Septocoll® E - Biomet

Septocoll ® EDual-Action Collagen Fleece1

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What can patients and surgeons expect from us?Reliable products, and expertise, which ensures secure application.Moreover, developments needed in the future.<strong>Biomet</strong> is one of the leading orthopaedic companies worldwide. Wedevelop and produce products for orthopaedic and trauma surgery.Our predominant competence enables us to accompany our clientscontinuously in clinical surgeries.This vicinity has an impact: We take impulses in, and our own Researchand Development Department is a direct contact partner for new ideas.Here we connect the clinically documented quality of our implants withthe future orientated possibilities of bioactive materials. Through thiswe become an innovation force and are able to face the continuousdevelopments in our markets more flexibly.The results are products and performances, that aid the surgeons’community, to support the healing process of their patients in amedically optimal, scientifically proven, and cost-effective manner.2Legal noticeThis material is intended for educational purposes only. Any medical information included herein isfor information purposes and shall not be used in any way as substitute for professional advice providedby a physician or other health care provider.

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Septocoll ® E – An OverviewSeptocoll E is a resorbable, equine collagen fleece. It hasa hemostatic effect and contains gentamicin providingprophylactic local antibiotic protection.Septocoll E is suitable for use in septic and aseptic surgery.The fleece can be employed in all disciplines of bone andsoft-tissue surgery.Resorbable Collagen for HemostasisDue to their favorable physical surface properties, collagenfleeces shorten the bleeding time, reducing blood loss.They support the overall wound healing process bypromoting rapid collagen and protein synthesis (1, 2) .The collagen used to manufacture Septocoll E is obtainedonly from equine tendons. TSE (Transmissible SpongiformEncephalopathy) does not occur in horses.Biological resorption of Septocoll E is complete afterapproximately four weeks. Additional surgery to removethe hemostatic material is not necessary. Thus the patient’smobility and sense of well-being can be restored quicklyand cost-effectively.Hemostatic collagen fleeceLocal antibiotic protectionBiological resorptionAdditional Local Antibacterial EffectSeptocoll E is impregnated with gentamicin to giveantibiotic protection. It can therefore be applied, wherereliable protection against secondary infection is required.Septocoll E is the only fleece on the market that contains acombination of two gentamicin salts:Gentamicin sulfate is highly water-soluble, enabeling arapid release of the active substance.Gentamicin crobefate – recognizable by its distinct yellowcolor – is less water-soluble and thus induces a slowrelease of the antibiotic.The combination of Gentamicin sulfate and crobefatetherefore result in a lasting antibiotic protection.The blend of hemostatic properties and durable localantibiotic protection create optimal conditions for a rapidand smooth healing process.3

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Septocoll ® E – Quality MattersEquine collagenGood fibrinogenesisBiocompatibleEase of handlingThe starting material for the manufacture of Septocoll Econsists of natural, pure collagen fibrils extracted from horsetendons. These are both fully resorbable and water-insoluble.High-Tech ProductA complex freeze-drying process connects the collagenfibrils to form a mesh (Fig. 01). The special manufacturingprocedure produces a fleece with a large, active surfaceand good moisture stability. Unlike other collagen fleeces,which typically adhere to surgical instruments or wetgloves, Septocoll E does not stick.Hemostatic EffectIn contact with blood, collagen causes platelet aggregation.Large numbers of platelets accumulate on the collagenfleece and release coagulation factors like thrombin. Inconjunction with plasma factors these induce fibrinogenesis.ResorptionComplete resorption of the collagen fleece takes placewithin approximately four weeks – depending on localblood circulation – by way of phagocytosis and enzymaticdegradation (3) .Fig. 01Type I collagen with high biocompatibility and low immunogenicitySeptocoll E contains exclusively type I collagen, which isbest suited for biological degradation. Notable propertiesin this connection are high biocompatibility and lowimmunogenicity, as well as good controllability of resorptionvia cross-linking agents (4) .The collagen used in Septocoll E is well tolerated andsupports the patient’s convalescence through significantlyshorter wound healing times (5) .4

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Septocoll ® E – Safety FirstThe antibiotic gentamicin has been used successfully insurgical wound care for many years (6, 7, 8, 9, 10, 11, 12, 13, 14) .Gentamicin still has a good resistance profile.Local or SystemicGentamicin can be administered systemically (Fig. 02) orlocally (Fig. 03). If applied locally, however, substantiallygreater concentrations of antibiotics accumulate at the siteof action than when it is administered systemically. At thesame time, serum concentrations – and therefore potentialadverse effects – are significantly lower (8, 15) .Dual Principle of ActionDue to its collagen matrix, Septocoll E induces hemostasisand promotes wound healing; in addition, because ofthe gentamicin contained in Septocoll E, a local antibioticprotection is also provided.Site of actionAntibioticSerumExcretionLocal application:Lower serum and urine concentrationsFewer adverse effectsDual principle of action:Hemostasis and antibiotic protectionTissue/OrganThis dual principle of action — hemostasis and antibioticprotection — is provided by Septocoll E throughouttreatment because the protracted release of thegentamicin ensures additional protection against secondaryinfections during the resorption phase of the fleece. Theapplication of Septocoll E can therefore be recommendedas a hemostat for:• potentially contaminated woundsAntibioticFig. 02Systemic application: high strain on the body with lowconcentration at the site of action• contaminated wounds• revision operations in septic surgerySite of actionSerumTissue/OrganExcretionThe application of Septocoll E has been documented innumerous studies (1, 4, 5, 16, 17) .Fig. 03Local application: high concentration at the site ofaction with little effect on the body5

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Septocoll ® E – PharmacokineticsGentamicin sulfate:Rapid releaseGentamicin crobefate:Protracted releaseg100050010050105g1 2 3 4 5 6 7 8 9 10 Tage DaysCollagen fleece with gentamicin sulfate and gentamicin crobefateCollagen fleece with gentamicin sulfateMIC (Minimum Inhibitory Concentration)1000Fig. 04500Fleeces only impregnated with gentamicin sulfatereleased 90% of their gentamicin sulfate content100within 48 hours. Fleeces also impregnated with50gentamicin crobefate, however, released gentamicinover a period of 10 days (18) .1051 2 3 4 5 6 7 8 9 10 TageSeptocoll E contains two gentamicin salts, which – basedon their active substance content – are combined at a ratioof 1:1. They have different release kinetics.High Initial ConcentrationGentamicin sulfate is highly water-soluble: The antibioticis therefore released rapidly from the carrier material. Thisleads to a very high initial gentamicin concentration at thesite of action. Within a short time, however, this level dropsagain to below the minimum inhibitory concentration (MIC)for causative microbes.Lasting EffectGentamicin crobefate is a gentamicin salt that we developedin-house. It is less watersoluble than the sulfate and cantherefore release the gentamicin on a protracted basis atthe site of action. Aside from the high initial concentration,therefore, the antibiotic’s release from the fleece iscontrolled. The gentamicin crobefate gives the Septocoll Efleece its distinctive yellow color.Fleeces only impregnated with gentamicin sulfate released90% of their gentamicin sulfate content within 48 hours.Fleeces also impregnated with gentamicin crobefate,however, released gentamicin over a period of 10days (18, 19) (Fig. 04).6

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Septocoll ® E – ApplicationWe have optimized the use of Septocoll E in surgical applications:The fleece does not stick to surgical instrumentsand can be handled, shaped and cut easily with precision.Scope of ApplicationSeptocoll E is suitable for use in bone and soft-tissue surgeryin all disciplines of septic and aseptic surgery. The fleece canbe inserted as a hemostat into clean, clean-contaminated andcontaminated wound cavities and can also be used for thefollowing:• diffuse capillary, arteriovenous, arterial or venoushemorrhagesSeptocoll ® E 20LOT: 33MO107025 x 4 cm• extensive capillary hemorrhages from parenchymatousorgans• as a support measure in conjunction with othermethods of hemostasisDue to its impregnation with gentamicin Septocoll E providesreliable protection against bacterial contamination.ContraindicationsSeptocoll E must not be used in patients with known hypersensitivityto collagen and/or gentamicin.Restrictions for UseSeptocoll E should only be used in conjunction with othermethods of hemostasis at bleeding sites requiring ligationor at larger arterial and/or venous bleeding sites requiringsuturing.There is a lack of clinical experience regarding the safetyof use in pregnant women, nursing mothers and children.PresentationSeptocoll E is a medical device of class III. It is available inthree sizes, 20 cm 2 , 40 cm 2 und 80 cm 2 , containing 35 mg,70 mg and 140 mg of gentamicin, respectively. Each fleeceis packed individually in sterile packaging.Instructions for UseBefore implantation, all infected and necrotic tissue mustbe surgically removed.The Septocoll E fleece should not be moistened beforebeing inserted into the wound cavity, as this would reduceits hemostatic effect.The use of an overflow drain is indicated in many cases toallow the wound secretion to drain off. Irrigation/suctiondrainage, however, causes too rapid elimination of thegentamicin and should therefore not be used in conjunctionwith Septocoll E.Wounds treated with Septocoll E may produce a clear,yellowish secretion due to the gentamicin crobefate contentFor further information, please review the instructions leafletof the product.7

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Septocoll ® E – Clinical StudiesSeptocoll E is the enhanced version of the establishedproduct Septocoll. Both products have the same pharmacokineticprofile and identical specifications as regards theirgentamicin content. The only difference is their collagencontent and the origin of this collagen.Biological Resorption StudiesComprehensive tests were carried out to examine thebiocompatibility of Septocoll E. All the studies wereperformed at independent, accredited institutes inaccordance with the specifications of the German MedicalDevices Act (MPG) and in compliance with ISO 10993.• Cytotoxicity test• Mouse lymphoma assay• Magnusson/Kligman sensitization test• Systemic toxicity• Short-term implant – 4 weeks• Long-term implant – 12 weeks• Carcinogenicity test on gentamicin crobefateThese tests confirmed unreservedly the biocompatibilityof Septocoll E. In particular, no allergic reactions wereobserved. No implant remains were detected four weeksafter insertion of the fleece.Pharmacokinetic Studies (11)Study to evaluate the pharmacokinetic behavior afterimplantation of Septocoll or a collagen fleece loaded onlywith gentamicin sulfate in patients with bone infections.DesignProspective, randomized, single-blind study with parallelgroups.Patient Population40 patients: 20 in the Septocoll group,20 in the sulfate fleece groupTreatments and DosagesSeptocoll group: 2 fleeces Septocoll 40(equivalent to 140 mg gentamicinbase)Sulfate fleece group: 1 sulfate fleece(equivalent to 120 mg gentamicinbase)The values measured were adjusted accordingly(factor 0.8 =120 :140)8Results/Target Criteria/EndpointComparison of the pharmacokinetics of the two gentamicinloadedcollagen fleeces, control period: 10 daysThe pharmacokinetic behavior of Septocoll is superiorto that of sulfate fleeces: In the Septocoll group, higher,longer-lasting and more evenly distributed gentamicinconcentrations were found. In the Septocoll group, theurine and serum concentrations of gentamicin were lower.

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ConclusionHemostatic, resorbable and well toleratedEasy handlingMedical device – class IIIProtracted gentamicin releaseTSE-safety due to equine collagenSeptocoll in Abdominoperineal RectalResection (16)DesignMulticenter, prospective, randomized, singleblind comparativestudyPatient Population97 patients with stage I-III rectal carcinoma,49 in the Septocoll group,48 in the control groupTreatments and DosagesSeptocoll group: 1 x 2 g cefazolin i.v.1 x 500 mg metronidazole i.v.3 fleeces Septocoll 40Control group:1 x 2 g cefazolin i.v.1 x 500 mg metronidazole i.v.Results/Target Criteria/Endpointcontrol period: 8 weeksTolerability in the Septocoll group was very good with aprimary wound healing rate of 88%, compared with 75% inthe control group. As a result, there was neither hematomanor seroma formation.Septocoll After Surgical Treatment of aPilonidal Sinus (5)DesignMulticenter, controlled, single-blind studyPatient Population103 patients,51 in the Septocoll group,52 in the control groupTreatments and DosagesSeptocoll group: 1 fleece Septocoll 40,primary wound closureControl group: open treatmentResults/Target Criteria/EndpointSeptocoll combined with primary wound closure resultedin a significantly shorter wound healing time, 17 days inthe Septocoll group, compared with 68 days in thecontrol group.9

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Ordering InformationSeptocoll E – Collagen FleeceProduct Description and Size Order No.Septocoll E 20, 5 x 4 cm, 1 fleece5 fleeces30 2001 000130 2001 000580 mg collagen (equine)29 mg gentamicin sulfate (equivalent to 17.5 mg gentamicin)87 mg gentamicin crobefate (equivalent to 17.5 mg gentamicin)Septocoll E 40, 5 x 8 cm, 1 fleece5 fleeces30 2002 000130 2002 0005160 mg collagen (equine)58 mg gentamicin sulfate (equivalent to 35 mg gentamicin)175 mg gentamicin crobefate (equivalent to 35 mg gentamicin)Septocoll E 80, 10 x 8 cm, 1 fleece5 fleeces30 2003 000130 2003 0005320 mg collagen (equine)116 mg gentamicin sulfate (equivalent to 70 mg gentamicin)350 mg gentamicin crobefate (equivalent to 70 mg gentamicin)10

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Notes11

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ReferencesIW 85039102/20101. Stemberger A. et al.: „Local treatment of bone and soft tissue infectionswith the collagen-gentamicin-sponge“. Europ. J. Surg., 163(Suppl. 578): 17-26 (1997).2. Berthod F., Sahuc F., Hayek D., Damour O., Collombel C.: „Depositionof collagen fibrils bundles by long term culture of fibroblasts in a collagensponge“. J-Biomed-Mater. Res. 1996 Sep 32(1) 87-93.3. Engelhardt G. H., Gerhardt H.-J., Nagelschmidt M.: „Wirksamkeitund Biokompatibilität zweier Hämostyptika auf Kollagenbasis imTierexperiment“. Arzneim Forsch/drug research 1989, 39 (I) 259-262.4. Chevallay B., Roche St., Herbage D.: „Collagen tissue based biomaterialsand tissue engineering“. Biomaterials in surgery edited byGHIM Walenkamp Thieme, 3-10 (1998).5. Holzer B., Grüßner U., Brückner B., Houf M., Kiffner E., Schildberg F.,Vogel P., Rosen H. R.: „Efficacy and tolerance of a new gentamicincollagen fleece (Septocoll®) after surgical treatment of a pilonidalsinus“. Colorectal Disease 5, 222-227 (2003).6. Klemm K. W.: „Gentamicin-PMMA Chains (Septopal ® Chains) for theLocal Antibiotic Treatment of Chronic Osteomyelitis”. Reconstr. Surg.Traumat., 20: 11-35 (1988).7. Engesæter L. B., Lie S. A., Espehaug B., Furnes O., Vollset S. E.,Havelin L. I.: „Antibiotic prophylaxisin total hip arthroplasty. Effects ofantibiotic prophylaxissystemically and in bone cement on the revisionrateof 22,170 primary hip replacements followed 0–14 years inthe Norwegian Arthroplasty Register“.Acta Orthop Scand 2003; 74(6): 644-651.8. Knaepler H., Klemm K., Dingeldein E., Wahlig H.: „Gentamicin PMMA-Miniketten in der septischen Knochen- und Weichteilchirurgie“.Unfallchirurgie 88, 457-464 (1985).9. Malchau H., Herberts P., Södermann P., Odeén A.: „Prognosis ofTotal Hip Replacement“. Scientific Exhibition presented at the 67thAnnual Meeting of the American Academy of Orthopaedic Surgeons,March 15-19, 2000, Orlando, USA10. Weise K., Weller S.: „Indication and use of Septopal ® in chronicosteitis“. In: van Rens Th. J. G., Kayser F. H.: Local antibiotic treatmentin osteomyelitis and soft-tissue infections. Proceedings ofa Symposium, Amsterdam, 25. Oktober 1980. Excerpta MedicaAmsterdam, Int. Congress Series 556, 82-90 (1981).11. Sachweh D.: „Lokale Antibiotika-Behandlung mit protrahierterWirkstoff-Freisetzung in der Weichteilchirurgie“. In: Suckert R., VécseiV.: Antibiotikaträger – ein neuer Weg der lokalen Infektionsbehandlungin Chirurgie und Unfallchirurgie. Medizinisch-pharmazeutischeVerlagsgesellschaft, Purkersdorf bei Wien, 28-32 (1986).12. Schmidt Hergo G. K., Gerlach U., Wurm M., Grosser V.: „Diagnostikund Therapie von Schulterund Ellengelenkempyemen“. TraumaBerufskrankheit, 3 [Suppl 3]: 404-414 (2001).13. Bühler M., Schmidt Hergo G. K., Börner M.: „Infektionen nachVerletzungen am Fuß“. Trauma Berufskrankheit, 3: 240-243 (2001).14. Bonnaire F., Hohaus T., Cyffka R., Lein T.: „Knocheninfektionen“.Unfallchirurg 73: 716-733 (2002).15. Wahlig H.: „Gentamicin PMMA beads, a drug delivery system; basicresults“. In: van Rens Th. J. G., Kayser F. H.: Local antibiotic treatmentin osteomyelitis and soft-tissue infections. Proceedings ofa Symposium, Amsterdam, 25. Oktober 1980. Excerpta MedicaAmsterdam, Int. Congress Series 556, 9-17 (1981).16. Grüßner U. et al.: „Improvement of perineal wound healing by localadministration of gentamicinimpregnated collagen fleeces after abdominoperinealexcision of rectal cancer“. Am. Journal of Surgery,November 2001, Volume 182, No. 5.17. Grüßner U. et al.: Humanpharmakokinetik des neuen Gentamicin-Kollagen-Vlieses Septocoll ® bei Knochenchirurgischen Eingriffen“.Osteosynthese International [Suppl 1], 43-48 (2000).18. Dingeldein E.: „Gentamicin-Kollagen-Vlies Untersuchungen zurGentamicinfreisetzung in vitro“ (1987) und „Gentamicin-Kollagen-VliesUntersuchungen zur Gentamicinfreisetzung in vitro, Gentamicinsulfatund schwerlösliches Gentamicinsalz“ (1987) (Data on file).19. Dingeldein E.: „In vitro Untersuchungen zur Gentamicin-freisetzung“(1988) (Data on file).This material is intended for the sole use and benefit of physicians. It is not tobe redistributed, duplicated or disclosed without the express written consent of<strong>Biomet</strong>.Responsible manufacturer<strong>Biomet</strong> Deutschland GmbHGustav-Krone-Str. 2D-14167 Berlin0123Worldwide distributor<strong>Biomet</strong> Deutschland GmbHGustav-Krone-Str. 2D-14167 BerlinTel.: +49 / 30 / 845 81-0Fax: +49 / 30 / 845 81-110www.biomet.de