ESSENTIAL HEALTH TECHNOLOGIES CLINICAL PROCEDURES HTP/EHT/CPR 1 LN 2004 WHO and Transplantation Clinical Procedures-Essential Health Technology CPR/EHT/HTP

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


CLINICAL PROCEDURES

HTP/EHT/CPR

2 LN 2004

WHO and Transplantation

• Background

• WHO 1991 Guiding Principles

• Recent developments

• Workplan

• Standardisation issues


CLINICAL PROCEDURES

HTP/EHT/CPR

3 LN 2004

Transplantation Annual Global Estimates

LungHeart Liver Kidney

10006000 13 000 50 000

Organs

Tissues

Cells20 000 allogeneic transplantations of haematopoietic stem cells(3000 across national boundaries)

3-5 million tissue transplants take place every year globally


CLINICAL PROCEDURES

HTP/EHT/CPR

4 LN 2004

0.0

10.0

20.0

30.0

40.0

50.0

60.0

0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0

HDI

KTX/million pop

Kidney Transplantations per million pop. per Country

per Human Development Index (HDI)

Low Medium High


CLINICAL PROCEDURES

HTP/EHT/CPR

5 LN 2004

Kidney Transplantation (TX)Annual Global Estimates

Development

according to

UNDP

No. of

countries

>500,000

population

% Global

population

% of

countries with

kidney TX

Total kidney

TX

Total kidney

TX per million

population

Donor ratio

cadaveric/

living

Low HDI 37 14 8.1 800 0.95 0.03

Medium HDI 71 68 64.8 17,500 4.33 0.21

High HDI 43 18 97.7 32,000 30.32 2.47

Globally 151 100 60.3 50,300 8.44 1.01


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).


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


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


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;


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;


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


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)

Written guidanceWritten guidance Global measurement standardsGlobal measurement standards


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 )


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


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


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?


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


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


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


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


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]

(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;


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.


CLINICAL PROCEDURES

HTP/EHT/CPR

23 LN 2004


• 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


CLINICAL PROCEDURES

HTP/EHT/CPR

24 LN 2004


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



CLINICAL PROCEDURES

HTP/EHT/CPR

25 LN 2004


• 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



CLINICAL PROCEDURES

HTP/EHT/CPR

26 LN 2004


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


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

Documents

ESSENTIAL HEALTH TECHNOLOGIES CLINICAL PROCEDURES HTP/EHT/CPR 1 LN 2004 WHO and Transplantation Clinical Procedures-Essential Health Technology CPR/EHT/HTP