Background Paper for the Tissue Expert Committee:

Transcription

1 Background Paper for the Tissue Expert Committee: What will the role of Canadian allograft processing be in the future? Contents 1. Introduction... 2 A. Background Scope Tissue Processing Models Ocular Skin Cardiac Tendons and Soft Tissues Musculoskeletal Base Tissues, Machined and Demineralized Grafts... 9 APPENDIX A: Canadian Tissue Banks Production Functions Original version: January 2010 Reformatted: October 2011

2 1. Introduction A. Background Recognizing the need to improve the organ and tissue donation and transplantation (OTDT) system in Canada, the federal, provincial (except Quebec) and territorial governments in April asked Canadian Blood Services to take on new responsibilities related to OTDT. This included the development of a strategic plan for an integrated OTDT system, in collaboration with the OTDT community. As part of this work, three committees were formed the Steering Committee, Organ Expert Committee and Tissue expert Committee to help develop the recommendations through a formal, structured planning process. This document is one of a series of background documents developed to help the committees in their discussions. These documents focused on the critical issues within the system, describing the current state and examining potential options and solutions. Conclusions from the committee discussions were consolidated and incorporated in the final recommendations of the final report. The full report, Call to Action: A strategic plan to improve organ and tissue donation and transplantation performance for Canadians, can be found at organsandtissues.ca, along with the other background documents in this series. Limitations of these documents: These documents were intended for an audience familiar with the subject matter and contain terms and acronyms that may not be in common usage outside the field. In some cases, original documents referenced draft materials which have now been finalized. In these cases, where possible, references have been updated. These situations are clearly marked. These documents provided an overview of the issue for further discussion by experts in the field of OTDT. The findings and evaluations contained in these documents are not comprehensive they reflect what was considered to be most applicable to the issue at the time. Information in these documents presents knowledge available at the time of the OTDT committee meetings. These documents have been edited for consistency in style and format, but have not been updated to reflect new information or knowledge. References and web links also remain unchanged and may no longer be accurate or available. As these are background documents to the Call to Action report which is available in both English and French, they are available in English only. Requests for translation can be made to Canadian Blood Services using the contact information below. Note: Production of this document has been made possible through a financial contribution from Health Canada. The views expressed herein do not necessarily represent the views of the federal, provincial or territorial governments. For more information on these documents or the Call to Action report, please contact: Canadian Blood Services Organ and Tissues Donation and Transplantation 1800 Alta Vista Drive Ottawa ON K1G 4J5 Phone: feedback@blood.ca 2

3 2. Scope What will the role of Canadian allograft processing be in the future? This paper is intended to generate discussion about the role of Canadian tissue banks in the production of allografts to meet demand for ocular, skin, cardiac, tendons and musculoskeletal tissue. This paper briefly outlines the Canadian, US and UK tissue processing models, as well as their similarities and differences. Each tissue type is presented with an overview of the current state of processing and demand in Canada. Market trends for the use of each type of tissue are described, and a number of questions are posed to inform discussion about the future role of Canadian tissue banks with respect to processing this type of tissue. Direction and advice are sought from the Tissue Expert Committee to identify what the Canadian production role should be, and what would be required to support that role. Should Canadian capacity be maintained or expanded, or should alternative production strategies be explored? Given market trends with respect to new product types, will there continue to be demand for the types of tissue being produced in Canada? Can new types of tissue be produced to adjust to any changes in demand? Discussions should take into account the principals of quality, safety, equitable access, efficacy and efficiency. Surgical bone banking and the supply of donor tissue are addressed in separate papers. Discussions assume an increasing supply of Canadian donor tissue. 3. Tissue Processing Models Canada The majority of Canadian eye and tissue banks operate within hospital surgical or laboratory services. The competition for limited resources within the hospital environment has been identified as a barrier to enabling growth and the adoption of best practices. 1 The cost of allografts are assigned to cost centres within hospitals or, in the case of dental procedures, covered by private insurance. The use of allografts within the hospital environment may be limited by budgetary restrictions. Some Canadian tissue and eye banks recover costs for allografts distributed outside their host institution. In, there were a total of 29 eye, tissue and surgical bone banks in Canada, including four banks in Quebec and two islet cell programs. Excluding the islet programs and the banks in Quebec, the other 23 institutions are made up of: 1 Canadian Blood Services, Supply of Human Allograft Tissue in Canada: Final Report, 2010 three comprehensive tissue banks; one recovery bank with processing partnerships; seven surgical bone banks; seven tissue-specific banks (five musculoskeletal, one cardiac and one skin); and five stand-alone eye banks. In, Canadian tissue banks (outside Quebec) produced 8,192 allografts from deceased donors. 2 A comparative analysis of Canadian tissue banks between 2002 and indicated significant changes in the production numbers of some types of tissue allografts, which are detailed in this paper. Canadian tissue banks yield an average of 21 allografts per donor. 3 Centres with higher donor volumes and that process multiple tissues have 2 Canadian Blood Services, Supply of Human Allograft Tissue in Canada: Final Report, American Association of Tissue Banks. Report on the 2007 Annual Survey. March

4 previously been shown to be more cost effective. 4 The comprehensive tissue banks within Canada provide over 80% of Canada s supply of musculoskeletal, cardiac and skin allografts and have the higher tissue yields than tissue specific banks. 5 for an average production yield of 49 allografts per donor. 7 The Eye Bank Association of America identified 86 accredited recovery programs, eye banks and distribution organizations that accounted for a 2007 distribution of 50,122 corneas. 8 A 2006 review indicated that emerging technologies including synthetics, xenografts and gene and stem cell therapy in orthopedics would not displace traditional tissue banking within the next ten years, but may have the potential to reduce demand. 6 Production and utilization data is presented in this report with the exclusion of Quebec activity. United States The US tissue system operates in a competitive private-sector market. Not-for-profit and for profit organizations provide a range of products for the US market, and for export to Canada. A 2007 survey of 109 US tissue banks identified 32 facilities that, when combined, processed 49,000 donors and distributed 2,141,452 allografts and tissue devices 4 Canadian Council for Donation and Transplantation. Human Tissue Banking in Canada; Costing and Economic Analysis, September 16, Canadian Blood Services, Supply of Human Allograft Tissue in Canada: Final Report, Canadian Council for Donation and Transplantation. Tissue Banking Innovation Practices August United Kingdom In the late 1990s, the four largest multi-tissue banks amalgamated into a single service within the National Health Service Blood and Transplant (NHSBT). The amalgamation was driven by the potential for operational efficiencies and to take advantage of existing support services in the National Blood Service. NHSBT - Tissue Services is the major provider of tissue within the UK, managing approximately 400 cadaver donor recoveries annually. The tissue service competes with other UK banks and international suppliers for market share, and currently accounts for 100 per cent of market share for skin, 70 per cent for base bone products, 50 per cent for surgical bone and 10 per cent for heart valves. Eye banking is distinct from the tissue service. 9 Advanced tissue products such as DBM and machined bone drafts are sold into the market by commercial organizations, and are not manufactured by the NHSBT Tissue Service 7 American Association of Tissue Banks. Report on the 2007 Annual Survey. March Eye Bank Association of America. Retrieved from December 1, Helen Gillian. Manager Liverpool Tissue Facility, NHSBT Tissue Service, Personal Communication September 8, Ocular Current State Canadian eye banks have identified 61 ophthalmologists currently transplanting corneas. 10 Transplants are generally scheduled electively. Based on a survey of ophthalmologists, factors resulting in cancellations of surgeries have been identified to be 11 : 10 Canadian Blood Services. Demand for Ocular Tissue in Canada. January Mahta Rasouli. Efficacy of Routine Notification and Request on Reducing Corneal Transplantation Wait Times in Canada. Can J Ophthalmology Vol. 44, No tissue availability (75 per cent of respondents; 21/28) a medical condition in patients (32 per cent of respondents; 9/28), and operating room time shortage (14 per cent of respondents; 4/28). The average wait times for transplantation vary widely by region (median of 18 months, range 7 36 months; 13 per cent of transplanted corneas are 4

5 imported from other provinces. 12 Héma-Québec is currently engaged in an initiative to decrease its ocular waitlist by importing corneas from both US and Canadian eye banks. Historically, Canadian eye banks have not practiced cost recovery for ocular tissue (except sclera) an approach that has impeded interprovincial distribution. 13 Héma- Québec is expected to reimburse Canadian eye b anks who provide corneas for Quebec. A comparative analysis indicates that ocular tissue processing increased 14 per cent from 2002 to. In, two stand-alone Canadian eye banks were amalgamated into existing tissue programs. Héma-Québec is currently in the process of incorporating existing eye programs into its organization. 12 Canadian Blood Services. Demand for Ocular Tissue in Canada. January Canadian Blood Services, Supply of Human Allograft Tissue in Canada: Final Report, 2010 Figure 1 Canadian Ocular Supply and Demand Allograft Product Production 14 Utilization 15 Waiting List 16 Median of Waiting Time in Months 17 Corneas (PK, DALK, DSAEK) 2,404 1,969 2, (range 7-36) Sclera (1/8,1/3,1/4,1/2 and full globe) 1, None Not applicable Amniotic membrane 200 Unknown None Not applicable 14 Canadian Blood Services, Supply of Human Allograft Tissue in Canada: Final Report, Canadian Blood Services. Demand for Ocular Tissue in Canada. January Canadian Blood Services. Demand for Ocular Tissue in Canada. January Canadian Blood Services. Demand for Ocular Tissue in Canada. January 2010 Market direction Since 2005, partial-thickness corneal transplant procedures such as DSAEK (Descemet s stripping automated endothelial keratoplasty) and DALK (deep anterior lamellar keratoplasty) have increased from 2.4 per cent to 36.1 per cent of all transplants. 18 In a penetrating keratoplasty, the recipient s entire cornea is removed. In partial thickness transplants the recipient s healthy endothelium is left intact and used to host donor tissue from which the endothelium is removed reducing the potential for rejection and improving 18 Boimer C, Lee K, Sharpen, L, Shehadeh, R, Slomovic AR, Evolving surgical techniques of and indications for corneal transplantation in Ontario from 2000 to 2009, Canadian Journal of Ophthalmology Volume 46, Issue 4, Pages , August 2011 outcomes. This advanced processing procedure is commonly performed in US eye banks and has been implemented by two Canadian eye banks. While still infrequently used in Canada, DMEK (Descemet s membrane endothelial keratoplasty) is becoming more common in the US. DMEK is commonly performed in the operating room and leaves the patient s cornea closer to its original condition than other techniques. 19 There is a significant corneal discard rate (30 per cent) with this procedure, increasing the demand for corneal tissue. 19 Cornea Research Foundation of America, Retrieved from on December 8,

6 Questions for consideration: What is required to address the significant disparity of waiting times and support the equitable distribution of corneas across provincial boundaries? What is required to support the emerging demand for partial thickness grafts? 5. Skin Current state Skin grafts produced by Canadian tissue banks support the 14 burn treatment centres in Canada. Skin allografts are also used in dentistry, although there is no Canadian skin-processing activity directed to the dental market. Of the four Canadian tissue banks that supply skin, the two programs produce 71 per cent of the total Canadian supply. The other two programs produce 27 per cent and two per cent respectively. A comparative analysis indicates that skin allograft production by Canadian tissue banks decreased by 65 per cent between 2002 and. One tissue program supplies unprocessed tissue to US processors; this allograft production is not captured in Canadian production data. In the United States, a 2007 survey of 109 tissue banks identified 14 skin processing centres that process and distribute 312,000 allografts from 17,000 skin donors. Figure 2 Skin Allografts Supply and Demand Canadian Production 20 Est Surgical Utilization 21 Est Canadian Utilization Canadian Skin 768 1,513 50% Unknown Unknown 20 Canadian Blood Services, Supply of Human Allograft Tissue in Canada: Final Report, Canadian Council for Donation and Transplantation. Demand for Human Allograft Tissue in Canada. May 2003, Table 27 Medium Range. Market trends Human skin is used to cover wounds and burns, providing a barrier to infection and a matrix for colonization by the patient s own cells. Autologous skin grafts achieve wound coverage without risk of rejection and are used when graft sites are available. Emerging practice includes growing autografts in the laboratory by culturing the patient s donated skin cells. Commercially available products that incorporate both human (Alloderm), cultured human (Dermagraft) or xenograft (Integra) tissue sources are available for a variety of surgical and wound care applications. In the past, burn surgeons obtained skin allografts from their own hospital tissue banks. Recently, however, the trend has been toward ordering skin from commercial US allografts suppliers BCC Research: Organ and Tissue Transplantation and Alternatives.. Questions for Consideration: Is there sufficient demand for skin allografts to support maintaining or expanding the production of this tissue by Canadian tissue banks? Should experts of donor tissue to the US for processing and repatriation be maintained or expanded? 6

7 6. Cardiac Current state Heart valves are regulated as medical devices; the production of valves is a high-cost, low-volume activity. Besides Hema-Quebec, three Canadian tissue banks process cardiac valves. Canadian banks produce aortic segments but do not produce vascular tissue (veins and arteries). Current Canadian utilization data on heart valves, conduits and vascular tissue is not available. A comparative analysis indicates that cardiac tissue processing by Canadian tissue banks declined by 58 per cent between 2002 and, which corresponds to the 56 per cent decrease in cardiac tissues recovered over the same period. One tissue program supplies unprocessed cardiac tissue to US processors, and this allograft production is not captured in Canadian production data. In the United States, a 2007 survey of 109 tissue banks identified four cardiovascular processing centres that produce and distribute 5,349 cardiac and 3,592 vascular grafts from 8,800 cardiovascular donors. One company Cryolife, Inc. provides 65 per cent of the cardiac valve allografts Robert Rigney. American Association of Tissue Banks Report on the 2007 Annual Survey. March Figure 3 Cardiac Allograft Supply and Demand Allograft Product Canadian Production 24 Est Surgical Utilization 25 Est Canadian supply % Utilization Canadian Valves % Unknown Unknown Conduits % Unknown Unknown Vascular (Aorta, Veins, Arteries) 5 Unknown Unknown Unknown Unknown 24 Canadian Blood Services, Supply of Human Allograft Tissue in Canada: Final Report, Canadian Council for Donation and Transplantation. Demand for Human Allograft Tissue in Canada. May 2003 Table 26 Low Range. Market Trends At present, there are two principal heart valve types: bioprosthetic (made from human or animal tissue) and mechanical valves. Human bioprosthetic valves are limited in availability, while mechanical valves pose risks related to thrombosis. Human allograft valves are used in approximately four per cent of cardiac valve replacements. Cardiac valves are most commonly used in pediatric and young-adult cardiac surgical Questions for Consideration: procedures where demand is primarily for smaller valves. The US heart valve market is projected to increase by 5.2 per cent by Coronary bypass surgeries are normally performed with autologous grafts; however, in cases where autologous is not an option, allograft can be used. 26 BCC Research. Market Research Report: Organ and Tissue Transplantation and Alternatives, October. Should the capacity of Canadian tissue banks to process cardiac valves and vascular tissue be maintained or expanded? Should exports of donor cardiac and vascular tissue to the US for processing and repatriation be maintained or expanded? 7

8 7. Tendons and Soft Tissues Current state Tendons are currently produced by five Canadian tissue banks. Two of these banks also produce fascia and meniscus, and one also produces pericardium. The attributes and characteristics of these soft tissue grafts vary between programs. Communication channels to end-users are underdeveloped and data on tendon and soft-tissue allograft utilization is not readily available. In the United States, a 2007 survey of 109 tissue banks identified 20 soft-tissue processing centres that produced a total of 152,000 allografts from 12,000 tendon, 8,600 ligament, 7,500 fascia and 5,000 pericardium donors. 27 A comparative analysis indicates tendon processing increased by 103 per cent between 2002 and ; during that same period in Canada, soft tissue processing decreased by 75 per cent. 28 One Canadian tissue program supplies this tissue to the US for processing and distribution an activity that is not captured in Canadian production data. 27 American Association of Tissue Banks. Report on the 2007 Annual Survey. March Canadian Blood Services, Supply of Human Allograft Tissue in Canada: Final Report, Figure 4 Tendon Supply and Demand Surgical Grafts Canadian Production 29 Est Utilization 30 Est Canadian supply % Utilization Canadian Tendons 945 1,232 77% Unknown Unknown 29 Canadian Blood Services, Supply of Human Allograft Tissue in Canada: Final Report, 30 Canadian Council for Donation and Transplantation. Demand for Human Allograft Tissue in Canada. May Table 27 Medium Range. Market direction Sourced by the orthopedic surgical community, tendons are in higher use among orthopedic surgeons who specialize in sports medicine. There are 1,181 orthopedic surgeons practicing in Canada. A 2009 survey of Canadian tissue banks identified tendons as high-demand products, and supply is not always available to meet end-user requests. 31 There is need for soft tissue (fascia) in the dental market, but no Canadian production is currently directed to meet this demand. This market is being served entirely by US commercial suppliers. 31 Canadian Blood Services, Supply of Human Allograft Tissue in Canada: Final Report. Questions for Consideration: Should the capacity of Canadian tissue banks to produce tendons or other soft tissues be maintained or expanded? Should exports of donor tendon and soft tissue to the US for processing and repatriation be maintained or expanded? 8

9 8. Musculoskeletal Base Tissues, Machined and Demineralized Grafts Current state Of the six Canadian tissue programs that process cadaver bone, two programs distribute cancellous and structural grafts to hospitals outside of their host institution or region. Two other programs have plans to begin processing cadaver bone. One program did not respond to the Canadian Blood Services survey; its activity is unknown. The attributes and characteristics of musculoskeletal products vary between programs. Communication channels to end-users are underdeveloped. In, there was no production by lyophilized, demineralized or machined products within Canada; however, one program has recently initiated the production of lyophilized products. 32 Data on Canadian bone allograft use is not readily available, and demand forecasting is not an established practice within Canadian programs. A comparative analysis indicates that the Canadian processing of ground cancellous bone increased by 100 per cent between 2002 and while the 32 Canadian Blood Services, Supply of Human Allograft Tissue in Canada: Final Report, 2010 processing of small and large structural grafts decreased by 67 per cent and 41 per cent respectively during the same time period. One program is currently supplying cadaver bone to the US for processing and distribution (US processing of this tissue is not captured within the Canadian production data). In the United States, a 2007 survey of 109 tissue banks identified 24 bone processing centres, 15 of which process demineralized bone. These centres processed a total of 23,000 donors, producing and distributing 1,166,969 musculoskeletal grafts and 501,559 tissue devices including machined screws, dowels and bone cages. 33 Musculoskeletal allografts are purchased as a medical supply within the Canadian surgical and dental communities. These communities include 1,181 orthopedic surgeons, 239 neurosurgeons, 355 oral and maxillofacial surgeons, 230 periodontists and 19,000 dentists. 33 American Association of Tissue Banks. Report on the 2007 Annual Survey. March Figure 5 Musculoskeletal Base Supply Utilization Alignment Surgical Grafts Canadian Production Estimated Utilization 35 Est Canadian Utilization Canadian Surgical bone 1,271 Unknown 100% % Cancellous 1,838 3,313 55% Unknown Unknown Small structural 139 2,762 5% Unknown Unknown Large structural 869 2,418 36% Unknown Unknown 34 Canadian Blood Services, Supply of Human Allograft Tissue in Canada: Final Report, Canadian Council for Donation and Transplantation. Demand for Human Allograft Tissue in Canada. May Cancellous Table 27 Medium Range, Small/Large Struc/Soft Tissue Table 26 Low Range. 9

10 Surgical Grafts Canadian Production 36 Est Utilization Est Canadian Utilization Canadian Machined grafts 0 Unknown 0 Unknown 0 36 Canadian Blood Services, Supply of Human Allograft Tissue in Canada: Final Report, 2010 Surgical and Dental Grafts Demineralized bone products Estimated 2005 Total Utilization Canadian Canadian Utilization 37 64,004 cc Unknown 0% 37 Canadian Council for Donation and Transplantation. Market Evaluation of Demineralized Bone Matrix Products. April Questions for consideration: Should Canadian capacity for base tissues be maintained or expanded? Should Canadian capacity for machined products be developed? Should Canadian capacity for demineralized products be developed? Should exports of donor tissue to the US for processing and repatriation be maintained or expanded? Given the breadth of products offered to Canadian end-users by US processors in a market-based competitive environment, what product lines should be the focus of Canadian processing? Should Canadian processors compete to gain market share from US manufactures in these product lines? Market direction A 2009 survey of Canadian tissue banks identified cancellous and small structural grafts as highdemand products often in short supply to meet end-user needs. 38 Demand for orthopedic biomaterials is primarily being driven by an aging, yet active population that requires greater care and maintenance of joints. Growing awareness of new products that feature such innovations as stem cell incorporation is helping to drive adoption. 39 Three types of products account for bone allograft sales revenue in the United States: base tissues (48 per cent), demineralized bone matrix (26 per cent) and machined implants (26 per cent). Base tissue is 38 Canadian Blood Services, Supply of Human Allograft Tissue in Canada: Final Report, Millennium Research Group. US markets for Orthopedic Biomaterials losing market share as the industry moves toward more specialized products to meet specific needs. 40 Use of autologous grafting in orthopedic and spinal procedures is decreasing in favour of substitutes including demineralized bone, collagen based products, and synthetics. 41 A review of three large US-based processors revealed a range of 200 to 650 different products and size-differentiated allografts. By 2013, the US market is projected to increase by five per cent for base tissues, 12.5 per cent for demineralized bone, and 8.5 per cent for 40 BCC Research. Market Research Report: Organ and Tissue Transplantation and Alternatives, October. 41 Spine Arthroplasty Society Journal. Basic Science Symposium 1: Bone Graft Substitutes, Winter Volume 2 Issue 1. 10

11 machined implants. 42 Fresh osteochondral grafts for which Canadian demand is increasing are a 42 BCC Research. Market Research Report: Organ and Tissue Transplantation and Alternatives, October high-cost, low-volume allograft utilized in sports medicine. US manufacturers provide the use of specialized implantation surgical equipment with the purchase of these products. 11

12 APPENDIX A: Canadian Tissue Banks Production Functions Figure 6 Tissue Bank Functions The processing functions of Canadian tissue banks, including those programs that recover tissue for processing at external centres have been detailed. Bank Type Location Surg. Bone Amnion Ocular Bone Skin Cardiac 1 Southern Alberta Tissue Program 2 Comprehensive Tissue Centre 3 Regional Tissue Bank 4 Eye Bank of British Columbia 5 Lions Eye Bank of Saskatchewan 6 Lions Eye Bank of Manitoba 7 Eye Bank of Canada Ontario Division 8 New Brunswick Eye and Tissue Bank 9 Saskatoon Health Region Bone and Tissue Bank 10 Manitoba Tissue Bank 11 National Capital Regional Bone Bank 12 Kingston Tissue Bank 13 Mount Sinai Allograft Technologies Comprehensive Calgary X X X X Recover Comprehensive Edmonton X X X X X X Comprehensive Halifax X X X X X Ocular Vancouver X Ocular Saskatoon X Ocular Winnipeg X X Ocular Toronto X Ocular and Surgical bone Musculoskeletal and recovery St. John X X Saskatoon X X X Recover Recover Recovery Winnipeg Recover Recover Recover Musculoskeletal Ottawa X X Musculoskeletal Kingston X Status unknown Musculoskeletal Toronto X X 14 Dr. Donald MacLellan Tissue Bank Musculoskeletal and Recovery 15 BC Tissue Bank Surgical Bone Vancouver X 16 Vancouver Island Health Authority Tissue Bank Surgical Bone Victoria X Moncton X Restart 2009 Recover Recover 12

13 17 Regina Surgical Bone Regina X Qu Appelle Health Region Bone Bank 18 St. Michael s Surgical Bone Toronto X Hospital 19 London Health Surgical Bone London X 20 Regenmed Surgical Bone Thunder X 21 St. Joseph s Healthcare 22 The Hospital for Sick Children 23 Sunnybrook Health Sciences Centre Bay Surgical Bone Hamilton X Planned Cardiac Toronto X Skin Toronto X X 13