Medical Devices: Challenges for FDA in Conducting Manufacturer Inspections
Published: 2008-01-29T00:00:00

Fast Facts:

Highlights:
section_title: Why GAO Did This Study
paragraphs: 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.
section_title: What GAO Found
paragraphs: 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.

section_title: Letter
paragraphs: 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—such as  hearing aids and pacemakers—marketed in the United States, whether  manufactured in domestic or foreign establishments. 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.  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. 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. 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. 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.  Additionally, in partnership with Health Canada, 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.
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. 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 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. 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. 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.
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. 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. 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.  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.
subsections: section_title: Background
paragraphs: 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. 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. 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. 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. 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. 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.
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. Manufacturers that  meet eligibility requirements may request a postmarket inspection by an  FDA-accredited organization. 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.
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.
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.
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.
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. 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. 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, pacemakers, and contact lenses.
section_title: FDA Is Not Inspecting Domestic Establishments Biennially as Required and Faces Challenges in Inspecting Foreign Establishments
paragraphs: 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.
subsections: section_title: FDA Is Not Inspecting Domestic Establishments Biennially and Inspects Relatively Few Foreign Establishments
paragraphs: 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. 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.)
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. 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.)
section_title: FDA’s Databases Provide Inconsistent Information Regarding the Number of Foreign Medical Device Manufacturing Establishments Subject to Inspection
paragraphs: 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.  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. 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.
section_title: Challenges Unique to Foreign Inspections Influence the Manner in Which FDA Conducts Such Inspections
paragraphs: 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, 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. 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.
section_title: Few Third-Party Inspections Are Conducted, but Recent Changes Could Eliminate Some Obstacles to Manufacturers’ Participation
paragraphs: 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.
As of January 11, 2008, 16 third-party organizations were accredited, and  individuals from 8 of these organizations had completed FDA’s training  requirements and been cleared to conduct independent inspections. As of  January 8, 2008, FDA and accredited organizations had conducted 44 joint  training inspections. Fewer manufacturers volunteered to host training  inspections than have been needed for all of the accredited organizations  to complete their training. 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, 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, 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.
section_title: Concluding Observations
paragraphs: 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.
section_title: Contacts and Acknowledgments
paragraphs: For further information about this testimony, please contact Marcia  Crosse at (202) 512-7114 or crossem@gao.gov. 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.
section_title: Appendix I: Summary of GAO Testimony on FDA’s Program for Inspecting Foreign Drug Manufacturers
paragraphs: 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. 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, 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.
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, 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.
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