Medical Devices: FDA Should Take Steps to Ensure That High-Risk Device Types Are Approved through the Most Stringent Premarket Review Process
Published: 2009-01-15T00:00:00

Fast Facts:

Highlights:
section_title: Why GAO Did This Study
paragraphs: The Food and Drug Administration (FDA) within the Department of Health and Human Services (HHS) is responsible for oversight of medical devices sold in the United States. Regulations place devices into three classes, with class III including those with the greatest risk to patients. Unless exempt by regulation, new devices must clear FDA premarket review via either the 510(k) premarket notification process, which determines if a new device is substantially equivalent to another legally marketed device, or the more stringent premarket approval (PMA) process, which requires the manufacturer to supply evidence providing reasonable assurance that the device is safe and effective. Class III devices must generally obtain an approved PMA, but until FDA issues regulations requiring submission of PMAs, certain types of class III devices may be cleared via the 510(k) process. The FDA Amendments Act of 2007 mandated that GAO study the 510(k) process. GAO examined which premarket review process--510(k) or PMA--FDA used to review selected types of device submissions in fiscal years 2003 through 2007. GAO reviewed FDA data and regulations, and interviewed FDA officials.
section_title: What GAO Found
paragraphs: In fiscal years 2003 through 2007, as part of its premarket review to determine whether devices should be permitted to be marketed in the United States, FDA: (1) reviewed 13,199 submissions for class I and II devices via the 510(k) process, clearing 11,935 (90 percent) of these submissions; (2) reviewed 342 submissions for class III devices through the 510(k) process, clearing 228 (67 percent) of these submissions; and (3) reviewed 217 original and 784 supplemental PMA submissions for class III devices and approved 78 percent and 85 percent, respectively, of these submissions. Although Congress envisioned that class III devices would be approved through the more stringent 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. GAO found that in fiscal years 2003 through 2007 FDA cleared submissions for 24 types of class III devices through the 510(k) process. 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.

section_title: Letter
paragraphs: The federal government, through the Food and Drug Administration (FDA)  within the Department of Health and Human Services (HHS), is  responsible for ensuring that medical devices sold in the United States  provide reasonable assurance of safety and effectiveness and do not pose  a threat to public health. These devices range from simple tools like  bandages and surgical clamps to complicated devices like pacemakers.
FDA classifies each device type into one of three classes—class I, II, or  III—based on the level of risk it poses and the controls necessary to  reasonably ensure its safety and effectiveness. According to FDA, the risk  the type of device poses to the patient or the user is a major factor in the  class it is assigned: class I includes devices with the lowest risk, and   class III includes devices with the highest risk. Examples of types of  devices in each class include the following:    class I: tongue depressors, elastic bandages, reading glasses, and forceps;   class II: electrocardiographs, powered bone drills, and mercury    class III: pacemakers and replacement heart valves.
In general, unless exempt under FDA regulations, devices are subject to  one of two types of FDA premarket review before they may be legally  marketed in the United States.
Premarket approval (PMA): The manufacturer must provide evidence,  typically including clinical data, providing reasonable assurance that the  new device is safe and effective. The PMA process is the most stringent  type of premarket review. A successful submission results in FDA  approval.
Premarket notification (510(k)): The manufacturer must demonstrate  to FDA that the new device is substantially equivalent to a device already  legally on the market that does not require a PMA. A successful  submission results in FDA clearance.
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. 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. The Safe  Medical Devices Act of 1990 (SMDA) 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.
The FDA Amendments Act of 2007 mandated that GAO study FDA’s  premarket review of devices under section 510(k) of the Federal Food,  Drug, and Cosmetic Act (FDCA). This report discusses (1) the premarket  review process—510(k) or PMA—FDA used to review class I, II, and III  device submissions in fiscal years 2003 through 2007 and (2) the extent to  which FDA has determined that devices reviewed through the 510(k)  process had new intended uses or new technological characteristics.
To determine the premarket review process FDA used to review class I, II,  and III device submissions, as well as the number of submissions reviewed  and cleared in fiscal years 2003 through 2007, we obtained and analyzed  data from FDA’s 510(k) and PMA databases. These databases contain  information on 510(k) and PMA submissions, respectively, including the  name of the device, the FDA-assigned product code, the status of the  submission, and any FDA decisions related to the submission and the  dates of those decisions. We also used data from FDA’s Device  Nomenclature Management System to determine other attributes of the  device types covered by the 510(k) and PMA submissions. We obtained  and analyzed data on submissions for which FDA made review decisions  in fiscal years 2003 through 2007. Our analysis included traditional and  abbreviated 510(k) submissions, original PMA submissions, and  submissions for certain types of PMA supplements (panel-track and   180-day user-fee supplements). To assess the reliability of these data, we  interviewed FDA officials knowledgeable about these databases,  performed electronic testing for accuracy and completeness, and where  applicable compared our results to aggregate information from other  sources, such as published FDA reports and the FDA Web site. We  determined that the data were sufficiently reliable for the purposes of this  report.
To examine the extent to which FDA has determined that devices  reviewed through the 510(k) process had new intended uses or new  technological characteristics, we used FDA’s 510(k) database to select and  review all class III 510(k) submission files and a stratified random sample  of class II 510(k) submission files for which FDA reached a determination  of substantially equivalent (SE) or not substantially equivalent (NSE) in  fiscal years 2005 through 2007. The sample totaled 459 submissions to the  Office of Device Evaluation within FDA’s Center for Devices and  Radiological Health and did not include submissions to other FDA offices  or centers. In each case, we collected data primarily from the FDA  reviewer’s memo, which outlined the decisions that FDA made to reach its  determination and summarized FDA’s rationale for finding the submission  SE or NSE. Because our sample of class II device submissions is  representative of all class II device submissions meeting our selection  criteria, in reporting the results of our analysis we provide estimates for  the universe of all 4,900 traditional and abbreviated 510(k) submissions for  class II devices for which FDA made determinations of SE or NSE in fiscal  years 2005 through 2007. To assess the reliability of the data we obtained  from FDA’s files, we compared our results with information from FDA’s  510(k) database. In addition, we discussed cases where the determination  path or rationale was unclear with knowledgeable FDA officials. We  determined that the data were sufficiently reliable for the purposes of this  report.
In addition to our data analysis, we reviewed relevant laws, regulations,  and FDA guidance, and interviewed FDA officials, representatives of  professional associations representing device manufacturers, and  consumer advocates. We conducted this performance audit from March  2008 to January 2009 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.
subsections: section_title: Background
paragraphs: The Medical Device Amendments of 1976 established three classes of  medical devices. Under current law, these three device classes are  defined as follows:    Class I devices are those for which compliance with general controls, such  as good manufacturing practices specified in FDA’s quality system  regulation, are sufficient to provide reasonable assurance of their safety  and effectiveness.
Class II devices are subject to general controls and may also be subject to  special controls, such as postmarket surveillance, patient registries, or  specific FDA guidelines, if general controls alone are insufficient to  provide reasonable assurance of the device’s safety and effectiveness.
Class III devices are subject to general controls, but are distinguished from  class I and II devices because class III devices are those (1) for which  insufficient information exists to determine whether general and special  controls are sufficient to provide a reasonable assurance of the safety and  effectiveness of the device and (2) that support or sustain human life or  are of substantial importance in preventing impairment of human health,  or that present a potential unreasonable risk of illness or injury.
subsections: section_title: Devices Exempt from FDA Premarket Review
paragraphs: Under federal regulations, many types of devices are exempt from FDA  premarket review. Although FDA does not track the number of devices  that are actually sold or marketed in the United States, manufacturers are  required to register with FDA and provide a list of devices intended for  commercial distribution, including device types that are exempt from  premarket review. As shown in figure 1, about 67 percent of the more  than 50,000 separate devices that manufacturers listed with FDA during  fiscal years 2003 through 2007 were exempt from premarket review. Of  the exempt devices that manufacturers listed with FDA, about 95 percent  were class I devices, for example reading glasses and forceps. About   5 percent were class II devices, for example wheeled stretchers and  mercury thermometers.
section_title: Premarket Review Process for Class III Devices
paragraphs: 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, when it passed the 1976 amendments, Congress distinguished  between those devices in commercial distribution before the date of  enactment and those entering the market on or after enactment.
Preamendment devices. Class III devices that were in commercial  distribution prior to May 28, 1976 (referred to as preamendment devices)  were allowed to be reviewed and cleared for the U.S. market without PMA  approval until FDA published final regulations requiring each device type  to obtain approval for the U.S. market through the PMA process.
Postamendment devices. Devices that were not in commercial  distribution prior to May 28, 1976 (referred to as postamendment devices)  were classified automatically into class III and required to go through the  PMA process unless FDA either (1) determined they were substantially  equivalent to a preamendment device type for which premarket approval  is not required or (2) reclassified the device type into class I or class II.
Within this framework, Congress thus envisioned that class III devices  would be approved through the more stringent PMA process and that the  premarket review of class I and class II devices would entail a lesser  degree of scrutiny.
By the late 1980s, FDA had not acted to require PMAs for many  preamendment class III device types. In 1990, the SMDA required FDA to  1.  before December 1, 1995, order industry submission of safety and  effectiveness information for preamendment class III device types that  were not yet required to go through the PMA process;  2.  after ordering industry submission of safety and effectiveness  information but before December 1, 1995, publish regulations for each  such device either revising its classification into class I or class II or  requiring it to remain in class III; and  3.  as promptly as is reasonably achievable, but not later than 12 months  after the effective date of a regulation requiring a device to remain in  class III, establish a schedule for the promulgation of regulations  requiring the submission of PMAs for the preamendment class III  device types required to remain in class III.
The House of Representatives report accompanying the SMDA stated that  “In formulating these schedules, the FDA should take into account its  priorities and limited resources, together with the Committee’s intention  that the evaluation process be expeditious.”
In May 1994, FDA published a notice in the Federal Register announcing a  strategy for implementation of the SMDA. According to the FDA  memorandum outlining this strategy, the agency planned the following:    To publish proposed regulations by 1996 requiring PMAs for 15 device  types that FDA had determined to present an unreasonably high risk to  public health because significant issues of safety or effectiveness or both  were not being resolved or, to the best of FDA’s knowledge, had little  probability of being resolved. According to FDA, the timetable for  publication of each final regulation would be based on specific data needs,  comments received (in response to the proposed rule), and the existence,  if any, of petitions received to reclassify the devices.
To order manufacturers to submit information on safety and effectiveness  by 1998 for 58 device types. FDA identified 27 of these device types as not  presenting as great a risk to the public health in light of FDA’s knowledge  and experience with the devices. FDA identified the other 31 device types  as strong candidates for reclassification. FDA’s strategy stated that after  receipt of the safety and effectiveness information, the agency would  proceed with rule making to either reclassify the devices or retain them in  class III.
To issue one proposed regulation in 1994 requiring PMAs for 44 device  types in limited use.
The agency’s strategy established a plan to start addressing the class III  device types that were allowed to go through the 510(k) process, but it did  not establish completion dates for doing so. See appendix III for additional  information on the FDA strategy.
section_title: FDA’s 510(k) Review Process
paragraphs: As a general rule, devices are subject to 510(k) premarket review unless  exempt or required to go through the PMA process. Specifically, the 510(k)  process, established in 1976, requires a device manufacturer to notify FDA  90 days before it intends to market a device and to establish that the  device is substantially equivalent to a legally marketed device that does  not require a PMA. The legally marketed device is referred to as a  predicate device. Under federal regulations, a predicate device can be a  device that    was legally marketed prior to May 28, 1976, for which a PMA is not    was marketed on or after May 28, 1976, and was found to be substantially  equivalent to a legally marketed device through the 510(k) process; or   was reclassified by FDA from class III to class II or I.
FDA reviews each 510(k) submission to determine whether the device in  question is SE or NSE to a predicate device. To be SE, a device must   (1) have the same intended use as the predicate device and (2) have the  same technological characteristics as the predicate device or have  different technological characteristics and submitted information  demonstrates that the device is as safe and effective as the marketed  device and does not raise different questions of safety or effectiveness.  Because the predicate device may be a device that was marketed on or  after May 28, 1976, that was found SE when compared to another legally  marketed device through the 510(k) process, there could be multiple  iterations of a given device type cleared through the 510(k) process. As a  result, a 510(k) submission for a new device in 2008 could be compared to  the 20th iteration of a device type that was on the market before 1976.  Figure 2 shows FDA’s 510(k) decision-making process.
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. In addition, other  aspects of FDA’s premarket review are less stringent for 510(k)  submissions than for PMA submissions. For example, FDA generally does  not inspect manufacturing establishments as part of the 510(k) premarket  review process—the 510(k) review process focuses primarily on the end  product of the manufacturing process rather than the manufacturing  process itself. In contrast, the agency does inspect manufacturing  establishments as part of its review of original PMA submissions.  Manufacturing establishments that produce devices cleared through the  510(k) process, as well as those that produce devices approved through  the PMA process, are subject to periodic inspections under FDA’s normal  inspection program.
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.
Consumer advocates have raised questions regarding the number of  devices, particularly class III devices, that are cleared through the 510(k)  process and regarding the use of the 510(k) process to clear devices that  may utilize new technologies that are different than those in the marketed  devices to which they are compared. Officials of associations representing  medical device manufacturers, however, have asserted that the 510(k)  premarket review is an important tool for reviewing device submissions,  saying that it is a rigorous process that gives FDA the flexibility to identify  and request the information it needs to assess the safety and effectiveness  of medical devices.
section_title: FDA Used the 510(k) Process to Review Class I and II Device Submissions, and Used Both the 510(k) and PMA Processes to Review Class III Device Submissions
paragraphs: 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. Specifically, 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. Although Congress envisioned that class III devices  would be approved through the more stringent PMA process, we found  that FDA has not published regulations requiring PMA submissions for  some types of preamendment class III devices nor has it reclassified them.  As a result, some types of class III devices have been cleared for the U.S.  market through the 510(k) process.
Table 1 summarizes the FDA review decisions, by class of device, in fiscal  years 2003 through 2007 for 510(k) and PMA submissions.
subsections: section_title: FDA Reviewed All Submissions for Class I and Class II Devices through the 510(k) Process
paragraphs: FDA reviewed all class I and class II device submissions in fiscal years  2003 through 2007 through the 510(k) process. As shown in table 2, FDA  cleared approximately 9 out of every 10 of the 510(k) submissions for   class I and class II devices for which FDA made review decisions during  this time period.
Of the 10,670 510(k) submissions for class II devices that FDA cleared in  fiscal years 2003 through 2007, FDA’s databases identified one-quarter as  being for devices that were implantable; were life sustaining; or presented  significant risk to the health, safety, or welfare of a patient (see table 3). Of  these characteristics, implantable was the most frequently identified  characteristic. In terms of 510(k) submissions for class I devices,  according to FDA, none of the more than 1,200 510(k) submissions for  class I devices that FDA cleared during the same time period were for  devices that were implantable; were life sustaining; or presented  significant risk to the health, safety, or welfare of a patient.
section_title: FDA Reviewed Submissions for Some Class III Devices Types through the 510(k) Process and Others through the PMA Process
paragraphs: 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 SE to a predicate  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. 3.)
section_title: FDA Has Not Issued Regulations Requiring PMA Submissions for Some Types of Class III Devices
paragraphs: Although Congress envisioned that class III devices would be approved  through the more stringent PMA process, and the SMDA required that FDA  establish a schedule for doing so, this process remains incomplete. The  228 class III submissions that FDA cleared through the 510(k) process in  fiscal years 2003 through 2007 were allowed to undergo premarket review  through the 510(k) process because they were for preamendment class III  device types, or those substantially equivalent to them, for which FDA had  not yet issued regulations either requiring PMA submissions or  reclassifying them. These 228 510(k) submissions involved 24 device types  (see table 4). Of these types, 16 were included in one of the priority  groups in FDA’s 1994 strategy for reclassifying or requiring PMAs for   class III device types, and in particular 4 device types—accounting for 39  of the 228 submissions—were among those that FDA identified as  presenting an unreasonably high risk to public health.
The class III submissions FDA cleared through the 510(k) process 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 (see fig. 4). This  compares to no 510(k) submissions for class I devices and 25 percent of  510(k) submissions for class II devices.
Four of the 24 class III device types for which FDA cleared 510(k)  submissions in fiscal years 2003 through 2007 have since been reclassified  by FDA as class II device types. Twenty of the 24 device types, however,  may still be cleared through the 510(k) process. Further, there are other  preamendment class III device types that did not happen to have any  510(k) submissions cleared in fiscal years 2003 through 2007 that are also  still eligible to be cleared through the 510(k) process.
FDA officials have acknowledged the importance of publishing regulations  requiring PMA submissions or reclassifying preamendment class III device  types. When asked for their time frame for doing so, the officials did not  provide one. Rather, they responded that that the agency is committed to  addressing this issue as resources and priorities permit.
section_title: Relatively Few Class II and Class III 510(k) Submissions Had a New Intended Use or New Technological Characteristics
paragraphs: In our review of 510(k) submission files for which FDA reached a  determination of SE or NSE in fiscal years 2005 through 2007, we found  that FDA determined that relatively few devices had a new intended use or  new technological characteristics. Overall, we found that FDA determined  about 1 percent of class II and III submissions had a new intended use and  about 15 percent had new technological characteristics. For the 510(k)  submissions that FDA cleared, FDA found that all of the devices had the  same intended use as their predicate devices, and 86 percent also had the  same technological characteristics. In contrast, of the 510(k) submissions  that FDA determined to be NSE, more than half were for devices that had  a new intended use or new technological characteristics.
Figure 5 shows the estimated percentage of 510(k) submissions reaching  each step in the review process. See appendix V for additional information  on FDA’s decision-making process.
subsections: section_title: All 510(k) Submissions That FDA Cleared Had the Same Intended Use and Most Had the Same Technological Characteristics as Predicate Devices
paragraphs: All 510(k) submissions for class II and class III devices that FDA cleared in  fiscal years 2005 through 2007 had the same intended use and most had  the same technological characteristics as predicate devices. In all 4,815  class II and class III submissions cleared through the 510(k) process  during this time period, FDA determined that the new devices had the  same intended use as their predicate devices. In 86 percent of these  submissions, we found that FDA determined that the new devices also had  the same technological characteristics as their predicate devices. (See   fig. 6.)
In 14 percent of the class II and class III submissions cleared through the  510(k) process in fiscal years 2005 through 2007, FDA determined that the  new device had new technological characteristics. For the cleared  submissions with new technological characteristics, FDA determined,  among other things, that either  1.  the new technological characteristics could not affect safety or  effectiveness—for example, FDA determined that software  modifications to a defibrillator allowing physicians greater control  over the device’s CPR (cardiopulmonary resuscitation) settings could  not affect the safety or effectiveness of the defibrillator—or  2.  the new characteristics do not raise new types of safety or  effectiveness questions—for example, FDA determined that a digital  electrocardiograph did not raise new types of effectiveness questions  relative to the predicate device, an analog electrocardiograph.
Table 5 shows the distribution of cleared submissions by class and  characteristics of the determination.
section_title: More Than Half of the 510(k) Submissions FDA Determined Not Substantially Equivalent Were for Devices That Had a New Intended Use or New Technological Characteristics
paragraphs: We found that of the 248 class II and III submissions that FDA determined  to be NSE in fiscal years 2005 through 2007, slightly more than half    had a new intended use,   had a new technological characteristic that raised new types of safety or    had a new technological characteristic that could affect safety or  effectiveness and did not have performance data to demonstrate  equivalence to the predicate device.
We also found that about one in every three 510(k) submissions FDA  determined to be NSE had the same intended use and the same  technological characteristics as the predicate device, but FDA determined  the submissions NSE because of a lack of performance data. An additional  13 percent of submissions were determined NSE for other reasons, such as  not providing adequate data early in the review or not having a predicate  device (see table 6).
section_title: Conclusions
paragraphs: The 510(k) process plays a major role in FDA’s oversight of medical  devices. During fiscal years 2003 through 2007, FDA reviewed over 2,400  510(k) submissions annually and cleared about 90 percent of these  submissions for the U.S. market. These included 228 cleared submissions  for class III devices. In establishing device classes in 1976, Congress  envisioned that all class III devices would eventually be required to  undergo premarket review through the more stringent PMA process,  which requires the manufacturer to provide evidence, which may include  clinical data, providing reasonable assurance that the new device is safe  and effective. However, certain preamendment class III device types may  be reviewed through the 510(k) process until such time as FDA publishes  regulations requiring them to go through the PMA process. In 1990 the  SMDA directed FDA to take action on the remaining preamendment   class III device types by reclassifying them to a lower class or requiring  them to remain in class III and go through the PMA process, but we found  that more than 14 years after FDA published its strategy and plans for  doing so, a significant number of class III devices—including device types  that FDA has identified as implantable; life sustaining; or posing a  significant risk to the health, safety, or welfare of a patient—still enter the  market through the less stringent 510(k) process.
FDA has stated that eventually all class III devices will require FDA  approval through the PMA process and FDA officials reported that the  agency is committed to addressing this issue, but the agency has not  specified time frames for doing so. Without FDA action, the remaining  preamendment class III device types—including device types that FDA  identified in 1994 as presenting an unreasonably high risk to public  health—may enter the U.S. market through FDA’s less stringent premarket  notification process.
section_title: Recommendation for Executive Action
paragraphs: We are recommending 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  requiring it to remain in class III, and (2) for those device types remaining  in class III, require approval for marketing through the PMA process.
section_title: Agency Comments
paragraphs: We received comments on a draft of this report from HHS. (See app. VI.)  The department commented that the draft report fairly and accurately  describes FDA’s 510(k) program and the department agreed with our  conclusions and recommendation.
HHS agreed with our recommendation that FDA expeditiously take steps  to reclassify or require PMAs for each class III device type currently  allowed to enter the market through the 510(k) process, noting that since  1994 (when FDA announced it 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, do 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, 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.
The department also provided technical comments, which we  incorporated as appropriate.
We are sending copies of this report to the Secretary of Health and Human  Services and other interested parties. The report is also available at no  charge on the GAO Web site at http://www.gao.gov.
If you or your staff have any questions about this report, please contact me  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 report. GAO staff who made major contributions to this report are  listed in appendix VII.
section_title: Appendix I: Scope and Methodology
paragraphs: To review the Food and Drug Administration’s (FDA) use of the 510(k)  and premarket approval (PMA) processes to review class I, II, and III  device submissions in fiscal years 2003 through 2007, we used FDA’s  510(k) and PMA databases. These databases contain information on device  submissions, including the name of the device, the FDA-assigned product  code, the status of the submission, and any FDA decisions related to the  submission and the dates of those decisions. In both cases, we obtained  and analyzed data on submissions for which FDA made a review decision  in fiscal years 2003 through 2007. We also used FDA’s Device  Nomenclature Management System to determine other attributes of the  device types covered by the device submissions.
The 510(k) submissions we analyzed included traditional and abbreviated  510(k) submissions. We did not include special 510(k) submissions, which  are requests for clearance of modifications to devices that have already  been cleared through the 510(k) process (see table 7). The PMA  submissions we analyzed included original PMA submissions and some  supplemental PMA submissions. Specifically, we included supplemental  PMA submissions that represented requests for approval for a significant  change in a device: panel-track supplements, which are requests for  approval for a significant change in design, performance, or use of a  device for which clinical data are necessary to provide a reasonable  assurance of safety and effectiveness; and 180-day (user-fee)  supplements, which are requests for approval for a significant change in  components, materials, design, specification, software, color additives, or  labeling. We did not include other types of PMA supplements, such as real- time supplements, which are requests for approval for a minor change to a  device, such as a minor change in design, sterilization, software, or  labeling.
To assess the reliability of these data, we interviewed FDA officials  knowledgeable about these databases, performed electronic testing for  accuracy and completeness, and where applicable compared our results to  aggregate information from other sources, such as published FDA reports  and the FDA Web site. We determined that the data were sufficiently  reliable for the purposes of this report.
In order to examine the extent to which FDA has determined that devices  reviewed through the 510(k) process had new intended uses or new  technological characteristics, we used FDA’s 510(k) database to select and  review a stratified random sample of class II and all class III 510(k)  submission files from fiscal years 2005 through 2007. See table 7 for the  scope of our file review.
All 163 class III submissions that met the inclusion criteria were included  in the sample. The 296 class II cases included in the sample constituted a  random sample of the 4,900 class II submissions that met the inclusion  criteria. The class II submissions included in the sample were stratified by  decision, meaning that class II submissions determined not substantially  equivalent (NSE) were oversampled so that the results could be  generalizable to the universe of all class II submissions, to class II  submissions determined NSE, or to class II submissions determined  substantially equivalent (SE). The sample contained a total of 459  submissions. See tables 8 and 9 for the number of submissions by fiscal  year, class, and decision.
We conducted our file review in June 2008. We collected data primarily  from the FDA reviewer memo, which contained information concerning  the steps FDA took to reach its determination of SE or NSE. This  information included the incremental decisions FDA made concerning the  use and technological characteristics of the new device, and in sum,  defined the path through an FDA decision tree the reviewer took to reach  a determination of SE or NSE. See figures 7 and 8 for detailed and  simplified versions, respectively, of FDA’s decision tree. We recorded the  individual decisions made in each case, and analyzed the results with  respect to the path the FDA reviewer took to reach the final determination  of SE or NSE.
In the 10 cases where we could not determine the steps FDA took to reach  its determination during our file review, we requested additional  information from FDA officials. Officials from the Office of Device  Evaluation in FDA’s Center for Devices and Radiological Health reviewed  the files in question and provided us with the information we requested.
To assess the reliability of these data, we compared our results with  information from FDA’s 510(k) database and Device Nomenclature  Management System. In addition, FDA officials stated that the data in the  files were accurate and reliable and provided input in the development of  our data collection instrument.
In addition to our data analysis, we reviewed relevant laws and regulations  concerning the premarket review process. We also interviewed FDA  officials from the FDA centers and offices that process device submissions  (Center for Biologics Evaluation and Research, Office of Device  Evaluation, and Office of In Vitro Diagnostic Device Evaluation and  Safety). Finally, we interviewed representatives from professional  associations representing device manufacturers (the Advanced Medical  Technology Association, the ECRI Institute, the Medical Device  Manufacturers Association, and the Medical Imaging and Technology  Alliance) and consumer advocates (the National Research Center for  Women & Families and Public Citizen).
We conducted this performance audit from March 2008 to January 2009 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.
section_title: Appendix II: Third-Party Review of 510(k) Submissions
paragraphs: The FDA Modernization Act of 1997 directed FDA to accredit third parties  (called accredited persons) in the private sector to conduct the initial  review of 510(k) submissions for low- to moderate-risk devices. Under  FDA’s Accredited Persons Program, device manufacturers may contract  with accredited organizations (third parties) to review certain 510(k)  submissions for a negotiated fee. The third party uses the same statutory  and regulatory criteria as FDA to determine substantial equivalence,  documents its review and recommendation, and forwards the 510(k)  submission and documentation to FDA’s Center for Devices and  Radiological Health. At the center, a third-party 510(k) submission is  assessed by an FDA supervisor, who may accept or change the substantial  equivalence recommendation of the third party. After completing the  supervisory assessment, FDA issues a letter to the 510(k) applicant via the  third-party reviewer with a final determination on the 510(k) submission.  During the third-party review, the FDA supervisor can request additional  information from the third party and the third party can request additional  information from the 510(k) applicant.
FDA expanded the program to include more than 670 class I and class II  device types to be eligible for 510(k) review by a third party. These  include device types for diagnostic ultrasound systems, computed  tomography X-ray systems, and surgical lasers. However, not all of the  accredited third parties are authorized to review all device types eligible  for third-party review. For example, in October 2008 FDA’s Web site listed  7 of 11 accredited third parties as authorized to review 510(k) submissions  for hearing aids.
Device types that are not eligible for third-party review include all class III  devices; class II devices intended to be permanently implantable, life  sustaining, or life supporting; and class II devices requiring clinical data to  support their 510(k) clearance. During our review of FDA’s 510(k)  database, we found three instances of 510(k) submissions in which class II  devices that were life sustaining were cleared for market through the  third-party review program during fiscal years 2003 through 2007. FDA  officials explained that about five life-sustaining, class II device types,  hemodialysis devices, had inadvertently been added to the list of devices  eligible for third-party review when the list was expanded in 2001, and that  in May 2003, FDA removed the life-sustaining class II device types from  the list of devices eligible for third-party review on FDA’s Web site. The  FDA officials said that while the three 510(k) submissions for class II life- sustaining device submissions had been submitted through the third-party  review program, FDA also conducted its own review of the three 510(k)  submissions before they were cleared for marketing.
During fiscal years 2003 through 2007, FDA reviewed and made final  determinations on 1,082 third-party 510(k) submissions (see table 10).  According to FDA, the number of third-party submissions increased as the  result of (1) increased familiarity with the third-party review program  among potential applicants, (2) the increase in the number of device types  eligible for the program, and (3) less financial disincentives to use the  third-party review program as FDA instituted device user fees. An FDA  official familiar with the program stated that the third-party review  program may be more attractive to device manufacturers because third- party review 510(k) submissions are processed faster than traditional  510(k) submissions. The official noted, however, that as FDA’s review of  traditional 510(k) submissions becomes more efficient, the advantages of  the third-party review program in terms of timeliness may diminish, which  could lead to fewer third-party review 510(k) submissions.
Table 11 shows the third-party review 510(k) submissions by medical  specialty.
section_title: Appendix III: FDA’s Implementation of Safe Medical Devices Act Provisions
paragraphs: The Safe Medical Devices Act of 1990 (SMDA) amended the definition of  class II devices and required FDA, for each preamendment class III device  type and before December 1, 1995, to (1) order manufacturers to submit  information on safety and effectiveness to FDA and (2) publish proposed  and final regulations to reclassify each device type into class II or class I or  to require it to remain in class III. For those devices for which FDA  published a regulation requiring the device to remain in class III, the  SMDA further directed FDA to, as promptly as reasonably achievable but  not later than 12 months after the effective date of the regulation requiring  the device to remain in class III, establish a schedule for the promulgation  of regulations requiring the submission of PMAs.
In an April 19, 1994, memorandum from the Acting Director of the FDA  Center for Devices and Radiological Health’s Office of Device Evaluation,  FDA outlined its strategy for implementation of the SMDA. Specifically,  FDA grouped 117 preamendment class III device types for which FDA had  not yet initiated any action to require the submission of PMAs into three  groups and prioritized the devices to facilitate the SMDA activities. (See  table 12.) The agency’s proposed strategy established a plan for beginning  to address the class III device types that were continuing to be reviewed  through the 510(k) process, but did not establish completion dates for  doing so.
As of October 2008, FDA had reclassified 45 device types and published  regulations requiring PMAs for 53 device types. Therefore, of the 117  preamendment class III device types covered by FDA’s strategy, 19 device  types remain in class III and may be cleared through the 510(k) process.  Four of those 19 device types are types that FDA had placed in group 3  and designated high priority—that is, they are device types that FDA had  determined to present an unreasonably high risk to public health because  significant issues of safety or effectiveness were not being resolved or, to  the best of FDA’s knowledge, had little probability of being resolved.
section_title: Appendix IV: Additional Information on 510(k) Submissions for Class III Devices Reviewed by FDA
paragraphs: This appendix summarizes the results from GAO analysis of FDA’s data for  class III 510(k) submissions with FDA review decisions in fiscal years 2003  through 2007. The following tables show FDA’s final decisions for  submissions for class III devices for each fiscal year through the 510(k)  process (table 13); the primary medical specialties for submissions for  class III devices cleared through the 510(k) process (table 14); and a  detailed list of all device types covered by the class III devices cleared  through the 510(k) process, including the status of these device types as of  October 2008 (table 15).
section_title: Appendix V: FDA’s 510(k) Decision-Making Process
paragraphs: This appendix presents the additional information from GAO analysis of  FDA’s 510(k) submission files for which FDA reached a determination of  SE or NSE in fiscal years 2005 through 2007. The following figures show  FDA’s detailed decision-making process for class II and class III  submissions (fig. 9); the decision-making process for class II devices alone  (fig. 10); and the decision-making process for class III devices alone   (fig. 11).
section_title: Appendix VI: Comments from the Department of Health and Human Services
section_title: Appendix VII: GAO Contact and Staff Acknowledgments
subsections: section_title: Acknowledgments
paragraphs: In addition to the contact named above, Kim Yamane, Assistant Director;  Susannah Bloch; Matt Byer; Sean DeBlieck; Linda Galib; Julian Klazkin;  and Dan Ries made key contributions to this report.
section_title: Related GAO Products
paragraphs: 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.
Medical Devices: Status of FDA’s Program for Inspections by Accredited  Organizations. GAO-07-157. Washington, D.C.: January 5, 2007.
Food and Drug Administration: Limited Available Data Indicate That  FDA Has Been Meeting Some Goals for Review of Medical Device  Applications. GAO-05-1042. Washington, D.C.: September 30, 2005.
Food and Drug Administration: Data to Measure the Timeliness of  Reviews of Medical Device Applications Are Limited. GAO-04-1022.  Washington, D.C.: August 30, 2004.