THE TRUTH ABOUT HIGHLY CROSSLINKED POLYETHYLENE

Transcription

1 THE TRUTH ABOUT HIGHLY CROSSLINKED POLYETHYLENE BIOMET BROCHURE ANALYSIS HIGHLY CROSSLINKED POLYETHYLENE, A STEP FORWARD OR A STEP BACK Biomet recently produced a brochure entitled Highly Crosslinked Polyethylene, A Step Forward Or a Step Back 1 which contains a variety of inaccurate, misleading, and untrue statements. The purpose of this document is to Familiarize you with the brochure and its claims Review the major claims Biomet makes and assess their validity Provide you accurate information about Longevity and Prolong highly crosslinked polyethylenes and how it relates to Biomet s claims. Enclosed is a critique of the major points contained within the Biomet brochure. Biomet has entitled page one of their brochure, Highly Crosslinked Polyethylene Facts. This page contains 10 claims which are evaluated within this document. Additionally, several other erroneous claims are also evaluated. Reality is radically different than what is portrayed in the Biomet brochure. The fact is that Longevity and Prolong polyethylenes - start with fully consolidated, well controlled polyethylene. - are low-wear articulating surfaces, even in the presence of third bodies. - are virtually free from the damaging effects of free radicals. - are based upon documented, long-term clinically proven crosslinked polyethylene material. If you are interested in being more aware of Biomet s position, and gaining a better understanding of Longevity and Prolong polyethylenes, review the claims, Biomet references, and the analysis that follows.

2 Major Biomet s & References #1 Highly crosslinked polyethylene uses GUR resins which require extra irradiation in order to achieve the same crosslinking levels as the ArCom 1900H resin. 1) Biomet internal research Highly crosslinked polyethylenes produced by different manufacturers receive different levels of energy according to each manufacturer s specifications. All of these highly crosslinked polyethylenes receive more energy than Biomet s ArCom polyethylene which is only gamma sterilized at low dose levels, and is therefore not highly crosslinked. Highly crosslinked polyethylenes demonstrate a substantially higher level of crosslinking than ArCom polyethylene. Biomet s own data (p.4 of their brochure) shows that Arcom 1900H would have the same level of crossllinking as Longevity polyethylene if Arcom polyethylene was irradiated at an equivalent energy dose. The fact is that ArCom polyethylene has a lower level of crosslinking than Longevity and Prolong Highly Crosslinked Polyethylenes. A higher level of crosslinking has been shown to be related to lower wear. 2 #2 Highly crosslinked polyethylenes are consolidated using outside vendors, whose processes may lead to voids in the polyethylene. 1) Tanner, M. et al., Polyethylene Quality Variations in Currently Available Bar Stock. AAOS, Feb The paper cited by Biomet never even addresses highly crosslinked polyethylene, but rather a 1st generation polyethylene resin, GUR 4150, that major orthopaedic manufacturers no longer use. This statement is not specific to highly crosslinked polyethylene, but rather all polyethylenes. Any process, whether done by an outside vendor or internally, is dependent on processing parameters and the control of those parameters. Zimmer conducts rigorous qualifications of all its vendors as well as extensive testing of all polyethylene used in its manufacturing. #3 Highly crosslinked polyethylenes are processed from ram extruded and sheet molded polyethylene which require extra irradiation in order to achieve the same crosslink density as isostatically molded (ArCom) polyethylene. 1) Biomet internal research This is essentially claim #1 restated. Again, Biomet s own data suggest that ArCom polyethylene would not be any more crosslinked at 100 kgy than Longevity Highly Crosslinked Polyethylene. The fact remains that ArCom polyethylene has less crosslinking than Longevity or Prolong Highly Crosslinked Polyethylenes.

3 Major Biomet s & References #4 Highly crosslinked polyethylenes do not receive consistent irradiation doses, leading to inconsistencies in the crosslink levels of the polyethylene. 1) Tanner, M. et al., Polyethylene Quality Variations in Currently Available Bar Stock. AAOS, Feb The reference that Biomet uses does not even address highly crosslinked polyethylene. The industry standard is that polyethylenes receive a dose that falls within a minimum/maximum range established independently by each manufacturer. The truth is that e-beam irradiation, the process used to crosslink Longevity and Prolong Highly Crosslinked Polyethylene, can be more precisely controlled than is gamma irradiation, the process used to sterilize ArCom polyethylene. 3 #5 Highly crosslinked polyethylenes irradiated through electron beam irradiation tend to develop bubbles in the material due to the high dose rate. 1) Wang, A., et al., Void Formation in Electron- Beam Irradiated UHMWPE at Molten State. ORS, Feb. 2001, San Francisco, CA. The reference that Biomet cites talks to polyethylene that is e-beam irradiated when the polyethylene is in the melt state. Biomet chose not to communicate the important fact that neither of the manufacturers that use e-beam irradiation do so when the polyethylene is in the melt state, and so the issue raised by Biomet is irrelevant. One may infer from this statement published by Biomet that any polyethylene crosslinked using e-beam irradiation will develop bubbles. This is simply not supported by the reference and it is certainly not supported by our experience. #6 Highly crosslinked polyethylenes are more brittle and may fracture more easily than ArCom polyethylene. 1) Baker, D., et al., Study of Fatigue Resistance of Chemical and Radiation Crosslinked Medical Grade UHMWPE. JBMR 46: , ) Eberhardt, A., et al., The Effects of Irradiation Level and Resin on Fatigue Crack Resistance in UHMWPE. Society for Biomaterials, ) Gomoll, A., et al., Quantitative Measurement of the Morphology and Fracture Toughness of Radiation Crosslinked UHMWPE. ORS, Feb ) Gillis, A., et al., An Independent Evaluation of the Mechanical, Chemical, and Fracture Properties of UHMWPE Crosslinked by 34 Different Conditions. ORS, Feb ) Cole, J., et al., Gamma Irradiation Level and Resin Effects on Fatigue Crack Resistance in UHMWPE. Society for Biomaterials, Crosslinking polyethylene tends to make the material less ductile, but there are no data to suggest that highly crosslinked polyethylene will fracture in-vivo more easily than ArCom polyethylene. Prior to its market introduction, highly crosslinked polyethylene had been exhaustively tested. Devices have been evaluated in long term (20 to 30 million cycles) wear simulations as well as fatigue environments such as delamination and impingement. The FDA has reviewed this data and cleared highly crosslinked polyethylene for use in hip and knee applications. In fact, in-vivo data on highly crosslinked polyethylene shows no catastrophic failure after twenty years in several studies Interestingly, the second reference they use to support this claim states the 1900 resin did not demonstrate improved crack resistance over the 1050 resin. Once again the references do not support the claims that Biomet tries to make.

4 Major Biomet s & References #7 Highly crosslinked polyethylenes may shed more particles than ArCom polyethylene. 1) Scott, M., Wear Particle Analyses of Conventional and Crosslinked UHMWPE Tested in an Anatomic Hip Simulator. ORS, Feb #8 Highly crosslinked polyethylenes shed smaller, rounder particles, potentially leading to higher osteolysis rates and systemic complications. 1) Scott, M., Wear Particle Analyses of Conventional and Crosslinked UHMWPE Tested in an Anatomic Hip Simulator. ORS, Feb ) Williams, P., et al., Polyethylene Wear Debris from Total Knees Compared to Extruded and Molded Hips. Society for Biomaterials, ) Green, T., et al., Effect of Size and Dose on Bone Resorbtion Activity of Macrophages by In Vitro Clinically Relevant UHMWPE Particles. JBMR 53: , ) Mabrey, J., et al., Comparison of UHMWPE Particles in Synovial Fluid and Tissues from Failed THA. JBMR 58: , ) Ries, M., The New Polys: Bridges too Far?. CCJR, May #9 Some early retrievals of highly crosslinked polyethylene show a leathery, pockmarked appearance, along with numerous fatigue cracks. 1) Biomet internal research #10 There is no in-vivo data on highly crosslinked polyethylene. False The reference for this claim is based upon a presentation which did not even mention ArCom polyethylene. Further, it concluded that 5 Mrad (50 kgy) gamma irradiated material produced more particles than did 10 Mrad (100 kgy) gamma irradiated material or E+O sterilized material. More importantly, the author of the cited work has subsequently reported that some assumptions used to reach this conclusion were incorrect. 4 None of the cited references support this claim. None of these references tie crosslinked polyethylene particles to higher osteolysis rates. There are several reports showing that crosslinked polyethylene particles are not significantly different in size and shape compared to standard polyethylene. These studies show that highly crosslinked polyethylenes generate fewer particles compared to conventional polyethylene. 5,6 One landmark study indicates that lower wear rates are associated with lower levels of osteolysis. 7 This leads one to the logical conclusion that osteolysis rates could be expected to be much lower with crosslinked polyethylene. Biomet did not demonstrate that any of these highly crosslinked polyethylenes actually developed cracks. What Biomet shows are small features which could have existed in the original device due to the manufacturing process (i.e. remnants of machining marks). A surface picture of the polyethylene before it was implanted was not provided. This type of unsupported conjecture is inappropriate and inconclusive at best. There are peer-reviewed journal articles of invivo results of highly crosslinked polyethylenes from a number of researchers. Some of these articles report results in excess of 20 years. In-vivo studies include data from Oonishi, Grobbelaar, and Muratoglu Further, Biomet claims on p. 5 of their brochure that ArCom is the only crosslinked polyethylene to demonstrate a reduction in wear in-vivo over conventional polyethylene. This is a misstatement of the facts.

5 Additional Biomet s & References Pages 3, 7 Biomet is the first and only company to bring the process of polyethylene consolidation in-house. False This statement is a curious one for Biomet to make since Zimmer s in-house molding of polyethylene predates Biomet s founding. Clearly this makes the statement false. Page 4 GUR resin has a lower molecular weight than 1900H. False Molecular weight is a measure of the mass of the atoms which make up a molecule of a substance. Ultra high molecular weight polyethylene is used in orthopaedics because its large molecules give it properties which are inherently beneficial in resisting wear. The molecular weight of GUR 1050 resin is typically greater than 5x10 6 g/mol. The molecular weight of 1900H is generally greater than 4x10 6 g/mol. GUR 1050 does not have a lower molecular weight than 1900H. 3 Page 9 Free radicals are not a factor due to effectively eliminating the availability of oxygen, free radicals are trapped in the crystalline domains where they are unable to react. Any free radicals trapped in the crystalline domain will remain trapped for an extended time period after implantation. Oxidation is virtually non-existent invivo. 1) Pramanik, S.I., et al., A Study of Free Radicals in Clinically Retrieved and Stored UHMWPE Tibial Plateau Inserts. Society for Biomaterials, ) Furman, B., et al., Differences in Oxidation Between Shelf Life Aged and Retrieved UHMWPE Components. ORS, Feb. 1998, New Orleans, LA. Page 10 Reductions in tensile strength may also make the material more susceptible to higher wear rates from third bodies. Inconclusive False Biomet makes three claims about oxidation and supports their conclusions with two references. This ignores conflicting data that shows that free radicals do not remain trapped in the crystalline domains of the polyethylene and are able to react with oxygen Furthermore, other studies show that oxidation does occur at significant levels in the body At a minimum, Biomet should have indicated that the body of data that exists is inconclusive regarding oxidation and its effects in the body. Regardless of the data on oxidation in the body, a highly crosslinked polyethylene that contains virtually no free radicals will not react whether oxygen is present or not. There are virtually no free radicals to bond with oxygen in Longevity or Prolong highly crosslinked polyethylenes. Biomet had no data to support this supposition. In reality, Zimmer s data, presented as part of our 510k submissions, showed that Longevity and Prolong Highly Crosslinked Polyethylenes had better wear rates than conventional polyethylene even in a third body environment. 3,19

6 THE TRUTH ABOUT HIGHLY CROSSLINKED POLYETHYLENE Additional Biomet s & References Page 17 There may be a high degree of inconsistency within the various processes due to uncontrolled variables and lack of uniform controls. Page 17 Many of the companies currently marketing highly crosslinked polyethylene have changed their recipe since introducing it to the market. References and Biomet has no data to support this statement. Zimmer s validated manufacturing processes are audited and certified by regulatory agencies from both the U.S. and Europe. Part of this process includes a review of our controls and their effectiveness. There are NO uncontrolled variables and lack of uniform controls. Again, for Biomet to make such a bold claim, they should support it with a reference. Zimmer has certainly not changed its processing parameters for Longevity or Prolong Crosslinked Polyethylenes since their introductions. Extensive testing went into the development and establishment of each parameter and they were optimized to best balance wear and mechanical property retention. Surgeons should challenge Biomet to provide evidence to back up this claim. 1 Biomet Orthopedics, Inc. Brochure, A Step Forward or a Step Back? Form No. Y-BMT-741/013102/M. 2 Muratoglu OK et al. Unified wear model for highly crosslinked ultra-high molecular weight polyethylenes (UHMWPE), Biomaterials 20, Data on file at Zimmer. 4 Scott M, Morrison, M, et al. A method to quantify wear particle volume using atomic force microscopy, Paper 0132, 48th Annual Meeting of the Orthopaedic Research Society, McKellop HA, et. al. Morphological Comparison of the Wear Debris from non crosslinked, gamma-sterilized (crosslinked) and gamma-crosslinked-remelted low-wear polyethylene, Poster PO67, American Academy of Orthopaedic Surgeons, Shanbhag AS, Vai CW, Quereshi SA, Rubash HE. Characteristics of cross-linked UHMPE wear debris, Session 1 Biology of Biomaterials, 47th Annual Meeting of the Orthopaedic Research Society, Dumbleton JH, Manley MT, Edidin AA. A literature review of the association between wear rate and osteolysis in total hip arthroplasty, The Journal of Arthroplasty, Vol. 17, No. 5, Oonishi H, et al. Wear of high-dose gamma irradiated polyethylene in total joint replacement. -long term radiological evaluation-, 44th Annual Meeting of the Orthopaedic Research Society, 1998, New Orleans, Louisiana. 9 Grobbelaar CJ. Long term performance of gamma irradiated HDPE cups in total hip replacement: a 14 to 18 year follow up. Trans. From the combination meeting of the South African Arthroplasty Society, Muratoglu OK et al. Surface analysis of early retrieved acetabular polyethylene liners: A comparison of standard and highly crosslinked polyethylene, Poster 1029, 48th Annual Meeting of the Orthopaedic Research Society, Dallas, Haggard WO, et al. Effects of thermal annealing on free radicals in gamma-sterilized UHMWPE, 45th Annual Meeting of the Orthopaedic Research Society, Anaheim, Jahan MS. Investigation of free radicals in shelf-aged polyethylene tibial components, Fifth World Biomaterials Conference, Toronto, Rimnac CM, et al. Post-Irradiation aging of ultra-high molecular weight polyethylene, Journal of Bone and Joint Surgery, Vol. 76-A, NO. 7, July Walsh HA, et al. Role of oxidation in the clinical fracture of acetabular cups, 45th Annual Meeting of the Orthopaedic Research Society, 1999, Anaheim, California. 15 Carotenuto G, et al. Comparison between in vitro and in vivo UHMW-PE degradation, J. Biomaterial Sci. Polymer Edn, Vol. 8, No. 6, Costa L. In vivo UHMWPE biodegradation of retrieved prosthesis, Biomaterials 19, del Prever E, et al. Unacceptable biodegradation of polyethylene in vivo, Biomaterials 17, Eyerer P, Ke YC. Property changes of UHMW polyethylene hip cup endoprostheses during implantation, Journal of Biomedical Materials Research Vol. 18, Laurent MP. Wear of highly crosslinked UHMWPE acetabular liners under adverse conditions, 6th World Biomaterials Congress/26th Annual Meeting of Society for Biomaterials, Hawaii, May, p.874. Contact your Zimmer Representative or visit us at Zimmer, Inc. Printed in USA