Background

FDA’s responsibilities related to medical devices include premarket and  postmarket oversight—spanning, for example, both premarket review of  devices and postmarket surveillance (the collection and analysis of data  on marketed devices). As part of both premarket and postmarket  oversight, FDA is responsible for inspecting certain foreign and domestic  establishments to ensure they meet required manufacturing standards.

		Premarket Review

Relative to the PMA process, the 510(k) premarket review process is  generally:    Less stringent. For most 510(k) submissions, clinical data are not  required and substantial equivalence will normally be determined based on  comparative device descriptions, including performance data. In contrast,  in order to meet the PMA approval requirement of providing reasonable  assurance that a new device is safe and effective, most original PMAs and  some PMA supplements require clinical data.
Faster. FDA generally makes decisions on 510(k) submissions faster than  it makes decisions on PMA submissions. FDA’s fiscal year 2009 goal is to  review and decide on 90 percent of 510(k) submissions within 90 days and  98 percent of them within 150 days. The comparable goal for PMAs is to  review and decide upon 60 percent of original PMA submissions in 180  days and 90 percent of them within 295 days.
Less expensive. The estimated cost to FDA for reviewing submissions is  substantially lower for 510(k) submissions than for PMA submissions. For  fiscal year 2005, for example, according to FDA the estimated average cost  for the agency to review a 510(k) submission was about $18,200, while the  estimate for a PMA submission was about $870,000. For the applicant, the  standard fee provided to FDA at the time of submission is also  significantly lower for a 510(k) submission than for a PMA submission. In  fiscal year 2009, for example, the standard fee for 510(k) submissions is  $3,693, while the standard fee for original PMA submissions is $200,725.
In general, class I and II device types subject to premarket review are  required to obtain FDA clearance through the 510(k) process, and class III  device types are required to obtain FDA approval through the more  stringent PMA process. With the enactment of the Medical Device  Amendments of 1976, Congress imposed requirements under which all  class III devices would be approved through the PMA process before being  marketed in the United States. However, certain types of class III devices  that were in commercial distribution in the United States before May 28,  1976 (called preamendment device types) and those determined to be  substantially equivalent to them may be cleared through the less stringent  510(k) process until FDA publishes regulations requiring them to go  through the PMA process or reclassifies them into a lower class. Prior to  1990, FDA issued regulations requiring some class III device types to go  through the PMA process but many class III device types continued to be  reviewed through the 510(k) process. The Safe Medical Devices Act of  1990 required FDA (1) to reexamine the preamendment class III device  types for which PMAs were not yet required to determine if they should be  reclassified to class I or II or remain in class III and (2) to establish a  schedule to promulgate regulations requiring those preamendment device  types that remain in class III to obtain FDA approval through the PMA  process. Accordingly, all class III devices are eventually to be reviewed  through the PMA process.

		Postmarket Surveillance

In addition to its responsibilities for premarket review of devices, FDA’s  postmarket activities to help ensure that devices already on the market  remain safe and effective include collecting and analyzing reports of  device-related adverse events and reviewing annual reports required from  manufacturers. FDA’s reporting framework for device-related adverse  events includes both mandatory and voluntary components. Under FDA’s  Medical Device Reporting regulation,    manufacturers are required to report device-related deaths, serious  injuries, and certain malfunctions to FDA and    user facilities, such as hospitals and nursing homes, are required to report  device-related deaths to FDA and to the device manufacturer and to report  serious injuries to the manufacturer (or, if the manufacturer is unknown,  to FDA).
Manufacturers and user facilities, as well as health professionals and  consumers, may also voluntarily report less serious device-related events  to FDA. FDA maintains databases that include both mandatory and  voluntary reports of device-related adverse events, which agency officials  can search to conduct research on trends or emerging problems with  device safety. FDA scientists review these reports, request follow-up  investigations, and determine whether further action is needed to ensure  patient safety. Such action may include product recalls, public health  advisories to notify health care providers and the public of potential  device-related health and safety concerns, or requiring a manufacturer to  change the instructions in its device labeling.

		Inspections of Device Manufacturing Establishments

Finally, as part of both premarket and postmarket oversight of medical  devices, FDA is responsible for inspecting certain foreign and domestic  establishments to ensure they meet required manufacturing standards.  Such inspections are FDA’s primary means of assuring that the safety and  effectiveness of devices are not jeopardized by poor manufacturing  practices. Requirements governing domestic and foreign inspections  differ. Specifically, FDA is required to inspect domestic establishments  that manufacture class II or III devices every 2 years. There is no  comparable requirement to inspect foreign establishments.
In 2002, in response to concerns about FDA’s ability to meet its  responsibilities for inspecting device manufacturing establishments,  Congress included certain provisions in the Medical Device User Fee and  Modernization Act of 2002 (MDUFMA). These provisions were designed  to (1) increase the number of inspected device manufacturing  establishments and (2) help device manufacturers meet the inspection  requirements of both the United States and foreign countries in a single  inspection. Specifically, MDUFMA required FDA to accredit third-party  organizations to conduct inspections of certain foreign and domestic  establishments. In response, FDA implemented its Accredited Persons  Inspection Program, which permits certain establishments to voluntarily  request inspections from third-party organizations to meet inspectional  requirements. Additionally, in September 2006, in partnership with Health  Canada, FDA established another program for inspection by accredited  third parties—the Pilot Multi-purpose Audit Program—that allows  accredited organizations to conduct a single inspection to meet the  regulatory requirements of both countries.

	FDA Has Not Ensured That All Class III Devices Are Approved through the Most Stringent Premarket Review Process

Although Congress envisioned that all class III devices would eventually  be approved through the more stringent PMA process, we found that this  was not always the case. In January 2009, we reported that in fiscal years  2003 through 2007, FDA reviewed all submissions for class I and II devices  through the 510(k) process, and reviewed submissions for some types of  class III devices through the 510(k) process and others through the PMA  process.
FDA reviewed all 13,199 submissions for class I and class II devices  through the 510(k) process, clearing 11,935 (90 percent) of these  submissions.
FDA also reviewed 342 submissions for class III devices through the  510(k) process, clearing 228 (67 percent) of these submissions.
In addition, the agency reviewed 217 original PMA submissions and 784  supplemental PMA submissions for class III devices and approved   78 percent and 85 percent, respectively, of these submissions.
Table 1 summarizes the FDA review decisions, by class of device, in fiscal  years 2003 through 2007 for 510(k) and PMA submissions.
With respect to class III devices, in fiscal years 2003 through 2007, FDA  reviewed submissions for some types of class III devices through the  510(k) process, and other types of class III devices through the PMA  process. Specifically, FDA reviewed 342 submissions for new class III  devices through the 510(k) process, determining 228 (67 percent) of these  submissions to be substantially equivalent to a legally marketed device.
During the same time period, FDA reviewed 217 original PMA submissions  and 784 supplemental PMA submissions for class III devices and approved  78 percent and 85 percent of them, respectively. (See fig. 1.)
The 228 class III device submissions FDA cleared through the 510(k)  process in fiscal years 2003 through 2007 were for devices such as artificial  hip joints, implantable blood access devices, and automated external  defibrillators. Class III 510(k) submissions were more likely than other  510(k) submissions to be for device types that were implantable; were life  sustaining; or pose a significant risk to the health, safety, or welfare of a  patient. Of the 228 510(k) submissions for class III devices that FDA  cleared in fiscal years 2003 through 2007, FDA’s databases flagged   66 percent as being for device types that are implantable, life sustaining, or  of significant risk. This compares to no 510(k) submissions for class I  devices and 25 percent of 510(k) submissions for class II devices.
Although the Medical Device Amendments of 1976 imposed requirements  under which all class III devices would be approved through the PMA  process, and the Safe Medical Devices Act of 1990 required that FDA  either reclassify or establish a schedule for requiring PMAs for class III  device types, this process remains incomplete. The 228 class III device  submissions cleared by FDA through the 510(k) process in fiscal years  2003 through 2007 represented 24 separate types of class III devices. As of  October 2008, 4 of these device types had been reclassified to class II, but  20 device types could still be cleared through the 510(k) process. FDA  officials said that the agency is committed to issuing regulations either  reclassifying or requiring PMAs for the class III devices currently allowed  to receive clearance for marketing via the 510(k) process, but did not  provide a time frame for doing so.
We recommended that the Secretary of Health and Human Services direct  the FDA Commissioner to expeditiously take steps to issue regulations for  each class III device type currently allowed to enter the market through  the 510(k) process. These steps should include issuing regulations to   (1) reclassify each device type into class I or class II, or require it to  remain in class III, and (2) for those device types remaining in class III,  require approval for marketing through the PMA process. In commenting  on a draft of our report, HHS agreed with our recommendation, noting that  since 1994 (when FDA announced its strategy to implement provisions of  the Safe Medical Devices Act of 1990) FDA has called for PMAs or  reclassified the majority of class III devices that did not require PMAs at  that time. The department’s comments, however, did not specify time  frames in which FDA will address the remaining class III device types  allowed to enter the market via the 510(k) process, stating instead that the  agency is considering its legal and procedural options for completing this  task as expeditiously as possible, consistent with available resources and  competing time frames. Given that more than 3 decades have passed since  Congress envisioned that all class III devices would eventually be required  to undergo premarket review through the more stringent PMA process, we  believe it is imperative that FDA take immediate steps to address the  remaining class III device types that may still enter the market through the  less stringent 510(k) process by requiring PMAs for or reclassifying them.
In April 2009, FDA took what it termed “the first step towards completing  the review of Class III device types predating the 1976 law, as was  recommended by the U.S. Government Accountability Office (GAO) in a  January 2009 report to Congress.” Specifically, FDA announced that it was  requiring manufacturers of 25 types of class III medical devices marketed  prior to 1976 to submit safety and effectiveness information to the agency  by August 7, 2009, so that it may evaluate the risk level for each device  type. In the Federal Register notice announcing the requirement, FDA  stated that once the safety and effectiveness information was submitted,  the agency would be able to determine which device types would be  required to undergo the agency’s most stringent premarket review process.  FDA’s requirement that manufacturers submit safety and effectiveness  information is an essential initial step toward implementing our  recommendation and fully implementing the law. However, FDA did not  specify a time frame for how quickly it will review the submitted  information, determine whether to reclassify the device types, and require  PMAs for those that remain in class III.
It should be noted, however, that while the PMA process is more stringent  than the 510(k) process, FDA can approve a device through the PMA  process without clinical data demonstrating the safety and effectiveness of  the device. For example, in our review of FDA’s approval of PMAs for  certain temporomandibular joint (jaw) implants, FDA managers overruled  their review staff to approve one of the devices, despite the review staff’s  concern over the sufficiency of the clinical data. The review decision  stated that either good engineering data or good clinical data—not  necessarily both—were acceptable to approve a device and accepted the  engineering data as a basis for approving an implanted device for which  the review staff had determined that the clinical data were inadequate.

	FDA Faces Challenges in Postmarket Surveillance

In our recent high-risk report, we noted that FDA’s monitoring of  postmarket safety of approved products, including medical devices, has  been questioned by numerous groups. In 2008, we reported that the  number of adverse event reports associated with all devices increased  substantially from about 77,000 reports in 2000 to about 320,000 reports in  2006. FDA’s review and analysis of these reports provides information  about trends such as infection outbreaks or common user errors caused  by inadequate instructions and may result in actions such as device recalls.  During fiscal year 2006, FDA initiated 651 recall actions involving 1,550  medical devices. This included 21 recall actions in which FDA determined  that it was likely that the use of the medical device would cause serious  health problems or death.
We and FDA have identified shortcomings in FDA’s postmarket  surveillances. In 2006, FDA reported that the agency’s Center for Devices  and Radiological Health’s ability to understand the risks of adverse events  related to the use of medical devices—whether used in the in the home of  a patient, in a hospital, in a laboratory, or in the office of a private  practitioner—is limited both by a lack of informative, validated adverse  event reports and by a lack of quality epidemiologic information. FDA  specifically reported:    One major constraint is the lack of objective data about device use and  device-related problems.
Underreporting of adverse events continues to be a problem.
FDA’s medical device reporting system is a passive system—that is, the  reports are entered as reported by manufacturers, facilities, practitioners,  or patients—and, as a result, some reports are incomplete or difficult to  understand.
The volume of submitted reports exceeded the center’s ability to  consistently enter or review the data in a routine manner.
In its 2006 report, FDA identified areas for improvement in postmarket  problem assessment for the center. In 2008, FDA officials told us that  while they have a number of strategies to prioritize their reviews, they still  cannot review all the reports they receive.
We have also found shortcomings in FDA’s monitoring of manufacturers’  compliance with requirements following device approval. In 2007, we  found that manufacturers do not always submit their required annual  reports in a timely manner. For example, FDA was missing five annual  reports from the manufacturer of one device we were examining, but it  was not until we requested these reports that FDA contacted the  manufacturer to obtain the missing information. Without these annual  reports, FDA cannot adequately monitor manufacturers’ compliance with  postmarket requirements.

	FDA Has Not Conducted Required Inspections of Manufacturing Establishments

Our work has also identified challenges faced by FDA in terms of  inspecting establishments that manufacture medical devices. In January  2008, we testified that FDA has not met a statutory requirement to inspect  certain domestic manufacturing establishments every 2 years. FDA  officials estimated that the agency has inspected these establishments  every 3 years (for establishments manufacturing class III devices) or every  5 years (for establishments manufacturing class II devices). There is no  comparable requirement to inspect foreign establishments, and agency  officials estimate that these establishments have been inspected every   6 years (for class III devices) or 27 years (for class II devices).
We also testified that FDA faces additional challenges in managing its  inspections of foreign device establishments. We found that two databases  that provide FDA with information about foreign device establishments  and the products they manufacture for the U.S. market contain  inaccuracies that create disparate estimates of establishments subject to  FDA inspection. Although comparing information from these two  databases could help FDA determine the number of foreign establishments  marketing devices in the United States, these databases cannot exchange  information and any comparisons must be done manually. Moreover,  inspections of foreign device manufacturing establishments pose unique  challenges to FDA, such as difficulties in finding translation services and  in extending trips if the inspections uncover problems. FDA has taken  some steps to address shortcomings related to inspections of foreign  establishments, including changes to its registration database to improve  the accuracy of the count of establishments and initiatives to address  unique challenges related to inspections of foreign manufacturers, but we  have not evaluated whether these changes will improve FDA’s inspection  program.
In addition, FDA’s accredited third-party inspection programs may be  unable to quickly help FDA fulfill its responsibilities. In January 2007, we  reported on the status of the Accredited Persons Inspection Program,  citing, among other things, concerns regarding its implementation and  potential incentives and disincentives that may influence manufacturers’  participation. We found that several factors may influence  manufacturers’ interest in voluntarily requesting an inspection by accredited organization. According to FDA and representatives of affecte entities, there are potential incentives and disincentives to reques ting an  inspection, as well as reasons for deferring participation in the program.  Potential incentives include the opportunity to reduce the number of  inspections conducted to meet FDA and other countries’ requirements and  to control the scheduling of the inspection. Potential disincentives include  bearing the cost for the inspection and uncertainty about the potential  consequences of making a commitment to having an inspection to assess  compliance with FDA requirements in the near future. Some  manufacturers might be deferring participation. For example,  manufacturers that already contract with a specific accredited  organization to conduct inspections to meet the requirements of other  countries might defer participation until FDA has cleared that organization  to conduct independent inspections. In both our January 2008 and May  2008 testimonies, we reported that few inspections of device  manufacturing establishments had been conducted through FDA’s two  d  accredited third-party inspection programs. As of June 12, 2009, FDA  reported that a total of 21 inspections—8 inspections of domestic  establishments and 13 inspections of foreign establishments—had been  conducted under these programs. The small number of inspections  completed by accredited third-party organizations raises questions about  the practicality and effectiveness of these programs to quickly help FDA  increase the number of establishments inspected.
Taken together, these shortcomings in both premarket and postmarket  activities raise serious concerns about FDA’s regulation of medical  devices.
Mr. Chairman, this completes my prepared statement. I would be happy to  respond to any questions you or the other members of the subcommittee  may have at this time.

	Contacts and Acknowledgments

For further information about this statement, please contact Marcia  Crosse, at (202) 512-7114 or crossem@gao.gov. Contact points for our  Offices of Congressional Relations and Public Affairs may be found on the  last page of this statement. Kim Yamane and Geraldine Redican-Bigott,  Assistant Directors; Susannah Bloch; Matt Byer; Sean DeBlieck; Helen  Desaulniers; and Julian Klazkin made key contributions to this report.

Related GAO Products

High-Risk Series: An Update. GAO-09-271. Washington, D.C.: January  2009.
Medical Devices: FDA Should Take Steps to Ensure That High-Risk  Device Types Are Approved through the Most Stringent Premarket  Review Process. GAO-09-190. Washington, D.C.: January 15, 2009.
Health-Care-Associated Infections in Hospitals: Number Associated with  Medical Devices Unknown, but Experts Report Provider Practices as a  Significant Factor. GAO-08-1091R. Washington, D.C.: September 26, 2008.
Medical Devices: FDA Faces Challenges in Conducting Inspections of  Foreign Manufacturing Establishments. GAO-08-780T. Washington, D.C.:  May 14, 2008.
Reprocessed Single-Use Medical Devices: FDA Oversight Has Increased,  and Available Information Does Not Indicate That Use Presents an  Elevated Health Risk. GAO-08-147. Washington, D.C.: January 31, 2008.
Medical Devices: Challenges for FDA in Conducting Manufacturer  Inspections. GAO-08-428T. Washington, D.C.: January 29, 2008.
Medical Devices: FDA’s Approval of Four Temporomandibular Joint  Implants. GAO-07-996. Washington, D.C.: September 17, 2007.
Food and Drug Administration: Methodologies for Identifying and  Allocating Costs of Reviewing Medical Device Applications Are  Consistent with Federal Cost Accounting Standards, and Staffing Levels  for Reviews Have Generally Increased in Recent Years. GAO-07-882R.  Washington, D.C.: June 25, 2007.
Medical Devices: Status of FDA’s Program for Inspections by Accredited  Organizations. GAO-07-157. Washington, D.C.: January 5, 2007.
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Summary:
Why GAO Did This Study

Americans depend on the Food and Drug Administration (FDA) to provide assurance that medical devices sold in the United States are safe and effective. FDA classifies medical device types into three classes, with class I including those with the lowest risk to patients (such as forceps) and class III including those with the greatest risk (such as pacemakers). FDA's responsibilities include premarket and postmarket oversight--spanning, for example, both premarket review of devices and postmarket surveillance (the collection and analysis of data on marketed devices). These responsibilities apply to all devices marketed in the United States, regardless of whether they are manufactured domestically or overseas. In 2009, GAO added FDA's oversight of medical products, including devices, to its list of high-risk areas warranting attention by Congress and the executive branch. GAO was asked to testify on recent work related to FDA's responsibilities for medical devices, including premarket review, postmarket surveillance, and inspection of manufacturing establishments. This statement is based on a recent GAO report, Medical Devices: FDA Should Take Steps to Ensure That High-Risk Device Types Are Approved through the Most Stringent Premarket Review Process ( GAO-09-190 , January 15, 2009) and on other GAO reports and testimonies related to FDA oversight.

What GAO Found

GAO found that FDA does not review all class III devices through its most stringent premarket review process. Unless exempt by regulation, new devices must clear FDA premarket review through either the 510(k) premarket notification process, which is used to determine if a new device is substantially equivalent to another legally marketed device, or through the more stringent premarket approval (PMA) process, which requires the manufacturer to supply evidence providing reasonable assurance that the device is safe and effective. In 1976, Congress envisioned that FDA would eventually approve all class III devices through the more stringent PMA process, but this process remains incomplete. GAO found that in fiscal years 2003 through 2007, FDA cleared 228 submissions representing 24 types of class III devices through the 510(k) process. GAO recommended in its January 2009 report that FDA expeditiously take steps to issue regulations requiring PMAs for or reclassifying class III device types currently allowed to enter the market via the 510(k) process. In response, in April 2009, FDA required manufacturers to submit information on the safety and effectiveness of these types of devices. However, FDA did not specify a time frame for how quickly it will reclassify them or require PMAs for those device types that remain in class III. FDA also faces challenges in postmarket surveillance of medical devices. In 2008, GAO reported that the number of adverse event reports associated with medical devices increased substantially from 2000 to 2006. Both GAO and FDA, however, have identified shortcomings in FDA's postmarket oversight. For example, in 2006 FDA reported that the agency's ability to understand the risks related to the use of medical devices is limited by the fact that the volume of submitted reports exceeded FDA's ability to consistently enter or review the reports in a routine manner. In 2008, FDA officials told us that while they have a number of strategies to prioritize their reviews of adverse event reports, they still cannot review all the reports they receive. Finally, GAO has found that FDA has not conducted required inspections of manufacturing establishments, another key FDA responsibility for medical devices marketed in the United States. In 2008, GAO reported that FDA has not met a statutory requirement to inspect certain domestic manufacturing establishments every 2 years. Instead, FDA officials estimated that the agency has inspected domestic establishments every 3 years (for class III devices) or 5 years (for class II devices). There is no comparable requirement to inspect foreign establishments, and FDA officials estimate that they have been inspected every 6 years (for class III devices) or 27 years (for class II devices). GAO reported that FDA has taken some steps to address shortcomings related to inspections of foreign establishments, but GAO has not evaluated whether these changes will improve FDA's inspection program. Taken together, these shortcomings in both premarket and postmarket activities raise serious concerns about FDA's regulation of medical devices.