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  MEMORANDUM               F O R T H E R E C O R D

                           
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**Date:** April 26, 2004

**From:** Biomedical Engineer

Orthopedic Devices Branch

Division of General, Restorative, and Neurological Devices

HHS/FDA/CDRH/ODE

**Subject:** Review Memo for Reclassification Petition for Mobile
Bearing Knees

**To:** The Record, Reclassification Petition for Mobile Bearing Knees

**Summary:**

This petition, sponsored by the Orthopedic Surgical Manufacturers
Association (OSMA), was officially filed on June 13, 2003. An amendment
to the petition, in response to the FDA deficiency letter of February
18, 2004, was dated March 31, 2004, and received April 1, 2004.

This petition seeks reclassification of mobile bearing knee prostheses
from post-amendment Class III Pre-Market Approval (PMA) status to Class
II Pre-Market Notification (510k) status. These mobile bearing knees are
currently Class III PMA devices. This petition breaks the mobile bearing
knee prostheses into two general groups: mobile bearing total knees and
mobile bearing unicompartmental knees.

Presented in this petition are:

-   A brief introduction to the petition (see Section I).

-   General device information and proposed intended use (see Section
    II).

-   Proposed device descriptions for the Code of Federal Regulations
    (CFR) (see Section III).

-   The regulatory history of the devices considered for
    reclassification (see Section IV).

-   Basis for the petition (see Section V).

-   A summary of test results on wear, kinematics, and biomechanics from
    more than 45 articles published in peer-reviewed journals (see Sec.
    VI).

-   A summary of unpublished clinical data from seven on-going
    investigational device exemption (IDE) clinical studies and two
    large international clinical outcomes studies (see Section VII).

-   A summary of published clinical data from more than 50 articles
    published in peer-reviewed journals, together with a meta-analysis
    comparing clinical outcomes for different mobile bearing knees, and
    a meta-analysis comparing survivorship of mobile bearing knees
    versus fixed bearing knees (see Section VIII).

-   A listing of adverse events reported through the FDA's Medical
    Device Reporting (MDR) system (see Section IX).

-   A risk analysis, and suggested special controls to address the
    identified risks, such as labeling, preclinical tests and test
    methods (see Section X).

-   A list of mobile bearing knees currently or previously on the
    market, including 46 devices that are available internationally,
    five of which are also available in the U.S. (see Section XI).

-   Letters in support of the reclassification petition from orthopedic
    surgeons (see Appendix 1).

-   A summary of published literature from more than 40 articles
    published in peer-reviewed journals on the subject of 'wear in total
    knee arthroplasty' (see Appendix 1a of Amendment 1, Response to FDA
    letter of 2/18/04).

-   A description of the many different types of mobile bearing knee
    designs, their characteristics, biomechanical
    advantages/disadvantages, survival rates, risks, and proposed
    controls (for the identified risks) for each of the different device
    designs (see Appendix 1c, Amendment 1, Response to FDA letter of
    2/18/04).

-   A summary comparing the clinical results for various mobile bearing
    knee device designs with fixed bearing devices (see Appendix 1d,
    Amendment 1, Response to FDA letter of 2/18/04).

**Intended Use:**

It is believed by FDA that patient indications for each device type
(total knee and unicompartmental knee) are sufficiently different to
warrant separation of the two devices.

[Mobile Bearing Total Knee]{.underline}

The mobile bearing total knee is a device intended to be implanted to
replace a knee joint. The device is indicated for:

-   Patients with knee pain and disability due to rheumatoid arthritis,
    osteoarthritis, traumatic arthritis, polyarthritis, collagen
    disorders and/or avascular necrosis of the femoral condyle

-   Post-traumatic loss of joint configuration (particularly when there
    is patellofemoral erosion, dysfunction, or prior patellectomy)

-   Moderate valgus, varus, or flexion deformities

-   The salvage of previously failed surgical attempts if the knee can
    be satisfactorily balanced and stabilized at the time of surgery.

The device may be used with or without bone cement.

No further device design specific indications were provided for the
various types of mobile bearing total knees.

[Mobile Bearing Unicompartmental Knee]{.underline}

The mobile bearing unicompartmental knee is a device intended to be
implanted to replace part (one compartment) of a knee joint. The device
is indicated for:

-   Patients with knee pain and disability due to osteoarthritis or
    traumatic arthritis

-   Previous tibial condyle or plateau fractures with loss of anatomy or
    function

-   Varus or valgus deformities

-   Use with an intact anterior cruciate ligament (ACL)

-   Revision of previous unicompartmental arthroplasty procedures

The device may be used with or without bone cement.

**Device Description/Principle of Operation:**

The sponsor has proposed the following classification description for
mobile bearing total knees and mobile bearing unicompartmental knees:

[Mobile Bearing Total Knee]{.underline}

'Knee joint patellofemorotibial metal/polymer mobile bearing cemented or
porous coated uncemented prosthesis'.

A knee joint patellofemorotibial metal/polymer mobile bearing cemented
or porous coated uncemented prosthesis is a device intended to be
implanted to replace a knee joint. The device permits either
unconstrained or constrained rotation of the articular surface in the
transverse plane and may or may not permit limited anteroposterior
and/or mediolateral movement of the articular surface upon the tibial
component. It has not linkage across the joint. The device may use
affixed structural porous metal in place of the porous coating. This
generic type of device is designed for use with bone cement and/or to
achieve biological fixation to bone without the use of bone cement.

[Mobile Bearing Unicompartmental Knee]{.underline}

'Knee joint femorotibial (unicompartmental) metal/polymer mobile bearing
cemented or porous coated uncemented prosthesis'.

A knee joint femorotibial (unicompartmental) metal/polymer mobile
bearing cemented or porous coated uncemented prosthesis is a device
intended to be implanted to replace part of a knee joint. The device
permits either unconstrained or constrained rotation of the articular
surface in the transverse plane and may or may not permit limited
anteroposterior and/or mediolateral movement of the articular surface
upon the tibial component. It has not linkage across the joint. The
device may use affixed structural porous metal in place of the porous
coating. This generic type of device is designed for use with bone
cement and/or to achieve biological fixation to bone without the use of
bone cement.

**Risk to Health /Special Controls**

The sponsor performed a search of the MDR reporting information on FDA's
MAUDE website database which yielded 385 reports. The dates searched
ranged from November 15, 1993 to December 31, 2002. All hits were from
the DePuy LCS Mobile Bearing Knee System, the only approved mobile
bearing knee system on the market in the U.S. during this time. The 385
reports contained 365 adverse events, of which 333 were reported as
injuries, 29 as malfunctions, 2 were other/no answer, and 1 report was
submitted as a death. The event descriptions are included in Section IX.
The greatest number of adverse events were reported for pain (with
effusion, hemarthrosis, or swelling), fractured bearings, and loosening,
respectively.

The risks to health presented in this petition have been grouped into
three general categories: infection, adverse tissue reaction, and loss
or reduction of joint function/revision (see Section X). These risks are
evaluated in two tables using a common engineering tool, a Failure Modes
and Effects Analysis (FMEA). Table 5 (in Section X) contains the hazards
common to both fixed and mobile bearing knees, while Table 6 contains
hazards deemed specific to mobile bearing knees, exclusively. Each
hazard (risk) is identified along with ways they can be controlled to
reduce the potential risk to the patient. Finally, special controls are
identified for each of the hazards. Many of the common risks can be
mitigated by material standards, proper device design, labeling, Good
Manufacturing Practices (GMP) and Quality System Regulations (QSR). As
noted in Table 5, most risks identified are common to both fixed and
mobile bearing knees. Only two hazards were identified as unique to
mobile bearing knees, and they are related to 'loss of reduction of
joint function/revision'. Specifically, the potential for the mobile
bearing to rotate beyond design objectives and the potential for greater
wear due to additional articulating surfaces were the hazards cited as
uniquely related to the design of mobile bearing knees.

The sponsor believes that risks associated with mobile bearing knees are
known, and can be mitigated to acceptable levels with the general and
special controls available to the FDA for other class II knee devices
(e.g., FDA guidance documents, ASTM/ISO standards, labeling
restrictions - indications/contraindications/warnings, etc.) to provide
reasonable assurance of safety and efficacy. In addition, suggested
tests and test methods for mobile bearing knees are provided. In the
original submission none of the suggested testing differed from what is
currently required by FDA for evaluating fixed bearing knee devices.

However, as noted in the tables in appendix 1c of the March 31, 2004,
amendment, there are numerous 'sub-categories' of the two types of
mobile bearing knees identified above. These include devices with
multidirectional platforms, rotating platforms, meniscal bearings,
tricompartmental (mobile bearing patella), bicompartmental (femorotibial
-- total), unicompartmental, cone-in-cone, tibial tray post,
longitudinal curved tracks, with and without rotational stops, and all
with varying levels of femorotibial congruency. In Section XI of the
original submission the sponsor provides a listing of 46 mobile bearing
devices that are currently, or were, on the market either in the U.S. or
overseas. They represent a wide variety of design approaches to mobile
bearing knees, as noted above. In the U.S., only the DePuy LCS Rotating
Platform, LCS Meniscal Bearing, LCS Unicompartmental Knee, P.F.C. Sigma
Rotating Platform, P.F.C. Sigma Stabilized Rotating Platform, and
Biomet's Oxford Meniscal Unicompartmental Knee have been approved for
use.

Due to the unique risks that may exist within each of the various
designs it may only be possible to evaluate these designs on a case by
case basis. One set of special controls may not be appropriate to
encompass the whole range of mobile bearing knees. These concerns were
addressed to OSMA in the FDA letter of February 18, 2004. Their March 31
amendment attempts to address these concerns.

In response to the FDA questions posed in the 2/18/04 letter, the
sponsor did identify additional risks unique to mobile bearing knees.
These included 'spinout' of the tibial bearing insert, disassociation of
the insert from the tibial tray, and insert deformation due to overhang.
The sponsor also provided specifics on preclinical testing (special
controls) to address these risks. In appendix 1c of the March 31, 2004,
amendment, descriptions of preclinical testing to evaluate
characteristics unique to mobile bearing knees were provided. In
particular, standardized wear test methods originally developed for
fixed bearing knees (ASTM F-1715 "Standard Guide for Wear Assessment of
Prosthetic Knee Designs in Simulator Devices, and ISO 14243-1, "Implants
for Surgery -- Wear of total knee joint prostheses -- Part 1: Loading
and displacement parameters for wear-testing with load control and
corresponding environmental conditions for test") were noted along with
two potential methods for evaluating backside wear (wear between the
tibial tray and tibial insert). It was also suggested that particulate
analysis (size/morphology/quantity) of wear particles be performed and
compared with that seen from a clinically successful predicate control
to determine if there is an increased risk of osteolysis due to the
mobile bearing design (i.e., dual articulating surfaces). 'Spinout' was
noted as a risk unique to mobile bearing knees. 'Spinout' is defined as,
"excessive rotation of the tibial insert resulting from at least one
femoral condyle riding up and over the lip of the insert such that the
femoral condyle disassociates from the inserts articular surface". The
sponsor states this should be evaluated to limit or eliminate the
potential for bearing spinout. They suggest it may be assessed using
modified constraint testing standard ASTM F-1223 (Standard Test Method
for Determination of Total Knee Replacement Constraint) after adapting
for physiologic compressive loads, rotary torques, and varus moments
that are deemed to be causative of insert spinout.

The risks of disassociation of the insert from the tibial tray or
increased impingement of the insert against other portions of the device
due to design (e.g. sliding tracks, captured tibial tray posts, etc.)
have also been identified. The sponsor states that this should be
evaluated to determine that there is not an increased risk of
occurrence, and that a successful result (insert does not bind or
disassociate under physiological loads) would provide reasonable
assurance that it will not occur during normal use.

Overhang deformation of the polyethylene tibial insert is another risk
unique to mobile bearing knees that was identified in the petition.
Overhang refers to any portion of the tibial insert that is not directly
supported by the tibial tray. Mobile bearing knees should be designed to
limit overhang and/or tested to determine if any overhang presents a new
failure mechanism by restricting rotation due to deformation or
increasing wear due to deformation. Although there is no standard for
this evaluation, the sponsor suggests this can be assessed during knee
simulator wear testing.

The sponsor also states that those mobile bearing knees that utilize a
mechanical stop to limit or eliminate rotation, spinout, or sliding
movements should be evaluated for polyethylene wear/fracture caused by
contact with the stop. Again, modified wear simulator testing is
suggested as the method of evaluation.

In summary, most of the preclinical testing identified for the mobile
bearing knees is the same type of testing currently asked by FDA for
fixed bearing knee devices (tibial tray fatigue, contact area/stress,
constraint, etc.). For risks unique to mobile bearing knees most of the
'new' testing suggested revolves around some sort of modified wear
simulator testing to evaluate a specific characteristic (i.e.,
particulate analysis, overhang deformation, mechanical stop impingement,
disassociation, etc.). The hard part is going to be actually defining
what these modified tests are, and trying to determine whether they are
truly predictive from one mobile bearing design to another. Can
reasonable assurance of safety and efficacy for myriad device designs be
made based on modifications to existing test methods (e.g., knee
simulator wear testing)? That is, are the proposed special controls (or
others) adequate to address the inherent risks of the mobile bearing
knee designs (or some subset of these knee designs) identified in this
petition, and to provide reasonable assurance of safety and
effectiveness?

Although labeling has been identified as a special control with which to
address the above risks to health, the proposed labeling requirements
are consistent with those generally found in current fixed bearing total
and unicompartmental knee package labeling. No specific labeling
requirements were identified for any of the mobile bearing specific
risks.

**Known Potential Benefits**

No specific benefits of mobile bearing knee prostheses were stated in
this petition, however, evidence has been provided to show that
available long term data suggests that mobile bearing devices are
equally safe and effective as compared with fixed bearing devices in
total or unicompartmental knee arthroplasty.

Dual surface articulation between a polyethylene insert and metallic
femoral and tibial tray components are a consequence of mobile bearing
knee designs. Their advantage may lay in the maximization of
femoral-tibial contact area which results in the attenuation of peak
stresses, minimizing the potential for UHMWPE damage. Additionally, the
mobility of the tibial insert allows for reduction of implant-bone
interface torque contributing to in-vivo component fixation longevity.
An increasing number of these designs are being utilized globally in
total knee reconstruction, particularly among younger age groups with
degenerative joint pathology.

Potential benefits for both fixed and mobile bearing knees include a
decrease or cessation of pain, and increased mobility and function
post-operatively as compared to pre-operatively.

**Summary of Clinical Data**

Please see Dr. Buch's review memo for a complete evaluation of the
clinical data presented in this petition. Selected series of 48 studies
have been summarized in Table 7, 8, and 9 of appendix 3 of the original
submission. Data presented includes available demographics, study
design, safety, effectiveness, and survivorship data. Included in these
tables are 4 studies for multidirectional mobile bearing knees, 4 for
rotating bearing knees, 8 for meniscal bearing knees, 11 for combination
rotating platform and meniscal bearing in same study, and 21 for
unicompartmental devices. Minimum follow-ups ranged from roughly 2 years
to 12 years. These experiences underscore the strong influence of the
technical performance of the operation on the long-term success of a
knee device. Properly aligned knee arthroplasties that have restored
ligament balance (medial and lateral, flexion and extension) appear to
have survival rates of ten years or greater, irrespective of bearing
mobility. These data indicate that when provided with medial-lateral
stabilization, mobile bearing knees provide equivalent results as fixed
bearing knees.

**Bibliography and References**

An extensive bibliography containing 193 citations was provided in the
original petition, which included case studies, well controlled
investigations, studies without matched controls, non-clinical bench
studies, and retrieval studies. In addition, unpublished data from 7
ongoing IDE studies was provided. An additional 43 articles on wear were
provided in the March 31, 2004, amendment.

**Comments**

A number of orthopedic surgeons have provided letters expressing their
desire to include mobile bearing knees in their list of treatment
options, particularly for younger patients (appendix 1 of original
submission).