1. ESSENTIAL HEALTH TECHNOLOGIES CLINICAL PROCEDURES HTP/EHT/CPR 1 LN 2004 WHO and Transplantation Clinical Procedures-Essential Health Technology CPR/EHT/HTP Ethics, Trade, Human Rights, and Health Legislation ETH/SDE Quality and Safety of Biologicals QSB/IVB/FCH

2. ESSENTIAL HEALTH TECHNOLOGIES CLINICAL PROCEDURES HTP/EHT/CPR 2 LN 2004 WHO and Transplantation Background WHO 1991 Guiding Principles Recent developments Workplan Standardisation issues

3. ESSENTIAL HEALTH TECHNOLOGIES CLINICAL PROCEDURES HTP/EHT/CPR 3 LN 2004 Transplantation Annual Global Estimates LungHeartLiverKidney 1000600013 00050 000 Organs Tissues Cells 20 000 allogeneic transplantations of haematopoietic stem cells (3000 across national boundaries) 3-5 million tissue transplants take place every year globally

4. ESSENTIAL HEALTH TECHNOLOGIES CLINICAL PROCEDURES HTP/EHT/CPR 4 LN 2004 Kidney Transplantations per million pop. per Country per Human Development Index (HDI) Low Medium High

5. ESSENTIAL HEALTH TECHNOLOGIES CLINICAL PROCEDURES HTP/EHT/CPR 5 LN 2004 Kidney Transplantation (TX) Annual Global Estimates

6. ESSENTIAL HEALTH TECHNOLOGIES CLINICAL PROCEDURES HTP/EHT/CPR 6 LN 2004 WHO 1991 Guiding Principles on Human Transplantation I.Organs should come preferably from deceased persons (though living ADULT donors may be used with consent). II.Living donors should generally be genetically related to recipients. III.No payment may be given or received for organs (but may be given to cover the cost of recovery, preservation and supply).

7. ESSENTIAL HEALTH TECHNOLOGIES CLINICAL PROCEDURES HTP/EHT/CPR 7 LN 2004 Challenge: Safety, Quality Efficacy and Access Safety of human material for transplantation Safety of the recipient, short and long term outcomes Safety of the living donor Access to essential transplantation –Kidney –Cornea –Skin, bone… –Haematopoietic stem cells

8. ESSENTIAL HEALTH TECHNOLOGIES CLINICAL PROCEDURES HTP/EHT/CPR 8 LN 2004 Xenotransplantation Transplantation of animal material to humans Specific risks –Immunologic –Functional –Infectious: introduction of animal agents into humans -> Urgent need for effective regulatory oversight

9. ESSENTIAL HEALTH TECHNOLOGIES CLINICAL PROCEDURES HTP/EHT/CPR 9 LN 2004 Resolution WHA57.18 Allogeneic Transplantation 1.URGES Member States: (1) to implement effective national oversight of procurement, processing and transplantation of human cells, tissues and organs, including ensuring accountability for human material for transplantation and its traceability; (2) to cooperate in the formulation of recommendations and guidelines to harmonize global practices in the procurement, processing and transplantation of human cells, tissues and organs, including development of minimum criteria for suitability of donors of tissues and cells; (3) to consider setting up ethics commissions to ensure the ethics of cell, tissue and organ transplantation; (4) to extend the use of living kidney donations when possible, in addition to donations from deceased donors; (5) to take measures to protect the poorest and vulnerable groups from "transplant tourism" and the sale of tissues and organs, including attention to the wider problem of international trafficking in human tissues and organs;

10. ESSENTIAL HEALTH TECHNOLOGIES CLINICAL PROCEDURES HTP/EHT/CPR 10 LN 2004 Resolution WHA57.18 Xenogeneic Transplantation 1.URGES Member States: (1) to allow xenogeneic transplantation only when effective national regulatory control and surveillance mechanisms overseen by national health authorities are in place; (2) to cooperate in the formulation of recommendations and guidelines to harmonize global practices, including protective measures in accordance with internationally accepted scientific standards to prevent the risk of potential secondary transmission of any xenogeneic infectious agent that could have infected recipients of xenogeneic transplants or contacts of recipients, and especially across national borders; (3) to support international collaboration and coordination for the prevention and surveillance of infections resulting from xenogeneic transplantation;

11. ESSENTIAL HEALTH TECHNOLOGIES CLINICAL PROCEDURES HTP/EHT/CPR 11 LN 2004 Transplantation Workplans 2 Tissue and cells Requirements for the safety, quality and efficacy of cell, tissue (and organs for transplantation) Guidance on quality management for tissue banks Guidance for national regulatory authorities in charge of cell and tissue bank oversight Coordinated research project on use of tissue grafts in constrained resource settings

12. ESSENTIAL HEALTH TECHNOLOGIES CLINICAL PROCEDURES HTP/EHT/CPR 12 LN 2004 Role of WHO Expert Committee on Biological Standardisation Scientific advice on quality and safety issues Advice published by WHO (website www.who.int/biologicals; also in Technical Report Series or in Weekly Epidemiological Record) www.who.int/biologicals Written guidance Global measurement standards

13. ESSENTIAL HEALTH TECHNOLOGIES CLINICAL PROCEDURES HTP/EHT/CPR 13 LN 2004 Safety Challenges Public health concerns increasing –1980’s: CJD transmitted by dura matar –1990’s: CJD transmitted by corneas; eye tissue –1992: Seven people infected with HIV through transplantation of organ and tissue(single donor) –Since 1997, over 50 reports of bacterial/fungal infection from tissues –2002: Organ and tissue recipients infected with hepatitis (single donor )

14. ESSENTIAL HEALTH TECHNOLOGIES CLINICAL PROCEDURES HTP/EHT/CPR 14 LN 2004 REGULATORY OVERSIGHT Public expectation for safety is high Over 100 transplants from a single donor- many at risk if inadequate communicable disease risk asessment Demand for tissue/cell products likely to increase Perception of poorly regulated industry could thwart tremendous technological promise

15. ESSENTIAL HEALTH TECHNOLOGIES CLINICAL PROCEDURES HTP/EHT/CPR 15 LN 2004 Patient safety - Donor screening; recipient follow-up Product Safety (tissues and cells) –Donor screening and testing –Product testing Adventitious agents, tumorigenicity, pyrogenicity –Biocompatibility testing with device Product Characterization –Identity, Purity, Potency, Viability, Stability Standardisation issues

16. ESSENTIAL HEALTH TECHNOLOGIES CLINICAL PROCEDURES HTP/EHT/CPR 16 LN 2004 Donor screening for cells, tissues and organs Same as for screening for blood products? Should additional pathogens be screened? If so, are gene amplification tests the most appropriate?

17. ESSENTIAL HEALTH TECHNOLOGIES CLINICAL PROCEDURES HTP/EHT/CPR 17 LN 2004 Product testing for cells and tissues Conventional test method may not be suitable for cell and tissue products - Sterility : 14 days - Mycoplasma : 28-35 days Mycoplasma Q-PCR assay??? - Fast turnaround time - Long culture assay not suitable for products with short shelf life

18. ESSENTIAL HEALTH TECHNOLOGIES CLINICAL PROCEDURES HTP/EHT/CPR 18 LN 2004 Next steps Convene Working Group to review needs for both written standards and reference preparations Aim to have written guidance reviewed by 2005 ECBS Seek input from groups of experts for reference preparation needs e.g. this SoGAT meeting Determine priority for any such reference preparations against priorities for other international standards

19. ESSENTIAL HEALTH TECHNOLOGIES CLINICAL PROCEDURES HTP/EHT/CPR 19 LN 2004 WHO Guiding Principles Guiding Principles were endorsed by World Health Assembly in 1991 (WHA44.25) Have influenced national legislation and professional codes But challenged by: –Success of transplantation and technical progress –Insufficient supply of human material for transplantation to meet demand –Cost of transplantation

20. ESSENTIAL HEALTH TECHNOLOGIES CLINICAL PROCEDURES HTP/EHT/CPR 20 LN 2004 Challenge: Ethics from leaders in the field who urge that policies be changed to allow the use of "incentives" to increase the number of organs for transplantation from the involvement of organ donation programmes in commercialized tissue operations and from "organ trafficking" and "transplant tourism" which occur in a number of countries in all WHO Regions

21. ESSENTIAL HEALTH TECHNOLOGIES CLINICAL PROCEDURES HTP/EHT/CPR 21 LN 2004 Resolution WHA57.18 Allogeneic Transplantation 2. REQUESTS the Director-General: (1) to continue examining and collecting global data on the practices, safety, quality, efficacy and epidemiology of allogeneic transplantation and on ethical issues, including living donation, in order to update the Guiding Principles on Human Organ Transplantation;[1][1] (2) to promote international cooperation so as to increase the access of citizens to these therapeutic procedures; (3) to provide, in response to requests from Member States, technical support for developing suitable transplantation of cells, tissues or organs, in particular by facilitating international cooperation; (4) to provide support for Member States in their endeavours to prevent organ trafficking, including drawing up guidelines to protect the poorest and most vulnerable groups from being victims of organ trafficking;

22. ESSENTIAL HEALTH TECHNOLOGIES CLINICAL PROCEDURES HTP/EHT/CPR 22 LN 2004 Resolution WHA57.18 Xenogeneic Transplantation 2. REQUESTS the Director-General: (1) to facilitate communication and international collaboration among health authorities in Member States on issues relating to xenogeneic transplantation; (2) to collect data globally for the evaluation of practices in xenogeneic transplantation; (3) to inform proactively Member States of infectious events of xenogeneic origin arising from xenogeneic transplantation; (4) to provide, in response to requests from Member States, technical support in strengthening capacity and expertise in the field of xenogeneic transplantation, including policy-making and oversight by national regulatory authorities; (5) to report at an appropriate time to the Health Assembly, through the Executive Board, on implementation of this resolution.

23. ESSENTIAL HEALTH TECHNOLOGIES CLINICAL PROCEDURES HTP/EHT/CPR 23 LN 2004 Transplantation Workplans 1 Updated Guiding Principles to ensure ethical, safe and effective transplantation on the basis of: –Global database on cell, tissue and organ transplantation activities and practice –Country based examples –Updated analysis of health legislations on transplantation –Regional/interregional advisory groups → Transparency of transplantation activities

24. ESSENTIAL HEALTH TECHNOLOGIES CLINICAL PROCEDURES HTP/EHT/CPR 24 LN 2004 Transplantation Workplans 3 Safety of the Living Donors Global medical and scientific criteria for the selection of living kidney donors (Transplantation Society) Guidance for national database including follow-up of living donors → Transparency of transplantation activities

25. ESSENTIAL HEALTH TECHNOLOGIES CLINICAL PROCEDURES HTP/EHT/CPR 25 LN 2004 Transplantation Workplans 4 Xenotransplantation –Guidance and support to Member States on the oversight of xenotransplantation trials including vigilance –Collaborating institutions and laboratories to assist in case of untoward event –International register of xenotransplantation trials → Transparency of transplantation activities

26. ESSENTIAL HEALTH TECHNOLOGIES CLINICAL PROCEDURES HTP/EHT/CPR 26 LN 2004 Transplantation Workplans 4 Increasing access Facilitating bilateral and multilateral support in response to country needs –Legislative framework –Comprehensive capacity building Support to national programmes of procurement of human material for transplantation from deceased donors Coordinated research project on kidney transplantation in the context of constrained resources → Innovative approaches and guidance

27. ESSENTIAL HEALTH TECHNOLOGIES CLINICAL PROCEDURES HTP/EHT/CPR 27 LN 2004 Sterility Mycoplasma Pyrogenicity/Endotoxin Freedom from adventitious agents Cell therapy products are exempt from general safety testing Product Characterization in cellular therapy