Medical Devices: FDA's Approval of Four Temporomandibular Joint  
Implants (17-SEP-07, GAO-07-996).				 
                                                                 
It is estimated that over 10 million people in the United States 
suffer from jaw joint and muscle disorders. Artificial		 
temporomandibular joint (TMJ) implants have been used to replace 
the jaw joint in some patients in an effort to decrease pain and 
increase jaw function. The safety and effectiveness of these	 
implants, like other medical devices, is overseen by the Food and
Drug Administration (FDA), an agency within the Department of	 
Health and Human Services (HHS). Two implants used in the 1970s  
and 1980s that were later removed from the market caused severe  
side effects for some patients. In 1998, FDA began to require	 
certain TMJ implant manufacturers sponsoring these devices to	 
demonstrate the implants' safety and effectiveness before	 
receiving approval. Since 1998, four TMJ implants from three	 
sponsors were approved. In response to your request, GAO	 
described (1) the types of concerns raised by FDA and how it	 
addressed these concerns for the implants approved since 1998 and
(2) how FDA has monitored sponsors' compliance with conditions of
approval. GAO examined documentation related to the four TMJ	 
implants approved by FDA since 1998 and sponsors' annual reports,
which FDA uses to monitor compliance with conditions of approval.
GAO also interviewed FDA officials, TMJ implant sponsors, and	 
patient advocacy groups.					 
-------------------------Indexing Terms------------------------- 
REPORTNUM:   GAO-07-996 					        
    ACCNO:   A76328						        
  TITLE:     Medical Devices: FDA's Approval of Four Temporomandibular
Joint Implants							 
     DATE:   09/17/2007 
  SUBJECT:   Accountability					 
	     Federal regulations				 
	     Health research programs				 
	     Medical equipment					 
	     Medical research					 
	     Medical technology 				 
	     Oral health					 
	     Product evaluation 				 
	     Program evaluation 				 
	     Program management 				 
	     Reporting requirements				 
	     Risk assessment					 
	     Safety regulation					 
	     Policies and procedures				 
	     Underreporting					 

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GAO-07-996

   

     * [1]Results in Brief
     * [2]Background
     * [3]FDA Raised Concerns on All Implants and Addressed Many by Ob

          * [4]FDA Raised Concerns That Generally Applied to All Four TMJ I
          * [5]FDA Obtained Additional Information from Sponsors and Requir
          * [6]Concerns Raised about Two Implants Resulted in Differing Opi

     * [7]FDA Monitored Compliance through Review of the Sponsors' Ann

          * [8]FDA Reviewed the Annual Reports It Received, but Some Were M
          * [9]FDA Required Some Sponsors to Take Additional Actions to Com

     * [10]Agency Comments
     * [11]Appendix I: Concerns Left Unaddressed upon FDA Approval of T
     * [12]Appendix II: Comments from the Department of Health and Huma
     * [13]Appendix III: GAO Contact and Staff Acknowledgments

          * [14]GAO Contact
          * [15]Acknowledgments

               * [16]Order by Mail or Phone

Report to Congressional Requesters

United States Government Accountability Office

GAO

September 2007

MEDICAL DEVICES

FDA's Approval of Four Temporomandibular Joint Implants

GAO-07-996

Contents

Letter 1

Results in Brief 4
Background 6
FDA Raised Concerns on All Implants and Addressed Many by Obtaining
Additional Information and Establishing Conditions of Approval 10
FDA Monitored Compliance through Review of the Sponsors' Annual Reports It
Received and Required Some Sponsors to Take Additional Action 16
Agency Comments 20
Appendix I Concerns Left Unaddressed upon FDA Approval of TMJ Implants 21
Appendix II Comments from the Department of Health and Human Services 23
Appendix III GAO Contact and Staff Acknowledgments 25

Tables

Table 1: GAO Categorization of Concerns Raised by FDA during the PMA
Process for TMJ Implants 11
Table 2: GAO Categorization of Concerns Left Unaddressed by FDA during the
Premarket Approval Process for TMJ Implants 21

Figure

Figure 1: Illustration of Temporomandibular Joint 7

Abbreviations

FDA Food and Drug Administration 
HS Department of Health and Human Services
MAUDE Manufacturer and User Facility Device Experience Database
PMA premarket approval
TMJ temporomandibular joint

This is a work of the U.S. government and is not subject to copyright
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separately.

United States Government Accountability Office
Washington, DC 20548

September 17, 2007

The Honorable Edward M. Kennedy
Chairman Committee on Health, Education,Labor, and Pensions
United States Senate

The Honorable Tom Harkin
United States Senate

The Honorable Herb Kohl
United States Senate

The National Institutes of Health report that over 10 million people in
the United States suffer from temporomandibular joint (i.e., jaw joint)
and muscle disorders. Although most people have relatively mild forms of
these disorders, others experience long-term persistent and debilitating
pain. Artificial temporomandibular joint (TMJ) implants have been used to
replace the jaw joint in an effort to decrease pain and increase jaw
function for this latter group.

The Food and Drug Administration (FDA), an agency within the Department of
Health and Human Services (HHS), is responsible for overseeing the safety
and effectiveness of medical devices, including TMJ implants. Beginning in
1976, medical devices, including TMJ implants, were allowed to enter the
market without the submission of safety and effectiveness information to
FDA if the devices were determined to be "substantially equivalent" to
previously marketed devices.^1 Many patients who received certain TMJ
implants--one that was on the market prior to 1976 and one that entered
the market in 1983 and was deemed substantially equivalent to a pre-1976
device--faced severe consequences associated with the materials contained
in the implants. These included chronic pain, bone degeneration, and
implant fragmentation or displacement. In 1991, one device was recalled by
FDA, and in 1993, the other was voluntarily discontinued by the
manufacturer--who is also known as the sponsor--of the implant.

^1Medical devices may be deemed substantially equivalent to devices
marketed prior to 1976 through the premarket notification process,
referred to as the 510(k) process, which does not require the submission
of additional information on the safety and effectiveness of the device.
Substantial equivalence means, for example, that a device has the same
intended use and same technological characteristics as a marketed device.

On December 30, 1998, FDA issued regulations requiring certain TMJ implant
sponsors to submit a premarket approval (PMA) application. Applications
were required for TMJ implants marketed prior to May 28, 1976, and for
such implants deemed substantially equivalent to a device marketed prior
to May 28, 1976. The PMA process requires sponsors to demonstrate the
safety and effectiveness of their devices before receiving approval. To
demonstrate safety and effectiveness of these devices, sponsors conduct
clinical studies and perform engineering tests on the implant, such as
testing the implant's strength, and include the results in the PMA
application submitted for FDA's review. As part of the PMA process, FDA
staff evaluate these studies through a review of the implant applications,
and FDA management makes decisions regarding approval for marketing the
implants. Since the implementation of these requirements, four TMJ implant
applications from three sponsors have been submitted for approval. FDA
conditionally approved all four devices--meaning the sponsors had to
comply with specific conditions established by FDA, following approval.
For example, these sponsors were required to conduct postmarket studies,
among other conditions. Given your concerns for patients with
temporomandibular joint and muscle disorders, you expressed interest in
FDA's safety requirements for, and oversight of, TMJ implants.

This report examines (1) the types of concerns raised by FDA and how it
addressed concerns raised during the TMJ implant approval process since
December 30, 1998, when it began requiring data on implant safety and
effectiveness and (2) how FDA has monitored TMJ sponsors' compliance with
conditions of approval.

To determine how FDA addressed the concerns raised during the PMA process,
we reviewed documentation provided by FDA for each of the four TMJ
implants approved since December 30, 1998: (1) TMJ Concepts implant, (2)
TMJ Implants, Inc., total joint implant, (3) TMJ Implants, Inc., partial
joint implant, and (4) Walter Lorenz implant.^2 We identified FDA's
concerns related to safety and effectiveness and the methods used to
address these concerns through a review of internal documents, such as the
approval review package. Among other documents, this package includes
results of FDA's reviews of the PMA application, a recommendation
regarding approval, and final decisions for each implant. Throughout our
review we considered concerns addressed by FDA as those in which the
agency identified an issue concerning safety and effectiveness of an
implant and dealt with the issue by contacting the sponsor. We also
reviewed FDA's correspondence with the TMJ implant sponsors. In addition,
to further understand FDA's concerns, we examined summaries of meetings
held by FDA's dental products panel--an advisory body of external experts
convened to provide advice to the agency--on each of the four PMA
applications. An FDA official indicated that although the agency may not
have documentation of all concerns raised during the PMA process, the
documents we reviewed contained the most complete information possible to
address our objectives. Therefore, it is possible that other relevant
documents existed that we were unable to review. We grouped concerns
raised during the PMA process into broad categories, such as study
protocol, patient follow-up, and engineering testing.^3 In addition, we
further sorted these categories to provide additional explanations on the
types of concerns we identified. We also identified actions taken by FDA
such as whether FDA approved the device with conditions to address certain
concerns. We discussed our determinations of whether and how concerns were
addressed with FDA officials to gain their confirmation. However, we did
not evaluate the appropriateness of FDA's approval decisions for each of
the implants or its assessment of the medical, scientific, or engineering
data provided by the sponsors. To better inform our discussion of concerns
raised during the PMA process for TMJ implants, we contacted the three TMJ
implant sponsors^4 and several groups representing patients with
temporomandibular joint and muscle disorders, including the TMJ
Association, the TMJ and Orofacial Pain Society of America, and the Jaw
Joints & Allied Musculo-Skeletal Disorders Foundation, Inc.

^2The TMJ Concepts implant PMA application was approved in July 1999, the
TMJ Implants, Inc., total joint implant PMA application was approved in
January 2001, the TMJ Implants, Inc., partial joint implant PMA
application was approved in February 2001, and the Walter Lorenz implant
PMA application was approved in September 2005.

To determine how FDA has monitored TMJ implant sponsors' compliance with
the conditions of approval, we reviewed annual reports, which FDA required
from the three TMJ implant sponsors as a condition of approval. Among
other things, these annual reports provide the sponsors an opportunity to
update FDA on the status of their required conditions of approval. We
discussed the status of conditions of approval with FDA officials to
obtain their views on sponsors' compliance with these conditions and
collected related documentation. In addition, we gathered information
related to FDA's overall efforts to collect and review annual reports.
With the exception of FDA's review of annual reports, this report focuses
on how FDA addressed concerns raised during the PMA process and excludes
FDA's postmarket oversight activities.^5

^3Study protocol and patient follow-up concerns relate to the clinical
studies sponsors must conduct to prove that their devices are safe and
effective. Engineering testing refers to testing that is conducted on the
TMJ implant to ensure it can withstand daily jaw activity.

^4One of the three sponsors, TMJ Implants, Inc., declined to speak with
us.

Through our interviews with FDA officials and our examination of documents
provided, we determined that the data we used were sufficiently reliable
for purposes of this report. We conducted our review from October 2006
through August 2007 in accordance with generally accepted government
auditing standards.

Results in Brief

FDA officials raised similar concerns for all four TMJ implants' PMA
applications. We grouped these concerns into four main categories: study
protocol, patient follow-up, engineering testing, and other concerns, such
as device labeling. For example, FDA found that all the studies supporting
the four PMA applications had deficient patient follow-up, which made it
difficult to determine outcomes over time, such as improvement in patient
symptoms. FDA used two methods to address many, but not all, concerns upon
approval. FDA addressed some concerns raised in the approval process by
obtaining additional information from sponsors to clarify and supplement
data contained in their PMA applications before approval. FDA addressed
other concerns by approving the TMJ implants but requiring sponsors to
comply with certain conditions of approval. As a condition of approval,
FDA required the sponsors to continue their clinical studies postmarket
and to collect data on patients for all four implants for at least 3
years. Because FDA staff, who review the device applications, and FDA
management, who approve the devices for marketing, held differing views as
to whether an implant's health benefits outweighed its risks, they did not
agree on the approval decisions of two of the four TMJ implants, both
sponsored by TMJ Implants, Inc. Ultimately, both devices were approved.
FDA management acknowledged that the concerns raised about these implants
were legitimate; however, they concluded that the need for the devices
outweighed these concerns. According to FDA management, they approved the
devices primarily because they play an important role in helping patients
obtain relief from chronic pain and there did not appear to be a
prohibitory risk associated with the devices.

^5We included FDA's monitoring of the conditions of approval, through the
use of annual reports, in the scope of our work because these conditions
relate to concerns raised in the PMA process. We excluded other FDA
postapproval issues unrelated to concerns raised by FDA during the
approval process. Many of FDA's postapproval activities for medical
devices were reviewed recently in an Institute of Medicine report: Marilyn
J. Field and Hugh Tilson, Safe Medical Devices for Children (Washington,
D.C.: The National Academies Press, 2006),
[17]http://www.nap.edu/catalog/11313.html (downloaded Oct. 16, 2006). In
addition, FDA announced plans to improve postmarket programs for medical
devices in November 2006.

FDA monitored sponsors' compliance with conditions of approval by
evaluating information contained in their annual reports and often
required additional actions by the sponsors to resolve questions raised
through its review of the reports. Although a total of 18 annual reports
should have been submitted to FDA at the time we conducted our work, only
13 had been received by the agency. One implant sponsor--TMJ Concepts--did
not submit 5 of 7 required annual reports. FDA has since requested these
reports and has issued draft guidance to all medical device sponsors,
which outlines best practices for submitting annual reports. When
reviewing the annual reports from all of the sponsors to determine if
conditions of approval were met, we found that 7 of the 13 submitted
reports did not provide FDA with sufficient information to assess
compliance. To address the lack of sufficient data provided in these 7
annual reports, specifically with regard to patient history and patient
follow-up, FDA contacted the sponsors and required them to provide
additional information. TMJ Implants, Inc., submitted several annual
reports for both of its devices that lacked sufficient information
regarding patient follow-up. In addition, FDA said the sponsor also
underreported problems experienced by patients--known as adverse
events--associated with the devices. FDA issued letters to the sponsor
asking it to resolve these concerns, yet the sponsor repeatedly provided
inadequate responses. This situation ultimately led FDA to file an
administrative complaint for civil monetary penalties against the sponsor,
which resulted in a decision from an administrative law judge in favor of
FDA on July 6, 2007. A separate decision is expected on the amount of the
penalties to be assessed, after which either side may appeal.

In commenting on a draft of this report, HHS provided clarification on the
postmarket requirements that apply to approved devices. In addition, it
updated information concerning the administrative complaint for civil
monetary penalties.

Background

Symptoms of temporomandibular joint and muscle disorders vary but
typically include pain of the jaw joint and surrounding muscles. Other
symptoms include limited or no movement of the jaw joint, clicking or
grating in the jaw joint when opening or closing the mouth, headaches, and
shoulder or back pain. According to the National Institutes of Health,
most patients' symptoms improve significantly or disappear within weeks or
months, while a smaller number of patients have significant long-term
symptoms. Trauma to the jaw or jaw joint can contribute to
temporomandibular joint and muscle disorders in some instances; however,
the causes of most cases of temporomandibular joint and muscle disorders
are unknown.

There are a range of treatments available for temporomandibular joint and
muscle disorders; some are conservative and temporary while others are
irreversible. Experts recommend that the most conservative treatment be
used to relieve symptoms before irreversible treatments are used.
Conservative treatments can include taking pain medications, using a
splint or bite guard, applying ice packs, or eating soft food.
Irreversible treatments include grinding down the teeth to change a
person's bite or surgical procedures such as replacing all or a portion of
the jaw joint with TMJ implants. Total TMJ implants replace both the upper
(articular fossa) and lower (condyle) portions of the jaw joint, whereas
partial TMJ implants replace only the upper portion. (See fig. 1.) TMJ
implants may improve the function of the jaw joint, however, pain, which
is a chief complaint of many who suffer from temporomandibular joint and
muscle disorders, is not always relieved.

Figure 1: Illustration of Temporomandibular Joint

Medical devices, including TMJ implants, are regulated by FDA, through its
Center for Devices and Radiological Health. TMJ implants are classified as
Class III devices. Class III devices include those that present a
significant risk of illness or injury to the patient.^6

Prior to the marketing of most Class III devices, FDA must approve a PMA
application.^7 The PMA review requires sufficient and valid scientific
evidence to assure that a medical device is safe and effective for its
intended use. In making this determination, FDA officials--including FDA
staff known as the review team^8 and two levels of FDA management--must
consider if there is reasonable assurance that the probable benefits to
health of the device outweigh any probable risks. They must also consider
whether the device is effective by evaluating data provided by the sponsor
for "clinically significant results."^9 The review team examines clinical
studies of the device involving human subjects, engineering testing
performed on the device, and other aspects of the PMA application such as
device labeling. It may also obtain input from one of its external
advisory boards--in the case of TMJ implants, its dental products
panel--for its evaluation and recommendation regarding approval. If the
review team has concerns about the PMA application it contacts the sponsor
for more information.^10 In some cases the review team may determine that
it needs significant additional information to complete the scientific
review, in which case it issues a deficiency letter to the device sponsor
indicating the information that is needed. The sponsor can respond by
submitting an amendment to the original application. The review team can
continue to issue deficiency letters and receive amendments from sponsors
until it determines that it has the information needed to make a
recommendation regarding approval.

^6While TMJ implants designed to treat temporomandibular joint and muscle
disorders are classified as Class III devices, those that are used for a
temporary period, such as to treat cancer patients with bone plate
restructuring, are classified as Class II devices. Such devices present
less risk than Class III devices. Class II TMJ implants have an intended
use of 1 year or less. This review only includes the four Class III TMJ
implants approved since December 30, 1998.

^7Submission of a PMA application is required for Class III devices unless
the device was on the market prior to the enactment of the Medical Device
Amendments of 1976 (Pub. L. No. 94-295) and FDA has not published a
regulation requiring PMA submissions for the device. FDA issued
regulations on December 30, 1998, requiring sponsors of all Class III TMJ
implants to submit a PMA application for approval.

Once the PMA review is complete, the review team makes a recommendation
regarding approval. This recommendation is subject to review by the two
levels of FDA management. Along with the recommendation, information
provided by the sponsor and the review team's assessment of the PMA
application, including the individual reviews, such as engineering,
clinical, and statistical reviews, and a team leader summary, are
forwarded. The review team sends this package to the first level of
management. If this level of management agrees with the review team's
recommendation, the review package is sent to the second level for final
review.^11 The second level of management may concur or override the
decision made at the previous management level. Management can make a
recommendation regarding approval even if some concerns regarding the PMA
remain unaddressed; however, a device can only be approved for marketing
if FDA concludes that its benefits outweigh its risks. If a member of the
review team or the first level of FDA management disagrees with the final
decision, an internal "respectful disagreement memo" can be written
indicating the reason for the disagreement.^12

^8Each review team includes an engineer, statistician, and clinician who
assess the PMA application.

^9FDA regulations do not define "clinically significant results." See 21
C.F.R. S 860.7(e)(1). However, an FDA official stated such results
indicate that use of the device would have a positive effect on the
disease being treated according to the standards of care for the related
field.

^10For example, the review team may resolve application issues through
meetings, phone calls, letters, or e-mails with the sponsor.

FDA decisions regarding approval of devices can take four forms: (1)
issuing an order approving the application, which allows the sponsor to
begin marketing the device; (2) sending the sponsor an "approvable" letter
indicating that the sponsor needs to provide more information; (3) issuing
a "not approvable" letter informing the sponsor of the application's
weaknesses; or (4) issuing an order denying approval of the application.

Once a device has been approved, the sponsor must comply with postmarket
regulations and restrictions that apply to the device. FDA may also impose
postmarket approval or condition of approval requirements that apply
specifically to the device that is the subject of the PMA. Conditions of
approval can include requirements such as the continuation of a clinical
study to collect additional data. Some conditions of approval do not
expire, such as reporting adverse events and submitting annual reports,
including a summary of all changes to the device.^13 Others are
time-limited, such as continuing a clinical study for a specified number
of years after the approval of a device.

^11If the first level of management disagrees with the review team's
recommendation regarding approval, the manager prepares a different
recommendation and includes it in the review package that is forwarded to
the second level of management, which makes the final decision regarding
approval.

^12An FDA official told us that it is not uncommon for officials to write
respectful disagreement memos when they feel strongly about their
divergent views. He explained that this type of disagreement is an
indicator of a healthy review process, in which officials are encouraged
to think independently and thoroughly examine all aspects of a new device
to help ensure its safety and effectiveness.

^13The regulations require these reports to be filed at intervals
specified by FDA, and FDA has required reports annually. See 21 C.F.R. S
814.82 (a)(7) (2006).

FDA Raised Concerns on All Implants and Addressed Many by Obtaining Additional
Information and Establishing Conditions of Approval

In their review of the four PMA applications, FDA officials raised
concerns that were similar for all four devices. FDA addressed many
concerns raised in the approval process by obtaining additional
information from sponsors to clarify and supplement data contained in
their PMA applications. It also approved all four devices but required
sponsors to comply with conditions of approval. However, some concerns
were left unaddressed upon approval. In addition, the FDA review team and
two levels of FDA management did not agree on the assessment of the safety
and effectiveness of the two TMJ Implants, Inc., devices. Ultimately,
according to FDA management, the primary justification for approving these
devices was that the potential benefit to the patients outweighed the
concerns raised and there did not appear to be a prohibitory risk
associated with the devices.

FDA Raised Concerns That Generally Applied to All Four TMJ Implants

We grouped the concerns FDA raised during the PMA process into four main
categories: study protocol, patient follow-up, engineering testing, and
other concerns. These categories and types of concerns are shown in table
1.

Table 1: GAO Categorization of Concerns Raised by FDA during the PMA
Process for TMJ Implants

Categories of concerns Types of concerns included in categories            
Study protocol            o Inadequate or inaccurate clinical study        
                             results, including:                              
                                                                              
                                     o Inaccurate measurement of data (e.g.,  
                                     problems with procedures used to measure 
                                     pain over time)^a                        
                                     o Data not separated appropriately       
                                     (e.g., results from different implants   
                                     analyzed together)^a                     
                                     o Questionable conduct by sponsor (e.g., 
                                     underreporting of adverse events)^a      
                                     o Incomplete or insufficient data to     
                                     draw conclusions^a                       
                                     o Lack of long-term data collection^a    
                                     o Unsupported or poorly defined          
                                     indications for use^a                    
                                                                              
                             o Lack of patient history data, including:       
                                                                              
                                     o Patients' clinical diagnosis unknown   
                                     (e.g., rheumatoid arthritis, cancer)^a   
                                     o Patients' treatment history unknown    
                                     (e.g., first implant, multiple implants) 
                                                                              
                             o Original sample size of study too small        
Patient follow-up^b       o Lack of patient follow-up, including:          
                                                                              
                                     o Long-term data lacking due to poor     
                                     follow-up^a                              
                                     o Number of patients in study too small  
                                     due to poor follow-up^a                  
Engineering testing       o Inadequate wear testing, including:            
                                                                              
                                     o Analysis of wear debris from implant   
                                     lacking^a                                
                                     o No examination for wear of implants    
                                     removed from patients^a                  
                                     o No analysis of wear on natural         
                                     condyle^a,c                              
                                                                              
                             o Inadequate fatigue testing^a,d                 
                             o Other engineering testing inadequate^a         
Other                     o Inadequate device labeling^a                   
                             o Unaddressed microbiology,^e packaging, and     
                             shelf-life issues                                
                             o Incomplete sponsor manufacturing inspections   

Source: GAO analysis of FDA documents.

Notes: This table applies to the four TMJ implants approved since December
30, 1998.

aThese concerns were also raised by the dental products panel in its
review of the PMA applications for the four implants.

bPatient follow-up refers to the number of patients who remain in a study
over time.

cThe TMJ Concepts, TMJ Implants, Inc., total implant, and Walter Lorenz
implants replace both the articular fossa (the upper portion of the
temporomandibular joint) and the condyle (the lower portion). The TMJ
Implants, Inc., partial implant only replaces the articular fossa,
therefore there were concerns related to its effects on a patient's
natural condyle.

dFatigue testing refers to the amount of weight an implant can bear
without breaking. Tests are conducted to ensure that the implant can
withstand the weight that a functioning jaw joint would encounter during
activities such as talking and chewing.

eMicrobiology issues relate to the sponsors' processes to ensure the
devices are sterile when shipped to the device user.

From FDA's review of the PMA applications, we observed similar concerns
across most PMA applications. For example:

           o All four PMA applications had incomplete or insufficient data to
           draw conclusions from the clinical studies. For example, FDA
           officials were concerned that because the Walter Lorenz clinical
           study was primarily conducted at one site, the physician at this
           site might have more expertise in implanting the device than a
           typical physician, potentially biasing the results. Officials were
           uncertain if equally favorable results would be obtained at other
           sites when the implant procedure was performed by less-experienced
           physicians.

           o All four PMA applications had deficient patient follow-up
           information, which prevented a satisfactory evaluation of the
           study results, such as improvement in patient symptoms and
           survivability of the implant.^14

           o In three of the four PMA applications, concerns were raised
           about the lack of information specifying the clinical diagnosis of
           the patients included in their clinical studies. This made it
           difficult for the review team to interpret the types of clinical
           conditions for which the devices are appropriate.

           o In three of the four PMA applications, concerns existed
           regarding inaccurate measurement of data. For example, neither TMJ
           Concepts's nor TMJ Implants, Inc.'s, total implant clinical data
           followed the same cohort of patients over time. This made it
           difficult for the review team to determine whether the device
           produced improvements in patients. The clinical data for TMJ
           Implants, Inc.'s, partial implant were compromised because
           medications used by patients were not documented in the study. Any
           use of medications could have affected patient outcomes.
			  
			  o In three of the four PMA applications, the review team indicated
           that additional implant wear and fatigue testing needed to be
           conducted. For example, the team wanted TMJ Implants, Inc., (total
           implant) to conduct wear debris analysis. This analysis could help
           determine if material wears off the implant over time, which could
           be absorbed into the patient's body.

^14Survivability of the implant refers to the implant's ability to
function in the jaw as originally intended over time.

           FDA Obtained Additional Information from Sponsors and Required
			  Conditions of Approval to Address Most, but Not All, Concerns

           FDA addressed the concerns it raised in its review of the PMA
           applications in two ways: (1) by communicating with sponsors and
           collecting additional information from them and (2) by approving
           the devices with conditions. FDA addressed many of its concerns by
           clarifying and collecting information for sponsors' PMA
           applications, before approving the devices. For example, FDA
           officials met with representatives of TMJ Concepts and TMJ
           Implants, Inc., (partial implant) to discuss concerns, such as
           unsupported indications for use of the device and inconsistent
           patient follow-up in the clinical studies. In addition, in many
           instances throughout the review process, FDA officials wrote the
           sponsors--highlighting problems with the applications--and
           reviewed their written responses. For example, FDA sent e-mails to
           Walter Lorenz regarding concerns related to the microbiology,
           packaging, and shelf life of its device. Walter Lorenz replied to
           FDA's questions and requests for information and these concerns
           were addressed. Correspondence between FDA officials and sponsors
           often continued for at least 3 months and in most cases longer
           until concerns were addressed.

           The second manner in which FDA addressed concerns was by approving
           the four TMJ implants with certain conditions. A condition of
           approval common to all four TMJ implants included the requirement
           that a postmarket study be conducted, which would collect patient
           data for at least 3 years. This condition of approval addressed
           FDA's concerns regarding study protocol and patient follow-up.
           Other conditions of approval addressed concerns related to a lack
           of patient history data and inadequate wear testing, among others.
           TMJ Concepts and TMJ Implants, Inc., (total implant) were required
           to include patient history data in their postmarket studies.
           Further, TMJ Concepts and TMJ Implants, Inc., (partial implant)
           were required to conduct wear analysis in order to address
           concerns related to inadequate wear testing.

           While FDA addressed the majority of concerns for each implant, we
           identified some concerns that remained unaddressed--concerns that
           were not offset or countered by a condition of approval or by FDA
           correspondence with the sponsor--upon approval. FDA officials
           examined these unaddressed concerns during the PMA process.
           However, they determined that the probable benefits of the devices
           outweighed the probable risks and therefore approved them. The
           unaddressed concerns for the devices were as follows and are
           expanded upon in appendix I:

           o TMJ Concepts: The unaddressed concerns related to inadequate and
           inaccurate study results. For example, FDA officials indicated
           that data for implants on the right and left sides of the jaw
           should have been analyzed separately, but the data collected did
           not allow for this type of analysis.

           o TMJ Implants, Inc. (total implant): The unaddressed concerns
           related to the category of other concerns--unaddressed
           microbiology, packaging, and shelf-life issues. For example, there
           was a concern regarding the procedures used for implants that will
           be shipped multiple times, which could occur if a physician
           shipped an unused implant back to the sponsor.

           o TMJ Implants, Inc. (partial implant): The majority of the
           unaddressed concerns related to inadequate and inaccurate study
           results and lack of patient history data. For example, there were
           concerns that the indications for use the sponsor cited in the
           device labeling were not supported by the clinical study. In
           addition, information about patients' treatment history was not
           included in the study, so it was unknown whether patients tried
           more conservative treatments before receiving the device. The
           remaining unaddressed concerns related to other
           topics--unaddressed microbiology, packaging, and shelf-life issues
           and outstanding manufacturing inspection matters.

           o Walter Lorenz: The unaddressed concern related to lack of
           patient history data, specifically that the sponsor generalized
           the clinical study results to all patients, even though patients
           in the study had varying clinical histories.
			  
			  Concerns Raised about Two Implants Resulted in Differing Opinions
			  among FDA Officials Regarding Approval

           Although FDA's review team and FDA management agreed that the TMJ
           Concepts and Walter Lorenz implants should be approved with
           conditions, there was disagreement among the review team and the
           two levels of management related to the approval of both TMJ
           Implants, Inc., devices. The review team recommended that the TMJ
           Implants, Inc., (total implant) application be considered not
           approvable. The team had concerns because it felt that the
           enrollment in the sponsor's clinical study was too small to draw
           significant conclusions related to the safety and effectiveness of
           the device. In addition, the review team believed the indications
           for use of the device were unsupported. However, the first level
           of FDA management recommended that the device be approved because
           it has a role in the treatment of TMJ and muscle disorders. The
           second level of management agreed with this recommendation. In its
           approval decision, FDA management acknowledged that there were
           concerns about the quality and quantity of clinical data provided
           by the sponsor. However, it stated that either good engineering
           data or good clinical data was acceptable to approve a device--not
           necessarily both--and that it deemed the engineering data for the
           TMJ Implants, Inc., total implant to be satisfactory. Further, FDA
           management indicated that the clinical data were not expected to
           be of high quality because the sponsor was a small manufacturer,
           the data available at the time of approval did not indicate an
           extraordinary problem with the implanted devices, and the data
           provided appeared consistent and favorable. The total implant was
           approved with conditions to address the FDA review team's concerns
           mentioned above.

           There was also conflict regarding the decision to approve the TMJ
           Implants, Inc., (partial implant) application. Although the second
           level of management ultimately approved the device for marketing
           with conditions, both the FDA review team and first level of
           management found that there was insufficient data to assure that
           the device was safe and effective. The review team recommended
           that the device be considered not approvable. The first level of
           management agreed with this recommendation for the following
           reasons:

           o The data were limited due to lack of patient follow-up. For
           example, the group of patients with 2-year and 3-year follow-up
           data in the sponsor's clinical study was too small to draw
           significant conclusions about the device. Of approximately 100
           patients with implants, only 29 completed the 24-month follow-up.
           Only 11 patients completed the intended 36-month follow-up.

           o Outstanding concerns existed related to (1) questionable conduct
           by the sponsor in classifying and reporting adverse events, (2)
           lack of engineering testing to determine the long-term effect of
           the partial TMJ implant on the natural condyle, (3) unsupported
           indications for use of the device, and (4) lack of data on
           patients' clinical and treatment history.

           While the second level of management recognized and agreed with
           the scientific concerns that had been raised, the sponsor was sent
           an approvable letter requiring minor application changes, such as
           revised device labeling, and the device was eventually approved.
           An internal memo outlining the second level of management's
           approval decision stated that there was a compelling argument in
           favor of approving the device. It argued that there appeared to be
           a small group of patients, although poorly defined, for whom the
           device seemed to provide an option for relief of chronic pain. In
           addition, it noted that there did not appear to be a prohibitory
           risk associated with the device in patients who are appropriately
           educated about all treatment alternatives, their disorder, and the
           device, and this information is provided in the implant's
           labeling. However, the approval memo also stated that the decision
           to approve the partial implant did not imply that the previous
           concerns raised by the review team and first level of management
           related to the inadequacy of the data were reversed. Of these
           concerns raised, those related to engineering testing on the
           device's effect on the natural condyle were addressed through
           conditions of approval; the others remained unaddressed.

           Upon the approval of the partial implant, two individuals--a
           member of the review team and an official from the first level of
           FDA management--wrote "respectful disagreement memos." Their memos
           indicated that they did not agree with the second level of
           management's decision to approve the TMJ implants, Inc., (partial
           implant) application for marketing. These memos outlined concerns
           raised during the PMA process related to the safety and
           effectiveness of the device. The concerns highlighted in these
           memos were that (1) lack of patient follow-up in the clinical
           study potentially biased the results, and consequently, the
           sponsor's claim that the implant resulted in decreased patient
           pain was unsupported, (2) the clinical study protocol lacked
           scientific rigor, and (3) outstanding questions remained related
           to the indications for using the device. In addition, a member of
           the review team told us that the conditions of approval did not
           mitigate the concerns she highlighted in her respectful
           disagreement memo.
			  
			  FDA Monitored Compliance through Review of the Sponsors' Annual
			  Reports It Received and Required Some Sponsors to Take Additional
			  Action

           In order to evaluate how the sponsors complied with the conditions
           of approval, FDA received and reviewed the majority of the
           required annual reports from TMJ implant sponsors. However, the
           review team had not received most of the required annual reports
           from one sponsor. Of the annual reports the review team evaluated,
           some of them were incomplete and FDA required sponsors to take
           additional actions to ensure compliance with conditions of
           approval. In addition, the FDA review team had concerns about one
           sponsor's--TMJ Implants, Inc.--annual reports. FDA found that
           these reports lacked sufficient information that prevented them
           from monitoring safety and effectiveness. This eventually led FDA
           to investigate the sponsor, resulting in the subsequent filing of
           an administrative complaint for civil monetary penalties for the
           company's failure to file certain adverse event reports with FDA.
			  
			  FDA Reviewed the Annual Reports It Received, but Some Were Missing

           FDA received and reviewed all required annual reports for TMJ
           Implants, Inc., total and partial implants between 2002 and 2006
           and the Walter Lorenz implant in 2006. However, the review team
           was missing five of seven required annual reports between 2000 and
           2006 from TMJ Concepts. It was not until we requested to review
           these reports that FDA contacted the sponsor to obtain the missing
           information. In addition, FDA officials told us that they are
           developing an improved postmarket surveillance effort to assist
           sponsors with annual report submission. As part of this effort,
           FDA recently issued draft guidance on October 26, 2006, which
           outlines FDA's recommendations for submitting annual reports.^15

           Though many annual reports were missing from TMJ Concepts, FDA was
           able to review the two annual reports submitted by the sponsor in
           2000 and 2004. For both reports, TMJ Concepts included information
           related to a number of conditions of approval, such as providing
           data on its postmarket study and including a patient quality of
           life question in that study. In 2000, the sponsor did not comply
           with the condition of approval to separate data by patients'
           clinical histories, but did complete this in its 2004 annual
           report. Therefore, in 2004, TMJ Concepts addressed all conditions
           of approval except one--submitting annual reports each year.
           Although all conditions of approval were not met and FDA was not
           able to review 5 years of annual reports, FDA found that the 2000
           and 2004 annual reports provided adequate data and no additional
           information was required of the sponsor for those two reports.
			  
			  FDA Required Some Sponsors to Take Additional Actions to Comply
			  with Their Conditions of Approval

           FDA evaluated information contained in the 13 annual reports it
           received and found that 7 reports--6 from TMJ Implants, Inc., (3
           for the total joint implant and 3 for the partial joint implant)
           and 1 from Walter Lorenz--did not provide sufficient information
           to assess their compliance with conditions of approval.^16 For 1
           of the 7 annual reports, FDA directed TMJ Implants, Inc., to
           submit new information about changes to the approved labeling and
           to the manufacturing processes for its total implant. FDA sent
           deficiency letters to the sponsors regarding the other 6 annual
           reports. These deficiency letters required the sponsors to address
           questions regarding the lack of certain data that relate to the
           safety and effectiveness of the devices, including patient
           history, patient follow-up, and adverse events. For example, in
           its 2006 annual report, Walter Lorenz was required to submit data
           on its postmarket clinical study. During the review of these data,
           the FDA review team identified concerns about data that were
           included in the report and sent a deficiency letter to the sponsor
           to resolve this issue. FDA officials discussed the deficiency
           letter with the sponsor and are waiting for a response.

^15The draft guidance, which was available for public comment for 90 days
after issuance, advises sponsors on how to best organize data and present
the required information and what to expect from FDA in response to its
annual report submission. This includes a new response format to
standardize the review process and indicates that annual reports be
reviewed by FDA within 90 days of receipt.

^16FDA received a total of 13 annual reports from the four TMJ implant
sponsors: 2 annual reports from TMJ Concepts, 5 annual reports from TMJ
Implants, Inc., for the total implant, 5 annual reports from TMJ Implants,
Inc., for the partial implant, and 1 from Walter Lorenz.

           FDA took further steps to obtain compliance from TMJ Implants,
           Inc., which had not responded adequately to FDA's 2002 deficiency
           letter requesting additional information, following receipt of the
           sponsor's annual reports for its total and partial TMJ
           implants.^17 Specifically, in 2002 FDA indicated that TMJ
           Implants, Inc. had not followed up with the required number of
           patients during its postmarket study. Also, the sponsor was not
           submitting adverse events, which it described in its annual
           reports, to FDA's Manufacturer and User Facility Device Experience
           Database (MAUDE).^18 The sponsor reported that the reason for the
           implant removals was not specifically due to the failure of the
           implant and therefore concluded that they did not need to be
           reported as adverse events. However, after reviewing the 2003
           annual reports where there was still a lack of adverse event
           reporting, FDA issued a deficiency letter. This letter informed
           the sponsor that all removed implants should be reported to the
           MAUDE system. In addition, supplemental data were required to be
           submitted for the conditions of approval related to patient
           follow-up and adverse event reporting. After FDA's review of the
           sponsor's 2004 annual reports, the outstanding concerns from the
           2002 and 2003 reports remained. For example, issues regarding lack
           of patient follow-up were unresolved. At the time of the 2004
           annual reports, the sponsor submitted data for 75 out of a total
           of 183 patients for whom data should have been provided. The
           sponsor maintained that the events related to the removed devices
           were not caused by device failure or function and concluded that
           they did not require reporting to FDA. Subsequently, FDA took
           action on the 2004 annual reports by sending another deficiency
           letter to the sponsor. In addition, FDA required that the sponsor
           submit a complete account of all patients to clarify its analysis
           of patients who were lost to follow-up.
			  
^17TMJ Implants, Inc., submitted two annual reports each year after
approval; one for the total implant and one for the partial implant.

^18Manufacturers are required to submit reports to FDA, which are included
in its MAUDE database, whenever they receive information that reasonably
suggests that one of their marketed devices (1) may have caused or
contributed to a death or serious injury, or (2) has malfunctioned and
that a recurrence would be likely to cause or contribute to a death or
serious injury. Medical device user facilities and distributors also have
responsibilities to report certain adverse events associated with medical
devices or to maintain records of such events. In addition to these
reports, FDA's MAUDE system includes reports that are voluntarily
submitted by manufacturers, clinicians, and patients.

           According to FDA officials, the sponsor's response to these
           deficiency letters did not resolve the outstanding concerns. As a
           result, the review team raised the concerns with FDA's Office of
           Compliance and the sponsor was inspected from July 29 through
           August 11, 2003. During its inspection, FDA found that the
           sponsor's devices may have malfunctioned or caused or contributed
           to serious injuries. The inspection results also showed these
           adverse events had not been reported by the sponsor as required.
           In response to these findings, FDA issued a warning letter^19 on
           February 24, 2004, requiring the sponsor to submit written medical
           device reports for specific adverse events detailed in the letter
           within 15 working days of receipt.^20 When the sponsor did not
           adequately respond to the warning letter, FDA filed an
           administrative complaint on July 14, 2005, for civil monetary
           penalties, which resulted in a decision from an administrative law
           judge in favor of FDA on July 6, 2007. A separate decision is
           expected on the amount of the penalties to be assessed, after
           which either side may appeal. The FDA's Office of Regulatory
           Affairs instructed the review team not to pursue any deficiencies
           found in the sponsor's annual reports until the matter is
           resolved. Therefore, the review team has reviewed TMJ Implants,
           Inc.'s, 2005 and 2006 annual reports, but decisions on the
           sponsor's compliance with the conditions of approval are pending.
			  
^19FDA may issue a warning letter to a sponsor if it believes that one or
more of its products or practices violates the Federal Food, Drug, and
Cosmetic Act, its implementing regulations, or other federal statutes. It
is one of the principal methods used by FDA to achieve voluntary
compliance with the applicable laws and regulations.

^20TMJ Implants, Inc., did not submit adverse event reports to the MAUDE
database within 15 days of receiving the warning letter from FDA. However,
from June 24, 2004, through March 27, 2007, 52 adverse events related to
TMJ Implants, Inc., devices have been reported into the MAUDE database. Of
those, 17 were reported by TMJ Implants, Inc., and all were determined by
the sponsor not to be related to the device itself but to surgical
complications, the surgeon, or other factors beyond the sponsor's control.

           Agency Comments

           In commenting on a draft of this report, HHS provided
           clarification on the postmarket requirements that apply to
           approved devices and updated information concerning the
           administrative complaint for civil monetary penalties. We revised
           our report to reflect these comments. It also provided technical
           comments, which we incorporated, as appropriate. HHS's comments
           appear in appendix II.

           As arranged with your offices, unless you publicly announce the
           contents of this report earlier, we plan no further distribution
           of it until 30 days after its issue date. At that time we will
           send copies of this report to the Secretary of HHS, the
           Commissioner of the FDA, relevant congressional committees, and
           other interested parties. We will also make copies available to
           others upon request. In addition, this report will be available at
           no charge on GAO's Web site at http://www.gao.gov.

           If you or your staffs have any questions concerning this report,
           please contact me at (202) 512-7114 or [email protected]. 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
           III.

           Marcia Crosse
			  Director, Health Care
			  
			  Appendix I: Concerns Left Unaddressed upon FDA Approval of TMJ
			  Implants

           While the Food and Drug Administration (FDA) addressed most
           concerns for each of the four temporomandibular joint (TMJ)
           implants we reviewed, we identified a number of concerns that were
           left unaddressed--concerns that were not offset or countered by a
           condition of approval or by FDA correspondence with the
           sponsor--upon approval. These unaddressed concerns fell into two
           of the four categories of concerns we identified previously: study
           protocol and other concerns. Table 2 lists the unaddressed
           concerns using the categories we established in table 1.

Table 2: GAO Categorization of Concerns Left Unaddressed by FDA during the
Premarket Approval Process for TMJ Implants

                                                          Types of concerns   
Concerns left unaddressed by FDA,       Categories of  included in         
sorted by sponsor                       concerns^a     categories^b        
TMJ Concepts                                                               
Data on the effectiveness and           Study protocol Inadequate or       
survivability of the implant over time                 inaccurate clinical 
are not reliable because of flawed                     study results       
analyses.                                                                  
Data on right and left side of the      Study protocol Inadequate or       
prostheses need to be analyzed                         inaccurate clinical 
separately; however, the sponsor did                   study results       
not provide data to allow for this                                         
analysis.                                                                  
TMJ Implants, Inc. (total implant)                                         
The data that demonstrate the           Other concerns Unaddressed         
performance of the implant will not                    microbiology,       
diminish as a result of shipping and                   packaging, and      
distribution are limited and                           shelf-life issues   
questionable. In addition, there are                                       
specific concerns regarding the                                            
procedures that will be used for                                           
implants that will be shipped multiple                                     
times.                                                                     
More information is needed related to   Other concerns Unaddressed         
shelf life and packaging of the                        microbiology,       
implant.                                               packaging, and      
                                                          shelf-life issues   
TMJ Implants, Inc. (partial implant)                                       
Data that indicate the performance of   Other concerns Incomplete sponsor  
the implant will not diminish as a                     manufacturing       
result of manufacturing processes must                 inspections         
be submitted.                                                              
The sponsor has not yet submitted data  Other concerns Unaddressed         
related to outstanding microbiology,                   microbiology,       
packaging, and shelf-life issues for                   packaging, and      
its total implant, which it must do                    shelf-life issues   
before approval of the partial implant.                                    
Clarification and definition of patient Study protocol Lack of patient     
inclusion criteria for the clinical                    history data        
study is needed to understand the                                          
clinical conditions of patients who                                        
received the implant.                                                      
The sponsor has not provided a summary  Study protocol Lack of patient     
of preoperative conditions of patients                 history data        
enrolled in the study.                                                     
The data do not indicate if patients    Study protocol Lack of patient     
enrolled in the clinical study have                    history data        
confounding conditions, which could                                        
affect results.                                                            
The sponsor did not provide information Study protocol Lack of patient     
on patients' past history, such as                     history data        
treatment history, to substantiate the                                     
use of an implant.                                                         
The sponsor did not provide specific    Study protocol Lack of patient     
information about the nature of other                  history data        
treatments used with patients in the                                       
study.                                                                     
The use of broad diagnostic terms, such Study protocol Inadequate or       
as internal derangement--displacement                  inaccurate clinical 
of the jaw joint--makes it impossible                  study results       
to adequately identify patients who are                                    
candidates for this surgical treatment.                                    
The sponsor needs to provide more       Study protocol Inadequate or       
clearly defined indications and support                inaccurate clinical 
for these indications.                                 study results       
The sponsor has not provided data on    Study protocol Inadequate or       
the adverse events associated with the                 inaccurate clinical 
device.                                                study results       
Walter Lorenz                                                              
The sponsor generalizes data for all    Study protocol Lack of patient     
study subjects when they have different                history data        
clinical history indicators.                                               

Source: GAO analysis of FDA documents.

Notes: This table applies to the four TMJ implants approved since December
30, 1998.

aWe categorized concerns raised during the PMA approval process into four
categories: study protocol, patient follow-up, engineering testing, and
other concerns.

bThis column provides detail on the type of concern within the category to
which the unaddressed concern relates. See table 1 for the four categories
and the types of concerns we placed within these categories.

Appendix II: Comments from the Department of Health and Human Services

Appendix III: GAO Contact and Staff Acknowledgments

GAO Contact

Marcia Crosse, (202) 512-7114 or [email protected]

Acknowledgments

In addition to the contact named above, Geraldine Redican-Bigott,
Assistant Director; Deirdre Brown; Cathy Hamann; Julian Klazkin; Michaela
M. Monaghan; and Sari B. Shuman made key contributions to this report.

(290572)

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[23]www.gao.gov/cgi-bin/getrpt?GAO-07-996 .

To view the full product, including the scope
and methodology, click on the link above.

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Highlights of [24]GAO-07-996 , a report to congressional requesters

September 2007

MEDICAL DEVICES

FDA's Approval of Four Temporomandibular Joint Implants

It is estimated that over 10 million people in the United States suffer
from jaw joint and muscle disorders. Artificial temporomandibular joint
(TMJ) implants have been used to replace the jaw joint in some patients in
an effort to decrease pain and increase jaw function. The safety and
effectiveness of these implants, like other medical devices, is overseen
by the Food and Drug Administration (FDA), an agency within the Department
of Health and Human Services (HHS). Two implants used in the 1970s and
1980s that were later removed from the market caused severe side effects
for some patients. In 1998, FDA began to require certain TMJ implant
manufacturers sponsoring these devices to demonstrate the implants' safety
and effectiveness before receiving approval. Since 1998, four TMJ implants
from three sponsors were approved.

In response to your request, GAO described (1) the types of concerns
raised by FDA and how it addressed these concerns for the implants
approved since 1998 and (2) how FDA has monitored sponsors' compliance
with conditions of approval. GAO examined documentation related to the
four TMJ implants approved by FDA since 1998 and sponsors' annual reports,
which FDA uses to monitor compliance with conditions of approval. GAO also
interviewed FDA officials, TMJ implant sponsors, and patient advocacy
groups.

FDA officials raised concerns during the approval process that were
similar for all four TMJ implants. These concerns generally involved the
adequacy of the sponsors' clinical study protocols, patient follow-up,
engineering testing, and other matters, such as device labeling. FDA
addressed many, but not all, concerns upon approval. Some concerns were
addressed by obtaining additional information from sponsors to clarify and
supplement data contained in their device applications before approval.
Other concerns were addressed when FDA approved the implants but required
sponsors to comply with certain conditions of approval, such as continuing
clinical studies postmarket and collecting patient data. Because FDA
staff, who review the device applications, and FDA management, who approve
the devices for marketing, held differing views as to whether the
implants' health benefits outweighed its risks, they did not agree on the
approval decisions of two of the four TMJ implants. FDA management
acknowledged that the concerns raised about the implants were legitimate.
However, they ultimately concluded that the benefits provided by these two
devices outweighed the concerns and approved both devices to help patients
obtain relief from chronic pain.

FDA monitored sponsors' compliance with conditions of approval by
evaluating information contained in their annual reports. FDA often
required additional actions by the sponsors to resolve questions that were
raised through its review of these reports. However, GAO found that not
all annual reports were received by FDA. At the time GAO conducted its
work, FDA had only received 13 of 18 required reports. One implant sponsor
did not submit 5 of 7 required annual reports. FDA has requested these
reports and has issued draft guidance on annual report submissions to all
medical device sponsors. In addition, when reviewing the available annual
reports to determine if sponsors were complying with conditions of
approval, many of the submitted reports did not provide FDA with
sufficient information to assess compliance. FDA required these TMJ
implant sponsors to provide additional information to address this lack of
sufficient information. In most instances, once FDA received additional
information from the sponsors, the annual reports were considered
adequate. However, one sponsor submitted several annual reports for both
of its devices that FDA said lacked sufficient information regarding
patient follow-up and also underreported problems experienced by patients
associated with the devices. FDA notified the sponsor that it must address
these concerns, but the sponsor repeatedly provided inadequate responses.
This situation ultimately led FDA to inspect the sponsor's records and
file an administrative complaint for civil monetary penalties against the
sponsor for failure to file certain reports with FDA. On July 6, 2007, an
administrative law judge ruled in favor of FDA.

In commenting on a draft of this report, HHS provided clarification on
postmarket requirements for approved devices and updated information on
the administrative complaint for civil monetary penalties.

References

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  21. mailto:[email protected]
  22. mailto:[email protected]
  23. http://www.gao.gov/cgi-bin/getrpt?GAO-07-996
  24. http://www.gao.gov/cgi-bin/getrpt?GAO-07-996
*** End of document. ***