SUMMARY OF SAFETY AND EFFECTIVENESS

I.  [General Information]{.underline}

#### Device Generic Name: Total temporomandibular joint implant 

## Device Trade Name: Total Temporomandibular Joint (TMJ) 

##  Replacement System 

Applicant's Name: Biomet , Inc.

56 East Bell Drive

P.O. Box 587

Warsaw, Indiana 46582 U.S.A.

Premarket Approval Application (PMA) Number:

Date of Panel Recommendation:

Date of Notice of Approval to the Applicant:

####### Indications for Use

The Total TMJ Replacement System is indicated for use in cases of:

1.  1\. arthritic conditions: e.g. osteoarthritis, rheumatoid arthritis,
    or traumatic

    arthritis,

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2.  malignancy (e.g. post-tumor excision),

3.  benign neoplasms,

4.  functional deformity,

5.  revision procedures where other treatments (e.g. alloplastic
    reconstruction, autogenous grafts) have failed,

6.  avascular necrosis,

7.  ankylosis including but not limited to recurrent ankylosis with
    excessive heterotopic bone formation,

8.  fracture,

9.  multiple operated joints, and

10. developmental abnormality

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II. **[Device Description]{.underline}**

# 

#  The Total Temporomandibular Joint (TMJ) Replacement System is implanted in 

#  the jaw to functionally reconstruct a diseased and/or damaged temporomandibular 

#  joint. The Total TMJ Replacement System is a two component system comprised 

#  of mandibular condyle and glenoid fossa components. Both components are 

#  available in multiple sizes as right and left side specific designs and are attached 

#  to bone by screws. The individual components are not for use in partial joint 

#  reconstruction. 

#  Materials:

#  Mandibular Component -- Cobalt-Chromium-Molydenum (Co-Cr-Mo) alloy per 

#  ASTM F 1537 with titanium alloy (Ti-6Al-4V per 

#  ASTM F 136) plasma spray porous coating 

#  Fossa Component -- ArCom® ultra-high-molecular-weight (UHMWPE) per 

#  ASTM F 648

#  Screws -- Titanium alloy (Ti-6Al-4V per ASTM F 136)

### [Contraindications]{.underline}

> 1\. Active or chronic infection.

3.  2\. Patient conditions where there is insufficient quantity or
    quality of bone to

    support the components.

    3\. Systemic disease with increased susceptibility to infection.

    4\. Patients with perforations in the mandibular fossa and/or bony
    deficiencies in

    the articular eminence or zygomatic arch comprising support for the
    artificial

    fossa component.

    5\. Partial TMJ joint reconstruction.

    6\. Known allergic reaction to any materials used in the components.

> NOTE: Patients with known or suspected nickel sensitivity should not
> have
>
> Co-Cr-Mo devices implanted since this material contains nickel.

11. 7\. Patients with mental or neurological conditions who are
    unwilling or unable to

    follow postoperative care instructions.

    8\. Skeletally immature patients.

    9\. Patients with severe hyper-functional habits (e.g. clenching,
    grinding etc.)

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III. **[Warnings]{.underline}**

The following risks are associated with the use of a total TMJ system.

1\. Implant loosening or displacement can occur.

15. 2\. The screws used to anchor the implant may loosen causing changes
    in bite,

    difficulty in chewing, limited joint function and/or unpredictable
    wear on

    implant components.

    3\. Implant breakdown may result in erosion or resorption of the
    glenoid fossa,

    which may result in intense pain.

    4\. A foreign body reaction may occur resulting in implant
    deterioration and

    migration of materials.

5\. If the implant is not properly sterilized, infection may result.

22. 6\. If the implant materials are unable to withstand the forces or
    pressure placed

    on the implant, the implant can be torn, worn, perforated,
    fragmented,

    fatigued, or fractured resulting in failure of the device to
    function properly.

    7\. Degenerative changes within the joint surfaces and components of
    the TMJ

    due to implant breakdown may result in chronic pain.

    8\. Degenerative changes in the joint cartilage and/or bone from
    disease or

    previous implants may lead to failure of this device.

    9\. If the implant materials are subject to the production of
    particles or corrosion,

    toxic elements may migrate to various parts of the body.

    10\. Placement of the implant in one joint only may result in
    harmful effects to the

    joint on the opposite side.

    11\. Placement of the implant may produce an improper relationship
    between the

    teeth surfaces that should contact during biting.

    12\. Implant breakdown may cause bony erosion, heterotopic bone
    formation, or

    reactive bone within the joint.

    13\. Use of implants may result in tinnitus or other ear problems.

    14\. Limited range of motion and chronic pain may continue after
    total TMJ

    surgery.

    15\. Infection can occur which may result in implant removal.

    16\. Damage to the facial and/or trigeminal nerve with temporary or
    permanent

    paralysis of the facial muscle and/or loss of feeling in the chin,
    teeth, tongue,

    or lower jaw may occur.

> The surgeon must be thoroughly knowledgeable with the components,
>
> instruments and surgical procedure. In all cases sound medical
> practice is to be

followed and the surgeon must select the type of device appropriate for
treatment.

Existing mandibular and/or zygomatic arch screw holes may compromise

fixation. The Total TMJ Replacement System is designed for total joint

reconstruction and components are to be used as a system. Do not use the

individual components for partial joint reconstruction.

The patient is to be warned that the system does not replace normal
healthy bone

in their TMJ and they may continue to have chronic pain and limited
range of

motion. The system can break or loosen as a result of stress, activity,
or trauma.

Patients with severe hyper-functional habits may have an undesirable
outcome.

The patient is to be made aware of surgical risks and possible adverse
effects prior

to surgery and warned that failure to follow postoperative care
instructions can

cause failure of the implant and the treatment.

####### Precautions

1.  DO NOT USE if there is loss of sterility of the devices.

2.  Discard and DO NOT USE opened or damaged implants and only use

> implants that are packaged in unopened or damaged containers.

3.  DO NOT USE the individual components of this total system (e.g.
    mandibular

components, fossa components, or screws) for partial joint
reconstruction.

4.  Infection can lead to failure and subsequent removal of the devices.

5.  Damage to the implant can occur as a result of traumatic injury or
    excessive activity.

6.  Neurovascular injuries can occur due to surgical trauma.

7.  Metal sensitivity or foreign body reaction can occur due to the
    device materials or materials from previously implanted devices.

8.  Implant breakdown and/or degenerative changes in the TMJ may cause
    pain, which may lead to re-operation.

9\. Use of the system with filler material:

The fossa component may be used with a filler material when it is
desired to

fill voids between the fossa prosthesis and the glenoid fossa bone. The
filler

should never be used for fixation of the device or in any load bearing

application. If a filler is used in the fossa region, screws are placed
after

polymerization of the filling material, if applicable. Use of any
legally

marketed craniomaxillofacial filler material is recommended.

IV. **[Alternative Practices and Procedures]{.underline}**

Alternative practices and procedures include autogenenous or allogeneic
bone

grafting, soft tissue grafts or implantation of other devices for
partial or total TMJ

reconstruction.

**VIII. [Potential Adverse Effects]{.underline}**

Adverse events can occur following placement of TMJ implants and
specific risks

are associated with this type of surgery. See the package insert for
adverse events

reported with the use of this system during an approved Food and Drug

Administration (FDA) clinical study. The occurrence of a complication
may be

related to or influenced by prior medical conditions or treatment and
may require

further treatment. These adverse events include but are not limited to
the

following:

• Infection

• Post-operative pain, swelling, bruising, jaw muscle spasm, or hematoma

formation

• Chronic or recurring pain

• Heterotopic bone formation, neuroma formation, adhesions, resorption
or bony

erosion, and/or ankylosis

• Facial nerve dysfunction

• Dislocation

• Removal of components(s) and/or revision

• Harmful effects to the contralateral joint in unilateral cases

• Implant wear, loosening, damage, migration or displacement

44. • Changes in bite, difficulty in chewing, limited joint function

    • A foreign body or allergic reaction to implant materials

• Ear problems

46. • Degenerative changes in the joint cartilage and/or bone

### IX. [Marketing History]{.underline}

#### [Approval for marketing has been granted by Europe (EC-Certificate issued November 23, 2000) and marketing efforts are just beginning. The system has been marketed in South Africa since January 2000.]{.mark} 

####### Summary of Preclinical Studies

> The following biomechanical tests were conducted on the Total TMJ
> Replacement System. Test results were all determined to be sufficient
> for the intended use of the construct/component.

A.  Fatique Testing of Fossa and Mandibular Component Construct

B.  Static Testing of the Mandibular Component

C.  Fatigue Testing of Bone Cement

D.  Fossa Screw Head Pull-Through Test

E.  Compression Strength of Fossa Component Flange

F.  2.7mm Self-Tapping Screw Pull-Out Strength

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A.  **[Fatique Testing of Fossa and Mandibular Component
    Construct]{.mark}**

> [Initial fatigue testing was performed on five joints with mandibular
> components minus the titanium plasma spray coating. No failures were
> seen after 10 million cycles at a maximum load of 145 lbs. at
> frequencies between 10 and 30 hertz. The same testing was repeated on
> four joints with mandibular components coated with titanium plasma
> spray. There were no failures after 10 million cycles and no porous
> coating delamination was observed as expected from previous testing on
> orthopedic devices.]{.mark}
>
> [**B.** **Static Strength Testing of the Mandibular
> Component**]{.mark}
>
> [A mandibular component was fixed to porcine bone using four 2.7mm
> diameter screws and a load was applied to ultimate failure. At 575.9
> lbs. the component's neck portion bent with neither fracture/pull-out
> of the bone screws or fracture of the component.]{.mark}

C.  **[Fatigue Testing of Bone Cement]{.mark}**

> [A total of five joints were tested with the fossa components secured
> to the test fixture using bone cement. The testing was conducted under
> cyclic compression with a maximum load of 145 lbs. at frequencies
> between 10 and 30 hertz for 10 million cycles. Following the 10
> million cycles fatigue test, no cement failure (e.g. cracking or
> chipping) was noted.]{.mark}

D.  **[Fossa Screw (2.0mm) Head Pull -Through Test]{.mark}**

> [Twelve specimens were tested to determine the force required to pull
> the fossa screw head through the UHMWPE zygomatic arch flange of the
> fossa component. A standard static tensile test was performed using a
> cross-head travel rate of 0.05″/minute and the ultimate tensile loads
> were recorded. The mean tensile strength was 79.8 ± 2.5 lbs. It was
> noted that clinical failure is highly unlikely because of the large
> shearing load and displacements required.]{.mark}

**[F. Compression Strength of Fossa Component Flange]{.mark}**

[A fossa component was tested to establish the load required to collapse
an]{.mark}

[unsupported fossa body and assure that failure in this fashion does not
cause]{.mark}

[tearing or cracking of the UHMWPE junction between the body and flange
of]{.mark}

[the fossa component. The fossa body collapsed against the flange at 83
lbs.]{.mark}

[without material failure at the body/flange junction.]{.mark}

[]{.mark}

[**G. 2.7mm Self-Tapping Screw Pull-Out Strength**]{.mark}

[Five 2.7mm screws used to fixate mandibular components were tested
for]{.mark}

[pull-out strength in fresh frozen bovine cortical bone. This substrate
was]{.mark}

[chosen to mimic the clinical application. The mean pull-out strength
was 373.2]{.mark}

[± 68.8 lbs.]{.mark}

####### Summary of the Clinical Studies

> A. [Objective]{.underline}
>
> The study was designed to obtain clinical data to support the safety
> and effectiveness of this device.
>
> B. [Inclusion / Exclusion Criteria]{.underline}

Inclusion Criteria:

1.  Patients requiring total joint reconstruction due to:

> arthritis (osteo-, rheumatoid, traumatic) malignancy
>
> ankylosis functional deformity
>
> avascular necrosis revisions
>
> benign neoplasms fracture
>
> multiple operated joints
>
> 2\. Patients who are skeletally mature.

3.  Patients must have at least one of the following criteria for
    surgical TMJ treatment.

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a.  presence of considerable pain and/or limited function in the joint
    area.

b.  clinical and imaging evidence consistent with anatomic joint

> pathology.

c.  previous failure of non-surgical treatment/therapy or a failed
    implant.

d.  high probability of patient improvement by surgical treatment.

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4.  Patients [must]{.underline} be able to return for follow-up
    examinations.

5.  Patients without serious compromising general medical conditions.

Exclusion Criteria:

1.  Patients with active infection.

2.  Patient conditions where there is insufficient quantity or quality
    of bone to support the device.

3.  Patients with perforations in the mandibular fossa and/or bony
    deficiencies in the articular eminence compromising support for the
    artificial fossa component.

4.  Patients with mandibular and/or zygomatic arch screw holes
    compromising component fixation.

5.  Patients requiring partial joint reconstruction or other TMJ
    procedures not listed as an indication.

6.  Patients who are NOT skeletally mature.

7.  Patients who are incapable or unwilling to follow postoperative care
    instructions.

8.  Patients who are unable to return for follow-up examinations.

9.  Patients with severe hyper-functional habits.

10. Patients on chronic steroid therapy.

> C. [Patient Population and Demographics]{.underline}
>
> A total of 180 cases (268 joints) with a mean patient age of 40 years
> (range 12-82 years) were enrolled into the study. There were 161
> females (89%) and 19 males (11%) comprised of 88 (49%) bilateral cases
> and 92 (51%) unilateral cases. Of the 92 unilateral cases, 46 (50%)
> are the right side and 46 (50%) are left sides only. Demographic data
> are summarized in **Table 1**. Most cases had multiple diagnoses with
> osteoarthritis and ankylosis being the most common. See **Table 2**
> for a complete listing of diagnoses.
>
> The mean duration of symptoms prior to implantation with this device
> was 11 years (range 0.1- 34 years) with the mean number of 5.2 (range
> 0-29) prior surgeries.
>
> Patients were categorized according to the Wilkes Classification.
> There were 2 (1%) cases in Class I, none in Class II, 4 (2%) in Class
> III, 68 (38%) cases in Class IV, and 106 (59%) cases in Class V.
>
> D. [Evaluation Schedule]{.underline}
>
> Patients were evaluated preoperatively and postoperatively at 1 month,
> 3
>
> months, 6 months, 1 year, 1.5 years, and 3 years. All data collected
> past the 3
>
> years follow-up are included. The assessments carried out at each
> visit
>
> labeled as Visit 1-Visit 11 are summarized in **Table 3**.
>
> E. [Study Design]{.underline}
>
> The study was a prospective, multi-center, non-randomized controlled
> study. It was designed to compare baseline clinical and radiographic
> assessments to assessments made postoperatively.
>
> F. [Patient Accountability]{.underline}
>
> **Table 4** shows the number and percentage of cases with follow-up
> data at each of the visits. Compliance ranged from 95.0 % at the 1
> month follow-up visit to 82.5 % at 3 years follow-up.
>
> G. [Efficacy and Safety Parameters]{.underline}

1.  Primary efficacy endpoints include:

> · [Jaw pain intensity]{.underline} as measured on a 10 cm visual
> analogue scale (VAS)

from preoperative assessment to assessment 3 years postoperative,

adjusted for baseline at preoperative assessment,

> · [Interference with eating]{.underline} as measured on a 10 cm VAS
> from preoperative
>
> assessment to assessment 3 years postoperative, adjusted for baseline
> at
>
> preoperative assessment,
>
> · [Maximal incisal opening (MIO]{.underline}) measurement (in mm) from
>
> preoperative assessment to assessment 3 years postoperative, adjusted
>
> for baseline at preoperative assessment

Analysis was performed on cases with 3 years follow-up postoperatively.

These cases were defined as two groups. One is the cohort unimputed

group comprised of 45 cases and the second group, cohort imputed, is

comprised of 59 cases. The cohort imputed group used data points
obtained

at the follow-up visit closest to but not after the 3 years visit for
analysis for

the 14 cases missing data at the 3 years visit. The primary endpoints
are

summarized on the following chart.

+----------------------+-----------------------+-----------------------+
| Primary Efficacy     | Cohort Imputed Cases  | Cohort Unimputed      |
|                      |                       | Cases                 |
| Endpoints            | n=59                  |                       |
|                      |                       | n=45                  |
+----------------------+-----------------------+-----------------------+
|                      | Difference between    | Difference between    |
|                      |                       |                       |
|                      | Vs 1 & Vs 8 ± SD      | Vs 1 & Vs 8 ± SD      |
+----------------------+-----------------------+-----------------------+
| Jaw pain             | 5.43 ± 2.73 cm        | 5.70 ± 2.40 cm        |
+----------------------+-----------------------+-----------------------+
| Interference with    | 5.59 ± 2.95 cm        | 5.80 ± 2.27 cm        |
| eating               |                       |                       |
+----------------------+-----------------------+-----------------------+
| MIO                  | 10.61 ± 8.44 mm       | 10.27 ± 8.33 mm       |
+----------------------+-----------------------+-----------------------+

These primary efficacy endpoints showed a significant improvement from

baseline to 3 years postoperative. Multiple analyses (t-test and
repeated

measures) demonstrate that significant improvement is evidenced after

implantation of the Total TMJ Replacement System, same patterned effect
for

the cohort imputed and unimputed groups.

Further t-test analysis shows that in both the total group (n **=** 180)
and the

cohort imputed group (n = 59), there was a statistical difference
(p\<.0001) in

all three primary endpoints between baseline (Vs 1) and assessments at
all

time points from 1 month follow-up to 3 years follow-up.

**Figures 1, 2, and 3** graphically display the three primary endpoints
for the

total study group and the two cohort groups from baseline to the 3 years
visit.

> 2\. Secondary efficacy endpoints include (at visits Vs 1, Vs 3 -- 8):
>
> · Jaw pain intensity, interference with eating, and maximal incisal
>
> opening
>
> · Patient satisfaction, with a focus on the comparison from
> postoperative
>
> baseline (Vs 5) to 3 years follow-up (Vs 8):

-   in hindsight, whether the patient would choose to have this

> surgery;

-   degree of satisfaction with surgery across time

> The secondary efficacy endpoints demonstrated a gradual improvement
>
> over time in terms of jaw pain, interference with eating, and MIO**.
> Table**
>
> **5** lists the means and standard deviation for the three endpoints
> at visits
>
> Vs 1 - Vs 11.

Most patients were satisfied with their outcome as demonstrated with

over 90 % of cases reporting at least satisfied or better at every
follow-up

visit. Furthermore, over 90 % of the cases in hindsight would choose to

have this surgery at all time points. More specifically for Vs 3 -- Vs
8,

between 94 --99 % of the cases said yes to the question " In hindsight

would you choose to have this surgery?"

47. 3\. Safety

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a.  Radiographic assessment (position of components, heterotopic bone
    formation, osseous erosion, fossa resorption)

The position of mandibular and fossa components and the mandibular

and fossa screws were assessed by investigators in comparison to

immediate postoperative radiographs. There were three mandibular

components reported as having a change in position: two at Vs 4 and

one at Vs 7. One of these cases noted at Vs 4 also had a change of

position of the mandibular screws and the joint was removed at 6

months postoperative. No change of position was reported for fossa

screws.

Heterotopic bone formation was found in 13 joints, 7 rights and 6 left

joints. There are no reports of osseous erosion or fossa resorption.

> b\. Adverse events

50. 

> Adverse Events (AEs) were documented for all cases throughout the
>
> duration of the study. There have been no unanticipated device related
>
> adverse events reported. Overall, 90 AEs were reported in 55 cases
>
> (30.6 %) of the 180 cases. Four cases (2.2 %) terminated the study due
>
> to their permanent total joint removal AEs. **Table 6** summarizes AEs
>
> requiring device removal. **Table** **7** summarizes AEs not requiring
>
> device removal.

4.  Patient and Study Success

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a.  Patient Success

A patient was determined to be a success if:

1\. patient has not had a permanent total joint removal, and

51. 2\. patient meets two of the following three criteria:

> • reduction of pain by 1 cm (VAS) from baseline to 3 years follow-up
>
> • reduction of interference with eating by 1 cm (VAS) from baseline
>
> to 3 years follow-up
>
> • increase in MIO of 10% from baseline to 3 years follow-up

b.  Study Success

> The study was deemed to be a success with 60% or more of the patients
> receiving the device having met the above Patient Success at 3 years
> follow-up.
>
> In the cohort unimputed group, 44 of 45 (97.8%) cases are patient
> successes. In the cohort imputed group, 57 of 59 (96.6%) cases are
> patient successes. These patient success rates surpass the criteria
> for study success.
>
> H. [Safety Analysis]{.underline}

######## [1. Deaths]{.mark} 

> [There have been three deaths reported in the study.]{.mark}

1.  [Case \# 7 died from complications from back surgery at five years
    TMJ postoperative.]{.mark}

2.  [Case \# 24 died approximately 3 years postoperative. Death
    was]{.mark}

> [secondary to a recurrent brain tumor.]{.mark}
>
> [3. Case \# 46 died 11 days postoperative due to hepatic coma.]{.mark}
>
> []{.mark}

########  [2. Revisions/Removals]{.mark}

########  

a.  [[Total joint removed]{.underline}]{.mark}

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1.  [Case \# 20]{.mark}

> [Bilateral patient first had the right fossa component removed (10
> months postoperative) due to infection. A year later the right
> mandibular component was removed also due to infection. The right side
> (case #103) was re-implanted 7 months later. Case \# 20 is now a left
> side only.]{.mark}

2.  [Case \# 61]{.mark}

> [Unilateral patient first had her fossa removed 10 months
> postoperative and subsequent mandibular removal 6 months later due to
> infection. This case is lost to follow-up.]{.mark}

3.  [Case \# 84 and \# 134]{.mark}

> [Bilateral patient had only the left prosthesis removed at 4 months
> postoperative due to infection. Case \# 84 is now a right side only. A
> second prosthesis (case \# 134) was implanted 7 months after the
> removal. An early infection occurred again and the device was removed
> approximately 9 months postoperative. Case #134 is lost to follow-up
> due to the permanent joint removal.]{.mark}

4.  [Case \# 100]{.mark}

> [Unilateral (right side) patient had removal of prosthesis at 6 months
> postoperative due to chronic swelling and pain. This case is lost to
> follow-up.]{.mark}

5.  [Case \# 145]{.mark}

[This bilateral patient had difficulties with chronic left TMJ]{.mark}

[dislocation immediately after implantation of the devices. At his
6]{.mark}

[month visit he had a fistula in his right ear canal. At 10
months]{.mark}

[postop the fistula (late infection) was still present along
with]{.mark}

[significant ankylosis and adhesions and both total joints were]{.mark}

[removed. This case is now lost to follow-up.]{.mark}

b.  [[Fossa component only revised/removed]{.underline}]{.mark}

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1.  [Case \# 1]{.mark}

> [Bilateral patient had removal of left fossa component due to aseptic
> necrosis at almost 2 years postoperative and 3.5 years after the
> removal had it replaced.]{.mark}

2.  [Case \# 13]{.mark}

> [Fossa component was removed secondary to infection in the ear canal
> at 2.5 years postoperative and was replaced a month later.]{.mark}

3.  [Case \# 19]{.mark}

> [Fossa component removed 4 years postoperative due to a late infection
> of the ear.]{.mark}

4.  [Case \# 117]{.mark}

> [At 11 months postoperative the fossa was removed to see if this would
> decrease swelling. There were no signs of infection but]{.mark} [heavy
> encapsulation was noted.]{.mark}

[c. [Mandibular component only revised]{.underline}]{.mark}

1.  [Case \# 183]{.mark}

> [This bilateral case was treated for an anterior dislocation by
> removing the right 50mm mandibular component and replacing it with a
> 45mm component.]{.mark}
>
> 3\. Additional Safety Measurement

a.  Surgical Site (wound healing)

Most surgical wounds healed by 3 months postoperative with 99 %

> (right side) and 98 % (left side) healed. Redness and drainage
>
> accompanied with infection are documented as adverse events.

**XII. [Conclusions Drawn from Studies]{.underline}**

> The pre-clinical and clinical data provide reasonable assurance of the
> safety and effectiveness of the Total TMJ Replacement System for the
> stated indications.