inspection
program. Two databases that provide FDA with information about foreign
medical device establishments and the products they manufacture for the
U.S. market contain inaccuracies that create divergent estimates of
establishments subject to FDA inspection. Despite the divergent
estimates, FDA does not routinely verify these data. Although comparing
information from these two databases could help FDA determine the
number of foreign establishments marketing medical devices in the
United States, these databases cannot exchange information and any
comparisons must be done manually. While the agency has taken steps to
improve these databases, it is too soon to know if these changes will
improve FDA's data. Finally, inspections of foreign medical device
manufacturing establishments pose unique challenges to FDA, such as
difficulties in recruiting investigators to voluntarily travel to
certain countries and in extending trips if problems are identified
during inspections. Our results are consistent with our November 2007
testimony on FDA's foreign drug inspection program, as well as the
findings of the FDA Science Board.
Few inspections of medical device manufacturing establishments have
been conducted through FDA's two programs for inspections by accredited
third parties--the Accredited Persons Inspection Program and PMAP. From
March 11, 2004--the date when FDA first cleared an accredited
organization to conduct inspections--through January 11, 2008, five
inspections have been conducted by accredited organizations through
FDA's Accredited Persons Inspection Program. Manufacturers' decisions
to request an inspection by an accredited organization might be
influenced by both potential incentives and disincentives. An incentive
to participation in the program is the opportunity to reduce the number
of inspections conducted to meet FDA and other countries' requirements.
Disincentives include bearing the cost for the inspection, particularly
when the consequences of an inspection that otherwise may not occur in
the near future could involve regulatory action. The Food and Drug
Administration Amendments Act of 2007 (FDAAA) changed the requirements
for inspections by accredited third parties in several ways, which
could result in increased participation by manufacturers, although it
is too soon to tell. For example, an eligibility requirement that
foreign establishments be periodically inspected by FDA was eliminated.
Device manufacturers may also request an inspection by an accredited
third party through PMAP, which was established on September 7, 2006.
As of January 11, 2008, two inspections had been conducted by an
accredited organization through PMAP, which is more limited than the
Accredited Persons Inspection Program. The small number of inspections
completed to date by accredited third-party organizations raises
questions about the practicality and effectiveness of establishing
similar programs that rely on third parties to help FDA fulfill other
responsibilities.
Background:
FDA is responsible for overseeing the safety and effectiveness of
medical devices that are marketed in the United States, whether
manufactured in domestic or foreign establishments. All establishments
that manufacture medical devices for marketing in the United States
must register with FDA.[Footnote 18] As part of its efforts to ensure
the safety, effectiveness, and quality of medical devices, FDA is
responsible for inspecting certain domestic and foreign establishments
to ensure that they meet manufacturing standards established in FDA's
quality system regulation.[Footnote 19] FDA does not have authority to
require foreign establishments to allow the agency to inspect their
facilities. However, FDA has the authority to prevent the importation
of products manufactured at establishments that refuse to allow an FDA
inspection.[Footnote 20] Unlike food, for which FDA primarily relies on
inspections at the border, physical inspection of manufacturing
establishments is a critical mechanism in FDA's process to ensure that
medical devices and drugs are safe and effective and that manufacturers
adhere to good manufacturing practices.
Within FDA, CDRH assures the safety and effectiveness of medical
devices. Among other things, CDRH works with ORA, which conducts
inspections of both domestic and foreign establishments to ensure that
devices are produced in conformance with federal statutes and
regulations, including the quality system regulation. FDA may conduct
inspections before and after medical devices are approved or otherwise
cleared to be marketed in the United States.
* Premarket inspections are conducted before FDA will approve U.S.
marketing of a new medical device that is not substantially equivalent
to one that is already on the market.[Footnote 21] Premarket
inspections primarily assess manufacturing facilities, methods, and
controls and may verify pertinent records.
* Postmarket inspections are conducted after a medical device has been
approved or otherwise cleared to be marketed in the United States and
include several types of inspections: (1) Quality system inspections
are conducted to assess compliance with applicable FDA regulations,
including the quality system regulation to ensure good manufacturing
practices and the regulation requiring reporting of adverse
events.[Footnote 22] These inspections may be comprehensive or
abbreviated, which differ in the scope of inspectional activity.
Comprehensive postmarket inspections assess multiple aspects of the
manufacturer's quality system, including management controls, design
controls, corrective and preventative actions, and production and
process controls. Abbreviated postmarket inspections assess only some
of these aspects, but always assess corrective and preventative
actions. (2) For-cause and compliance follow-up inspections are
initiated in response to specific information that raises questions or
problems associated with a particular establishment. (3) Postmarket
audit inspections are conducted within 8 to 12 months of a premarket
application's approval to examine any changes in the design,
manufacturing process, or quality assurance systems.
FDA determines which establishments to inspect using a risk-based
strategy. High priority inspections include premarket approval
inspections for class III devices, for-cause inspections, inspections
of establishments that have had a high frequency of device recalls, and
other devices and manufacturers FDA considers high risk. The
establishment's inspection history may also be considered. A provision
in FDAAA may assist FDA in making decisions about which establishments
to inspect because it authorizes the agency to accept voluntary
submissions of audit reports addressing manufacturers' conformance with
internationally established standards for the purpose of setting risk-
based inspectional priorities.[Footnote 23]
FDA's programs for domestic and foreign inspections by accredited third
parties provide an alternative to the traditional FDA-conducted
comprehensive postmarket quality system inspection for eligible
manufacturers of class II and III medical devices. MDUFMA required FDA
to accredit third persons--which are organizations--to conduct
inspections of certain establishments. In describing this requirement,
the House of Representatives Committee on Energy and Commerce noted
that some manufacturers have faced an increase in the number of
inspections required by foreign countries, and that the number of
inspections could be reduced if the manufacturers could contract with a
third-party organization to conduct a single inspection that would
satisfy the requirements of both FDA and foreign countries.[Footnote
24] Manufacturers that meet eligibility requirements may request a
postmarket inspection by an FDA-accredited organization.[Footnote 25]
The eligibility criteria for requesting an inspection of an
establishment by an accredited organization include that the
manufacturer markets (or intends to market) a medical device in a
foreign country and the establishment to be inspected must not have
received warnings for significant deviations from compliance
requirements on its last inspection.[Footnote 26]
MDUFMA also established minimum requirements for organizations to be
accredited to conduct third-party inspections, including protecting
against financial conflicts of interest and ensuring the competence of
the organization to conduct inspections. FDA developed a training
program for inspectors from accredited organizations that involves both
formal classroom training and completion of three joint training
inspections with FDA. Each individual inspector from an accredited
organization must complete all training requirements successfully
before being cleared to conduct independent inspections. FDA relies on
manufacturers to volunteer to host these joint inspections, which count
as FDA postmarket quality system inspections.
A manufacturer that is cleared to have an inspection by an accredited
third party enters an agreement with the approved accredited
organization and schedules an inspection. Once the accredited
organization completes its inspection, it prepares a report and submits
it to FDA, which makes the final assessment of compliance with
applicable requirements. FDAAA added a requirement that accredited
organizations notify FDA of any withdrawal, suspension, restriction, or
expiration of certificate of conformance with quality systems standards
(such as those established by the International Organization for
Standardization) for establishments they inspected for FDA.[Footnote
27]
In addition to the Accredited Persons Inspection Program, FDA has a
second program for accredited third-party inspections of medical device
establishments. On September 7, 2006, FDA and Health Canada announced
the establishment of PMAP. This pilot program was designed to allow
qualified third-party organizations to perform a single inspection that
would meet the regulatory requirements of both the United States and
Canada. The third-party organizations eligible to conduct inspections
through PMAP are those that FDA accredited for its Accredited Persons
Inspection Program (and that completed all required training for that
program) and that are also authorized to conduct inspections of medical
device establishments for Health Canada. To be eligible to have a third-
party inspection through PMAP, manufacturers must meet all criteria
established for the Accredited Persons Inspection Program. As with the
Accredited Persons Inspection Program, manufacturers must apply to
participate and be willing to pay an accredited organization to conduct
the inspection.
FDA relies on multiple databases to manage its program for inspecting
medical device manufacturing establishments.
* DRLS contains information on domestic and foreign medical device
establishments that have registered with FDA. Establishments that are
involved in the manufacture of medical devices intended for commercial
distribution in the United States are required to register annually
with FDA. These establishments provide information to FDA, such as
establishment name and address and the medical devices they
manufacture. As of October 1, 2007, establishments are required to
register electronically through FDA's Unified Registration and Listing
System and certain medical device establishments pay an annual
establishment registration fee, which in fiscal year 2008 is
$1,706.[Footnote 28]
* OASIS contains information on medical devices and other FDA-regulated
products imported into the United States, including information on the
establishment that manufactured the medical device. The information in
OASIS is automatically generated from data managed by U.S. Customs and
Border Protection, which are originally entered by customs brokers
based on the information available from the importer.[Footnote 29]
* FACTS contains information on FDA's inspections, including those of
domestic and foreign medical device establishments. FDA investigators
enter information into FACTS following completion of an inspection.
According to FDA data, more than 23,600 establishments that manufacture
medical devices were registered as of September 2007, of which 10,600
reported that they manufacture class II or III medical
devices.[Footnote 30] More than half--about 5,600--of these
establishments were located in the United States. As of September 2007,
there were more registered establishments in China and Germany
reporting that they manufacture class II or III medical devices than in
any other foreign countries.[Footnote 31] Canada, Taiwan, and the
United Kingdom also had a large number of registered establishments.
(See fig. 1.) Registered foreign establishments reported that they
manufacture a variety of class II and III medical devices for the U.S.
market. For example, common class III medical devices included coronary
stents,[Footnote 32] pacemakers, and contact lenses.
Figure 1: Registered Establishments That Reported Manufacturing Class
II or Class III Medical Devices for the U.S. Market, by Country,
September 2007:
[See PDF for image]
This figure is a map of the world, with shading indicating registered
establishments that reported manufacturing Class II or Class III
medical devices for the U.S. market, by country, September 2007. There
are five classifications of shading as follows:
Establishment count of 0;
Establishment count of 1 to 50;
Establishment count of 51 to 100;
Establishment count of 101 to 200; and;
Establishment count of 201 or more; included in this group are the
following countries, with their establishment count:
* United States: 5,616;
* China: 675;
* Germany: 581;
* United Kingdom: 351;
* Taiwan: 349;
* Canada: 340;
* Japan: 264;
* South Korea: 240;
* Italy: 202.
Source: GAO analysis of FDA data.
Note: Counts of registered establishments in China do not include
establishments registered in Hong Kong or Taiwan as these
establishments are tracked separately in DRLS. In addition, DRLS
contained one additional registered establishment for which location
information was not available.
[End of figure]
FDA Is Not Inspecting Domestic Establishments Biennially as Required
and Faces Challenges in Inspecting Foreign Establishments:
FDA has not met the statutory requirement to inspect domestic
establishments manufacturing class II or III medical devices every 2
years. The agency conducted relatively few inspections of foreign
establishments. The databases that provide FDA with data about the
number of foreign establishments manufacturing medical devices for the
U.S. market contain inaccuracies. In addition, inspections of foreign
medical device manufacturing establishments pose unique challenges to
FDA--both in human resources and logistics.
FDA Is Not Inspecting Domestic Establishments Biennially and Inspects
Relatively Few Foreign Establishments:
From fiscal year 2002 through fiscal year 2007, FDA primarily inspected
establishments located in the United States, where more than half of
the 10,600 registered establishments that reported manufacturing class
II or III medical devices are located. In contrast, FDA inspected
relatively few foreign medical device establishments. During this
period, FDA conducted an average of 1,494 domestic and 247 foreign
establishment inspections each year.[Footnote 33] This suggests that
each year FDA inspects about 27 percent of registered domestic
establishments that reported manufacturing class II or class III
medical devices and about 5 percent of such foreign establishments. The
inspected establishments were in the United States and 44 foreign
countries. Of the foreign inspections, more than two-thirds were in 10
countries. Most of the countries with the highest number of inspections
were also among those with the largest number of registered
establishments that reported manufacturing class II or III medical
devices. The lowest rate of inspections in these 10 countries was in
China, where 64 inspections were conducted in this 6-year period and
almost 700 establishments were registered. (See table 1.)
Table 1: Number of FDA Inspections of Medical Device Establishments,
Fiscal Year 2002 through Fiscal Year 2007:
Country: United States;
Number of inspections[A]: FY2002: 1,261;
Number of inspections[A]: FY2003: 1,736;
Number of inspections[A]: FY2004: 1,631;
Number of inspections[A]: FY2005: 1,471;
Number of inspections[A]: FY2006: 1,501;
Number of inspections[A]: FY2007: 1,362;
Number of inspections[A]: Total: 8,962[C];
Number of registered class II or III manufacturing establishments[B]:
5,616.
Country: Germany;
Number of inspections[A]: FY2002: 39;
Number of inspections[A]: FY2003: 30;
Number of inspections[A]: FY2004: 34;
Number of inspections[A]: FY2005: 51;
Number of inspections[A]: FY2006: 25;
Number of inspections[A]: FY2007: 52;
Number of inspections[A]: Total: 231;
Number of registered class II or III manufacturing establishments[B]:
581.
Country: United Kingdom;
Number of inspections[A]: FY2002: 25;
Number of inspections[A]: FY2003: 31;
Number of inspections[A]: FY2004: 28;
Number of inspections[A]: FY2005: 14;
Number of inspections[A]: FY2006: 25;
Number of inspections[A]: FY2007: 43;
Number of inspections[A]: Total: 166;
Number of registered class II or III manufacturing establishments[B]:
351.
Country: Canada;
Number of inspections[A]: FY2002: 17;
Number of inspections[A]: FY2003: 17;
Number of inspections[A]: FY2004: 24;
Number of inspections[A]: FY2005: 11;
Number of inspections[A]: FY2006: 13;
Number of inspections[A]: FY2007: 26;
Number of inspections[A]: Total: 108;
Number of registered class II or III manufacturing establishments[B]:
340.
Country: Japan;
Number of inspections[A]: FY2002: 7;
Number of inspections[A]: FY2003: 8;
Number of inspections[A]: FY2004: 20;
Number of inspections[A]: FY2005: 21;
Number of inspections[A]: FY2006: 16;
Number of inspections[A]: FY2007: 25;
Number of inspections[A]: Total: 97;
Number of registered class II or III manufacturing establishments[B]:
264.
Country: Ireland;
Number of inspections[A]: FY2002: 15;
Number of inspections[A]: FY2003: 22;
Number of inspections[A]: FY2004: 13;
Number of inspections[A]: FY2005: 13;
Number of inspections[A]: FY2006: 16;
Number of inspections[A]: FY2007: 11;
Number of inspections[A]: Total: 90;
Number of registered class II or III manufacturing establishments[B]:
67.
Country: France;
Number of inspections[A]: FY2002: 16;
Number of inspections[A]: FY2003: 14;
Number of inspections[A]: FY2004: 17;
Number of inspections[A]: FY2005: 14;
Number of inspections[A]: FY2006: 12;
Number of inspections[A]: FY2007: 10;
Number of inspections[A]: Total: 83;
Number of registered class II or III manufacturing establishments[B]:
190.
Country: Switzerland;
Number of inspections[A]: FY2002: 6;
Number of inspections[A]: FY2003: 12;
Number of inspections[A]: FY2004: 19;
Number of inspections[A]: FY2005: 9;
Number of inspections[A]: FY2006: 7;
Number of inspections[A]: FY2007: 18;
Number of inspections[A]: Total: 71;
Number of registered class II or III manufacturing establishments[B]:
134.
Country: China[D];
Number of inspections[A]: FY2002: 0;
Number of inspections[A]: FY2003: 0;
Number of inspections[A]: FY2004: 21;
Number of inspections[A]: FY2005: 19;
Number of inspections[A]: FY2006: 11;
Number of inspections[A]: FY2007: 13;
Number of inspections[A]: Total: 64;
Number of registered class II or III manufacturing establishments[B]:
675[E].
Country: Mexico;
Number of inspections[A]: FY2002: 10;
Number of inspections[A]: FY2003: 7;
Number of inspections[A]: FY2004: 12;
Number of inspections[A]: FY2005: 8;
Number of inspections[A]: FY2006: 12;
Number of inspections[A]: FY2007: 11;
Number of inspections[A]: Total: 60;
Number of registered class II or III manufacturing establishments[B]:
143.
Country: Italy;
Number of inspections[A]: FY2002: 8;
Number of inspections[A]: FY2003: 7;
Number of inspections[A]: FY2004: 10;
Number of inspections[A]: FY2005: 6;
Number of inspections[A]: FY2006: 13;
Number of inspections[A]: FY2007: 11;
Number of inspections[A]: Total: 55;
Number of registered class II or III manufacturing establishments[B]:
202.
Country: All other countries;
Number of inspections[A]: FY2002: 66;
Number of inspections[A]: FY2003: 83;
Number of inspections[A]: FY2004: 102;
Number of inspections[A]: FY2005: 67;
Number of inspections[A]: FY2006: 69;
Number of inspections[A]: FY2007: 69;
Number of inspections[A]: Total: 456;
Number of registered class II or III manufacturing establishments[B]:
2,036.
Country: Total;
Number of inspections[A]: FY2002: 1,470;
Number of inspections[A]: FY2003: 1,967;
Number of inspections[A]: FY2004: 1,931;
Number of inspections[A]: FY2005: 1,704;
Number of inspections[A]: FY2006: 1,720;
Number of inspections[A]: FY2007: 1,651;
Number of inspections[A]: Total: 10,443;
Number of registered class II or III manufacturing establishments[B]:
10,600[F].
Source: GAO analysis of FDA data.
[A] We were unable to differentiate inspections according to medical
device classification. FDA's inspection database contains the most
recent information available to FDA about the class of device
manufactured at the establishment, and consequently does not contain
readily available information about the class of devices manufactured
at the time of a specific inspection. As a result, the data we present
include all inspections, regardless of the classification of the
manufactured device or devices. According to FDA officials, FDA
primarily conducts inspections of establishments manufacturing class II
or III medical devices.
[B] These counts represent the number of registered establishments as
of September 2007.
[C] In addition to inspections conducted by FDA personnel, from fiscal
year 2002 through fiscal year 2007, FDA contracted with states to
conduct 164 quality system inspections. These inspections are not
included in the total.
[D] The inspection counts for China do not include inspections
conducted in Hong Kong or Taiwan as these inspections are tracked
separately in FACTS.
[E] Counts of registered establishments in China do not include
establishments registered in Hong Kong or Taiwan as these
establishments are tracked separately in DRLS.
[F] Registration numbers do not add to total because DRLS contained one
additional registered establishment for which location information was
not available.
[End of table]
Despite its focus on domestic inspections, FDA has not met the
statutory requirement to inspect domestic establishments manufacturing
class II or III medical devices every 2 years. For domestic
establishments, FDA officials estimated that, on average, the agency
inspects class II manufacturers every 5 years and class III
manufacturers every 3 years. For foreign establishments--for which
there is no comparable inspection requirement--FDA officials estimated
that the agency inspects class II manufacturers every 27 years and
class III manufacturers every 6 years.
FDA's inspections of medical device establishments, both domestic and
foreign, are primarily postmarket inspections. While premarket
inspections are generally FDA's highest priority, relatively few have
to be performed in any given year.[Footnote 34] Therefore, FDA focuses
its resources on postmarket inspections. From fiscal year 2002 through
fiscal year 2007, 95 percent of the 8,962 domestic establishment
inspections and 89 percent of the 1,481 foreign establishment
inspections were for postmarket purposes. (See fig. 2.)
Figure 2: Number of Inspections of Domestic and Foreign Establishments
That Manufacture Medical Devices for the U.S. Market, by Type of
Inspection, Fiscal Year 2002 through Fiscal Year 2007:
[See PDF for image]
This figure is a vertical bar graph, depicting the following data:
Location of inspected establishment: domestic;
Premarket inspections: 430;
Postmarket inspections: 8,532.
Location of inspected establishment: foreign;
Premarket inspections: 164;
Postmarket inspections: 1,317.
Source: GAO analysis of FDA data.
Note: If an inspection had both premarket and postmarket components, we
classified it as a premarket inspection. Of the 430 domestic premarket
inspections, 256 contained both premarket and postmarket components. Of
the 164 foreign premarket inspections, 95 contained both premarket and
postmarket components. FDA may conduct other types of inspections--such
as a postmarket quality system, compliance follow-up, for-cause, or
postmarket audit inspection--at the same establishment at which they
are conducting a premarket inspection. These inspections may focus on
different products manufactured at the same establishment.
[End of figure]
FDA's Databases Provide Inconsistent Information Regarding the Number
of Foreign Medical Device Manufacturing Establishments Subject to
Inspection:
FDA's databases on registration and imported products provide divergent
estimates regarding the number of foreign medical device manufacturing
establishments. DRLS provides FDA with information about domestic and
foreign medical device establishments and the products they manufacture
for the U.S. market. According to DRLS, as of September 2007, 5,616
domestic and 4,983 foreign establishments that reported manufacturing a
class II or III medical device for the U.S. market had registered with
FDA.[Footnote 35] However, these data contain inaccuracies because
establishments may register with FDA but not actually manufacture a
medical device or may manufacture a medical device that is not marketed
in the United States. FDA officials told us that their more frequent
inspections of domestic establishments allow them to more easily update
information about whether a domestic establishment is subject to
inspection.
In addition to DRLS, FDA obtains information on foreign establishments
from OASIS, which tracks the import of medical devices. While not
intended to provide a count of establishments, OASIS does contain
information about the medical devices actually being imported into the
United States and the establishments manufacturing them. However,
inaccuracies in OASIS prevent FDA from using it to develop a list of
establishments subject to inspection. OASIS contains duplicate records
for a single establishment because of inaccurate data entry by customs
brokers at the border. According to OASIS, in fiscal year 2007, there
were as many as 22,008 foreign establishments that manufactured class
II medical devices for the U.S. market and 3,575 foreign establishments
that manufactured class III medical devices for the U.S.
market.[Footnote 36] Despite the divergent estimates of foreign
establishments generated by DRLS and OASIS, FDA does not routinely
verify the data within each database. Although comparing information
from these two databases could help FDA determine the number of foreign
establishments marketing medical devices in the United States, the
databases cannot exchange information to be compared electronically and
any comparisons are done manually.
Efforts are underway that could improve FDA's databases. FDA officials
suggested that, because manufacturers are now required to pay an annual
establishment registration fee, manufacturers may be more concerned
about the accuracy of the registration data they submit. They also told
us that, because of the registration fee, manufacturers may be less
likely to register if they do not actually manufacture a medical device
for the U.S. market. In addition, FDA officials stated that the agency
is pursuing various initiatives to try to address the inaccuracies in
OASIS, such as providing a unique identifier for each foreign
establishment to reduce duplicate entries for individual
establishments.
Challenges Unique to Foreign Inspections Influence the Manner in Which
FDA Conducts Such Inspections:
Inspections of foreign establishments pose unique challenges to FDA--
both in human resources and logistics. FDA does not have a dedicated
cadre of investigators that only conduct foreign medical device
establishment inspections; those staff who inspect foreign
establishments also inspect domestic establishments. Among those
qualified to inspect foreign establishments,[Footnote 37] FDA relies on
staff to volunteer to conduct inspections. FDA officials told us that
it is difficult to recruit investigators to voluntarily travel to
certain countries. However, they added that if the agency could not
find an individual to volunteer for a foreign inspection trip, it would
mandate the travel. Logistically, foreign medical device establishment
inspections are difficult to extend even if problems are identified
because the trips are scheduled in advance.[Footnote 38] Foreign
medical device establishment inspections are also logistically
challenging because investigators do not receive independent
translational support from FDA or the State Department and may rely on
English-speaking employees of the inspected establishment or the
establishment's U.S. agent to translate during an inspection.
Few Third-Party Inspections Are Conducted, but Recent Changes Could
Eliminate Some Obstacles to Manufacturers' Participation:
Few inspections of medical device manufacturing establishments have
been conducted through FDA's two accredited third-party inspection
programs--the Accredited Persons Inspection Program and PMAP. FDAAA
specified several changes to the requirements for inspections by
accredited third parties that could result in increased participation
by manufacturers.
Few inspections have been conducted through FDA's Accredited Persons
Inspection Program since March 11, 2004--the date when FDA first
cleared an accredited organization to conduct independent inspections.
Through January 11, 2008, five inspections had been conducted
independently by accredited organizations (two inspections of domestic
establishments and three inspections of foreign establishments), an
increase of three since we reported on this program one year
ago.[Footnote 39]
As of January 11, 2008, 16 third-party organizations were accredited,
[Footnote 40] and individuals from 8 of these organizations had
completed FDA's training requirements and been cleared to conduct
independent inspections.[Footnote 41] As of January 8, 2008, FDA and
accredited organizations had conducted 44 joint training
inspections.[Footnote 42] Fewer manufacturers volunteered to host
training inspections than have been needed for all of the accredited
organizations to complete their training.[Footnote 43] Moreover,
scheduling these joint training inspections has been difficult. FDA
officials told us that, when appropriate, staff are instructed to ask
manufacturers to host a joint training inspection at the time they
notify the manufacturers of a pending inspection. FDA schedules
inspections a relatively short time prior to an actual
inspection,[Footnote 44] and as we reported in January 2007, some
accredited organizations have not been able to participate because they
had prior commitments.
As we reported in January 2007, manufacturers' decisions to request an
inspection by an accredited organization might be influenced by both
potential incentives and disincentives. According to FDA officials and
representatives of affected entities, potential incentives to
participation include the opportunity to reduce the number of
inspections conducted to meet FDA and other countries' requirements.
For example, one inspection conducted by an accredited organization was
a single inspection designed to meet the requirements of FDA, the
European Union, and Canada. Another potential incentive mentioned by
FDA officials and representatives of affected entities is the
opportunity to control the scheduling of the inspection by an
accredited organization by working with the accredited organization.
FDA officials and representatives of affected entities also mentioned
potential disincentives to having an inspection by an accredited
organization. These potential disincentives include bearing the cost
for the inspection,[Footnote 45] doubts about whether accredited
organizations can cover multiple requirements in a single inspection,
and uncertainty about the potential consequences of an inspection that
otherwise may not occur in the near future--consequences that could
involve regulatory action.
Changes specified by FDAAA have the potential to eliminate certain
obstacles to manufacturers' participation in FDA's programs for
inspections by accredited third parties that were associated with
manufacturers' eligibility. For example, an eligibility requirement
that foreign establishments be periodically inspected by FDA was
eliminated. Representatives of the two organizations that represent
medical device manufacturers with whom we spoke about FDAAA told us
that the changes in eligibility requirements could eliminate certain
obstacles and therefore potentially increase their participation. These
representatives also noted that key incentives and disincentives to
manufacturers' participation remain. FDA officials told us that they
are currently revising their guidance to industry in light of FDAAA and
expect to issue the revised guidance during fiscal year 2008. It is too
soon to tell what impact these changes will have on manufacturers'
participation.
FDA officials acknowledged that manufacturers' participation in the
Accredited Persons Inspection Program has been limited. In December
2007, FDA established a working group to assess the successes and
failures of this program and to identify ways to increase
participation. Representatives of the two organizations that represent
medical device manufacturers with whom we recently spoke stated that
they believe manufacturers remain interested in the Accredited Persons
Inspection Program. The representative of one large, global
manufacturer of medical devices told us that it is in the process of
arranging to have 20 of its domestic and foreign device manufacturing
establishments inspected by accredited third parties.
As of January 11, 2008, two inspections, both of domestic
establishments, had been conducted through PMAP, FDA's second program
for inspections by accredited third parties. Although it is too soon to
tell what the benefits of PMAP will be, the program is more limited
than the Accredited Persons Inspection Program and may pose additional
disincentives to participation by both manufacturers and accredited
organizations. Specifically, inspections through PMAP would be designed
to meet the requirements of the United States and Canada, whereas
inspections conducted through the Accredited Persons Inspection Program
could be designed to meet the requirements of other countries. In
addition, two of the five representatives of affected entities noted
that in contrast to inspections conducted through the Accredited
Persons Inspection Program, inspections conducted through PMAP could
undergo additional review by Health Canada. Health Canada will review
inspection reports submitted through this pilot program to ensure they
meet its standards. This extra review poses a greater risk of
unexpected outcomes for the manufacturer and the accredited
organization, which could be a disincentive to participation in PMAP
that is not present with the Accredited Persons Inspection Program.
Concluding Observations:
Americans depend on FDA to ensure the safety and effectiveness of
medical products, including medical devices, manufactured throughout
the world. However, our findings regarding inspections of medical
device manufacturers indicate weaknesses that mirror those presented in
our November 2007 testimony regarding inspections of foreign drug
manufacturers. In addition, they are consistent with the FDA Science
Board's findings that FDA's ability to fulfill its regulatory
responsibilities is jeopardized, in part, by information technology and
human resources challenges. We recognize that FDA has expressed the
intention to improve its data management, but it is too early to tell
whether the intended changes will ultimately enhance the agency's
ability to manage its inspection programs. We and others have suggested
that the use of accredited third parties could improve FDA's ability to
meet its inspection responsibilities. However, the implementation of
its programs for inspecting medical device manufacturers has resulted
in little progress. To date, its programs for inspections by accredited
third parties have not assisted FDA in meeting its regulatory
responsibilities nor have they provided a rapid or substantial increase
in the number of inspections performed by these organizations, as
originally intended. Although recent statutory changes to the
requirements for inspections by accredited third parties may encourage
greater participation in these programs, the lack of meaningful
progress raises questions about the practicality and effectiveness of
establishing similar programs that rely on third parties to quickly
help FDA fulfill other responsibilities.
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 testimony, please contact Marcia
Crosse at (202) 512-7114 or [email protected]. Contact points for our
Offices of Congressional Relations and Public Affairs may found on the
last page of this testimony. Geraldine Redican-Bigott, Assistant
Director; Kristen Joan Anderson; Katherine Clark; Robert Copeland;
William Hadley; Cathy Hamann; Mollie Hertel; Julian Klazkin; Lisa
Motley; Daniel Ries; and Suzanne Worth made key contributions to this
testimony.
[End of section]
Appendix I: Summary of GAO Testimony on FDA's Program for Inspecting
Foreign Drug Manufacturers:
In congressional testimony in November 2007, we presented our
preliminary findings on the Food and Drug Administration's (FDA)
program for inspecting foreign drug manufacturers.[Footnote 46] We
found that (1) FDA's effectiveness in managing the foreign drug
inspection program continued to be hindered by weaknesses in its
databases; (2) FDA inspected relatively few foreign establishments; and
(3) the foreign inspection process involved unique circumstances that
were not encountered domestically.
Our preliminary findings indicated that more than 9 years after we
issued our last report on FDA's foreign drug inspection program,
[Footnote 47] FDA's effectiveness in managing this program
continued to be hindered by weaknesses in its databases. FDA did not
know how many foreign establishments were subject to inspection.
Instead of maintaining a list of such establishments, FDA relied on
information from several databases that were not designed for this
purpose. One of these databases contained information on foreign
establishments that had registered to market drugs in the United
States, while another contained information on drugs imported into the
United States. One database indicated about 3,000 foreign
establishments could have been subject to inspection in fiscal year
2007, while another indicated that about 6,800 foreign establishments
could have been subject to inspection in that year. Despite the
divergent estimates of foreign establishments subject to inspection
generated by these two databases, FDA did not verify the data within
each database. For example, the agency did not routinely confirm that a
registered establishment actually manufactured a drug for the U.S.
market. However, FDA used these data to generate a list of 3,249
foreign establishments from which it prioritized establishments for
inspection.
Because FDA was not certain how many foreign drug establishments were
actually subject to inspection, the percentage of such establishments
that had been inspected could not be calculated with certainty. We
found that FDA inspected relatively few foreign drug establishments, as
shown in table 2. Using the list of 3,249 foreign drug establishments
from which FDA prioritized establishments for inspection, we found that
the agency may inspect about 7 percent of foreign drug establishments
in a given year. At this rate, it would take FDA more than 13 years to
inspect each foreign drug establishment on this list once, assuming
that no additional establishments are subject to inspection.
Table 2: Number of FDA Inspections of Foreign Establishments Involved
in the Manufacture of Drugs for the U.S. Market, Fiscal Year 2002
through Fiscal Year 2007:
Country: India;
Number of inspections: FY2002: 11;
Number of inspections: FY2003: 19;
Number of inspections: FY2004: 38;
Number of inspections: FY2005: 33;
Number of inspections: FY2006: 34;
Number of inspections: FY2007[A]: 65;
Number of inspections: Total: 200;
Number of establishments[B]: 410.
Country: Germany;
Number of inspections: FY2002: 24;
Number of inspections: FY2003: 15;
Number of inspections: FY2004: 35;
Number of inspections: FY2005: 25;
Number of inspections: FY2006: 19;
Number of inspections: FY2007[A]: 22;
Number of inspections: Total: 140;
Number of establishments[B]: 199.
Country: Italy;
Number of inspections: FY2002: 17;
Number of inspections: FY2003: 30;
Number of inspections: FY2004: 26;
Number of inspections: FY2005: 21;
Number of inspections: FY2006: 18;
Number of inspections: FY2007[A]: 19;
Number of inspections: Total: 131;
Number of establishments[B]: 150.
Country: Canada;
Number of inspections: FY2002: 29;
Number of inspections: FY2003: 12;
Number of inspections: FY2004: 17;
Number of inspections: FY2005: 23;
Number of inspections: FY2006: 23;
Number of inspections: FY2007[A]: 19;
Number of inspections: Total: 123;
Number of establishments[B]: 288.
Country: United Kingdom;
Number of inspections: FY2002: 19;
Number of inspections: FY2003: 22;
Number of inspections: FY2004: 15;
Number of inspections: FY2005: 18;
Number of inspections: FY2006: 15;
Number of inspections: FY2007[A]: 13;
Number of inspections: Total: 102;
Number of establishments[B]: 169.
Country: France;
Number of inspections: FY2002: 14;
Number of inspections: FY2003: 15;
Number of inspections: FY2004: 13;
Number of inspections: FY2005: 12;
Number of inspections: FY2006: 16;
Number of inspections: FY2007[A]: 24;
Number of inspections: Total: 94;
Number of establishments[B]: 162.
Country: China;
Number of inspections: FY2002: 11;
Number of inspections: FY2003: 9;
Number of inspections: FY2004: 17;
Number of inspections: FY2005: 21;
Number of inspections: FY2006: 17;
Number of inspections: FY2007[A]: 13;
Number of inspections: Total: 88;
Number of establishments[B]: 714.
Country: Japan;
Number of inspections: FY2002: 11;
Number of inspections: FY2003: 13;
Number of inspections: FY2004: 14;
Number of inspections: FY2005: 21;
Number of inspections: FY2006: 13;
Number of inspections: FY2007[A]: 15;
Number of inspections: Total: 87;
Number of establishments[B]: 196.
Country: Switzerland;
Number of inspections: FY2002: 12;
Number of inspections: FY2003: 12;
Number of inspections: FY2004: 11;
Number of inspections: FY2005: 17;
Number of inspections: FY2006: 9;
Number of inspections: FY2007[A]: 14;
Number of inspections: Total: 75;
Number of establishments[B]: 83.
Country: Ireland;
Number of inspections: FY2002: 11;
Number of inspections: FY2003: 5;
Number of inspections: FY2004: 11;
Number of inspections: FY2005: 14;
Number of inspections: FY2006: 3;
Number of inspections: FY2007[A]: 11;
Number of inspections: Total: 55;
Number of establishments[B]: 61.
Country: All other countries;
Number of inspections: FY2002: 63;
Number of inspections: FY2003: 38;
Number of inspections: FY2004: 63;
Number of inspections: FY2005: 61;
Number of inspections: FY2006: 45;
Number of inspections: FY2007[A]: 80;
Number of inspections: Total: 350;
Number of establishments[B]: 817.
Country: Total;
Number of inspections: FY2002: 222;
Number of inspections: FY2003: 190;
Number of inspections: FY2004: 260;
Number of inspections: FY2005: 266;
Number of inspections: FY2006: 212;
Number of inspections: FY2007[A]: 295;
Number of inspections: Total: 1,445;
Number of establishments[B]: 3,249.
Source: GAO analysis of FDA data.
[A] Inspection data for fiscal year 2007 may not be complete because
FDA provided these data as of September 26, 2007, prior to the end of
the fiscal year.
[B] This count represents the number of establishments FDA used to plan
its fiscal year 2007 prioritized surveillance inspections.
[End of table]
FDA's data indicated that some foreign drug manufacturers had not
received an inspection, but FDA could not provide the exact number of
foreign drug establishments that had never been inspected. Most of the
foreign drug inspections were conducted as part of processing a new
drug application or an abbreviated new drug application,[Footnote 48]
rather than as current good manufacturing practices (GMP) surveillance
inspections, which are used to monitor the quality of marketed drugs.
FDA used a risk-based process, based in part on data from its
registration and import databases, to develop a prioritized list of
foreign drug establishments for GMP surveillance inspections in fiscal
year 2007. According to FDA, about 30 such inspections were completed
in fiscal year 2007, and at least 50 were targeted for inspection in
fiscal year 2008. Further, inaccuracies in the data on which this risk-
based process depended limited its effectiveness.
Finally, the very nature of the foreign drug inspection process
involved unique circumstances that were not encountered domestically.
For example, FDA did not have a dedicated staff to conduct foreign drug
inspections and relied on those inspecting domestic establishments to
volunteer for foreign inspections. While FDA may conduct unannounced
GMP inspections of domestic establishments, it did not arrive
unannounced at foreign establishments. It also lacked the flexibility
to easily extend foreign inspections if problems were encountered due
to the need to adhere to an itinerary that typically involved multiple
inspections in the same country. Finally, language barriers can make
foreign inspections more difficult to conduct than domestic ones. FDA
did not generally provide translators to its inspection teams. Instead,
they may have had to rely on an English-speaking representative of the
foreign establishment being inspected, rather than an independent
translator.
[End of section]
Footnotes:
[1] Medical devices include instruments, apparatuses, machines, and
implants that are intended for use to diagnose, cure, treat, or prevent
disease, or to affect the structure or any function of the body. 21
U.S.C. � 321(h).
[2] 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). Medical device manufacturers may have more than one
establishment. We use the term "manufacture" to refer to activities
including manufacturing, preparing, and processing devices.
[3] 21 U.S.C. � 360c. Medical devices are classified into one of three
classes. Class I includes "low risk" devices, such as tongue
depressors, elastic bandages, and bedpans. Class II includes "medium
risk" devices, such as syringes, hearing aids, and electrocardiograph
machines. Class III includes "high risk" devices, such as heart valves,
pacemakers, and defibrillators.
[4] 21 U.S.C. � 360(h). There is no statutory requirement for
inspection of class I medical 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 medical devices, due to ongoing problems
with leakage. FDA also periodically inspects manufacturers of randomly
selected class I devices.
[5] See Pub. L. No. 107-250, � 201, 116 Stat. 1588, 1602-09 (2002)
(codified as amended at 21 U.S.C. � 374(g)).
[6] In this report, unless otherwise noted, when we discuss
inspections, we are referring to those conducted by FDA investigators.
[7] GAO, Medical Devices: Status of FDA's Program for Inspections by
Accredited Organizations, GAO-07-157 (Washington, D.C.: Jan. 5, 2007).
[8] Health Canada is the governmental entity that regulates medical
devices marketed in Canada.
[9] H.R. Rep. No. 107-728, pt. 1, at 35-36 (2002).
[10] GAO, Drug Safety: Preliminary Findings Suggest Weaknesses in FDA's
Program for Inspecting Foreign Drug Manufacturers, GAO-08-224T
(Washington, D.C.: Nov. 1, 2007).
[11] The Science Board, which is an advisory board to the commissioner
of FDA, provides advice on, among other things, specific complex and
technical issues as well as emerging issues within the scientific
community.
[12] FDA Science Board, Subcommittee on Science and Technology, FDA
Science and Mission at Risk (November 2007), [hyperlink,
http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-
4329b_02_00_index.html] (accessed Jan. 18, 2008).
[13] In July 2007, the Interagency Working Group on Import Safety was
established to conduct a comprehensive review of current import safety
practices and determine where improvements could be made. Interagency
Working Group on Import Safety, Action Plan for Import Safety: A
roadmap for continual improvement (November 2007), [hyperlink,
http://www.importsafety.gov/report/actionplan.pdf] (accessed Dec. 6,
2007).
[14] See GAO, Food Safety: FDA's Imported Seafood Safety Program Shows
Some Progress, but Further Improvements are Needed, GAO-04-246
(Washington, D.C.: Jan. 30, 2004).
[15] GAO, Federal Oversight of Food Safety: FDA's Food Protection Plan
Proposes Positive First Steps, but Capacity to Carry Them Out is
Critical, GAO-08-435T (Washington, D.C.: Jan. 29, 2008).
[16] Within FDA, the Center for Biologics Evaluation and Research
regulates medical devices involved in human immunodeficiency virus
(HIV) testing and the collection, processing, testing, manufacture, and
administration of licensed blood, blood components, and cellular
products. We did not include medical devices regulated by this center
in the scope of our work.
[17] These affected entities included accredited organizations,
organizations that represent medical device manufacturers, and medical
device manufacturers.
[18] 21 U.S.C. � 360(b), (i).
[19] 21 C.F.R. pt. 820 (2007). The quality system regulation requires,
among other things, that domestic or foreign manufacturers have a
quality system in place to implement current good manufacturing
practices in the design, manufacture, packaging, labeling, storage,
installation, and servicing of finished medical devices intended for
human use in the United States. A quality system includes the
organizational structure, responsibilities, procedures, processes, and
resources for implementing quality management.
[20] See 21 U.S.C. � 381(a); 21 C.F.R. � 820.1(d) (2007).
[21] Currently, most medical devices are cleared for marketing in the
United States because they are "substantially equivalent" to a marketed
device. FDA generally does not conduct premarket inspections of
establishments manufacturing these types of medical devices.
[22] 21 C.F.R. pt. 803 (2007).
[23] Pub. L. No. 110-85, � 228, 121 Stat. 858 (2007).
[24] H.R. Rep. No. 107-728, pt. 1, at 32-36 (2002). Some foreign
countries have accredited, certified, or otherwise recognized
organizations to conduct inspections. We use the term "single
inspection" to mean a complete inspection that covers all requirements
of two or more countries, without repeating those activities covered
under more than one set of requirements. A complete inspection can be
conducted during a single block of time or in multiple phases. Two or
more separate inspection reports could be generated on the basis of
that single inspection.
[25] Accredited organizations may conduct comprehensive postmarket
quality system inspections, but not other types of inspections of
establishments that FDA has the authority to conduct, such as premarket
or for-cause inspections. FDA may conduct its own inspections of
establishments even after inspection by an accredited organization.
[26] 21 U.S.C. � 374(g). FDAAA eliminated certain previously
established eligibility requirements. For example, it eliminated a
limitation on the number of consecutive inspections allowed by an
accredited organization and a limitation that foreign establishments
must be inspected periodically by FDA.
[27] 21 U.S.C. � 374(g)(3)(F).
[28] 21 U.S.C. � 379j(a)(3), (b).
[29] Customs brokers are private individuals, partnerships,
associations, or corporations licensed, regulated, and empowered by
U.S. Customs and Border Protection to assist in meeting federal
requirements governing imports and exports.
[30] Throughout this testimony, we use DRLS data because FDA officials
told us that the agency would continue to use those data, as available
on September 19, 2007, until it is confident that all device
establishments required to register have done so through the new
electronic system, FDA's Unified Registration and Listing System.
[31] Counts of registered establishments in China do not include
establishments registered in Hong Kong or Taiwan as these
establishments are tracked separately in DRLS.
[32] A coronary stent is a small tube that is placed within a coronary
artery to keep the vessel open.
[33] We were unable to differentiate inspections according to medical
device classification. FDA's inspection database contains the most
recent information available to FDA about the class of device
manufactured at the establishment, and consequently does not contain
readily available information about the class of devices manufactured
at the time of a specific inspection. As a result, the data we present
include all inspections, regardless of the classification of the
manufactured device or devices. According to FDA officials, FDA
primarily conducts inspections of establishments manufacturing class II
or III medical devices.
[34] Currently, most medical devices are cleared for marketing in the
United States because they are "substantially equivalent" to a marketed
device. FDA generally does not conduct premarket inspections of
establishments manufacturing these types of medical devices.
[35] DRLS contained one additional registered establishment for which
location information was not available.
[36] According to FDA officials, a single establishment could be
manufacturing more than one class of device.
[37] Staff members must meet certain criteria in terms of their
experience and training to conduct inspections of foreign
establishments. For example, they are required to take certain training
courses and have at least 3 years of experience conducting domestic
inspections before they can be considered qualified to conduct a
foreign inspection.
[38] Typically, FDA investigators travel abroad for about 3 weeks at a
time, during which they inspect approximately three establishments.
[39] In January 2007, we reported that two inspections had been
independently conducted by accredited organizations through the
Accredited Persons Inspection Program--one inspection of a domestic
establishment and one inspection of a foreign establishment. GAO-07-
157, 11.
[40] FDA officials told us that no additional organizations have
applied for accreditation since we issued our January 2007 report.
[41] In January 2007, we reported that 7 of the 16 accredited
organizations had been cleared to conduct independent inspections. GAO-
07-157, 11. One additional accredited organization was cleared to
conduct independent inspections on October 18, 2007. Specific foreign
jurisdictions that have certified, accredited, or otherwise recognized
one or more of the FDA-accredited organizations that have been cleared
to conduct independent inspections include all member states of the
European Community, Australia, Canada, New Zealand, Norway, Taiwan, and
the United Kingdom. Of the 8 third-party organizations that have been
cleared to conduct independent inspections through the Accredited
Persons Inspection Program, 4 may conduct inspections through PMAP.
[42] In January 2007, we reported that FDA and accredited organizations
had conducted 37 joint training inspections. GAO-07-157, 11.
[43] As we reported in January 2007, some representatives of affected
entities speculated that manufacturers might not have volunteered to
host training inspections because they believed that training
inspections would require more time and effort for their staff (and
would thus be more disruptive) than inspections conducted by fully
trained personnel, or that manufacturers might have believed that
training inspections would be more rigorous than nontraining
inspections if the trainees and FDA personnel were to take particular
care to demonstrate their thoroughness to each other.
[44] FDA generally notifies manufacturers about a week in advance of
postmarket quality system inspections of domestic establishments and
about 6 to 8 weeks in advance of postmarket quality system inspections
of foreign establishments.
[45] In January 2007, we reported that representatives of accredited
organizations indicated that the cost to manufacturers would vary
depending on such factors as the size of the manufacturer and how much
extra time would be required to assess compliance with FDA
requirements. Representatives suggested that covering FDA's
requirements could take 2 or more days in addition to the time spent
assessing other countries' requirements, plus time for advance
preparation and writing the inspection report. They speculated that
they would probably charge manufacturers from $1,700 to $2,500 per day,
plus the cost of travel and living expenses.
[46] GAO, Drug Safety: Preliminary Findings Suggest Weaknesses in FDA's
Program for Inspecting Foreign Drug Manufacturers, GAO-08-224T
(Washington, D.C.: Nov. 1, 2007).
[47] GAO, Food and Drug Administration: Improvements Needed in the
Foreign Drug Inspection Program, GAO/HEHS-98-21 (Washington, D.C.: Mar.
17, 1998).
[48] FDA must approve a new drug application before a new drug product
may be marketed in the United States; approval for a generic drug is
sought through an abbreviated new drug application. FDA also reviews
scientific and clinical data contained in the applications, as part of
its process in considering them for approval to be marketed.
[End of section]
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