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Orthopaedics

SimplexP Bone CementSimplex P with Tobramycin

The Perfect Blend of Confidence and Performance

Simplex P Bone Cement

Reliable Predictable Trusted

2For over 40 years, Simplex P Bone Cement has earned thetrust and confidence of tens of thousands of surgeons. With over20 million doses implanted, no other bone cement can match theexperience of Simplex P Bone Cement. Hundreds of articles inrespected, peer-reviewed journals confirm the outstandingperformance of Simplex P Bone Cement.

At the heart of this illustrious history is the science behind thesuccess of Simplex P Bone Cement a unique chemicalcomposition that has become the orthopaedic standard by whichall other bone cements are measured the standard to which noother bone cement measures up.

The key to the outstanding long-term performance of Simplex Presides in its unique chemical formula and proprietarymanufacturing process. This formula imparts excellent viscosityand porosity characteristics that add up to superior fatiguestrength and mechanical properties.3-14

Chemical Composition:

Only Simplex P uses the proven 75-15-10 mix:75% Methylmethacrylate-styrene-copolymer for strength,15% Polymethylmethacrylate for handling and 10% BariumSulfate for radiopaqueness.

Cementing Success...begins with Simplex P

1958 Simplex C Cement introduced in Europe

1962 Simplex P Bone Cement introduced in Europe

1971 Simplex P Bone Cement first to receive FDAapproval in US for total hip arthroplasty

1973 Simplex P Bone Cement approved for total kneearthroplasty in US

1975 Simplex P Antibiotic Bone Cement withErythromycin and Colistin introduced in Europe

1976 Simplex P Bone Cement approved for use inpathological fractures and general prosthetic fixation

2000 Simplex P Bone Cement with Tobramycinintroduced in Europe

2003 Simplex P Bone Cement with Tobramycinintroduced in US

Bone Cement of Historic Proportion

Styrene and methylmethacrylate are combined via a proprietary manufacturing processto form beads of varying size.

Methylmethacrylate is processed to form the unique PMMA "flake" that increaseswettability and improves handling characteristics.

75%+Methylmethacrylate-styrene-copolymer plus...

15%+Polymethylmethacrylate (PMMA) plus...

3DePuy Endurance Powder Mixture CompleteNote different particle size and shape versus Simplex P below.

Simplex P Bone Cement provides the right ingredientsin the right formula, balancing unrivaled strength withconsistent handling for dependable intraoperative and long-termclinical results. Exclusive to the Simplex P manufacturing processis 1) the method by which benzoyl peroxide is encapsulated withineach Methylmethacrylate-styrene-copolymer bead and 2) theunique process of manufacturing the PMMA flake.

1) Benzoyl peroxide is crucial for determining the mixing, handlingand setting characteristics of bone cement. By encapsulating thebenzoyl peroxide in every copolymer bead, Simplex P deliversconsistent results. Products that include benzoyl peroxide as anadded ingredient to the entire polymer (powder) component mayinclude a statement in their labeling to explain that componentsof different lots cannot be mixed. A potential reason lot codes ofdifferent batches cannot be mixed is the variability in themanufacturing (benzoyl peroxide content) from batch to batch.With Simplex P Bone Cement, lot codes can be mixed frombatch to batch which is crucial for dependable, predictable results.

2) Unlike the styrene copolymer that looks like a bead, the PMMAcomponent is manufactured as a flake. It is due to these flakesthat the powder is noticeably fuller, and less dense than other bone

cement powders on the market. The combination of flakes andbeads in the Simplex P polymer allow for better wetting of thepolymer by the monomer (liquid component). This provides forthe optimal handling characteristics of Simplex P.

These manufacturing processes are unique only to Simplex PBone Cements. No other manufacturer of bone cement has beenable to copy this process.

Bone Cement Manufacturing...that is unequaled

Clumps of Barium

PMMAHomopolymer(no flake)

Co-polymer

Barium sulfate is blended under special controls to ensure uniform barium dispersionthat is free of clumps.

10%=Barium equals...

Note beads and flakes, as compared to DePuy Endurance above.

The Orthopaedic Standard Simplex P Powder Mixture Complete

4Low Viscosity Cements

Zimmer Osteobond is a low viscosity formulation.Simplex P has demonstrated superior survival results whencompared to low viscosity cements in both the Norwegianand Swedish hip registries1,2. Unlike Simplex P, theOsteobond formula does not balance styrene with PMMA.This results in a low-viscosity cement plagued byunfavorable handling properties.

Medium Viscosity Cements

DePuy Endurance is a medium viscosity cement, similarin handling characteristics to Simplex P. However,reformulated cements such as Endurance have attemptedto become a new copy-cat cement by blending a varietyof formulas. An unfavorable consequence of this approachis the development of a cement that lacks the clinical historyand data to support its use.

High Viscosity Cements

At the other end of the spectrum is DePuy 1, DePuySmartSet HV and Biomet Palacos R. High-viscositycements are compromised primarily of PMMA with noMethylmethacrylate-styrene-copolymer content. Highviscosity formulas that become doughy too quickly can be difficult to mix, causing air to become entrapped in thecement. This may increase porosity and consequentlyreduce fatigue strength3-13. Using a vacuum mixer to removeporosity and pressurizing high viscosity cements mayimprove the fatigue strength, although they have not beenshown to be able to be pressurized as easily as mediumviscosity cements.

Formulating Bone Cement...as the model for all others

5The Unique Simplex P FormulaProven for over forty years with over 18 milliondoses implanted. Simplex P Bone Cement is the original and most copied bonecement...often mimicked, never matched.

Note: Styrene content, molecular weight, and morphology vary by manufacturer. Formulations as per manufacturers package inserts.*The 1.7% Bpo content is contained within the styrene copolymer content and not as a separate ingredient.**Data unavailable.

Methyl MethacrylateStyrene Copolymer

Poly Methylmethacrylate

Barium Sulfate

Benzoyl Peroxide

Poly MethylmethacrylateMethacrylate Copolymer

MethylmethacrylateMethyl Acrylate Copolymer

Zirconium Dioxide

Chlorophyll

Many manufacturers of bone cement claim that all bonecements are alike and are attempting to sell bone cement as a commodity product. They are minimizing the fact that bonecement is an orthopaedic implant and the long-term performanceof bone cement is critical to the longevity of the orthopaedicprocedure performed.

6DePuy 1 CMW Simplex P

Greater Strength

When mixed mechanically in a vacuum, the fatigue strength ofSimplex P was 3-times greater than DePuy 1 (CMW) testing to 1,540 cycles x 103 versus 350 x 103. Similar results have beenreported in numerous other comparative studies3-14.

Fatigue Testing:

Mean number of cycles to failure of mechanically mixed cementin a vacuum3.

Greater Intrusion

Penetration of cement into bone can also bedirectly measured as intrusion depth. Simplex PBone Cement is superior to Palacos15. At roomtemperature, Simplex P achieves at least 50%deeper intrusion compared to Palacos15.

Cement Intrusion Depth into Cancellous Bone (mm):Measured at: 20psi, 40psi.

Palacos

20 psi

40 psi

1.4mm

2.4mm

2.2mm

4.2mm

Simplex P

Consistent Cement Performance...leading to clinical success

7Cement is formulated to just the right viscosity to achieve superiorbone penetration and maximum shear strength16. As a result, testsprove Simplex P Bone Cement withstands nearly twice the meanshear stresses at the cement to bone interface as DePuy 1, andalmost 20% more stress than Palacos16.

Deeper penetration means increased strength

The deeper cement penetrates into bone, the stronger the fixationand shear strength of the bond. Bone penetration is affected bycement viscosity. High viscosity cements such as DePuy 1,SmartSet HV and Palacos are too thick to penetrate deeply into the cancellous/trabecular bone matrix. Simplex P Bone

Mean Shear Strength at the Cement-to-Bone Interface (Mpa)Note: 1 Mpa (megapascal) = 145psi.

Palacos Simplex PDePuy CMW 1

3.7MPa

6.2MPa

7.3MPa

DeeperPenetration

SuperiorElution of

Tobramycin

ExcellentIntrusion

Depth

19%Simplex P

34%DePuy CMW1

62%Palacos

Creep Percent Relaxation at 500 hours

Less Creep

Creep or plastic deformation, is a mechanicalproblem that can slowly, steadily erode long-term implant performance. Bone cements thatcreep too much may lead to componentshifting, loosening, and failure. Simplex Pcreeps significantly less than Palacos17.

8The Perfect Blend...of Confidence and Performance

Simplex P with Tobramycin Bone Cement iscomprised of 40g of Simplex P Bone Cement powderplus 1g of tobramycin. The liquid monomer portion isunchanged from the original Simplex P Bone Cementmonomer. As a result, the superior mechanical propertiessurgeons expect with Simplex P Bone Cement areinherent in Simplex P Bone Cement with Tobramycin18,19.

Simplex P with Tobramycin Bone Cement isindicated for the fixation of prostheses to livingbone in the second stage of a two-stage revisionfor total joint arthroplasty.*

With pre-blended Simplex P with Tobramycin BoneCement, surgeons can feel confident that the tobramycin isbeing optimally delivered to the patient. It is manufactured,blended and tested to ensure even distribution of thetobramycin throughout the mixture, and that the mixtureis consistently smooth.

The controlled addition of tobramycin powder does notalter the unsurpassed mechanical properties of Simplex PBone Cement18,19. The graphs below demonstrate that thehandling properties, and strength of Simplex P withTobramycin Bone Cement are unchanged from Simplex P.

* U.S. indications only. Europe and Canada are not limited to the second stage of a two-stage revision. Note: 1 MPa (megapascal) = 145psi.

Data on file at Stryker Orthopaedics.

Handling Properties

The handling properties of Simplex Pwith Tobramycin are unchanged fromthose of Simplex P Bone Cement.

Fatigue Cycles to Failure

Tested at 20MPa and 3 cycles/second.

Internal mechanical testing confirmsthat fatigue strength is unaffected bythe addition of 1g. tobramycin.

9Tobramycin...the antibiotic of choice*

Other

Vancomycin

Gentamicin

Cephalosporin

More thanone antibioticcommonlyused

Antibiotic of Choice foruse with Bone Cement

Tobramycin is the antibiotic of choice for more than 75%of orthopaedic surgeons in the US20 for several important reasons:

Ability to withstand exothermic temperatures ofpolymerizing cement

Low allergy potential versus cephalosporins21

Excellent safety profile

Proven elution from Simplex P Bone Cement22-24

Better elution than gentamicin25

Broad spectrum antibiotic

Used safely for over 20 years in orthopaedics26, 27

* Percentages shown total greater than 100%. Surgeons surveyed were offered the choice to select more than one antibiotic.

10

Simplex with Tobramycin...the elution solution

Clinical Elution from Simplex P with Tobramycin13,14

Elution Characteristics: Tobramycin vs. Gentamicin

Simplex Pwith Tobramycin

Zimmerwith Gentamicin

Palacoswith Gentamicin

When antibiotics are blended with bone cement, serumlevels are controlled by the degree of antibiotic release. Tobramycinelutes in high concentrations from Simplex P Bone Cement and is concentrated locally. Low serum levels are maintained,minimizing the potential for toxicity and associated adverse sideeffects. In pre-clinical and clinical studies with Simplex P withTobramycin Bone Cement, systemic tobramycin levels remainedwell below the toxic threshold23, 28, 29 (see graph at right).

Lab studies comparing the release of 1g tobramycin from Simplex Pwith Tobramycin Bone Cement and 1g Gentamicin from Palacos,have found that tobramycin elutes in higher concentrations. Thisis consistent with data comparing the release of tobramycin andgentamicin from Simplex P, Zimmer and Palacos bonecements. The results: tobramycin released better than gentamicinfrom all three cements. In a direct comparison of average totalantibiotic release, there is a significant difference betweenSimplex P with Tobramycin as compared to Palacos andZimmer bone cements with gentamicin (see graph below right)25.

Simplex P with Tobramycin Bone Cement is the perfect blend offering surgeons the confidence of their number-one bonecement plus their first-choice antibiotic. For experience, strength,consistency and dependability, no other bone cement comes closeto Simplex P with Tobramycin Bone Cement.

Simplex P...the most documented bone cement

References1. Havelin LI, Espenhaug B, Vollset SE, Engester LB. The effect of the type of

cement on the early revision of Charnley total hip prostheses. J Bone Joint Surg.1995; 1543-1550.

2. Malchau H, Herberts P. Prognosis of total hip replacement Revision and re-revision rate in THR : a revision-risk study of 148,359 primary operations.AAOS national meeting 1998.

3. Linden U. Fatigue properties of bone cement: Comparison of mixing techniques.ACTA Orthop Scand. 1989: 60(4): 431-433.

4. Hansen D, Steen JJ. Mixing does not improve mechanical properties of all bonecements: manual and centrifugation-vacuum mixing compared for 10 cementbrands. Acta Orthop Scand. 1992; 63(1):13-18.

5. Davies J, Burke D, OConnor D, Harris W. Comparison of the fatiguecharacteristics of centrifuged and uncentrifuged Simplex P Bone Cement.J Orthop Res. 1987; 5:366-371.

6. Davies J, Jasty M, OConnor D, Burke DW, Harrigan T, Harris W. The effect of centrifuging bone cement. J Bone Joing Surg (Br). 1989; 71-B: 39-42.

7. Jasty M, Davies J, OConnor D, Burke D, Harrigan T, Harris W. Porosity ofvarious preparations of acrylic bone cements. Clin Orthop Rel Res. 1990; 259:122-129.

8. Wixson RI. Do we need to vacuum mix or centrifuge cement? Clin Orthop RelRes. 1992; 285: 84-90.

9. Lewis G. Properties of acrylic bone cement: State of the art review. J Bio MaterRes. 1997; 38: 155-182.

10. Holm N. The modulus of elasticity and flexural strength of some acrylic bonecements. Acta Orthop Scand. 1977; 48: 436-442.

11. Gates E, Carter D, Harris W. Comparative fatigue behavior of different acrylicbone cements. Clin Orthop Rel Res. 1984; 189: 294-299.

12. Davies J. OConnor D. Burke D. Jasty M, Harris W. The effect of centrifugationon fatigue life of bone cement in the presence of surface irregularities. ClinOrthop Rel Res. 1988; 229: 156-161.

13. Linden U. Mechanical properties of bone cement: Importance of the mixingtechnique. Clin Orthop Rel Res. 1991; 272: 274-278.

14. Hansen D, Steen JJ. Additional mechanical tests of bone cements. Acta OrthopBeligica. 1992; 58(3): 268-271.

15. Rey R, Paiement G, McGann W, et al. A study of intrusion characteristics of lowviscosity cement Simplex P and Palacos cement in a bovine cancellous bonemodel. Clin Orthop Rel Res. 1987; 215: 272-278.erences

16. MacDonald W, Phil M, Aust MIE, Swarts E, Beaver R. Penetration and shearstrength of cement-bone interfaces in-vivo. Clin Orthop Rel Res. 1993;286: 283-288.

17. Holm N. The relaxation of some acrylic bone cements. Acta Orthop Scand.1980; 51: 727-731.

18. Murray WR, Use of antibiotic-containing bone cement. Clin Orthop Rel Res1984 Nov(190): 89-95.

19. Davies JP, Harris WH. Effect of hand mixing tobramycin on the fatigue strengthof Simplex P. J Biomed Mater Res. 1991; 25(3):1409-1414.

20. Fish DN, Hoffman HM, Danziger LH. Antibiotic-impregnated cement use in US hospitals. Am J Hosp Pharm. 1992;49: 2469-2474.

21. Popham GJ, Mangino P, Seligson D, Henry SL. Antibiotic-impregnated beads.Part II: Factors in antibiotic selection. Orthop Rev. 1991 Apr; 20(4): 331-7.

22. Brien WW, Salvati EA, Klein R, Brause B, Stern S. Antibiotic impregnatedbone cement in total hip arthroplasty. Clin Orthop. 1993;296: 242248.

23. Nijhof M, Dhert W, Tillman P, Verbout A, Fleer A. Release of tobramycin-containing bone cement in bone and serum of rabbits. J Mat Sci Mat Med.1997;8(12):342353.

24. Scott CP, Higham PA, Dumbleton JH. Effectiveness of bone cement containingtobramycin: An in vitro susceptibility study of 99 organisms found in infectedjoint arthroplasty. J Bone Joint Surgery (Br). 1999; 81-B:440-443.

25. Nelson, CL, Griffin, FM, Harrison BH, Cooper RE. In vitro elutioncharacteristics of commercially and noncommercially prepared antibioticPMMA beads. Clin Orthop. 1992 Nov (284): 303-9. 1992.

26. Heck D, Rosenberg A, Schink Ascani M, Garbus S, Kiewitt T. Use of antibiotic-impregnated cement suring hip and knee arthroplasty in the United States.J of Arthrop. 1995;10(4): 470-475.

27. Soto Hall R, Saenz L, Tavernetti R, Cabaud HE, Cochran TP. Tobramycin inbone cement. An in-depth analysis of wound, serum, and urine concentrationsin patients undergoing total hip revision arthroplasty. Clin Orthop. 1983,May(175):60-4.

28. Sterling GJ, Potter JM, Koerbin G, Crawford S, Crawford R, 2002. Thepharmacokinetics of Simplex Tobramycin Bone Cement. A Study investigatingthe elution characteristics of Simplex Tobramycin Bone Cement in total hipreplacement. J Bone Joint Surg (Br) 2003; 85-B:646-9.

29. Physicians Desk Reference Edition 54, Medical Economics Company, Inc.,Montvale NJ. 2000; 1628-1631.

The information presented in this brochure is intended to demonstrate the breadth of Stryker product offerings. Always referto the package insert, product label and/or user instructions before using any Stryker product. Surgeons must always rely ontheir own clinical judgment when deciding which treatments and procedures to use with patients. Products may not beavailable in all markets. Product availability is subject to the regulatory or medical practices that govern individual markets.Please contact your Stryker representative if you have questions about the availability of Stryker products in your area.

The marks bearing the symbol are trademarks of Stryker.The marks bearing the symbol are registered trademarks of Stryker.

Depuy, Endurance, Generation 4, Osteobond, Palacos, SmartSet, and Zimmer are not trademarks of Stryker.

Literature Number: LSBTG/GS 2.5M 12/04 8352

Copyright Stryker 2004Printed in USA.

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Simplex P with Tobramycin

The Perfect Blend of Confidence and Performance

Simplex P Bone Cement

Reliable Predictable Trusted

Ordering Information

6197-9-010 Full Dose 10-pack

Ordering Information

6191-1-001 Full Dose Individual Box

6191-1-010 Full Dose 10-pack

6188-1-001 Half Dose Individual Box

6188-1-010 Half Dose 10-pack

Stryker Orthopaedics Customer Service (U.S.) 1-877-946-9678

Stryker Canada Customer Service 1-800-668-8323

For information on Stryker Bone Cement Mixers andAccessories call Stryker Instruments Customer Service 1-800-253-3210