Medical Devices: Shortcomings in FDA's Premarket Review, Postmarket Surveillance, and Inspections of Device Manufacturing Establishments
Released: 2009-06-18T00:00:00

Letter

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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