When we refer to consumer advocacy groups, we are referring to groups that advocate on behalf of consumers and patients. its safety and effectiveness. Class I includes devices with the lowest risk (e.g., tongue depressors, reading glasses, forceps), while class III includes devices with the highest risk (e.g., breast implants, coronary stents). Almost all class I devices and some class II devices (e.g., mercury thermometers, certain adjustable hospital beds) are exempt from premarket notification requirements. Most class III device types are required to obtain FDA approval through the PMA process, the most stringent of FDA’s medical device review processes. The remaining device types are required to obtain FDA clearance or approval through either the 510(k) or PMA processes. If eligible, a 510(k) is filed when a manufacturer seeks a determination that a new device is substantially equivalent to a legally marketed device known as a predicate device. In order to be deemed substantially equivalent (i.e., cleared by FDA for marketing), a new device must have the same technological characteristics and intended use as the predicate device, or have the same intended use and different technological characteristics but still be demonstrated to be as safe and effective as the predicate device without raising new questions of safety and effectiveness. Most device submissions filed each year are 510(k)s. For example, of the more than 13,600 device submissions received by FDA in FYs 2008 through 2010, 88 percent were 510(k)s. The medical device performance goals were phased in during the period covered by MDUFMA (the FYs 2003 through 2007 cohorts) and were updated for MDUFA. Under MDUFA, FDA’s goal is to complete the review process for 90 percent of the 510(k)s in a cohort within 90 days of submission (known as the Tier 1 goal) and to complete the review process for 98 percent of the cohort within 150 days (the Tier 2 goal).(See table 1 for the 510(k) performance goals for the FYs 2003 through 2011 cohorts). FDA may take any of the following actions on a 510(k) after completing its review: issue an order declaring the device substantially equivalent; issue an order declaring the device not substantially equivalent; or advise the submitter that the 510(k) is not required (i.e., the product is not regulated as a device or the device is exempt from premarket notification requirements). Each of these actions ends the review process for a submission. A sponsor’s withdrawal of a submission also ends the review process. Alternatively, FDA may “stop the clock” on a 510(k) review by sending a letter asking the sponsor to submit additional information (known as an AI letter). This completes a review cycle but does not end the review process. The clock will resume (and a new review cycle will begin) when FDA receives a response from the sponsor. As a result, FDA may meet its 510(k) performance goals even if the time to final decision (FDA review time plus time spent waiting for the sponsor to respond to FDA’s requests for additional information) is longer than the time frame allotted for the performance goal. For example, a sponsor might have submitted a 510(k) on March 1, 2009, to start the review process. If FDA sent an AI letter on April 1, 2009 (after 31 days on the clock), the sponsor provided a response on June 1, 2009 (after an additional 61 days off the clock), and FDA issued a final decision on June 11, 2009 (10 more days on the clock), then the FDA review time counted toward the MDUFA performance goals would be 41 days (FDA’s on-the-clock time). FDA would have met both the Tier 1 (90 day) and Tier 2 (150 day) time frames for that device even though the total number of calendar days (on- and off-the-clock) from beginning the review to a final decision was 102 days. (See table 2 for a comparison of FDA review time and time to final decision.) FDA tracks the time to final decision and reports on it in the agency’s annual reports to Congress on the medical device user fee program. A PMA is filed when a device is not substantially equivalent to a predicate device or has been classified as a class III PMA device (when the risks associated with the device are considerable). The PMA review process is the most stringent type of medical device review process required by FDA, and user fees are much higher for PMAs than for 510(k)s. PMAs are designated as either original or expedited. FDA considers a device eligible for expedited review if it is intended to (a) treat or diagnose a life- threatening or irreversibly debilitating disease or condition and (b) address an unmet medical need.submissions to determine which are appropriate for expedited review, regardless of whether a company has identified its device as a potential candidate for this program. FDA assesses all medical device To meet the MDUFA goals, FDA must complete its review of 60 percent of the original PMAs in a cohort within 180 days of submission (Tier 1) and 90 percent within 295 days (Tier 2). For expedited PMAs, 50 percent of a cohort must be completed within 180 days (Tier 1) and 90 percent within 280 days (Tier 2). (See table 3 for the PMA performance goals for the FYs 2003 through 2011 cohorts.) The various actions FDA may take during its review of a PMA are the following: major deficiency letter; not approvable letter; and denial order. The major deficiency letter is the only one of these actions that does not end the review process for purposes of determining whether FDA met the MDUFA performance goal time frame for a given submission. As with the AI letter in a 510(k) review, FDA can stop the clock during the PMA review process by sending a major deficiency letter (ending a review cycle) and resume it later upon receiving a response from the manufacturer. In contrast, taking one of the other four actions permanently stops the clock, meaning any further review that occurs is excluded from the calculation of FDA review time. In addition, the approval order and denial order are also considered final decisions and end FDA’s review of a PMA completely. A sponsor’s withdrawal of a submission also ends the review process. FDA’s review of medical device submissions has been discussed in recent congressional hearings, meetings between FDA and stakeholders about the medical device user fee program reauthorization, and published reports. In addition, in August 2010, FDA released reports which described the results of two internal assessments conducted by FDA of its medical device review programs. In January 2011, FDA released a plan of action that included 25 steps FDA intends to take to address the issues identified in these assessments. For FYs 2003 through 2010, FDA met all Tier 1 and Tier 2 performance goals for 510(k)s. In addition, FDA review time for 510(k)s decreased slightly during this period, but time to final decision increased substantially. The average number of review cycles and FDA’s requests for additional information for 510(k) submissions also increased during this period. FDA met all Tier 1 performance goals for the completed 510(k) cohorts that had Tier 1 goals in place. The percentage of 510(k)s reviewed within 90 days (the current Tier 1 goal time frame) exceeded 90 percent for the FYs 2005 through 2010 cohorts (see fig. 1.) Although the 510(k) cohort for FY 2011 was still incomplete at the time we received FDA’s data, FDA was exceeding the Tier 1 goal for those submissions on which it had taken action. FDA’s performance varied for 510(k) cohorts prior to the years that the Tier 1 goals were in place but was always below the current 90 percent goal. FDA met the Tier 2 goals for all three of the completed cohorts that had Tier 2 goals in place. Specifically, FDA met the goal of reviewing 98 percent of submissions within 150 days for the FYs 2008, 2009, and 2010 cohorts (see fig. 2.) Additionally, although the 510(k) cohort for FY 2011 was still incomplete at the time we received FDA’s data, FDA was exceeding the Tier 2 goal for those submissions on which it had taken action. FDA’s performance for 510(k) cohorts prior to the years that the Tier 2 goals were in place was generally below the current 98 percent goal. While the average FDA review time for 510(k) submissions decreased slightly from the FY 2003 cohort to the FY 2010 cohort, the time to final decision increased substantially. Specifically, the average number of days FDA spent on the clock reviewing a 510(k) varied somewhat but overall showed a small decrease from 75 days for the FY 2003 cohort to 71 days for the FY 2010 cohort (see fig. 3). However, when we added off-the- clock time (where FDA waited for the sponsor to provide additional information) to FDA’s on-the-clock review time, the resulting time to final decision decreased slightly from the FY 2003 cohort to the FY 2005 cohort before increasing 61 percent—from 100 days to 161 days—from the FY 2005 cohort through the FY 2010 cohort. FDA officials told us that the only alternative to requesting additional information is for FDA to reject the submission. The officials stated that as a result of affording sponsors this opportunity to respond, the time to final decision is longer but the application has the opportunity to be approved. Additionally, although the 510(k) cohort for FY 2011 was still incomplete at the time we received FDA’s data, the average FDA review time and time to final decision were lower in FY 2011 for those submissions on which it had taken action. The average number of review cycles per 510(k) increased substantially (39 percent) from FYs 2003 through 2010, rising from 1.47 cycles for the FY 2003 cohort to 2.04 cycles for the FY 2010 cohort (see fig. 4). In addition, the percentage of 510(k)s receiving a first-cycle decision of substantially equivalent (i.e., cleared by FDA for marketing) decreased from 54 percent for the FY 2003 cohort to 20 percent for the FY 2010 cohort, while the percentage receiving first-cycle AI requests exhibited a corresponding increase. (See fig. 5.) The average number of 510(k) submissions per year remained generally steady during this period. Although the 510(k) cohort for FY 2011 was still incomplete at the time we received FDA’s data, of the first-cycle reviews that had been completed, the percentage of submissions receiving a first-cycle decision of substantially equivalent was slightly higher than for the FY 2010 cohort (21.2 percent in FY 2011 compared with 20.0 percent in FY 2010). In addition, the percentage receiving a first-cycle AI request was lower (68.2 percent for FY 2011 compared with 77.0 for FY 2010). The percentage of 510(k)s that received a final decision of substantially equivalent also decreased in recent years—from a high of 87.9 percent for the FY 2005 cohort down to 75.1 percent for the FY 2010 cohort. The percentage of 510(k)s receiving a final decision of not substantially equivalent increased for each cohort from FYs 2003 through 2010, rising from just over 2.9 percent to 6.4 percent. (See fig. 6.) For FYs 2003 through 2010, FDA met most of the goals for original PMAs but fell short on most of the goals for expedited PMAs. In addition, FDA review time and time to final decision for both types of PMAs generally increased during this period. Finally, the average number of review cycles increased for certain PMAs while the percentage of PMAs approved after one review cycle generally decreased. Since FY 2003, FDA met the original PMA performance goals for four of the seven completed cohorts that had goals in place, but met the goals for only two of the seven expedited PMA cohorts with goals. Specifically, FDA met its Tier 1 performance goals for original PMAs for all three of the completed original PMA cohorts that had such goals in place, with the percentage increasing from 56.8 percent of the FY 2007 cohort to 80.0 percent of the FY 2009 cohort completed on time. (See fig. 7.) While the FY 2010 and 2011 cohorts are still incomplete, FDA is exceeding the goals for those submissions on which it has taken action. FDA’s performance had declined steadily in the years immediately before implementation of these goals—from 67.1 percent of the FY 2000 cohort to 34.5 percent of the FY 2006 cohort completed within 180 days. FDA’s performance in meeting the Tier 2 performance goals for original PMAs fell short of the goal for three of the four completed cohorts during the years that these goals were in place. FDA met the MDUFMA Tier 2 performance goal (320 days) for the FY 2006 original PMA cohort but not for the FY 2007 cohort, and did not meet the MDUFA Tier 2 performance goal (295 days) for either of the completed cohorts (FYs 2008 and 2009) to which the goal applied (see fig. 8). While the FYs 2010 and 2011 original PMA cohorts are still incomplete, FDA is exceeding the MDUFA FDA’s Tier 2 goals for those submissions on which it has taken action.performance varied for original PMA cohorts prior to the years that the Tier 2 goals were in place but was always below the current goal to have 90 percent reviewed within 295 days. For expedited PMAs, FDA met the Tier 1 and Tier 2 performance goals for only two of the seven completed cohorts for which the goals were in effect. FDA met the Tier 1 (180-day) goal for only one of the two completed cohorts during the years the goal has been in place, meeting the goal for the FY 2009 cohort but missing it for the FY 2008 cohort (see fig. 9). FDA’s performance varied for cohorts prior to the years that the Tier 1 expedited PMA goals were in place but was below the current goal of 50 percent in all but 1 year. FDA’s performance in meeting the Tier 2 performance goals for expedited PMAs fell short of the goal for four of the five completed cohorts during the years that these goals were in place. FDA met the MDUFMA Tier 2 performance goal (300 days) for the FY 2005 cohort but not for the FY 2006 or 2007 cohorts, and did not meet the MDUFA Tier 2 performance goal (280 days) for either of the completed cohorts (FY 2008 and 2009) to which the goal applied (see fig. 10). FDA’s performance varied for expedited PMA cohorts prior to the years that the Tier 2 goals were in place but always fell below the current goal to have 90 percent reviewed within 280 days. FDA review time for both original and expedited PMAs was highly variable but generally increased across our analysis period, while time to final decision also increased for original PMAs. Specifically, average FDA review time for original PMAs increased from 211 days in the FY 2003 cohort (the first year that user fees were in effect) to 264 days in the FY 2008 cohort, then fell in the FY 2009 cohort to 217 days (see fig. 11). When we added off-the-clock time (during which FDA waited for the sponsor to provide additional information or correct deficiencies in the submission), average time to final decision for the FYs 2003 through 2008 cohorts fluctuated from year to year but trended upward from 462 days for the FY 2003 cohort to 627 days for the FY 2008 cohort. The results for expedited PMAs fluctuated even more dramatically than for original PMAs—likely due to the small number of submissions (about 7 per year on average). Average FDA review time for expedited PMAs generally increased over the period that user fees have been in effect, from 241 days for the FY 2003 cohort to 356 days for the FY 2008 cohort, then fell to 245 days for the FY 2009 cohort (see fig. 12). The average time to final decision for expedited PMAs was highly variable but overall declined somewhat during this period, from 704 days for the FY 2003 cohort to 545 days for the FY 2009 cohort. The average number of review cycles per original PMA increased 27.5 percent from 1.82 in the FY 2003 cohort (the first year that user fees were in effect) to 2.32 cycles in the FY 2008 cohort. For expedited PMAs, the average number of review cycles per submission was fairly steady at approximately 2.5 cycles until the FY 2004 cohort, then peaked at 4.0 in the FY 2006 cohort before decreasing back to 2.5 cycles in the FY 2009 cohort. We found nearly identical trends when we examined the subsets of original and expedited PMAs that received a final FDA decision of approval. In addition, the percentage of original PMAs receiving a decision of approval at the end of the first review cycle fluctuated from FYs 2003 through 2009 but generally decreased—from 16 percent in the FY 2003 cohort to 9.8 percent in the FY 2009 cohort. Similarly, the percentage receiving a first-cycle approvable decision decreased from 12 percent in the FY 2003 cohort to 2.4 percent in the FY 2009 cohort. The percentage of expedited PMAs receiving first-cycle approval fluctuated from year to year, from 0 percent in 5 of the years we examined to a maximum of 25 percent in FY 2008. The percentage of original PMAs that ultimately received approval from FDA fluctuated from year to year but exhibited an overall decrease for the completed cohorts from FYs 2003 through 2008. Specifically, 74.0 percent of original PMAs in the FY 2003 cohort were ultimately approved, compared to 68.8 percent of the FY 2008 cohort. The percentage of expedited PMAs that were ultimately approved varied significantly from FYs 2003 through 2009, from a low of 0 percent in the FY 2007 cohort to a high of 100 percent in the FY 2006 cohort. The industry groups and consumer advocacy groups we interviewed noted a number of issues related to FDA’s review of medical device submissions. The most commonly mentioned issue raised by industry and consumer advocacy stakeholder groups was insufficient communication between FDA and stakeholders throughout the review process. Industry stakeholders also noted a lack of predictability and consistency in reviews and an increase in time to final decision. Consumer advocacy group stakeholders noted issues related to inadequate assurance of the safety and effectiveness of approved or cleared devices. FDA is taking steps that may address many of these issues. Most of the three industry and four consumer advocacy group stakeholders that we interviewed told us that there is insufficient communication between FDA and stakeholders throughout the review process. For example, four stakeholders noted that FDA does not clearly communicate to stakeholders the regulatory standards that it uses to evaluate submissions. In particular, industry stakeholders noted problems with the regulatory guidance documents issued by FDA. These stakeholders noted that these guidance documents are often unclear, out of date, and not comprehensive. Stakeholders also noted that after sponsors submit their applications to FDA, insufficient communication from FDA prevents sponsors from learning about deficiencies in their submissions early in FDA’s review. According to one of these stakeholders, if FDA communicated these deficiencies earlier in the process, sponsors would be able to correct them and would be less likely to receive a request for additional information. Two consumer advocacy group stakeholders also noted that FDA does not sufficiently seek patient input during reviews. One stakeholder noted that it is important for FDA to incorporate patient perspectives into its reviews of medical devices because patients might weigh the benefits and risks of a certain device differently than FDA reviewers. FDA has taken or plans to take several steps that may address issues with the frequency and quality of its communications with stakeholders, including issuing new guidance documents, improving the guidance development process, and enhancing interactions between FDA and stakeholders during reviews. For example, in December 2011, FDA released draft guidance about the regulatory framework, policies, and practices underlying FDA’s 510(k) review in order to enhance the transparency of this program. In addition, FDA implemented a tracking system and released a standard operating procedure (SOP) for developing guidance documents for medical device reviews to provide greater clarity, predictability, and efficiency in this process. FDA also created a new staff position to oversee the guidance development process. Additionally, according to an overview of recent FDA actions to improve its device review programs, FDA is currently enhancing its interactive review process for medical device reviews by establishing performance goals for early and substantive interactions between FDA and sponsors during reviews. This overview also notes that FDA is currently working with a coalition of patient advocacy groups on establishing mechanisms for obtaining reliable information on patient perspectives during medical device reviews. The three industry stakeholders that we interviewed also told us that there is a lack of predictability and consistency in FDA’s reviews of device submissions. For example, two stakeholders noted that review criteria sometimes change after a sponsor submits an application. In particular, one of these stakeholders noted that criteria sometimes change when the FDA reviewer assigned to the submission changes during the review. Additionally, stakeholders noted that there is sometimes inconsistent application of criteria across review divisions or across individual reviewers. Stakeholders noted that enhanced training for reviewers and enhanced supervisory oversight could help resolve inconsistencies in reviews and increase predictability for sponsors. In the two internal assessments of its device review programs that FDA released in August 2010, the agency found that insufficient predictability in its review programs was a significant problem. FDA has taken steps that may address issues with the predictability and consistency of its reviews of device submissions, including issuing new SOPs for reviews and enhancing training for FDA staff. For example, in June 2011, FDA issued an SOP to standardize the practice of quickly issuing written notices to sponsors to inform them about changes in FDA’s regulatory expectations for medical device submissions. FDA also recently developed an SOP to assure greater consistency in the review of device submissions when review staff change during the review.April 2010, FDA began a reviewer certification program for new FDA Additionally, in reviewers designed to improve the consistency of reviews. According to the overview of recent FDA actions to improve its device review programs, FDA also plans to implement an experiential learning program for new reviewers to give them a better understanding of how medical devices are designed, manufactured, and used. The three industry stakeholders we interviewed told us that the time to final decision for device submissions has increased in recent years. This is consistent with our analysis, which showed that the average time to final decision has increased for completed 510(k) and original PMA cohorts since FY 2003. Additionally, stakeholders noted that FDA has increased the number of requests for additional information, which our analysis also shows. Stakeholders told us they believe the additional information being requested is not always critical for the review of the submission. Additional information requests increase the time to final decision but not necessarily the FDA review time because FDA stops the review clock when it requests additional information from sponsors. Two of the stakeholders stated that reviewers may be requesting additional information more often due to a culture of increased risk aversion at FDA or because they want to stop the review clock in order to meet performance goals. According to FDA, the most significant contributor to the increased number of requests for additional information—and therefore increased time to final decision—is the poor quality of submissions received from sponsors. In July 2011, FDA released an analysis it conducted of review According to FDA, in over 80 percent times under the 510(k) program.of the reviews studied for this analysis, reviewers asked for additional information from sponsors due to problems with the quality of the submission. FDA officials told us that sending a request for additional information is often the only option for reviewers besides issuing a negative decision to the sponsor. FDA’s analysis also found that 8 percent of its requests for additional information during the first review cycle were inappropriate. Requests for additional information were deemed inappropriate if FDA requested additional information or data for a 510(k) that (1) were not justified, (2) were not permissible as a matter of federal law or FDA policy, or (3) were unnecessary to make a substantial equivalence determination. FDA has taken steps that may address issues with the number of inappropriate requests for additional information. For example, the overview of recent FDA actions indicates the agency is developing an SOP for requests for additional information that clarifies when these requests can be made for 510(k)s, the types of requests that can be made, and the management level at which the decision must be made. Three of the four consumer advocacy group stakeholders with whom we spoke stated that FDA is not adequately ensuring the safety and effectiveness of the devices it approves or clears for marketing. One of these stakeholders told us that FDA prioritizes review speed over safety and effectiveness. Two stakeholders also noted that the standards FDA uses to approve or clear devices are lower than the standards that FDA uses to approve drugs, particularly for the 510(k) program. Two stakeholders also expressed concern that devices reviewed under the 510(k) program are not always sufficiently similar to their predicates and that devices whose predicates are recalled due to safety concerns do not have to be reassessed to ensure that they are safe. Finally, three stakeholders told us that FDA does not gather enough data on long-term device safety and effectiveness through methods such as postmarket analysis and device tracking. These issues are similar to those raised elsewhere, such as a public meeting to discuss the reauthorization of the medical device user fee program, a congressional hearing, and an Institute of Medicine (IOM) report. For example, during a September 14, 2010, public meeting to discuss the reauthorization, consumer advocacy groups—including two of those we interviewed for our report—urged the inclusion of safety and effectiveness improvements in the reauthorization, including raising premarket review standards for devices and increasing postmarket surveillance. Additionally, during an April 13, 2011, congressional hearing, another consumer advocacy group expressed concerns about FDA’s 510(k) review process and recalls of high-risk devices that were cleared through this process. Finally, in July 2011, IOM released a report summarizing the results of an independent evaluation of the 510(k) program. FDA had requested that IOM conduct this evaluation to determine whether the 510(k) program optimally protects patients and promotes innovation. IOM concluded that clearance of a 510(k) based on substantial equivalence to a predicate device is not a determination that the cleared device is safe or effective. FDA has taken or plans to take steps that may address issues with the safety and effectiveness of approved and cleared devices, including evaluating the 510(k) program and developing new data systems. For example, FDA analyzed the safety of 510(k) devices cleared on the basis of multiple predicates by investigating an apparent association between these devices and increased reports of adverse events. FDA concluded that no clear relationship exists. FDA also conducted a public meeting to discuss the recommendations proposed in the IOM report in September 2011. FDA is also developing a device identification system that will allow FDA to better track devices that are distributed to patients, as well as an electronic reporting system that will assist with tracking and analyzing adverse events in marketed devices. While FDA has met most of the goals for the time frames within which the agency was to review and take action on 510(k) and PMA device submissions, the time that elapses before a final decision has been increasing. This is particularly true for 510(k) submissions, which comprise the bulk of FDA device reviews. Stakeholders we spoke with point to a number of issues that the agency could consider in addressing the cause of these time increases. FDA tracks and reports the time to final decision in its annual reports to Congress on the medical device user fee program, and its own reports reveal the same pattern we found. In its July 2011 analysis of 510(k) submissions, FDA concluded that reviewers asked for additional information from sponsors—thus stopping the clock on FDA’s review time while the total time to reach a final decision continued to elapse—mainly due to problems with the quality of the submission. FDA is taking steps that may address the increasing time to final decision. It is important for the agency to monitor the impact of those steps in ensuring that safe and effective medical devices are reaching the market in a timely manner. HHS reviewed a draft of this report and provided written comments, which are reprinted in appendix III. HHS generally agreed with our findings and noted that FDA has identified some of the same performance trends in its annual reports to Congress. HHS noted that because the total time to final decision includes the time industry incurs in responding to FDA’s concerns, FDA and industry bear shared responsibility for the increase in this time and will need to work together to achieve improvement. HHS also noted that in January 2011, FDA announced 25 specific actions that the agency would take to improve the predictability, consistency, and transparency of its premarket medical device review programs. Since then, HHS stated, FDA has taken or is taking actions designed to create a culture change toward greater transparency, interaction, collaboration, and the appropriate balancing of benefits and risk; ensure predictable and consistent recommendations, decision making, and application of the least burdensome principle; and implement efficient processes and use of resources. HHS also provided technical comments, which we incorporated as appropriate. As agreed with your office, unless you publicly announce the contents of this report earlier, we plan no further distribution until 30 days from the report date. At that time, we will send copies of this report to the Secretary of Health and Human Services, the Commissioner of FDA, and other interested parties. In addition, the report will be available at no charge on the GAO website 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 key contributions to this report are listed in appendix IV. 2002 (MDUFMA) (MDUFA) Cycles that were currently in progress at the time we received FDA’s data were included in this analysis. The average number of review cycles for the FY 2011 cohort may increase as those reviews are completed but will not decrease. — We treated PMA submissions as meeting the time frame for a given performance goal if they were reviewed within the goal time plus any extension to the goal time that may have been made. The only reason the goal time can be extended is if the sponsor submits a major amendment to the submission on its own initiative (i.e., unsolicited by FDA). The FYs 2010 and 2011 original PMA cohorts were considered still incomplete. Specifically, for 18.5 percent of the FY 2010 original PMA cohort and 48.8 percent of the FY 2011 cohort, FDA had not yet made a decision that would permanently stop the review clock for purposes of determining whether FDA met its performance goals (i.e., an approval, approvable, not approvable, withdrawal, or denial) at the time we received FDA’s data; this includes reviews by CBER through September 30, 2011, and reviews by CDRH through December 1, 2011. As a result, it was too soon to tell what the final results for these cohorts would be. It is possible that some of the reviews taking the most time were among those not completed when we received FDA’s data. The percentage of original PMAs reviewed within 180 days for the FY 2010 and FY 2011 cohorts may increase or decrease as those reviews are completed; the number reviewed within 180 days and the number and percentage reviewed within 320 days and within 295 days may decrease as those reviews are completed. Only original PMAs that had received a decision permanently stopping the review clock were used to determine the number and percentage of original PMAs reviewed within 180 days, within 320 days, and within 295 days. Cycles that were currently in progress at the time we received FDA’s data were included in this analysis. The average number of review cycles for the incomplete cohorts may increase as those reviews are completed but will not decrease. This analysis includes only those original PMAs for which FDA or the sponsor had made a final decision; this includes reviews by CBER through September 30, 2011, and reviews by CDRH through December 1, 2011. For this analysis, the FYs 2009 through 2011 original PMA cohorts were considered still incomplete. Specifically, 22 percent of the FY 2009 original PMA cohort, 46.3 percent of the FY 2010 cohort, and 65.1 percent of the FY 2011 cohort had not yet received a final decision. As a result, it was too soon to tell what the final results for these cohorts would be. It is possible that some of the reviews taking the most time were among those not completed when we received FDA’s data. The percentages of final decisions that were approval, denial, or withdrawal and the average time to final decision for original PMAs not meeting the 295-day time frame for the FYs 2009 through 2011 cohorts may increase or decrease as those reviews are completed. The average number of review cycles for the FYs 2009 through 2011 cohorts may increase as those reviews are completed but will not decrease. For the FYs 2010 through 2011 cohorts, there were no original PMAs that had received a final decision that did not meet the 295-day time frame. — We treated PMA submissions as meeting the time frame for a given performance goal if they were reviewed within the goal time plus any extension to the goal time that may have been made. The only reason the goal time can be extended is if the sponsor submits a major amendment to the submission on its own initiative (i.e., unsolicited by FDA). The FYs 2010 and 2011 expedited PMA cohorts were considered still incomplete. Specifically, 33 percent of the FY 2010 expedited PMA cohort and 71.4 percent of the FY 2011 cohort had not yet received a final decision; this includes reviews by CBER through September 30, 2011, and reviews by CDRH through December 1, 2011. Additionally, for 16.7 percent of the FY 2010 expedited PMA cohort and 71.4 percent of the FY 2011 cohort, FDA had not yet made a decision that would permanently stop the review clock for purposes of determining whether FDA met its performance goals (i.e., an approval, approvable, not approvable, withdrawal, or denial) at the time we received FDA’s data. As a result, it was too soon to tell what the final results for these cohorts would be. It is possible that some of the reviews taking the most time were among those not completed when we received FDA’s data. The percentage of expedited PMAs reviewed within 180 days for the FY 2010 and FY 2011 cohorts may increase or decrease as those reviews are completed; the number reviewed within 180 days and the number and percentage reviewed within 300 days and within 280 days may decrease as those reviews are completed. The percentages of final decisions that were approval, denial, or withdrawal and the average time to final decision for the FYs 2010 through 2011 cohorts may increase or decrease as those reviews are completed. The average number of review cycles for the FYs 2010 through 2011 cohorts may increase as those reviews are completed but will not decrease. Fiscal years for which there was no corresponding expedited PMA performance goal are denoted with a dash (—). “n/a” denotes not applicable. In these years, there was no corresponding expedited PMA performance goal and therefore no determination of whether the goal was met. For the FYs 2010 through 2011 cohorts, there were no expedited PMAs that had received a final decision that did not meet the 280-day time frame. FDA centers and offices Center for Devices and Radiological Health (CDRH) Office of Management Operations (OSM/OMO) Office of Information Technology (OIT) Office of Science and Engineering Laboratories (OST/OSEL) Office of Communication Education and Radiation Programs (OHIP/OCER) Office of Surveillance and Biometrics (OSB) Office of In Vitro Diagnostics (OIVD) Committee Conference Management (CCM) Center for Biologics Evaluation and Research (CBER) Center Director’s Office, Office of Management (OM), Office of Information Management (OIM), and Office of Communication, Outreach, and Development (OCOD) Office of Cellular, Tissue & Gene Therapies Office of Vaccines Research & Review Office of Therapeutics Research & Review Office of Biostatistics & Epidemiology Office of Compliance & Biologics Quality Office of Regulatory Affairs (ORA) Office of the Commissioner (OC) Shared Service (SS) OCD includes Medical Device Fellowship Program employees even though the Fellows were assigned to work throughout CDRH. OIT was included in the OMO FTE total prior to FY 2008. OIVD did not exist prior to FY 2004. Also, the Radiology Devices Branch was moved from ODE to OIVD between FY 2009 and FY 2010. CCM was included in the OMO FTE total prior to FY 2008. Shared Service FTE were not separated from the center FTE until FY 2004. In addition to the contact named above, Robert Copeland, Assistant Director; Carolyn Fitzgerald; Cathleen Hamann; Karen Howard; Hannah Marston Minter; Lisa Motley; Aubrey Naffis; Michael Rose; and Rachel Schulman made key contributions to this report.

Summary: The Food and Drug Administration (FDA) within the Department of Health and Human Services (HHS) is responsible for overseeing the safety and effectiveness of medical devices sold in the United States. New devices are generally subject to FDA review via the 510(k) process, which determines if a device is substantially equivalent to another legally marketed device, or the more stringent premarket approval (PMA) process, which requires evidence providing reasonable assurance that the device is safe and effective. The Medical Device User Fee and Modernization Act of 2002 (MDUFMA) authorized FDA to collect user fees from the medical device industry to support the process of reviewing device submissions. FDA also committed to performance goals that include time frames within which FDA is to take action on a proportion of medical device submissions. MDUFMA was reauthorized in 2007. Questions have been raised as to whether FDA is sufficiently meeting the performance goals and whether devices are reaching the market in a timely manner. In preparation for reauthorization, GAO was asked to (1) examine trends in FDAs 510(k) review performance from fiscal years (FY) 2003-2010, (2) examine trends in FDAs PMA review performance from FYs 2003-2010, and (3) describe stakeholder issues with FDAs review processes and steps FDA is taking that may address these issues. To do this work, GAO examined FDA medical device review data, reviewed FDA user fee data, interviewed FDA staff regarding the medical device review process and FDA data, and interviewed three industry groups and four consumer advocacy groups. Even though FDA met all medical device performance goals for 510(k)s, the elapsed time from submission to final decision has increased substantially in recent years. This time to final decision includes the days FDA spends reviewing a submission as well as the days FDA spends waiting for a device sponsor to submit additional information in response to a request by the agency. FDA review time excludes this waiting time, and FDA review time alone is used to determine whether the agency met its performance goals. Each fiscal year since FY 2005 (the first year that 510(k) performance goals were in place), FDA has reviewed over 90 percent of 510(k) submissions within 90 days, thus meeting the first of two 510(k) performance goals. FDA also met the second goal for all 3 fiscal years it was in place by reviewing at least 98 percent of 510(k) submissions within 150 days. Although FDA has not yet completed reviewing all of the FY 2011 submissions, the agency was exceeding both of these performance goals for those submissions on which it had taken action. Although FDA review time decreased slightly from FY 2003 through FY 2010, the time that elapsed before FDAs final decision increased substantially. Specifically, from FY 2005 through FY 2010, the average time to final decision for 510(k)s increased 61 percent, from 100 days to 161 days. FDA was inconsistent in meeting performance goals for PMA submissions. FDA designates PMAs as either original or expedited; those that FDA considers eligible for expedited review are devices intended to (a) treat or diagnose life-threatening or irreversibly debilitating conditions and (b) address an unmet medical need. While FDA met the performance goals for original PMA submissions for 4 out of 7 years the goals were in place, it met those goals for expedited PMA submissions only twice out of 7 years. FDA review time and time to final decision for both types of PMAs were highly variable but generally increased in recent years. For example, the average time to final decision for original PMAs increased from 462 days for FY 2003 to 627 days for FY 2008 (the most recent year for which complete data are available). The three industry groups and four consumer advocacy groups GAO interviewed noted a number of issues related to FDAs review of medical device submissions. The four issues most commonly raised by stakeholders included (1) insufficient communication between FDA and stakeholders throughout the review process, (2) a lack of predictability and consistency in reviews, (3) an increase in time to final decision, and (4) inadequate assurance of the safety and effectiveness of approved or cleared devices. FDA is taking stepsincluding issuing new guidance documents, enhancing reviewer training, and developing an electronic system for reporting adverse eventsthat may address many of these issues. It is important for the agency to monitor the impact of those steps in ensuring that safe and effective medical devices are reaching the market in a timely manner. In commenting on a draft of this report, HHS generally agreed with GAOs findings and noted that FDA has identified some of the same performance trends in its annual reports to Congress. HHS also called attention to the activities FDA has undertaken to improve the medical device review process.