MEMORANDUM

MEMORANDUM

Reclassification Petition: Clinical Consult Review

To: Orthopaedic Advisory Panel

From: Orthopaedic Devices Branch, Division of General, Restorative and Neurological Devices;

Date: April 26, 2004

Subject: Reclassification Petition: Mobile Bearing Knee Prostheses

____________________________________________________________________________________

Summary:

This reclassification petition presents data to support the petition for reclassification of all mobile bearing unicondylar, bicondylar condylar and tricompartmental knees from Class III to Class II. This includes clinical data from IDE and outcome studies, peer reviewed journal articles and meta- analysis comparison analyses between fixed and mobile bearing systems related to adverse events and effectiveness outcomes. The sponsor believes that this information provides strong evidence of the safety and efficacy of mobile bearing knees, and that the risks associated with these devices are now adequately defined. Before a decision can be made whether reclassification from Class III (Premarket Approval Application) to Class II (Special Controls) is justified, further information and clarification is needed.

Background:

Reclassification is requested from Class III to Class II.

There are numerous mobile bearing knee designs on the market worldwide

designed to increase contact area and /or to reduce implant-to-bone interface stresses by allowing mobility of the polyethylene bearing on the tibial plate in order to potentially reduce long-term wear.

Regulatory History of the Device Class

FDA issued a Proposed Rule classifying 77 orthopedic devices on July 2, 1982 (47 FR 29052), and the Final Rule on September 4, 1987 (52 FR 33686). The Final Rule established twelve separate categories of implantable knee prostheses (21 CFR 888.3480 through 888.3590). Each of the twelve types of knee prostheses described were assigned to either Class II or Class III depending on system attributes such as fixation method, level of constraint, and degree of resurfacing (e.g., patellofemorotibial versus femoral).

None of the categories, however, describes the type of total knee replacement system that has come to be known as the mobile bearing knee.

The question of reclassification of mobile bearing knees from Class III (Premarket Approval) to Class II (Special Controls) was considered by an FDA Advisory Committee on January 13, 1998. At that time, the panel's recommendation was to retain the Class III designation for all tricompartmental and unicompartmental mobile bearing knees with the exception of recommending reclassification of tricompartmental mobile bearing knees

that are cemented and have a rotating/translating base. The panel also recommended post-market surveillance for those mobile bearing knees reclassified to Class II. The FDA subsequently chose to recommend submission of a new reclassification petition for the entire class of mobile bearing knees, rather than reclassify specific subcategories.

Device History

The first mobile bearing knee designs were introduced in the late 1970's. The Oxford Unicondylar knee (Biomet, Inc., Warsaw, IN) was the first to utilize a mobile bearing to reduce contact stress while also reducing implant-to-bone interface stress. Since those early implants, several generations of mobile bearing knees have followed, and today there are nearly 50 unicondylar and bi-condylar implant designs with either platform-style or meniscal bearing design of the polyethylene articulating surface on the international market. There are numerous variations in the directional mobility of the polyethylene, type of constraint of the polyethylene, and treatment of the PCL. The first mobile bearing knee to be approved by the FDA for sale in the U.S. was the Low Contact Stress (LCS) Rotating Platform Knee (J&J DePuy, Warsaw, IN). PMA approval for this knee was received in 1985, and since then five other mobile bearing knees have been approved in the U.S.

Reclassification of several types of knees from Class III to Class II was considered by an FDA Advisory Panel on January 13, 1998 ("Petition for Reclassification, Patello-Femoral-Tibial Metal/Polymer/Metal/Polymer/Metal Biologically Fixed Prosthesis, submitted by the Orthopedic Surgical Manufacturers Association, July 25, 1997). Mobile bearing knees were included in that petition. At that time, the Panel believed there was insufficient evidence to provide reasonable assurance of safety and efficacy for the entire class of mobile bearing knees. They recommended reclassification only of tricompartmental mobile bearing knees that are cemented and have a rotating/translating base. However, they recommended the retention of Class III designation for all other tricompartmental and unicompartmental mobile bearing knees.

At this time 6 devices are available in the US:

• Low Contact Stress (LCS) Rotating Platform

• P.F.C. Sigma Rotating Platform

• P.F.C. Sigma Stabilized Rotating Platform

• Low Contact Stress (LCS) Meniscal Bearing

• Low Contact Stress (LCS) Unicompartmental Knee

• Oxford Meniscal Unicompartmental Knee

Intended Use:

The intended use differs depending on the subtype.

The mobile bearing total knee, fixed with or without bone cement 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 mobile bearing unicompartmental Knee, fixed with or without bone cement 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

Device Description/Principle of Operation:

This class of devices includes two subtypes: bicondylar knee joint patellofemorotibial metal/polymer mobile bearing cemented or porous coated uncemented prosthesis" and

Unicondylar knee joint femorotibial (uni-compartmental) metal/polymer mobile bearing

cemented or porous coated uncemented prosthesis"

The defining feature of a mobile bearing knee is the presence of a moving polyethylene bearing that articulates with both the femoral condyle and the tibial tray. It is theorized that mobile bearing knee designs potentially reduce polyethylene wear by their highly conforming surface that disperses contact forces over a large area. The mobility in the polyethylene bearing, which reduces implant-to-bone interface stresses, may prevent implant loosening, which has been attributed to high interface stresses in highly conforming fixed bearing knee designs.

Mobile bearing knees are available in PCL-retaining, PCL-sacrificing and PCL stabilizing designs. In general, knees with only rotating mobility utilize a PCL sacrificing or PCL-stabilizing design, while multidirectional platform knees generally are PCL-retaining.

These devices can be further categorized by the type of bearing surface (Platform, bicondylar meniscal bearing, and unicondylar meniscal bearing), type of constraint and type of fixation (cemented , porous coated uncemented).

Bearing Surface included:

Platform: a single polyethylene bearing that rotates in the transverse plane, with or without A/P motion (rotating only or multidirectional).
Meniscal Bearing: separate medial and lateral polyethylene bearings that slide

independently in arced tracks that run anteriorly and posteriorly in the fixed, metal

tibial component

Unicondylar Meniscal Bearing: an implant in which only the medial or lateral

compartment of the knee is replaced. The polyethylene may run in a track as

described above, or may move freely, held in place only by its reciprocal shape and

the tension of the surrounding ligaments.

Past experience and literature have shown that the use of cement has improved results and higher failure rates are associated with non cemented use. In light of this information, it should be considered whether we can include uncemented (porous coated) devices with cemented devices (i.e. do we have enough data to feel comfortable that special controls will predict safe use).

Type of Constraint (prevention of bearing dislocation)

Unconstrained designs have very low constraint forces over the entire range of normal (physiologic) displacements.

Semi-constrained designs have near physiologic constraint that rises over the range of normal displacements.

Constrained designs have constraint forces that exceed physiologic levels and rise sharply over the range of displacements

Cone-in-cone Design: incorporates a tapered projection of the polyethylene insert that inserts into a reciprocal concavity in the tibial tray
Tibial Tray Post: A post extending from the superior surface of the tibial tray fits into a recess on the polyethylene insert
Longitudinal Curved Sliding Tracks: Movement of the platform or meniscus is limited by a track formed in the upper surface of the tibial tray
Stops: elevated rim of the tibial tray that limits excessive A/P translation or rotation
Unconstrained Bearing: designs that lack a mechanical limit to movement, but instead rely on the conformity of the polyethylene mobile bearing to the femoral condyle and the tension of the soft tissues

Characterization of the Directional Mobility of the Bearing Surfaces:

Nine knee designs were tested in a dynamic testing system in which compressive load was applied as the knee was rotated or moved in the A/P or M/L direction. Torque or shear forces were measured and plotted against displacement, thus characterizing the ability of the knee design to constrain displacement during gait. The nine designs were then characterized as "unconstrained", "semiconstrained", and "constrained". Of the nine designs evaluated, all demonstrated unconstrained motion in the rotational direction and all the mobile bearing designs

demonstrated unconstrained mobility within a total of 15 degrees internal/external rotation. Relative to M/L mobility, the designs tested were evenly divided between semi-constrained and constrained mobility. Constrained and semiconstrained M/L mobility is characteristic of both mobile and fixed bearing knee designs, and does not adversely affect clinical performance. Analysis of A/P mobility revealed a wide range of constraint, with unconstrained designs prevailing. In order to achieve joint stability with the lower level of constraint, competent soft tissue, including balanced collaterals and/or the PCL are necessary.

• Congruence:

Fully congruent mobile bearing knees are those that have a high degree of conformity between the femoral condyle and the polyethylene bearing surface, over a wide range of flexion (approximately 120 degrees). accomplished by providing a constant sagittal femoral radius, limited by posterior impingement of the tibial component. A fully congruent prostheses has a large contact area between the femoral condyle and the bearing surface, disperses contact forces, thereby theoretically resulting in reduced polyethylene wear.

Gait congruent or partially congruent mobile bearing knees have large contact areas in the first 20 degrees of flexion. The contact area decreases with flexion due to a decreasing sagittal radius. These prostheses maximize contact areas in the low end of the flexion range, while decreasing the sagittal radius to improve flexion range.

The term "functionally congruent” is used to mean that a device has a single femoral radius for up to 75 degrees of flexion.

Summary of Unpublished IDE data

	BIOMET TRAC PS Rotating Platform	OXFORD UNICOND Phase II Meniscal Bearing	S&N GEN II Rotating P, Multidirectional P	PROFIX RP MP	STRYKER HO SCORPIO PS RP	ZIMMER MOBILE BEARING KNEES MP	ZIMMER NEXTGEN LPS FLEX RP
Type	P, MC, Rand	P,MC	P,MC,R	P,MC,R	P,MC,R	P,MC, NR	P,MC,R
#enrolled	130 (all cemented)	125 knees(all cemented) 107 pts	109/119 cemented 94/104knees uncemented 15 hybrid	59 50 cement 9 hybrid	62	179	61cemented
1 yr	103	104/125	106 pt		41 pts @ 7 weeks; (6 mo 12pts)	145	81/123(65%)
2 yr (%)	89		3			51%
3 yr	333
4 yr f/u	6
Mean F/U	2.2 yr	4.8	1 yr	9 mo	3 mo	1.5 yr
Age Mean	65 (40-87)	62 (34-85)	64-65	64	63	65	62
KSS/HSS Good-Excellent	KSS 1 yr 77.4% 2 yr 83.7% 3 yr 85% 4 yr 100%	HSS 95.2 95 14% required walking support	89= ave KSS	KSS 92%	75% 6mo	KSS 89.7 89.3	KSS 84%
Revisions	7	16 (7?) survivor ship 94% @ 6 yrs 88% cumulative @ 6yrs	2(1yr)	0	0	3	0
Reasons	-Poly (multiple) dislocation(11) -Insert subluxation (1) -Pt dislike	-Poly dislocation(4%) -Deep infection -Lat compartmt degeneration -Aseptic loosening :femur and tibia -poly wear -patellar complication -RA onset -Auto Accident -Patella Dislocat -improper alignment -meniscal cyst 1 pt death	-deep infection(1yr) -poly subluxation(3 mo) -Fracture -Fibroarthrosis -RSD		-Wound healing probs medial epicondyle avulsion IPL disruption	-deep infection -pain -PCL insufficiency
Rev Rate (sponsor)	5.4%	15.4	1.7			1.7

*Note that in all of the studies 85-100% of patients had OA as a primary diagnosis.

International Studies

	Zimmer MOBILE BEARING KNEES			NexGen LPS-Flex
# enrolled	1,254			390
Insall Categories	A	B	C	A	B	C
1 yr	447/552 (80%)	223/256	143/213 (81%)	80/86	24/30	55/60
2 yr (%)	223/256 (87%)	117/140 .(83.6%)	74/100 (74%)	15/15	3/5 (60%)	4/4
Mean F/U	33% at 2 yrs
KSS/HSS Good-Excellent	81% 85.7	87% 83.8%	67% 74%	93% 100	79 67	91 100
Revisions	8 total 0.6%			2 total
Reasons	-Patellar complications -Fixed flexion deformity/stiffness -unspecified Complication rate 3.6%			Deep infection (3 mo) Instability (6 mo)

Data from two international clinical outcomes studies provide robust evidence of the clinical success of mobile bearing knees in general usage. These data sets represent a variety of surgical skills among numerous surgeons, in numerous countries, from general patients not limited by inclusion/exclusion criteria. Currently, 2 year data is

available from a total of 243 patients. The published data is summarized in Volume 2, Appendix 3.

Overall Summary

The sponsor provides summaries of studies grouped by mobile bearing knees types. Even within these groupings, the results are variable and very few prospective randomized controlled studies are reviewed, particularly those comparing mobile bearing knees to fixed bearing total knee arthroplasty out comes. Patient population varies as do indications ( Unicondylar vs. bicondylar) Although retrospective studies are useful as they provide longer term information, the data collected retrospectively has inherent flaws due in large part to missing information and the need for interpretation. Thus this data should be reviewed with some caution. It is difficult to group all the different types of mobile bearing knees into one group as they appear to have very variable results, even within the same group. The FDA believes the mechanics and adverse events may be unique for tricompartmental (patellofemorotibial) mobile bearing knees as compared to bicompartmental (femorotibial)and therefore recommend that a separate category be proposed rather than grouping these two types of devices together.

Multidirectional platform devices

This consists of 2 prospective (none randomized) and 2 retrospective studies which discuss 4 different devices implanted in 425 patients/491 knees (includes bilateral) with a major diagnosis of osteoarthritis (>70%). Follow-up averaged 4.1 years in the range of 2-8 years with variable patient follow-up percentages( as low as 35%) . The outcomes results are variable and range from poorer results for the Accord device (Duffy) at 5 years with 16% severe pain, mean knee score 60/100 and function score 42/100 and 58% survivorship at 10 yrs., to better results for the Rotaglide (Polyzoides) with pain in less than 3% of the patients(knee scores not reported). Knee scores in the other 2 studies range from 155-188/200. Some of the patients in these reviews were excluded if they had a revision.

Multidirectional Platform Devices Meta analysis
reference	Duffy & Philipson	Kaper et. Al.	Morgan-Jones et. al. prospective	Polyzoides et. al. retrospective
Device Name	Accord TKA	Self Aligning I		Rotaglide TKA
Knees/patients	74/61 35% f/u	172/141 OA	75/62	170 cemented
Age mean (range)	68-69	71 (47-90)	67	66
Deaths	16 pts (20 knees)	41
Lost to f/u	6	1 @ 5 yrs
Revisions/surg	25 (19 instability) 34%	15 (8.1%)	0	0
Complications Infection Aseptic loosening Poly wear Fractures Stiffness Pain Dislocations Lysis Instability	1 8 2 3 8 19	4 4 2 4 1 1	No dislocation, subluxation, breakage, subsidence or osteolysis 1 patella replacement	No platform dislocation No mechanical implant failures 1ptw/fracture@6 wks
NSS (mean)	60 35% good –excellent, fxn 4% good to excellent	KSS pre 81 Post -155	KSS pre 96 Post 188	95% BritishOA score good/excellent
Function score	42	ROM 0^o Post 111^o	ROM 2yr 133^o
Survivorship	10yr= 58%	91.7 % (poly wear =98.8%
F/U (mean)	5 yrs, 4 mo	5.6 yrs (5-8yrs)	2.5 yrs	2-5 yrs
Comment	Poor as compared to conventional TKA 16% severe pain	Pt satisfaction = 94%

Rotating platform Devices

This consists of 2 prospective (one randomized) and 2 retrospective studies which discuss 1 device (LCS) implanted in 744 patients/939 knees (includes bilateral) with a major diagnosis of osteoarthritis (>70%). Follow-up averaged 1-12 years with variable patient follow-up percentages( as low as 55%) . The outcomes results are variable. Knee scores were not reported in one study, but range from KSS clinical of 90-91/100 (165/200) to 159/200 . 10% of knees had pain in one study. Survivorship ranged from 88-94% in 2 retrospective studies at 14 and 11 years. Revision rate from 3 studies range from 0-7%.

Rotating Platform Devices
Reference	Callaghan et.al.	Grodzki et. al.	Sorrells	Sorrells retro
Device Name	LCS	PFC/LCS	LCS	LCS
Knees/patients	119/86		665/521	1117/9
Age mean (range)	70	73	70	56
Deaths	18			15/18 knees
Lost to f/u	5 knees			26 knee/25 pt
Revisions/surg	0		13 (2%)	8 (6.8%)
Complications Infection Aseptic loosening Osteolysis Poly wear Fractures Stiffness Pain Dislocation Malpositioning Laxity Sublux/subside	0 0 0	No information because article was in German	4 1 2 7 6 1 1/1	1 1 2 2 4
NSS (mean)		PFC =130 LCS =160	98% good to excellent at 11 yrs	85% good-excellent
Function score	ROM ave: 0-102^o
Survivorship	100%	*	94.7%	88.1%@14yr
F/U (mean)		1 yr	1-11 yrs	8.5 yrs
Comment	Avoidance of a flexion gap thought to account for no dislocation/ osteolysis from backside wear

* blank spaces indicate that information was not available in reference

Meniscal Bearing Devices

This consists of 5 prospective (one randomized) and 3 retrospective studies which discuss 2 devices (LCS) implanted in 1666 knees (includes bilateral) with a major diagnosis of osteoarthritis (>70%). Follow-up averaged 1-11.5 years with variable patient follow-up percentages( as low as 60%). The outcomes results are variable. Knee scores were not reported in one study, but range from KSS clinical of 70-94/100. Survivorship 93-99% in 5 retrospective studies.. Revision rate from 5 studies range from 1-9%. In the one randomized study the mobile bearing knees and fixed knees were similar.

Meniscal Bearing Devices
Reference	Bert	Hartford	Jordan	Jordan	Kim	Minns	Muller	RosenbergHenderson
Device Name	LCS		LCS prosp	LCS Uncement	LCS/AMK	Minns Meniscal	LCS unresurfaced patella	LCS/PCR
Knees/patients	43/	139/104 80 cement 50unceme 9 hybrid	160/141	473/375	120 bilat	165 RA and OA (57%)	436	35/27
Age mean (range)	63	66	68 yr OA pts	68	65	67		72
Deaths	0	37 knees	66knees	39(34 after 24 mo)	0			3
Lost to f/u		47 knees		63	4			4
Revisions/surg	4 (9.3%)	10	2(0.8%)	18(3.8%)	2/2(1.7%)	8		1 (2.9%)
Complications Infection Aseptic loosening Fractures Dislocation Sublux/subside
		3		5				1
		7(hi in uncement 27%/31% loosening femur/tibia		2
					1
	4:3-2wk,1-6mo	1		5	1	8
				4/2
Fractures				7
NSS (mean)	91% good-excellent			92/93	94.4/93.3	75% excellent 9%fair	NJOHS =90 @ 5yr	83 (14PTS) 60(5=Fair)
Function score					ROM =123/121	Flexion 89-103o Dec instability Dec flexion def
Survivorship		93%	99.5%	94.6% (8yrs)	98%			97%
F/U (mean)	1 yr	7.8 yr	12 yr	2-10 (4.7)	7.4	0-5yr		?
Comment	Proper measurement of flexion gap critical to prevent dislocation of elements

Combination of Rotating Platform and meniscal Bearing in same study

This consists of 3 prospective (none randomized) and 7 retrospective studies which discuss 6 devices implanted in 8433 knees (includes bilateral) with a major diagnosis of osteoarthritis (>70%). Follow-up averaged 20 months-13.5 years with variable patient follow-up percentages. The outcomes results are variable. Survivorship is 90-100% in at 5-10 yrs. Revision rates range to 8%.

Combination of Rotating Platform and meniscal Bearing in same study details on table Vol. 2, Appendix 3,p.240
Reference	Buechel	Buechel /Pappas	Callaghan (8 reports)	Keblish	Keblish	Munzinger	Papchristou	Sanchez Sotelo	Steil et al	Weissinger	Thompson
Device Name	NJLCS	NJLCS	LCS/ Oxford	LCS	LCS Moveable-bearing w/ anatomic femoral groove	LCS	Oxford 9 pts Endo-model 18 pts	LCS	LCS 147 Meniscal 44 Rot Plat	LCS	LCS
Knees /patients	373/282	357: 149 cemented 208 uncement MB=140 RP= 217		963/918 (MC) 275 personal series	104/52 bilateral 1 side patella resurface 88 uncementd 16 cement	235		101 pts	290/250	42/41	33/31
Age mean (range)	68	62	35-90	68	69	68	63-72	66	69	65.8	73
Deaths		1	42		0	0	0	0	35	1
Lost to f/u						131 less than 2yr			99
Revisions /surg	1	15 (4%)	65	9 (personal 3.3%)	1	8 (3%)	3 total 2 Oxford (22%) 1 endo	8 /(8%)	5 (5.4%)	0
Infection	3	7				1	1	1			1
Aseptic loosening	3	6		4			2	1
Osteolysis	3(1.8%)	0						2
Poly wear				3				1
Fractures	1	2
Stiffness
Pain
Dis location	5	MB=.7% RP= 3.2%	Most common			1Patellar probs responsible for comps		2
Sublux/ subside				4
Fractures	1	2+ 1 trauma		2 patellar				femur
NSS (mean)	PCR 68% excellent CRP 47%	cement 85% excellent 11.5% poor uncement 92% excellent 6% poor		Cemented LCS-96% excellent Uncement LCS-97% excellent	89.9 mean	95% excellent/good 4.2 yr		93			Dec pain All to 21 pain free 12 occasional
Function score								78 ave			Dec ROM
Survivor ship									97.5%MB 7 yrs 100% RP
F/U (mean)	20 yr	91mo/52mo	5-11 yrs	2-8yr	5.24 yr			5.2yr		21 mo	20 mo
Comment					Nonresurf patella same as resurfaced patella	Acceptable results re: -degree of stability - pain relief			IM alignmt flexi/extgap balancing impt

Unicondylar Meniscal Bearing
REF	Device	Pts/Knee	Age	Revision	F/U	KSS	Fxn	Survivorship	Complications
Argenson	oxford	552		45(8.2%)	14			92%
Barrett	Oxford bicompart	62 pts RA 46% OA 54%	75	4 (7%)	4.5 yr	83% pain relief	ROM: 93-103^o 93-73^o		4 DVT 2 Dislocation 2 aseptic loosening 5 infxn
Bourne	Oxford Meniscal Oxford Kinematic I	67 66	67	20 (30%) 3	5.5 yr	82 88		9 deaths	15 aseptic loosening 2 patellofemoral syn 1 dislocatn 1 infexn
Carr	25 bilateral medial compartment	121/96	69	1(0.8%)	44.4 mo	75% pts no pain	ROM 95-106	99.1% @ 9yrs 1 death	Loosening displacement
Cohen	NJOHS	21/20	60	1	10 yrs	16 good-excellent		2 death	Aseptic loosening
Goodfellow	Oxford Uni Meniscal	103/85	70 OA	9 rev (9.2%)	36 mo	92% No pain		5 deaths	4 Aseptic loosening 2 Lysis 3 dislocn 2 infexn Subluxation ACL absence greater incidence of failure
Goodfellow O’Conner	Oxford	125/107	67	8 rev 4 failures	49 mo	89% pain free	Flexion deformity Flexion worse post op	1death	1 infxn 5disloc 6Aseptic loosening 2lysis
Goodfellow	Uni	25/22	67 OA, AVN,fx	1	21 mo	92% no –mild pain	Flexion worse post op		1Loosning tibia
Gunther	Oxford Uni	53/51	68	11 (21%)	5.2 yr	53% report pain w/activity		Bearing dislocation greater in lateral compartment	6 Bearing dislocation 1Plateau fracture
Harding	Oxford I, II	50/50		14 (28%)