United States GAO General Accounting Washington, Office D.C. 20648 Health, Education and Human Services Division B-277157 June 3, 1997 The Honorable James M. Jeffords Chairman The Honorable Edward M. Kennedy Ranking Minority Member Committee on Labor and Human Resources United States Senate Subject: Medical Devices: FDA Review Times. 1989 Through 1996 The Food and Drug Administration (FDA) regulates the manufacture and marketing of tens of thousands of medical devices in this country. This regulatory function is carried out in a number of ways, perhaps the most important of which is the review of submissions from manufacturers wishing to market medical devices for the first time. Device manufacturers have admonished FDA for taking too much time to conduct these reviews and have argued that the agency’s review imposes inordinate delays upon the introduction of new devices into the market. FDA, while admitting that device review times were lengthy, responded that it has made considerable gains recently iti improving the timeliness of reviews. We issued a report on medical device review times in 1995 that addressed this issue. ’ We found that review times for the most prevalent type of device submissions had lengthened throughout the early part of the decade but had improved slightly in 1994. FDA maintained that the increases in review time for submissions from 1990 through 1993 created a backlog of thousands of cases. The decrease in review time between 1993 and 1994 was portrayed as evidence that FDA had succeeded in cleaning up this backlog. Critics of FDA had a very different interpretation of the data in our 1995 report. These data, they said, showed increases in review times for each year with only ‘Medical Devices: FDA Review Time (GAOPEMD-96-2, Oct. 30, 1995). GAOIHEHS-97-146R FDA Device Review Times p-ii +g-3 B-277157 one exception. Furthermore, it would be difficult to use the 1 year in which review times decreased (1994) as evidence of any positive trend. Data on review times beyond the 1994 date would be helpful for resolving the question of whether the downturn in that year was a one-time event or indicated that agency performance was truly improving. Therefore, at your request we have measured review times for medical device submissions to FDA in fiscal years 1995 and 1996.2 We present our results along with those for submissions between 1989 and 1994 in order to show the trends in review times. Our examination focused on the three major types of device submissions received by FDA - Premarket notifications or 510(k)s3-These are notifications to FDA of a manufacturer’s intent to market a device that the manufacturer considers substantiahy equivalent to a device already on the market. In evaluating 510(k) notifications, FDA makes a determination whether the new device is substantiahy equivalent to a legally marketed device. - Premarket approval (PM& applications-These are applications requesting FDA approval to market a medical device. A PMA is needed when the risks associated with a device are considerable (as would be the case, if the device is implanted in the body for life-supporting purposes, such as a defibrillator) or when the device is new (and therefore, the risks are not well understood). - PMA supplements-These are applications to modify a device originally approved through the PMA process in some way that may affect the safetyor effectiveness of that device. Such modifications include new uses for the device, device design, materials used in constructing the device, quality control procedures used in manufacturing, or a change in the manufacturing facility or the packaging for the device. 2AUreferences in this report are to fiscal years. The federal fiscal year begins on Oct. 1 and ends on Sept. 30. 3Premarket notification is commonly called 510(k) in reference to section 510(k) of the Federal Food, Drug, and Cosmetic Act. 2 GAo/HEBs9%146R F’DA Device Review Times B-277157 We obtained data for all the notifications and applications in these three categories received by FDA from the beginning of 1989 through March 31, 1997.4 Our primary measure of time was the interval between FDA’s receipt of an application and the “final decision” made on that application. Alternative measures of time were also calculated and are included in our analysis. We deleted cases that had missing values or apparent data entry errors for the values relevant to calculating review time. Because the validity of FDA’s raw data on review times has not been questioned even by critics of the review process, we did not, for this or our earlier review, verify those data With this exception, we performed our work between March and May 1997 in accordance with generally accepted government auditing standards. RESULTS IN BRIEF The trends in review times for premarket notifications, original PMAs: and PMA supplements submitted from 1989 through 1996 are strikingly similar. As figures 1 through 3 show, the decrease in review times that began in 1994 continued in 1995 and 1996 for each of these types of submissions. 4Because 1997 notifications and applications are still being received and reviewed, our results on review times are presented only for submissions through the end of fiscal year 1996. 5The term “original PMA” is used to distinguish this type of application from a PMA supplement. 3 GAO/EEHS-97-146R FDA Device Review Times B-277157 Figure 1: Median Review Time for 51OCk>sbv Fiscal Year 300 Day8 250 200 150 100 1966 1630 1661 1962 1993 1694 1965 1366 Fiad Year Figure 2: Median Review Time for Original PEAS bv Fiscal Ye= 1200 Days 1100 1000 9w 600 766 606 500 466 300 206 100 0 lSQ0 la01 1962 1693 1991 1996 1998 Fiscal Year 4 B-277157 Figure 3: Median Review Time for PMA Supnlements bv Fiscal Year 350 Days 300 250 200 150 100 50 0 1969 1990 1991 1992 1993 1994 1995 1995 FiscalYear The pattern in review times in each of the figures is consistent with FDA’s claims that the increases early in the period reflected a growing backlog of applications and notifications and that the improvements in the later years indicated that this backlog had been successfully cleared. At the same time, despite the overall positive trend in these results, it should be noted that between 1995 and 1996 the review time for PMA supplements increased slightly. Despite this increase, the median review time for 1996 PMA supplements remains shorter than for those submitted in 1994. Thus, it is not clear whether this is the start of a new trend of increasing review times or a single exception to the overall positive trend seen since 1992. GAO ANALYSIS In figures 1 through 3, we used the median as the measure of “typicality” and show the median for all submissions to FDA, irrespective of FDA’s ultimate determinations. We relied on the median because it is acknowledged to be the preferred measure of central tendency in situations where there are extreme values (as is the case with device review tunes). We included all submissions 5 GAOAEEBS-97-1488 FDADeviceReviewTimes B-277157 because even those that were never approved required FDA resources for review. In the tables that follow, however, we present some alternative measures of review time. We also present some basic descriptive information on the medical device submissions. Tables 1, 3, and 5 show the number of 51O(k)s, original PM& and PMA supplements, respectively, that were submitted to FDA. Each table also shows the disposition of those submissions. Tables 2,4, and 6 show the average (or “mean”) review times for 51O(k)s, original PMAs, and PMA supplements, respectively. We present average review times for each type of submission because this statistic has been frequently reported and to show that the trends remain the same notwithstanding the measure that is used. The data in these tables also differ from those in figures 1 through 3 in that (1) they are restricted to submissions that were eventually cleared or approved, and (2) they distinguish between average “FDA time” (the amount of time the application was under active review by the agency) and average “non-FDA time” (any time that the sponsor of the application took to respond to inquiries from FDA for additional information). Premarket Notifications /51O(k)s) FDA does not approve 510(k) notifications. Bather, the agency makes a determination of whether the device is substantially equivalent to devices already on the market. If so, the manufacturer can market the new device. Table 1 shows the number of 510(k) notifications submitted to FDA from 1989 through 1997 and the disposition of those notifications. Table 2 shows review tunes for those 510(k) submissions judged to be “equivalent.” 6 GAOIHEFlS-97.146R F’DA Device Review Times B-277157 Table 1: Disnosition of 510(k) Notification Submitted. 1989-97 Fiscal year Judged Judged Other” Open Total submitted equivalent nonequivalent 1989 5,258 108 1,657 0 7,023 1990 4,631 142 1,062 0 5,835 1991 4,513 146 1,114 1 5,774 1992 4,912 202 1,409 10 6,533 1993 4,752 109 1,428 21 6,310 1994 4,827 96 1,500 27 6,450 1995 4,789 71 1,153 65 6,078 1996 4,073 43 662 538 5,316 1997b 967 8 172 1,360 2,507 Total 38,722 925 10,157 2,022 51,826 me “Other” category includes the following FDA disposition codes: additional information requested, applicant cannot respond within 30 days; forwarded to drugs/biologics; deleted/duplicate; deleted; drug (CDER) review required; exempted by regulation; general purpose article; closeout letter issued; not actively regulated; not a device; not a finished product; not a required submission; preamendment exempt; refuse to accept; reconditioner/remanufacturer; transitional device; and withdrawn by applicant. bThrough Mar. 31, 1997. GAOIEEEIS-9%146R FDA Device Review Times B-277157 Table 2: Review Time (in Davs) for 510(k) Notifications JudPed to Be Eauivalent Fiscal year Median total Average total Average FDA Average non- submitted time time time FDA time 1989 I 78 1 98 I 77 I 21 1990 78 100 80 21 1991 88 124 96 28 1992 142 209 169 41 1993 199 247 207 40 1994 125 177 134 44 1995 89 126 99 27 1996 85 109 89 19 As can be seen from table 2, the pattern of increases in review times during the early years followed by decreasing times that was seen for a.U51O(k) notifications combined also held for each measure in the group of notifications that were eventually cleared for marketing. Moreover, the data are also consistent across measures in that times for the 1996 cohort remained longer than for the 1989 cohort. Original Premarket Atxxovals (PM&) To market a “new” device (that is, one that is not substantially equivalent to a device already on the market) or a device that is seen as having considerable risks, a manufacturer must submit an application to FDA seeking premarket approval. The number of original PMAs submitted is considerably less than the number of 510(k) applications. However, because FDA reviews a substantial amount of evidence to determine if these devices are safe and effective (unlike with 51O(k)s where the principal concern is whether they are substantially equivalent), original PM.& typically require considerably more resources for review than do 51O(k)s. Table 3 shows the number of original PMAs submitted to FDA from 1989 through 1997 and the disposition of those applications. Table 4 shows review times for original PMA submissions approved. 8 GAO/HEHS97-146R FDA Device Review Times B-277157 Table 3: Dimosition of Original PMA ADDtiCatiOnS Submitted. 1989-97 Fiscal year Approved Withdrawn OtheP Open Total submitted 1989 46 28 10 0 84 1990 38 28 10 2 78 1991 21 31 13 7 72 1992 33 21 8 4 66 1993 15 21 3 1 40 1994 21 9 1 11 42 1995 17 7 1 15 40 1996 12 6 5 21 44 1997b 1 0 1 27 29 Total 204 151 52 88 495 “I’he “Other” category includes the following FDA disposition codes: abandoned; converted, reclassified; PMA not appropriate; and other. “Through Mar. 31, 1997. 9 GAO/HERS-9%146R FDA Device Review Times B-277157 Table 4: Review Times (in Davs> for ADDroved Original PMAs Fiscal year Median total Average Average FDA Average non- submitted time total time time FDA time 1989 355 454 321 133 1990 531 788 541 247 1991 722 712 483 229 1992 907 1,016 667 349 1993 766 777 534 243 1994 623 600 452 148 1995 417 428 362 66 1996” 280 271 235 36 ?I’he median and average approval times for the 1996 PMA submissions will increase as applications currently open are approved. As can be seen from table 4, the pattern of increases in review times during the early years followed by decreasing times that was seen for all PMIA submissions also held for each measure in the group of applications that were eventually approved for marketing. PMA Supnlements Table 5 shows what happened to applications in the third category of medical device submissions that we examined, supplements to devices originally approved as PM&. Table 6 presents review times for these approved applications. 10 GAO/EEHS-97-146R FDA Device Review Times B-277157 Table 5: Disnosition PMA Sunnlements Submitted. 1989-97 Fiscal year Approved Withdrawn Other” Open Total submitted 1989 642 138 27 0 807 1990 559 75 25 1 660 1991 500 75 17 4 596 1992 478 105 21 3 607 1993 326 44 23 - 2 395 1994 315 42 9 6 372 1995 443 33 7 10 493 1996 323 17 5 66 411 1997b 85 5 0 130 220 Total 3,671 534 134 222 4,561 “fhe “Other” category includes the following FDA disposition codes: abandoned; converted; reclassified, PMA not appropriate; and other. ?‘hrough Mar. 31, 1997. 11 GAO/HERS-9%146R FDA Device Review Times B-277157 Table 6: Review Time (in Davs) for Apnroved P&IA Suunlements Fiscal year Median total Average total Average FDA Average non- submitted time time time FDA time 1989 160 190 157 33 1990 116 170 132 38 1991 140 240 169 71 1992 215 317 260 57 1993 215 277 234 43 1994 180 223 179 44 1995 142 171 139 32 1996” 127 133 122 11 “The median and average approval times for the 1996 PMA supplements will increase as applications currently open are approved. As can be seen from table 6, the pattern for review time for PMA supplements parallels that for the other submissions we examined. That is, times increased throughout the early years (1989 through 1993) and then decreased quickly through 1996. AGENCY COMMENTS We provided a draft of this letter to FDA They agreed with our Snding that review times had decreased since 1993. In addition, FDA provided a number of technical comments that have been incorporated into the text. ----- As agreed with your office, we will send copies of this letter to other interested congressional committees, the Secretary of Health and Human Services, and the Commissioner of Food and Drugs. Copies will also be made available to others upon request 12 GAO/HESS-97.149R FDA Device Review Times B-277157 This letter was prepared by Bertha Dong and George Silberman. 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Medical Devices: FDA Review Times, 1989 Through 1996
Published by the Government Accountability Office on 1997-06-03.
Below is a raw (and likely hideous) rendition of the original report. (PDF)