Medical Devices: Status of FDA's Program for Inspections by
Accredited Organizations (05-JAN-07, GAO-07-157).
The Food and Drug Administration (FDA) inspects domestic and
foreign establishments where U.S.-marketed medical devices are
manufactured to assess compliance with FDA's quality system
requirements for ensuring good manufacturing practices and other
applicable requirements. The Medical Device User Fee and
Modernization Act of 2002 (MDUFMA) required FDA to accredit
organizations to inspect certain establishments where devices
that are marketed in both the United States and other countries
are manufactured. This report includes information that MDUFMA
requires GAO to provide on (1) the number of organizations that
sought accreditation, the number that were accredited, and
reasons for denial of accreditation and (2) the number of
inspections conducted by accredited organizations. It also
includes information about factors that could influence
manufacturers' interest in voluntarily requesting and paying for
an inspection by an accredited organization. GAO examined FDA
documents, interviewed FDA officials, and obtained information
from FDA on the number of inspections conducted from March 11,
2004--when FDA first cleared an accredited organization to
conduct independent inspections--through October 31, 2006. GAO
also interviewed affected entities, including accredited
organizations and medical device manufacturers.
-------------------------Indexing Terms-------------------------
REPORTNUM: GAO-07-157
ACCNO: A64624
TITLE: Medical Devices: Status of FDA's Program for Inspections
by Accredited Organizations
DATE: 01/05/2007
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-07-157
* [1]MEDICAL DEVICES
* [2]Status of FDA's Program for Inspections by Accredited Organi
* [3]Contents
* [4]Results in Brief
* [5]Background
* [6]FDA Accredited 17 of 23 Organizations and Denied
Accreditati
* [7]Two Inspections Independently Conducted by an Accredited
Org
* [8]Several Factors Could Influence Manufacturers' Interest
in P
* [9]Agency Comments
* [10]Appendix I: Inspections Conducted by the Food and Drug Admin
* [11]Appendix II: Scope and Methodology
* [12]Appendix III: GAO Contact and Staff Acknowledgments
* [13]GAO Contact
* [14]Acknowledgments
* [15]Order by Mail or Phone
Report to Congressional Committees
United States Government Accountability Office
GAO
January 2007
MEDICAL DEVICES
Status of FDA's Program for Inspections by Accredited Organizations
GAO-07-157
Contents
Letter 1
Results in Brief 4
Background 6
FDA Accredited 17 of 23 Organizations and Denied Accreditation When
Criteria Were Not Met or Because MDUFMA Limited the Number That Could Be
Accredited 10
Two Inspections Independently Conducted by an Accredited Organization 11
Several Factors Could Influence Manufacturers' Interest in Participating
in the Program 13
Agency Comments 17
Appendix I Inspections Conducted by the Food and Drug Administration 18
Appendix II Scope and Methodology 20
Appendix III GAO Contact and Staff Acknowledgments 22
Tables
Table 1: Dates on Which FDA Cleared Accredited Organizations to Conduct
Independent Inspections 12
Table 2: Affected Entities with Which We Conducted Interviews 21
Abbreviations
FDA Food and Drug Administration GMP good manufacturing practices
MDUFMA Medical Device User Fee and Modernization Act of 2002
This is a work of the U.S. government and is not subject to copyright
protection in the United States. It may be reproduced and distributed in
its entirety without further permission from GAO. However, because this
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separately.
United States Government Accountability Office
Washington, DC 20548
January 5, 2007
The Honorable Edward M. Kennedy Chairman The Honorable Michael B. Enzi
Ranking Minority Member Committee on Health, Education, Labor and Pensions
United States Senate
The Honorable John D. Dingell
Chairman
The Honorable Joe Barton
Ranking Minority Member
Committee on Energy and Commerce
House of Representatives
The Food and Drug Administration (FDA) is responsible for regulating
medical devices that are marketed in the United States.^1 As part of its
responsibilities, FDA inspects domestic and foreign establishments^2 where
medical devices that are marketed in the United States are manufactured^3
to assess compliance with FDA's quality system requirements^4 for ensuring
good manufacturing practices (GMP) and other applicable requirements.
During quality system inspections, FDA investigators examine manufacturing
controls, processes, and records. These inspections are FDA's primary
means of assuring that the safety and effectiveness of medical devices are
not jeopardized by poor manufacturing practices. FDA is required, by
statute, to inspect certain domestic establishments where medical devices
are manufactured at least once every 2 years.^5 FDA has not, however, been
meeting this requirement. Instead, 5 or 6 years sometimes pass between FDA
inspections at any one establishment. In addition to FDA inspections, many
foreign countries require inspections of establishments where medical
devices are manufactured. As a result, manufacturers that market their
devices internationally may face multiple inspections of their
establishments to assess conformity with quality system requirements of
multiple regulatory authorities. Some foreign countries have accredited,
certified, or otherwise recognized organizations to conduct inspections.
^1Medical 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. S 321(h).
^2FDA 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. S 807.3(c)
(2006). Medical device manufacturers may have more than one establishment.
^3We use the term "manufacture" to refer to activities including
manufacturing, preparing, and processing devices.
^4The 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.
21 C.F.R. SS 820.1, 820.3(v), 820.20.
In 2002, the U.S. House of Representatives Committee on Energy and
Commerce recognized that the growth of the medical device industry,
combined with resource constraints at FDA, had made it difficult for FDA
to meets its obligation to inspect, every 2 years, domestic establishments
where class II and class III medical devices are manufactured.^6 It also
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 one
of these recognized organizations to conduct a single inspection that
would satisfy the requirements of both the FDA and foreign countries.^7
The Medical Device User Fee and Modernization Act of 2002 (MDUFMA),
enacted in October 2002, included provisions designed to (1) increase the
number of medical device manufacturers' establishments that are inspected
for compliance with FDA requirements and (2) help manufacturers who market
medical devices in both the United States and foreign countries meet
multiple inspection requirements with fewer inspections.^8
521 U.S.C. S 360(h). Although there is no similar requirement for FDA's
inspections of foreign medical device establishments, the products
manufactured at such establishments may be prohibited from importation
into the United States if an FDA request to inspect is denied. 21 U.S.C. S
381(a), 21 C.F.R. S 820.1(d) (2006).
^6Medical 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.
^7H.R. Rep. No. 107-728, at 32-36 (2002).
Specifically, MDUFMA, as amended by the Medical Devices Technical
Corrections Act,^9 required FDA to accredit persons--which are
organizations--to conduct inspections of certain establishments. In
response, FDA implemented an accredited persons inspection program, which
provides an alternative to a traditional FDA-conducted postmarket
inspection for eligible manufacturers of medical devices who apply to
participate and are willing to pay an accredited organization to conduct
the inspection.^10 (FDA conducts inspections at no cost to the
manufacturer.) Under this program, organizations accredited by FDA may
inspect establishments and submit reports to FDA, which makes the final
determination of compliance with applicable laws and regulations. MDUFMA
specified eligibility criteria for manufacturers to participate in the
program, including that the manufacturer markets, or intends to market, a
medical device in a foreign country, and that the establishment did not
receive warnings for significant deviations from compliance requirements
based on its last inspection.^11 MDUFMA also established minimum
requirements for organizations to be accredited to conduct inspections
through this program, including protecting against financial conflicts of
interest and ensuring the competence of the organization to conduct
inspections. MDUFMA required FDA to issue criteria for accreditation
within 180 days of its enactment, and limited the number of organizations
that FDA could accredit during the first year after issuance of criteria
for accreditation to 15.^12
^8See Pub. L. No. 107-250, S 201, 116 Stat. 1588, 1602-1609 (codified, as
amended, at 21 U.S.C. S 374(g)).
^9Pub. L. No. 108-214, S 2(b)(1), 118 Stat. 572-575.
^10FDA conducts both premarket and postmarket inspections of
establishments. Premarket inspections are conducted prior to the initial
introduction of devices into the U.S. market. Postmarket inspections occur
after a device has already been marketed.
^11FDA officials told us that they can not tell how many manufacturers
meet the criteria for participation in the accredited persons inspection
program because it does not routinely collect information about whether
manufacturers market, or intend to market, medical devices in foreign
countries.
^12FDA issued criteria for accreditation on April 28, 2003. 68 Fed. Reg.
22400. MDUFMA did not limit the number of organizations that FDA could
accredit after the 1st accreditation year.
MDUFMA requires us to report on several aspects of FDA's accredited
persons inspection program.^13 This report provides information on the
status of the program, specifically, (1) the number of organizations that
sought accreditation, the number that were accredited, and reasons for
denial of accreditation and (2) the number of inspections conducted by
accredited organizations. This report also provides information about
factors that could influence manufacturers' interest in voluntarily
participating in FDA's accredited persons inspection program. In addition,
MDUFMA also requires us to report on the number of inspections conducted
by FDA; this information is included in appendix I. MDUFMA also requires
us to report on other aspects related to the oversight and effectiveness
of the accredited persons inspection program, but data were too limited
for us to provide meaningful information on these aspects of the program
at this time.
To conduct our review, we examined FDA documentation of the number of
applications for accreditation it received and its evaluation of those
applications, and we interviewed FDA officials. We also asked FDA to
provide the number of inspections conducted from March 11, 2004--the date
when FDA first cleared an accredited organization to conduct independent
inspections--through October 31, 2006. We determined that the data FDA
provided were sufficiently reliable for the purposes of this report. To
gain perspective on manufacturers' interest in participating in the
accredited persons inspection program, we interviewed representatives of
FDA and affected entities--four accredited organizations, three
organizations that represent manufacturers, and six manufacturers. The
information we obtained from this nonscientific sample of representatives
of affected entities can not be generalized to other accredited
organizations or manufacturers. We conducted our work from February 2006
through November 2006 in accordance with generally accepted government
auditing standards. See appendix II for a more detailed discussion of our
methodology.
Results in Brief
FDA granted accreditation to 17 of 23 organizations that applied to
conduct inspections of establishments. FDA denied accreditation to
applicants that did not meet minimum criteria because their applications
were not correctly completed or did not demonstrate the applicants'
technical competence. During the first accreditation year--which started
in April 2003--FDA received 23 applications. Of the 23 applications, 2
were not correctly completed and 2 did not demonstrate that the applicants
had adequate technical competence. Although the remaining 19 applicants
met the minimum criteria, MDUFMA limited the number of organizations that
could be accredited to 15 during the first year after FDA issued criteria
for accreditation. FDA scored the 19 applications against these criteria
and rank-ordered them. It accredited the 15 organizations with the highest
ranking applications, but 1 organization later withdrew. After the initial
accreditation year, FDA received 2 additional applications for
accreditation and it accredited both organizations. These 16 organizations
remained accredited as of October 31, 2006.
^1321 U.S.C. S 374(g)(12).
Between March 11, 2004, and October 31, 2006, two accredited organizations
conducted independent inspections--one inspection of a domestic
establishment and one inspection of a foreign establishment. During this
same time period, 36 inspections of domestic establishments and 1
inspection of a foreign establishment were conducted by accredited
organizations jointly with FDA officials as part of the training FDA
requires of accredited organizations. As of October 31, 2006, individuals
from 7 of the 16 accredited organizations had completed all training
requirements and were cleared to conduct independent inspections. The
remaining 9 accredited organizations had not completed all training
requirements by that date.
Several factors may influence manufacturers' interest in voluntarily
participating in the accredited persons inspection program, either by
requesting an inspection or by hosting a training inspection. According to
FDA and representatives of affected entities, factors that might influence
manufacturers' decisions to request an inspection by an accredited
organization include (a) potential incentives, (b) potential
disincentives, and (c) reasons for deferring participation in the
inspection 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 by an
accredited organization. For example, the one inspection of a domestic
establishment that an accredited organization completed independently
before October 31, 2006, was a single inspection designed to meet the
requirements of FDA, the European Union, and Canada. Potential
disincentives to participation 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 in the
program. 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. Manufacturers may also
participate in the accredited persons inspection program by hosting
training inspections, and their interest in doing so might be influenced
by other factors. For example, some representatives of affected entities
speculated that some manufacturers may choose not to host training
inspections because of a concern that they might require more time and
effort for manufacturers' staff (and thus be more disruptive) than
inspections conducted by fully trained personnel.
The Department of Health and Human Services provided technical comments on
a draft of this report, which we incorporated as appropriate.
Background
FDA conducts quality system inspections of medical device manufacturers'
establishments to assess compliance with applicable FDA regulations,
including the quality system regulation to ensure good manufacturing
practices^14 and the regulation requiring reporting of adverse events.
FDA's routine postmarket quality system inspections include both
comprehensive and abbreviated inspections, which differ in the scope of
inspectional activity. A comprehensive postmarket inspection of an
establishment assesses multiple aspects of the manufacturer's quality
system, including management activities to establish, implement, and
review the quality system; procedures to control the design and the
production or processing of the device to ensure that it conforms to
specifications and user requirements; and procedures for preventing,
identifying, and correcting quality problems. Based upon its findings
during inspection, FDA classifies completed inspections into one of three
categories based on the extent to which the establishment deviates from
applicable requirements of the quality system regulation: No action
indicated (which indicates no deviations or only minor deviations),
voluntary action indicated (which indicates minor to significant
deviations), or official action indicated (which indicates significant
deviations and warnings).
MDUFMA required FDA to accredit third persons--which are organizations--to
conduct inspections of certain establishments. Manufacturers that meet
eligibility requirements may request a postmarket inspection by an
FDA-accredited organization.^15
^14See 21 C.F.R. pt. 820 (2006).
To be eligible to request an inspection of an establishment by an
accredited organization, a manufacturer must
o manufacture a class II or class III medical device;
o market at least one of those devices in the United States;
o market or intend to market at least one of those devices in a
foreign country and either (a) one of those countries certifies,
accredits, or otherwise recognizes the FDA-accredited organization
as authorized to conduct inspections of establishments or (b) the
manufacturer submits a statement to FDA that the law of one of the
countries recognizes an inspection by FDA or the FDA-accredited
organization;^16
o have received, after its most recent inspection, a
classification by FDA as "no action indicated" or "voluntary
action indicated" for the establishment that it seeks to have
inspected by an accredited organization;^17 and
o request and receive FDA's approval to use a specific accredited
organization.
In addition, to be eligible to request an inspection by an
accredited organization, domestic establishments may not have been
inspected by the accredited organization during the previous four
years, unless the manufacturer requests and receives a waiver from
FDA, and foreign establishments must be periodically inspected by
FDA.^18
Organizations seeking accreditation to conduct inspections through
the accredited persons inspection program submit applications to
FDA for review. FDA established criteria for accreditation that
incorporate the minimum requirements set out in MDUFMA, including
the independence and competence of the accredited organizations.
For example, to ensure the independence of organizations
accredited to conduct inspections of medical device
establishments, MDUFMA prohibits accredited organizations from
engaging in the design, manufacture, promotion, or sale of
articles regulated by FDA, and FDA's criteria include whether the
organization has procedures in place to prevent conflicts of
interest. To ensure that accredited organizations are competent to
conduct inspections, MDUFMA requires that accredited organizations
agree to limit their work to that for which they have sufficient
competence and capacity, and FDA's criteria include whether the
organizations' personnel have knowledge of pertinent FDA laws,
regulations, and inspection procedures. FDA developed a scoring
procedure to evaluate applications from organizations in light of
these and other criteria.
FDA also developed a training program for inspectors from
accredited organizations that involves both formal classroom
training and training inspections of establishments. The formal
classroom training includes instruction on FDA's regulations
pertaining to medical devices and FDA's techniques for conducting
quality system inspections. FDA also requires inspectors to
successfully complete three joint inspections with FDA before
being cleared to conduct independent inspections. FDA relies on
manufacturers to volunteer to host these joint inspections. During
the first training inspection, an FDA inspector leads the
inspection and the accredited organization's inspector acts
primarily as an observer. During the second training inspection,
the accredited organization's inspector conducts an inspection
while being observed and evaluated by an FDA inspector who may
provide assistance to the trainee. During the third training
inspection, the accredited organization's inspector conducts an
inspection while being observed and evaluated by an FDA inspector
who may not provide assistance to the trainee. Each individual
inspector from an accredited organization must complete all
training requirements successfully before being cleared to conduct
independent inspections.
Manufacturers that want to have an inspection through the
accredited persons inspection program submit a request to FDA that
identifies the accredited organization they intend to use and asks
for FDA's approval. Manufacturers include with that request
documentation showing that they meet the eligibility criteria. FDA
can then provide clearance and approve the request, ask for
additional information, or deny the request. If the request is
approved, the manufacturer 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. FDA makes the final assessment of
compliance with applicable requirements.
FDA granted accreditation to 17 of 23 organizations. FDA denied
accreditation to applicants that did not meet minimum criteria
because their applications were not correctly completed or did not
demonstrate technical competence. In addition, some applicants
were denied accreditation because MDUFMA limited the number of
organizations that could be accredited to 15 during the first year
after FDA issued criteria for accreditation.
FDA Accredited 17 of 23 Organizations and Denied Accreditation When
Criteria Were Not Met or Because MDUFMA Limited the Number That
Could Be Accredited
FDA granted accreditation to 17 of 23 organizations that applied
to conduct inspections of establishments through the accredited
persons inspection program. One or more foreign governments had
already authorized each of these accredited organizations to
conduct inspections to assess compliance with quality system
requirements. FDA announced accreditation of 15 of 22 applicant
organizations on November 6, 2003. One of these accredited
organizations withdrew from the program in December 2003, leaving
14 accredited organizations. After the initial accreditation year,
FDA received two additional applications for accreditation,
including one from an organization that had been denied
accreditation during the first year; FDA accredited both of these
organizations. The total number of accredited organizations as of
October 31, 2006, was thus 16.
FDA denied accreditation to applicants that did not meet minimum
criteria because their applications were not correctly completed
or did not demonstrate the applicants' technical competence and
because more organizations met the minimum criteria for
accreditation than FDA could legally accredit. During the first
accreditation year, FDA received a total of 23 applications from
22 organizations. Of these 23 applications, 2 were not correctly
completed and the applicants were denied accreditation. For
example, these applications did not include required documentation
showing the authority, responsibility, and reporting structure of
the individuals who would perform work through the accredited
persons inspection program. One of the organizations that had
initially submitted an application that was not correctly
completed submitted a second, correctly completed application
within the first accreditation year. (This second application is
included among the total of 23 applications FDA received during
the first accreditation year.) Thus, FDA received 21 correctly
completed applications from 21 organizations during the first
accreditation year.
FDA also denied accreditation to applicants that did not meet
minimum criteria because their applications did not demonstrate
that the applicants had adequate technical competence. To evaluate
organizations' qualifications, FDA developed a checklist for
scoring applications against the criteria for accreditation. A
group of FDA staff assessed the applications and assigned scores
to specific elements, such as technical competence and prevention
of conflict of interest. FDA determined that 2 of the 21 correctly
completed applications did not demonstrate that the organization
had adequate technical competence, and it denied accreditation to
these 2 organizations.
FDA found that the remaining 19 organizations that applied for
accreditation during the first accreditation year met the minimum
criteria for accreditation, but it was limited to accrediting 15
organizations during that year. FDA rank-ordered the applications
by the total score it assigned through use of the checklist. FDA
granted accreditation to the 15 organizations with the highest
ranking applications, and denied accreditation to the remaining 4
organizations with lower-ranking applications.
Two Inspections Independently Conducted by an Accredited Organization
Between March 11, 2004--the date when FDA first cleared an
accredited organization to conduct independent inspections of
establishments--and October 31, 2006, two accredited organizations
conducted independent inspections--one inspection of a domestic
establishment and one inspection of a foreign establishment.
During the same time period, 36 inspections of domestic
establishments and 1 inspection of a foreign establishment were
conducted by accredited organizations jointly with FDA officials
as part of the training FDA required of accredited organizations.
As shown in table 1, individuals from 7 of 16 accredited
organizations completed all training requirements and were cleared
to conduct independent inspections by October 17, 2006. The
remaining 9 accredited organizations had not completed all
training requirements as of October 31, 2006.
Table 1: Dates on Which FDA Cleared Accredited Organizations to
Conduct Independent Inspections
Accredited organization Date
# 1 March 11, 2004
# 2 May 17, 2004
# 3 June 1, 2004
# 4 July 28, 2004
# 5 April 27, 2005
# 6 September 26, 2006
# 7 October 17, 2006
# 8 through # 16 Pending completion of training requirements as of
October 31, 2006
Source: FDA.
To gain perspective on the number of inspections conducted by
accredited organizations, we asked FDA how many inspections it had
conducted from March 11, 2004, through October 31, 2006, that
could potentially have been conducted by accredited organizations.
FDA could not provide exact counts of these inspections for two
reasons. First, only those manufacturers that market, or intend to
market, a device in a foreign country are eligible to be inspected
by an accredited organization, but FDA does not routinely obtain
information about foreign marketing activities or plans. Second,
eligibility for an inspection by an accredited organization is
limited to manufacturers of class II or III medical devices, but
FDA does not have readily available information about the
classification of devices that were manufactured at establishments
at the time of inspection.^19 Instead of providing exact counts of
the number of inspections FDA had conducted that could potentially
have been conducted by accredited organizations, FDA told us how
many comprehensive postmarket quality system inspections it had
conducted of establishments where class II or III medical devices
were manufactured as of October 31, 2006, and that met the
criteria for an inspection by an accredited organization other
than the criterion that the manufacturer markets, or intends to
market, a medical device in a foreign country. These counts
provide an upper bound estimate of the number of inspections FDA
had conducted that could potentially have been conducted by
accredited organizations. From March 11, 2004, through October 31,
2006, FDA conducted 229 inspections of domestic establishments and
48 inspections of foreign establishments.^20
Several Factors Could Influence Manufacturers� Interest in
Participating in the Program
According to FDA and representatives of affected entities, several
factors could influence manufacturers' interest in voluntarily
participating in the accredited persons inspection program,
whether by requesting an inspection or by hosting a training
inspection. FDA and representatives of affected entities described
factors that could serve as potential incentives, disincentives,
or reasons to defer making a request for an inspection by an
accredited organization. Additional factors may influence
manufacturers' interest in participating in the program by hosting
required training inspections.
Potential incentives to having an inspection by an accredited
organization 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 by an
accredited organization.
o FDA and representatives of affected entities told us that
manufacturers would prefer to reduce the number of inspections
they need to undergo by having a single inspection cover
requirements of FDA and other governments, rather than having
separate inspections.^21 One reason for this preference is that
inspections are disruptive to manufacturers. FDA and
representatives of affected entities told us that FDA's
requirements are similar, but not identical, to the requirements
of other countries.^22 As a result, a single inspection designed
to cover multiple requirements would likely take more time than a
single inspection designed to meet any one set of requirements,
but less time than separate inspections. Representatives of the
accredited organizations with whom we spoke stated that they
expect to be able to address multiple inspection requirements in a
single inspection, and the one inspection of a domestic
establishment that an accredited organization completed
independently before October 31, 2006, was a single inspection
designed to meet the requirements of FDA, the European Union, and
Canada.
o According to FDA and many representatives of affected entities,
another potential incentive to requesting an inspection by an
accredited organization is that manufacturers can work with
accredited organizations to schedule inspections and can schedule
them months in advance. In contrast, FDA generally notifies
manufacturers of inspections about a week in advance. The reasons
representatives of affected entities gave for the preference for
scheduling inspections well in advance include that it enables
them to ensure the availability of their quality managers and
minimize disruption to their normal work activities.
FDA and representatives of affected entities told us that the
potential disincentives to having an inspection by an accredited
organization include bearing the cost for the inspection, doubts
about whether accredited organizations can cover multiple
requirements in a single 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.
o Manufacturers pay for inspections that are conducted by
accredited organizations; in contrast, manufacturers are not
charged for inspections conducted by FDA.^23 Manufacturers that
already pay for inspections to meet requirements of foreign
countries will likely face a higher cost for an inspection that
also covers FDA requirements because the requirements are not
identical and the inspection will therefore likely take longer.
FDA and representatives of affected entities stated that bearing
the cost for the inspection might be a disincentive to
participation in the program, and some of these representatives
suggested that cost could be particularly important to small
manufacturers.
o Although a goal of the accredited persons inspection program is
to reduce the total number of inspections for manufacturers that
market devices in the United States and other countries, some
representatives of FDA and manufacturers raised doubts about
whether the accredited organizations could cover multiple
requirements in a single inspection. One of them told us that the
accredited organization that inspects its establishments stated
that it would not combine the inspection to assess compliance with
FDA requirements with an inspection to address other requirements,
and would instead conduct two separate inspections. Similarly,
some FDA officials expressed uncertainty about whether all of the
accredited organizations would develop inspection strategies that
effectively address multiple requirements. FDA and Canada are in
the process of establishing a pilot program to assess whether
accredited organizations can meet the requirements of both
countries in a single inspection.
o In addition, uncertainty about the potential consequences of
making a commitment to having an inspection to assess compliance
with FDA requirements in the near future is a potential
disincentive. Manufacturers who request an inspection by an
accredited organization are committing to an inspection to assess
compliance with FDA requirements in the near future, even though
it is possible that FDA would not inspect them in the next 5 or 6
years--and inspections carry the risk of regulatory action. FDA
and most of the representatives of affected entities with whom we
spoke told us that this commitment to an inspection is a potential
disincentive to participation in the program. For example, one
industry representative questioned why manufacturers would ask
for--and pay for--inspections when the result could be that FDA
closes them down. In addition, because FDA will make the final
determination of compliance with its requirements, some
representatives of affected entities suggested that manufacturers
might be uncertain about whether the accredited organization's
inspection will satisfy FDA, or whether FDA will conduct an
additional inspection after reading the report prepared by the
accredited organization.
Some representatives of affected entities suggested that
manufacturers might defer a decision about whether to request an
inspection by an accredited organization until uncertainties about
the potential incentives and disincentives have been reduced. For
example, manufacturers might defer a decision until there is
greater certainty about whether accredited organizations are able
to conduct single inspections to cover multiple sets of
requirements and about how FDA will respond to the inspection
reports prepared by accredited organizations.
According to representatives of affected entities, some
manufacturers--those that are already paying to have routine
quality system inspections of their establishments to meet the
requirements of other countries--might have other reasons for
deferring a request for an inspection by an accredited
organization. Manufacturers that already contract with a specific
accredited organization to conduct inspections to meet the
requirements of other countries might defer participation until
that organization has completed all required training and been
cleared by FDA to conduct independent inspections. In addition,
because manufacturers want to minimize the disruptiveness of
inspections, they might defer requesting an inspection through
FDA's accredited persons inspection program until accredited
organizations have honed their procedures for conducting
inspections to cover FDA's requirements.
Manufacturers' participation in the accredited persons inspection
program also includes their willingness to host training
inspections. In addition to some of the potential incentives and
disincentives to requesting an inspection by an accredited
organization, other factors may have influenced manufacturers'
interest in hosting required training inspections. Fewer
manufacturers have volunteered to host training inspections than
needed for all of the accredited organizations to complete their
training. Some representatives of affected entities speculated
that manufacturers might have 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. Moreover, FDA and
representatives of affected entities indicated that scheduling
training inspections was difficult. For example, FDA schedules
inspections a relatively short period of time prior to the actual
inspection, and some accredited organizations were not available
to participate because they had already made prior commitments.
Agency Comments
We provided a draft of this report to the Department of Health and
Human Services for comment. The department stated that our report
provides an accurate and balanced explanation of the accredited
persons inspection program and provided technical comments, which
we incorporated as appropriate.
We are sending copies of this report to the Secretary of Health
and Human Services and the Commissioner of FDA, appropriate
congressional committees, and other interested parties. We will
also make copies available to others on request. In addition, the
report is available at no charge on the GAO Web site at
http://www.gao.gov . If you or your staffs have questions
about this report, please contact me at (202) 512-7119 or
[email protected]. Contact points for our Offices of Congressional
Relations and Public Affairs may be found on the last page of this
report. GAO staff who made major contributions to this report are
listed in appendix III.
Marcia Crosse
Director, Health Care
^15Accredited 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 (that is, inspections conducted in response to specific
information that raised questions, concerns, or problems such as a
potential serious health risk). FDA may conduct its own inspections of
establishments even after inspection by an accredited organization.
^16FDA officials told us that they are not aware of any country where the
law recognizes an inspection by FDA, and that only organizations that are
certified, accredited, or otherwise recognized by one or more foreign
countries to conduct inspections of establishments can conduct inspections
through FDA's accredited persons inspection program.
^17If a manufacturer's most recent inspection was conducted by an
accredited organization and FDA classified it as official action
indicated, but the manufacturer meets all other eligibility criteria for
the accredited persons inspection program, the manufacturer may petition
FDA for an exception. The petition should explain how the manufacturer
corrected the identified problems.
^18As enacted, MDUFMA prohibited an inspection of an establishment by an
accredited organization if its two immediately preceding inspections had
been conducted by an accredited organization, unless the manufacturer
requested and received approval from FDA. Because accredited organizations
often completed inspections in two or more visits, this provision, in
effect, limited manufacturers to no more than one completed inspection of
an establishment by an accredited organization. In part, in an attempt to
correct this limitation, Congress passed the Medical Devices Technical
Corrections Act, Pub. L. No. 108-214, S 2(b)(1), 118 Stat. 572, 573-574,
which included a provision excluding establishments inspected by
accredited organizations during the previous four years. According to a
report of the U.S. House Committee on Energy and Commerce accompanying the
act, this provision was intended to ensure "that [establishments] can work
with [accredited organizations] to allow them to complete a full [quality
system] inspection over the course of a two year period . . . [and] can
use [accredited organizations] for two consecutive [quality system]
inspections before requesting special permission from [FDA] for the third
such inspection." H.R. Rep. No 108-433, at 8 (2004). FDA guidance, which
reflects the objectives stated in the committee report, states: "The
change limits the use of [inspections by accredited organizations] to a
four-year period rather than a limit of two consecutive inspections. This
reflects [the Medical Devices Technical Corrections Act's] shift to permit
an inspection by an accredited [organization] to be completed in stages
during a two-year period. Because a complete [inspection by an accredited
organization] must be completed within two years, FDA expects two complete
[inspections by accredited organizations] during the four-year period
provided by this section." However, instead of expanding the use of
accredited organizations, this provision would appear to disqualify a
manufacturer for four years after any one inspection by an accredited
organization, contrary to the committee report and FDA guidance. An FDA
official acknowledged the problem and stated that it is considering a
proposal for an additional technical correction to address it. No
establishment has been found ineligible for an inspection by an accredited
organization on the basis of this criterion.
^19When a manufacturer changes its device inventory or when FDA
reclassifies a device, FDA replaces the existing information about device
classification in its inspection database with the new information. For
example, if a class II medical device was manufactured at an establishment
at the time when it was inspected, and the manufacturer subsequently
stopped manufacturing that device and now manufactures only class I
medical devices, then FDA's database would not indicate that class II
devices had been manufactured at the establishment at the time of
inspection. An FDA official told us that the classification of medical
devices handled by specific establishments is generally relatively stable
over time periods of approximately 2 years.
^20See app. I for information on the number of postmarket quality system
inspections of domestic establishments where class II or class III medical
devices are manufactured and the number of inspections of foreign
establishments where medical devices are manufactured that FDA conducted.
^21We 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.
^22The United States and other countries are working to bring their
requirements for inspections of medical device establishments into line
with one another, that is, to harmonize their requirements. The majority
of representatives of affected entities with whom we spoke supported
harmonization.
^23Representatives of the accredited organizations with whom we spoke
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.
Appendix I: Inspections Conducted by the Food and Drug
Administration
The Medical Device User Fee and Modernization Act of 2002 (MDUFMA)
requires us to report on the number of inspections of medical
device establishments conducted by the Food and Drug
Administration (FDA).^1 We are reporting the number of postmarket
quality system inspections of domestic establishments where medium
or high risk medical devices (referred to as class II or class III
medical devices) are manufactured^2 and the number of inspections
of foreign medical device establishments conducted by FDA.
To provide this information, we asked FDA how many inspections it
conducted from March 11, 2004--the date when FDA first cleared an
accredited organization to conduct independent
inspections--through October 31, 2006. With regard to domestic
establishments, we asked for the number of quality system
inspections of establishments where class II or class III medical
devices are manufactured. FDA provided us with the number of such
inspections based on the classification of medical devices as of
October 31, 2006, because FDA does not have readily available
information about the classification of devices manufactured at
the establishments at the time of inspection. FDA updates the
information about device classification in its inspection database
when the types of medical devices an establishment handles
changes, for example, when a manufacturer changes its device
inventory or when FDA reclassifies a device.^3 Based on our review
of FDA documents and discussions with FDA officials, we determined
that the data FDA provided were sufficiently reliable for the
purposes of this report.
FDA reported that from March 11, 2004, through October 31, 2006,
it conducted 2,814 postmarket quality system inspections of
domestic establishments where a class II or III medical device was
manufactured as of October 31, 2006. These establishments included
medical device manufacturers and remanufacturers, packers and
repackers, labelers and relabelers, contract sterilizers, software
manufacturers, and reprocessors. During this time period, another
86 domestic inspections were conducted by state investigators
under contract to FDA. FDA also reported that it conducted 656
inspections of foreign medical device establishments from March
11, 2004, through October 31, 2006.^4
^121 U.S.C. S 374(g)(12)(A).
^2We use the term "manufacture" to refer to activities including
manufacturing, preparing, and processing devices.
^3An FDA official told us that the classification of medical devices
handled by specific establishments is generally relatively stable over
time periods of approximately 2 years.
^4During this time period, FDA also conducted 36 inspections of domestic
establishments and 1 inspection of a foreign establishment jointly with
accredited organizations as part of the training FDA required of these
organizations.
Appendix II: Scope and Methodology
To determine the number of organizations that sought
accreditation, the number that were accredited, and reasons for
denial of accreditation, we reviewed FDA documentation of the
number of applications for accreditation it received and its
evaluation of those applications, and we interviewed FDA
officials.
To determine the number of inspections of foreign and domestic
establishments conducted by accredited persons, we asked FDA to
provide counts of the number of inspections conducted from March
11, 2004--the date when FDA first cleared an accredited
organization to conduct independent inspections--through October
31, 2006. Based on our review of FDA documents and discussions
with FDA officials, we determined that the data were sufficiently
reliable for our purposes.
To determine whether there are factors that could influence
manufacturers' interest in voluntarily participating in FDA's
accredited persons inspection program, we interviewed FDA
officials and representatives of affected entities. As indicated
in table 2, the affected entities with which we conducted
interviews were four accredited organizations, three organizations
that represent medical device manufacturers, and six global
medical device manufacturers. For our sample of accredited
organizations, we selected two that had been cleared by FDA to
conduct independent inspections as of April 2006 and two that had
not. To select our sample of manufacturers, we asked the
representatives of each of the three organizations that represent
manufacturers to provide us with a list of five manufacturers. Two
of the organizations provided lists of five manufactures and one
organization provided a list of four manufacturers. We randomly
selected two global manufacturers from each list. The information
we obtained from these representatives of affected entities can
not be generalized to other manufacturers or accredited
organizations.
Table 2: Affected Entities with Which We Conducted Interviews
Type of affected entity Specific entity
Organizations that FDA accredited o Danish Standards
to conduct inspections o KEMA Quality B.V.
o TUV Rheinland of North America,
Inc.
o Underwriters Laboratories, Inc.
Organizations that represent o Advanced Medical Technology
medical device manufacturers Association (AdvaMed)
o Medical Device Manufacturers
Association (MDMA)
o National Electrical Manufacturers
Association (NEMA)
Global manufacturers of medical o Abbott Laboratories
devices o Acorn Cardiovascular, Inc.
o Gen-Probe, Inc.
o Philips Medical Systems
o Siemens Medical Solutions
o Wescor, Inc.
Source: GAO.
We also reviewed applicable law, regulations, legislative history,
FDA guidance, and other relevant documents. We conducted our work
from February 2006 through November 2006 in accordance with
generally accepted government auditing standards.
Appendix III: GAO Contact and Staff Acknowledgments
GAO Contact
Marcia Crosse, (202) 512-7119 or [email protected]
Acknowledgments
In addition to the contact named above, James McClyde, Assistant
Director; Kristen Joan Anderson; Cathleen J. Hamann; and Julian
Klazkin made key contributions to this report.
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www.gao.gov/cgi-bin/getrpt?GAO-07-157 .
To view the full product, including the scope
and methodology, click on the link above.
For more information, contact Marcia Crosse at (202) 512-7119 or
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Highlights of [24]GAO-07-157 , a report to congressional committees
January 2007
MEDICAL DEVICES
Status of FDA's Program for Inspections by Accredited Organizations
The Food and Drug Administration (FDA) inspects domestic and foreign
establishments where U.S.-marketed medical devices are manufactured to
assess compliance with FDA's quality system requirements for ensuring good
manufacturing practices and other applicable requirements. The Medical
Device User Fee and Modernization Act of 2002 (MDUFMA) required FDA to
accredit organizations to inspect certain establishments where devices
that are marketed in both the United States and other countries are
manufactured.
This report includes information that MDUFMA requires GAO to provide on
(1) the number of organizations that sought accreditation, the number that
were accredited, and reasons for denial of accreditation and (2) the
number of inspections conducted by accredited organizations. It also
includes information about factors that could influence manufacturers'
interest in voluntarily requesting and paying for an inspection by an
accredited organization.
GAO examined FDA documents, interviewed FDA officials, and obtained
information from FDA on the number of inspections conducted from March 11,
2004--when FDA first cleared an accredited organization to conduct
independent inspections--through October 31, 2006. GAO also interviewed
affected entities, including accredited organizations and medical device
manufacturers.
FDA granted accreditation to 17 of 23 organizations that applied to
conduct inspections of establishments where medical devices are
manufactured. FDA denied accreditation to applicants that did not meet
minimum criteria because their applications were not correctly completed
or did not demonstrate the applicants' technical competence. During the
first accreditation year, which started in April 2003, FDA received 23
applications. Of the 23 applications, 2 were not correctly completed and 2
did not demonstrate that the applicants had adequate technical competence.
Although the remaining 19 applicants met the minimum criteria, MDUFMA
limited the number of organizations that could be accredited to 15 during
the first year after FDA issued criteria for accreditation. FDA scored the
19 applications against these criteria and rank-ordered them. It
accredited the 15 organizations with the highest ranking applications, but
1 organization later withdrew. After the initial accreditation year, FDA
received 2 more applications for accreditation and it accredited both
organizations. These 16 organizations remained accredited as of October
31, 2006.
Between March 11, 2004, and October 31, 2006, two accredited organizations
conducted independent inspections--one inspection of a domestic
establishment and one inspection of a foreign establishment. During that
same period, 36 inspections of domestic establishments and 1 inspection of
a foreign establishment were conducted by accredited organizations jointly
with FDA officials as part of training that FDA requires of accredited
organizations. As of October 31, 2006, individuals from 7 of the 16
accredited organizations had completed all training requirements and were
cleared to conduct independent inspections.
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.
The Department of Health and Human Services provided technical comments on
a draft of this report, which GAO incorporated as appropriate.
References
Visible links
24. http://www.gao.gov/cgi-bin/getrpt?GAO-07-157
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