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)

      United States
GAO   General Accounting
                    D.C. 20648

      Health,   Education   and Human Services Division


      June 3, 1997

      The Honorable James M. Jeffords
      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
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

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
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.


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
Figure 1: Median Review Time for 51OCk>sbv Fiscal Year

300        Day8





              1966            1630   1661   1962   1993   1694   1965   1366
              Fiad     Year

Figure            2:   Median Review Time for Original PEAS bv Fiscal Ye=

1200       Days













                              lSQ0   la01   1962   1693   1991   1996   1998
              Fiscal Year

Figure 3: Median Review Time for PMA Supnlements bv Fiscal Year

350       Days








             1969         1990   1991   1992   1993   1994    1995   1995

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.


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
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

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

bThrough Mar. 31, 1997.

                                                  GAOIEEEIS-9%146R    FDA Device   Review   Times
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
Table 3: Dimosition of Original PMA     ADDtiCatiOnS    Submitted. 1989-97

    Fiscal year     Approved        Withdrawn          OtheP             Open            Total
       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
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

 10                                                    GAO/EEHS-97-146R   FDA Device   Review   Times
Table 5: Disnosition PMA Sunnlements Submitted. 1989-97

     Fiscal year     Approved        Withdrawn        Other”            Open           Total
        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
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.


          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

    This letter was prepared by Bertha Dong and George Silberman. Lf you or your
    staff have any questions about this report, please call me at (202) 512-6543 or
    you may call Ms. Dong at (202) 512-8499 or Mr. Silberman at (202) 512-9226.

’   Bernice Steinhardt
    Director, Health Services Quality
     and Public Health Issues


    13                                      GAO/EEHS-97-146B   FDA Device   Review   Times
           . .
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