TISSUE PROCESSING MATTERS. - Medtronic · TISSUE PROCESSING MATTERS. The Medtronic Eatontown tissue...

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TISSUE PROCESSING MATTERS. The Medtronic Eatontown tissue processing facility is a purpose built facility that utilizes state of the art ISO Class 5 Clean Rooms, Onsite Microbiology Labs & Staffed Highly Trained Scientists and Engineers to ensure our tissue grafts have the most inductive and conductive properties on the market today. Our dedication to processing tissue began in 1986. And many of the industry standards that are followed today were established here. Partnering with us for your demineralized bone graft needs will ensure you are giving your patients the best opportunity to heal. D-MIN Aseptic Tissue Demineralization

Transcript of TISSUE PROCESSING MATTERS. - Medtronic · TISSUE PROCESSING MATTERS. The Medtronic Eatontown tissue...

Page 1: TISSUE PROCESSING MATTERS. - Medtronic · TISSUE PROCESSING MATTERS. The Medtronic Eatontown tissue processing facility is a purpose built facility that utilizes state of the art

TISSUE PROCESSING MATTERS.

The Medtronic Eatontown tissue processing facility is a purpose built facility that utilizes state of the art ISO Class 5 Clean Rooms, Onsite Microbiology Labs & Staffed Highly Trained Scientists and Engineers to ensure our tissue grafts have the most inductive and conductive properties on the market today. Our dedication to processing tissue began in 1986. And many of the industry standards that are followed today were established here. Partnering with us for your demineralized bone graft needs will ensure you are giving your patients the best opportunity to heal.

D-MIN™ Aseptic Tissue Demineralization

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Allograft bone that has undergone demineralization (the process of removing certain minerals and cellular elements) has been shown to be a useful graft material due to its combined osteoconductive and osteoinductive properties.1,2,3

THE NEXT ADVANCE IN THE EVOLUTION OF ALLOGRAFT TISSUE SCIENCE

While the effectiveness of demineralized bone matrix in bone defect reconstruction was reported as early as 1889,4 one of the first documented clinical uses of demineralized bone matrix was reported in 1961 by Sharrard and Collins,5 who successfully used the material for spinal fusion in children. More recently, Kang et al5 proved at a 2-year follow-up subjects who were randomized to Grafton™ Matrix and local bone achieved an 86% overall fusion rate and improvements in clinical outcomes that were comparable with those in the iliac crest bone graft group, which is considered the gold standard for clinicians. All of this information demonstrates how demineralized bone matrix plays an important role in many bone transplant procedures.

FUSION RATE

OVERALL AND IMPROVEMENTS IN CLINICAL OUTCOMES

86%

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Grafton™ DBM DBF

In describing the ideal demineralized bone, one should consider the relevant characteristics desired of any allograft material. As such, the ideal demineralized bone matrix would:

§ Have ample clinical evidence published in peer-reviewed journals.

§ Expose the graft’s inherent biologic potential.

§ Minimize the potential immune or inflammatory responses at the graft site.

§ Not be a source of infectious disease.

§ Be convenient to place and allow for a favorable graft to host interface.

§ Be available on a consistent basis in a variety of forms.

WHAT IS THE “IDEAL” DEMINERALIZED BONE?

Grafton™ Putty

Grafton™ Matrix Grafton™ Plus™ Paste

Xpanse™ Cylinder

Xpanse™ L

Magnifuse™ II DBM

Magnifuse™ DBM

Xpanse™ C

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All tissues undergoing the D-MIN™ Process are selected from donors following a detailed social and medical history screening, and are recovered using stringent aseptic technique.

D-MIN™ DONOR SCREENING & PROCESS SAFETY

Comprehensive serologic testing of donor blood is performed, which includes sensitive testing for HIV, hepatitis, and syphilis, in addition to screening for systemic infections. The tissues are aseptically processed by Medtronic in certified clean rooms where rigorous production standards and quality assurance protocols are applied. D-MIN™ Processing includes many safety-enhancing procedures such as double freeze-thaw cycles, ultrasonic cleaning, antibiotic soaks, the removal of blood and lipids, and complete low moisture levels lyophilization.

Medical History Interview with Family

Tissue Bank Medical Director Review

* eligibility criteria meets or exceeds AATB and FDA requirements

DONOR SCREENING – TWO STAGES

Decision to recover

No recovery

Recovery

Gather information*:

§ Autopsy § Physical

Examination § Swab

Culture § Serology

Decision to process

Excluded from processing facility

Processtissue

Yes Yes

No No

For added safety, all tissues are bathed in ethanol, a known virucidal agent. Microbiology tests are performed multiple times prior to and throughout the process.

A published university-based study has found that the D-MIN™ Process inactivates and eliminates HIV in infected human bone.7

It is this combination of stringent donor screening, rigorous testing, and proprietary processing technologies that contributes to safe allograft bone.

Stringent Donor Screening

Rigorous Testing

Proprietary Processing Technologies

Safe Allograft Bone

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RELATIVE RISK OF DISEASE TRANSMISSIONThe risk of transmitting HIV through an appropriately screened donor population has been reported as less than 1 in 4,669,173,600,000,000.*

D-MIN™ DONOR SCREENING & PROCESS SAFETY

RISK REDUCTION

<1

>25 YEARS OF CLINICAL

HISTORY

* More rigorous/selective/sensitive screening methods (questionnaire, testing, etc.) have become available since, further reducing the risk of transmission. Buck, et al, Clin Ortho Rel Res 240:129-136,1989 Scarborough, Nelson L. et al, Allograft Safety: Viral Inactivation with Bone Demineralization. Contemporary Orthopaedics, October 1995, Vol 31. No.4

in 4.6 Quadrillion

Each step in our aseptic process is designed to reduce the bio burden of the tissue. As tissue-based products move through our processing facility they become cleaner and therefore do not require terminal sterilization.

1. General Population

2. FDA & AATB Guidelines + GTP

3. Donor Acquisition & Selection

4. Plant Controls + Testing

5. Tissue Processing 5A. Acid

Demineralization5B. Ethanol

Treatment5C. Lyophilization

Viral Inactivation

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STRINGENT DONOR SCREENING AND RIGOROUS TESTING

MEDTRONIC PROPRIETARY PROCESS

PROCESS SAFETY STEPS

Medical and Social History Screening

Medical Director and Quality Assurance (QA) Review

-70°C (First Freeze Cycle)

Microbiology:

Complete Anaerobe and Aerobe Identification

Serology:

HIV-1 Ab, NATHIV-2 AbHTLV 1, 2 Ab*

*Required for international markets only

HBVsAg and NATHCV Ab, NATSyphillis (T. Pallidum)

Medtronic Process of Pretreatment Irradiation is conducted for selected donors based on bioburden results.

Physical Debridement, Ultrasonic Bath, Ethanol Treatment, Antibiotic Soak, and Blood/Lipid Removal

Controlled Acid Soak

Lyophilization: Freezing -70°C (Second Freeze Cycle)

Testing and Processing Protocol Verification (Manual and Computer)

GeneralPopulation

DonorSelection

Microbiologyand Serology

Freezing

MedicalReview

PretreatmentIrradiation

PhysicalProcessing

D-MIN™

Process

Preservation

Final QARelease

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Controlled Acid Soak

D-MIN™ ASEPTIC TISSUE DEMINERALIZATION THE NEXT ADVANCE

Red arrows indicate residual DBM. 10x Magnification

Green arrows indicate new bone deposits. 10x Magnification

Yellow arrows indicate bone marrow development. 10x Magnification

Black arrows indicate fibrous connective tissue. 10x Magnification

A

B

Despite demineralized bone matrix’s long and successful history of clinical performance, Medtronic has identified opportunities to improve the demineralization process. Medtronic has carefully developed the D-MIN™ Process — a controlled demineralization process built upon the foundations laid by Urist, Reddi, Glowacki, and other leading investigators.

Our attention is focused on what matters most to you: bone formation and safety.

10x Magnification of Hematoxylin eosin ( H&E) staining of donor matched DBM bone fibers after 28 day implantation in athymic rat muscle pouch model following treatment with either Medtronic’s D-MIN™ process (A) or a common competitive processing solution (B). Residual DBM (red arrows) is easily identified in both groups.

NOTE

DBM has been extensively repopulated with new cells and is associated with new bone deposition (green arrows), as well as mature bone marrow development (yellow arrows) following Medtronic’s D-MIN™ process (A) compared to a common competitive processing solution (B) where the cellular response is predominately encapsulation and /or infiltration of the DBM by fibrous connective tissue (black arrows).

Medtronic’s D-MIN™ treatment effectively maintains the activity of DBM enabling improved in vivo bone formation as compared to other common competitive processing solutions.

D-MIN Process

Common Competitive Process Solution

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Because allograft tissue processing, including demineralization, has evolved over time and is performed by numerous processors, it is important to recognize that not all demineralization processes are alike.

NOT ALL DEMINERALIZATION PROCESSES ARE ALIKE

Process variables include:

§ Acid application

§ Temperature

§ Demineralization time

§ Application of defatting agents such as ethanol

§ Aseptic processing methods versus those employing ethylene oxide or terminal sterilization

These variables may affect the processed tissue in multiple ways, including the levels of residual calcium, hydrochloric acid (HCl), and moisture, and thus may impact the performance and safety of the graft. Hence, it is imperative to control each aspect of the demineralization treatment through a validated process.

D-MIN™ ASEPTIC TISSUE DEMINERALIZATION THE NEXT ADVANCE

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OSTEOINDUCTIVITY BY PRODUCT

Animal testing is not necessarily indicative of human clinical outcome. Histological scoring table based on images from Edwards, JT et al. Clin Orthop Relat Res. 1998;357:219-228

Data on File from Medtronic internal testing (11/2016):Grafton™ DBM products, Magnifuse™ Bone Graft, Xpanse™ Bone Insert, Mastergraft™ Matrix ongoing final product testing (2006-2014); Accell Connexus®, three manufacturing lots tested on 2005; Accell Evo3®c, three manufacturing lots tested on 2010/2014; Intergro® Putty, one manufacturing lot tested on 2004; Accell TBM®, two manufacturing lots tested on 2010; DBX® Strip, three manufacturing lots tested on 2010; DBX® Mix, two manufacturing lots tested on 2010; DynaGraft® II, one manufacturing lot tested on 2003; Allomatrix® DBM, five manufacturing lots tested on 1999/2005; OrthoBlast® II DBM Putty, two manufacturing lots tested on 2003/2005; Accell DBM 100, two manufacturing lots tested on 2003/2005; OsteoSet®2 DBM, two manufacturing lots tested on 2008; Osteocel® Plus, four manufacturing lots tested on 2011-16; Osteocel® Pro, three manufacturing lots tested on 2016; Puros® one manufacturing lot tested on 2010.

Osteocel® Plus Bone Graft, FormaGraft® Collagen Bone Graft Matrix are trademarks of NuVasive. Accell Connexus® Grafts, Accell Evo3®c, Accell Total Bone Matrix®, OrthoBlast® II DBM Putty, DynaGraft ® II Demineralized Bone Matrix are trademarks of SeaSpine. Map3® Cellular Allogeneic Bone Graft is a trademark of RTI Surgical, Inc. InterGro® DBM is a trademark of Biomet. Puros® Demineralized Bone Matrix is a trademark of Zimmer Biomet. DBX® Strip, DBX® Mix Demineralized Bone Matrix are trademarks of DePuy Synthes. Allomatrix® DBM, OsteoSet®2 DBM are trademarks of Wright Medical Group. Accell DBM 100™ is a trademark of Integra LifeSciences Corporation. OsteoSponge® is a trademark of Bacterin. Vitoss® BA Bimodal Bioactive Bone Graft Substitute is a trademark of Stryker. NovaBone® synthetic bone graft is a trademark of NovaBone Products, LLC.

0 1 2 3 4

Osteocel® Plus

0.0FormaGraft®

0.0NovaBone®

0.0Vitoss® BA Foam Strip

0.0Puros®

0.2

0.2

OsteoSet® 2 DBM

0.3Accell DBM 100™

OsteoSponge® 0.3

0.3Map3® Cellular Allogenic Bone Graft

0.4Allomatrix®

0.4OrthoBlast® II

0.9DBX® Mix

0.9DynaGraft® II

1.0Accell TBM®

0.9Osteocel Pro™

1.0DBX® Strip

1.1InterGro® DBM Putty

1.1Accell Evo3®c

1.3Accell Connexus®

1.6Xpanse™ Bone Insert

1.8Grafton Orthoblend

1.0Progenix™ DBM Putty1.0Progenix™ DBM Plus

1.9Grafton Crunch

2.2Grafton Paste

2.3Grafton Gel

2.4Grafton Matrix

2.6Grafton Putty

2.6Grafton Flex

3.3Grafton™ DBM DBF

3.4Magnifuse™ Bone Graft

0.5

0.5Cortical Cancellous Chips

Cortical Cancellous Chips/Autograft 0.5

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IMPORTANT PRODUCT INFORMATION

Grafton™ and Grafton Plus™ Demineralized Bone Matrix (DBM)Indications

Grafton™ DBM and Grafton Plus™ DBM are intended for use as a bone graft extender, bone graft substitute, and bone void filler in bony voids or gaps of the skeletal system (i.e., spine, pelvis, and extremities) not intrinsic to the stability of the bony structure. The voids or gaps may be surgically created defects or defects created by traumatic injury to the bone. Grafton™ DBM (excluding the Orthoblend form) and Grafton Plus™ DBM are also intended to be packed into bony voids or gaps to fill and/or augment dental intraosseous, oral, and cranio-/maxillofacial defects. These defects may be surgically created osseous defects or osseous defects created from traumatic injury to the bone, including periodontal/infrabony defects; alveolar ridge augmentation (sinusotomy, osteotomy, cystectomy); dental extraction sites (ridge maintenance, implant preparation/placement); sinus lifts; cystic defects; craniofacial augmentation. Grafton™ DBM and Grafton Plus™ DBM may be used alone in a manner comparable to autogenous bone chips or allograft bone particulate (demineralized freeze dried bone), or they may be mixed with either allograft or autograft bone or bone marrow as a bone graft extender. Grafton™ DBM and Grafton Plus™ DBM are indicated only for bony voids or gaps not intrinsic to the stability of the bony structure. Grafton™ DBM and Grafton Plus™DBM are absorbed/remodeled and replaced by host bone during the healing process. Note: The user should consider the fact that Grafton™ DBM CRUNCH™ contains demineralized bone chips approximately 3 mm (±1 mm) in determining the appropriateness of this allograft for use in small defects.

Contraindications

The following are contraindications for the use of Grafton™ DBM and Grafton Plus™ DBM:

-The presence of infection at the transplantation site.

- Treatment of spinal insufficiency fractures.

Caution

This allograft may contain trace amounts of antibiotics (gentamicin), surfactant, and other processing solutions. Caution should be exercised if the patient is allergic to these antibiotics or chemicals. Grafton Plus™ DBM Paste contains starch. Therefore, caution should be exercised in using Grafton Plus™ DBM Paste in a patient with a starch allergy and/or amylase deficiency.

Grafton™ DBM DBF ProductsGrafton™ DBM DBF can be used in orthopedic or reconstructive bone grafting procedures. The product can also be used in bone grafting procedures in combination with autologous bone or other forms of allograft bone, or alone as a bone graft.

Contraindications

The presence of infection at the transplantation site is a contraindication for the use of this allograft.

Caution

This allograft may contain trace amounts of antibiotics (gentamicin), surfactant, and other processing solutions. Caution should be exercised if the patient is allergic to these antibiotics or chemicals.

Precautions

Despite the viral inactivation and extensive tissue donor selection and qualif ication processes used in providing this tissue graft (see DONOR SCREENING AND TESTING), transmission of a communicable disease through the use of this tissue graft is still possible. Bacterial infection at the graft site may also occur. Any adverse outcomes potentially attributable to Grafton™ DBM DBF must be reported promptly to Medtronic.

Magnifuse™ Bone Graft ProductsIndications

Intended for use as a bone graft substitute in bony voids or gaps of the skeletal system (i.e. spine, pelvis and extremities) not intrinsic to the stability of the bony structure. The voids or gaps may be surgically created defects or defects created by traumatic injury to the bone.

Magnifuse™ Bone Graft may be used in a manner comparable to autogenous bone or allograft bone. Magnifuse™ Bone Graft may be mixed with f luid such as bone marrow aspirate, blood, sterile water, or sterile saline in order to adjust the consistency and handling characteristics of the bone graft material.

Please see package insert for complete list of indications, warnings, precautions, and other important medical information.

Contraindications

The following are contraindications for the use of Magnifuse™ DBM

§ The presence of infection at the transplantation site

§ Treatment of spinal insufficiency fractures

Caution

This product may contain trace amounts of antibiotics (gentamicin), surfactant, and other solutions used in processing the bone tissue as well as the PGA mesh. Caution should be exercised if the patient is allergic to these antibiotics or chemicals.

Magnifuse™ II DBM ProductsIndications

Intended for use as a bone graft substitute in bony voids or gaps of the skeletal system (i.e., posterolateral spine and pelvis) not intrinsic to the stability of the bony structure. The voids or gaps may be surgically created defects or defects created by traumatic injury to the bone.

Magnifuse™ II DBM may be used in a manner comparable to autogenous bone or allograft bone. Magnifuse™ DBM may be mixed with blood, sterile water or sterile saline in order to adjust the consistency and handling characteristics of the bone graft material.

Magnifuse™ II DBM is resorbed/remodeled and replaced by host bone during the healing process.

Contraindications

The following are contraindications for the use of Magnifuse™ II DBM

§ The presence of infection at the transplantation site

§ Treatment of spinal insufficiency fractures

Caution

This product may contain trace amounts of antibiotics (gentamicin), surfactant, and other solutions used in processing the bone tissue as well as the PGA mesh. Caution should be exercised if the patient is allergic to these antibiotics or chemicals.

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Progenix™ Putty and Progenix™ PlusIndications

Progenix™ Putty is intended for use as a bone graft substitute in bony voids or gaps of the skeletal system not intrinsic to the stability of the bony structure (i.e. spine, pelvis and extremities). The voids or gaps may be surgically created osseous defects or osseous defects created from traumatic injury to the bone. Progenix™ Putty provides a bone void filler that is resorbed/remodeled and is replaced by host bone during the healing process. When used in the extremities or pelvis, the device is used by itself. When used in the spine, the device must be mixed with autograft bone and used as a bone graft extender. Progenix™ Plus is intended for use as a bone graft substitute in bony voids or gaps of the skeletal system not intrinsic to the stability of the bony structure (i.e. spine, pelvis and extremities). The voids or gaps may be surgically created osseous defects or osseous defects created from traumatic injury to the bone. Progenix™ Plus provides a bone void filler that is resorbed/remodeled and is replaced by host bone during the healing process. The device may either be use alone or mixed with autograft bone and used as a bone graft extender.

Contraindications

These products are contraindicated, and should not be used, in patients who have known allergies to bovine collagen, sodium alginate or polymyxim and/or bacitracin antibiotics. These products do not possess sufficient mechanical strength to support the reduction of a defect site prior to soft and hard tissue ingrowth. These products are contraindicated where stabilization of the defect is not possible.

Warnings and Precautions

A small number of patients may experience localized immunological reactions resulting from the use of this device (e.g. transient localized edema and swelling, and rash.) The safety and effectiveness of the device in these patients has not been established.

Over-pressurizing the device may result in extrusion beyond the site of its intended application and may damage the surrounding tissues.

Over-pressurizing the defect site may lead to fat embolization or embolization of the device’s material into the bloodstream.

Xpanse™ Bone Insert Xpanse™ Bone Insert is comprised of demineralized allograft and can be used in orthopedic or reconstructive bone grafting procedures. The product can also be used in bone grafting procedures in combination with autologous bone or other forms of allograft bone, or alone as a bone graft. The presence of infection at the transplantation site is a contraindication for the use of this allograft.

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©2017 Medtronic. All rights reserved. Medtronic, Medtronic logo andFurther, Together are trademarks of Medtronic. All other brands aretrademarks of a Medtronic company. UC201702239 EN PMD018689-1.0 32545

Please see the package insert for the complete list of indications, warnings, precautions, and other important medical information.

Consult instructions for use at this website www.medtronic.com/manuals.

Note: Manuals can be viewed using a current version of any major internet browser. For best results, use Adobe Acrobat® Reader with the browser.Medtronic Sofamor Danek USA, Inc.

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1. Tiedeman, J.J., et al: Healing of a large nonossifying fibroma after grafting with a bone matrix and marrow, Clin Ortho Rel Res. No. 265, pp. 302-305.

2. Covey, D.C., Albright, J.A.: Clinical induction of bone repair with demineralized matrix or a bone morphogenetic protein, Orth Rev. Vol. 18, No. 8, pp. 857-863.

3. Glowacki, J.: Cellular responses to bone-derived materials, bone and cartilage allografts, AAOS, 1991.

4. Senn, N.: On the healing of aseptic bone cavities by implantation of antiseptic decalcified bone. Am J Med Sci. 98:219, 1889.

5. Sharrard, W.J.W., and Collins, D.H.: The fate of human decalcified bone grafts. Proc Roy Soc Med. 54:1101, 1961.

6. Edwards JT, Diegmann MH, Scarborough NL. Osteoinduction of human demineralized bone: characterization in a rat model. Clin Orthop Relat Res. 1998;357:219-228.

7. Mellonig, J.T.: HIV inactivation in a bone allograft, J Perio. Vol. 63, No. 12, 1992.

8. Herron, L.D., Newman, M.H.: The failure of ethylene oxide gas-sterilized freeze-dried bone graft for thoracic and lumbar spinal fusion, Spine. Vol. 14, No. 5, pp. 496-500.

9. Gibbons, M.J., et al: Effects of gamma irradiation on the initial mechanical and material properties of goat bone-patellar tendon-bone allografts, J Orthop Res. Vol. 9, No. 2, pp. 209-218.

10. Urist M.R., et al: A chemosterilized antigen extracted alloimplant for bone banks, Arch Surg. 110, pp. 416-428, 1975.

REFERENCES

BIOGRAFT COMPARISON TOOLhttp://catalyst.medtronic.com/ catalyst/comparison

BIOGRAFTCOMPARISON

Accell, Dynagraft, and OrthoBlast are registered trademarks of Integra LifeSciences Corporation. AlloMatrix and OsteoSet are registered trademarks of Wright Medical Technology. InterGro® is a registered trademark of Zimmer Biomet. Osteocel is a registered trademark of Nuvasive. Puros is a registered trademark of Zimmer, Inc. OrthoBlast™ is a registered trademark of IsoTis, Inc.