Assurance qualité des produits sanguins et autres produits biologiques

1. Assurance qualité des produits sanguins et autres produits biologiques Dr Ana Padilla Assurance Qualité des Médicaments Médicaments Essentiels et Produits de Santé Organization Mondiale de la Santé

2. Web site addresses http://www.who.int/bloodproducts http://www.who.int/bloodproducts/snakeantivenoms http://www.who.int/bloodproducts/catalogue

3. Blood Products & related Biologicals Animal-derived immunoglobulins Anti-rabies Anti-venoms Anti-tetanus toxin Anti-diphteria toxin Anti-botulism toxin Human blood derived products Blood components (red cells, platelets, plasma) Blood Coagulation Factors Polyvalent Immunoglobulins (IV, IM) Specific Immunoglobulins Anti-hepatitis B Anti-rabies Anti-tetanus Anti-rhesus (anti-D) Albumin Other biological productsAnticoagulant & fibrinolysis biological therapeutic products • In vitro biological diagnostic devices (IVDs): Priority: Support of international regulations

4. Blood Products & related BiologicalsMission (Strategic Plan) A WHO normative programme: WHO is mandated by it's Member States to "…develop, establish and promote international standards for biological products." In practice, biological products cover: Vaccines, Blood and blood products; In vitro biological diagnostic devices; other biological products. An Essential Medicines Programme: To support the achievement of the health related MDGs by assisting governments and organizations to ensure equitable access to effective medicines of assured qualityand their rational use by prescribers and consumers

5. Blood Products & related Biologicals WHO standard setting functions*: • Develop/establish/provide WHO Biological Reference Preparations • Develop/adopt/provide evidence based WHO Guidelines on Quality Assurance and Control of specific products or procedures • Support enforcement and implementation of WHO Norms and Standards:strengthen technical/regulatory capacity of NRAs & NCLs • Support operational strategies to improve access to quality products (*) Consistent with the WHO mandate through the Expert Committee on Biological Standardization

6. Blood Products and related BiologicalsTarget Audiencies • National/Regional Regulatory Authorities • National/Regional Control and National/Regional Reference Laboratories • Blood Establishments and Plasma Fractionators • Manufacturers of animal derived blood products • Manufacturers of in vitro diagnostic tests • Public Health Departments/Public Healt Officers/Ministries of Health • Medical Professionals, Health Workers • Procurement agencies and NGO’s

7. WHO Working Groups WHO Consultations National/Regional Reg. Authorities Blood Establishments Representation WHO Collaborating Centres WHO ECBS Blood Products and IVD Track Industry: Manufacturers Associations Research & Public Health Institutions Other Standard setting Organizations (e.g.EDQM; ISO) Intnal Scientific Societies (e.g. ISBT, ISTH, IFCC)

8. Produits Sanguins d'origine Humain Human Blood Derived Products

9. Blood Plasma: a valuable human resource Medicinal products derived from human donations of blood and plasma play a critical role in health care

10. Blood Products: Life-Saving MedicinesWHA Resolution 63.12 Blood and blood components Whole blood collected into containers, anticoagulant to prevent clotting, cold chain Blood components, obtained from whole blood by separation (centrifuge or apheresis): Red blood cells: Oxygen transport Platelets: Hemostasis, preventing bleeding Plasma: clotting factors, immunoglobulins etc. Cryoprecipitate , FVIII source Plasma derivatives Plasma for "fractionation“, further purification of plasma proteins, e.g. Blood Coagulation Factors, e.g. Factor VIII for treatment of hemophilia A Specific Immunoglobulins, e.g. anti-hepatitis B, anti-rabies, anti-tetanus, anti-D IM and IV normal IgG Albumin, involved in the regulation of body fluids, used for resuscitation

11. WHO List of Essential Medicines • Human derived blood plasma products • Plasma for Fractionation • Blood Coagulation Factors: FVIII, PCC • Human Normal Immunoglobulin (IV and IM) • Anti-D immunoglobulin • Anti-tetanus immunoglobulin Blood-derived medicinal products for the treatment of haemophilia and immune diseases are included in the WHO Model List of Essential Medicines

12. TRACEABILITYFROM DONOR TO PATIENT Blood/Plasma donation Blood Components Patients Plasma-Derived Medicinal Product Plasma for Fractionation FRACTIONATION VIRAL INACTIVATION DONATION INFORMATION COMPONENTS PREPARATION TREATMENT Good Manufacturing Practices

13. Good Manufacturing Practices (GMP)*: an essential tool for improvement of safety GMP implementation in Blood/Plasma Establishments: a key element to Quality and safety of plasma for fractionation Plasma contract fractionation programs Supporting access to blood plasma products *Proposed WHO Guidelines: Final document for submission at ECBS 2010

14. Plasma Contract Fractionation Programs(Need for GMP implementation) Nat.Reg. Authority Nat.Reg. Authority PLASMA SUPPLIER FRACTIONATOR GMP- common principles GMP Licensing Quality Assurance Program GMP Licensing across countries

16. The ‘Achilles’ project*: A WHO initiative to assure safety and availability of blood products in developing countries * WHA Resolution 63.12 on "Availability, quality and safety of blood products" (adopted May 2010)

17. Overall Goals (WHA Resolution 63.12)The “Achilles” project • To raise quality standards in blood establishments (BE) • To reduce risk of transmission of infectious diseases • Effective regulatory systems for blood products worldwide • To make safe blood products available to patients

18. The “Achilles” project What do we have? • Materials and mechanisms on which training and technical capacity can be provided to BE and regulatory authorities: • WHO Guidelines: Production, control and regulation of plasma for fractionation; Viral Inactivation and Removal procedures; GMP for BE • Biological reference materials: quality control of blood products and of blood safety related in vitro biological diagnostic devices (IVDs) • Good Manufacturing Practices for Blood Establishments • Assessment tool for blood regulatory systems • Coordination of international expertise: ECBS, BRN, WHOCC….. • Expertise from other quality assurance programs in WHO

19. WHO Guidelines and Recommendationshttp://www.who.int/bloodproducts/en/ WHO Guidelines on good manufacturing practices for blood establishments WHO Recommendations for the production, control and regulation of human plasma for fractionation WHO Guidelines on viral inactivation and removal procedures intended to assure the viral safety of human blood plasma products

20. Préparations de Référence Internationale (Étalons Internationals)

21. Definition of Biologicals (WHO) • Biological sources • Crude, semi purified extracts or purified fractions • of microbial, animal or human tissues Produced by biological processes Traditional/ Recombinant DNA/ Other biological technologies Biological assay - Complex molecular structure- Cannot be characterized by physicochemical criteria alone

22. WHO Biological Reference Standards*Global measurement standards • Tool for comparison of biological measurement results worldwide • Facilitate transfer of laboratory science into worldwide clinical practice • Underpin apropriate clinical dosage • Facilitate convergence of international regulations (e.g. blood products; blood safety related IVDs) *Established by the Expert Committee on Biological Standardization

23. WHO Biological Reference Preparations A tool for comparison of results worldwide Regulatory Authorities Manufacturers and Blood Establishments WHO IS/IRP 2ndary Ref. Material Product Users

24. WHO Biological Reference PreparationsBlood Products and related Biologicals 60% of total IS or Ref Panels established between 1999-2009 WHO Catalogue of Biological Reference Preparations: www.who.int/bloodproducts

25. Documents

26. WHO Biological Reference Standards*Development & Establishment *Recommendations for the preparation, characterization and establishment of international and other biological reference standards (revised 2004); Annex 2, WHO TRS, No 932, 2005.

27. In vitro diagnostic devices (IVDs)*Medical devices used in vitro for the examination of human specimens • IVDs for infectious markers • Viruses, bacteria, parasites, unconventional agents • IVDs for • Blood/plasma screening (blood safety) • Confirmation of infection • Diagnosis and monitoring • Tests methods • Serological assays (e. g. ELISA) • Nucleic acid amplification techniques (NAT) *Priority: pathogens with impact on blood safety and international regulations

28. ECBS: HIV (IVD Technologies)http://www.who.int/bloodproducts/en/

29. ECBS: Hepatitis Viruses (IVD Technologies)http://www.who.int/bloodproducts/en/ Current IS both for HBsAg and HBV DNA are genotype A2: 1% of HBV infections worldwide

30. How do we work? • ECBS Blood Products and related Biologicals Track • WHO Blood Regulators Network: scientific/regulatory • WHO Collaborating Centres:Priority setting in the development of IBRPs • WHO disease control programmes (infectious diseases): Overview of global epidemiological data • WHO Working groups for specific topics: research & public health institutions; manufacturers associations; • Coordination with other standard setting organizations and professional organizations: ISBT, ISTH, IFCC, EDQM, EC

31. Immunoglobulines d'origine animal Produit thérapeutique d'origine animal

32. WHO Essential Medicines List • Animal derived blood products • Snake anti-venom immunoglobulins

33. SNAKE ANTIVENOM IMMUNOGLOBULINS VERY POOR REGULATORY CONTROL: Technology in the public domain A - Collection of venoms B – Horse Immunization Protocols C – Starting material of animal derived sera D – Fractionation & Purification process

34. WHO Guidelines and Recommendations ANIMAL DERIVED BLOOD PRODUCTS • WHO Guidelines on production, control and regulation of snake antivenom immunoglobulins • WHO Database: clinically important venomous snakes species and its worldwide geographical distribution together with antivenoms for treatment of snakebite envenomings • WHO website hosting both the Guidelines and database (maps, pictures, products, manufacturers)

35. WHO Database: Medically Important Snakes Distribution maps, pictures & antivenoms Red or orange question marks (?) (Indicates expected presence not yet confirmed due to lack of exploration Allocation to CATEGORY 1 shown in red (Indicates common, widespread species that causes numerous snake bites with high morbidity, disability or mortality) Allocation to CATEGORY 2 shown in orange (Indicates highly venomous and capable of causing morbidity, disability or mortality, but exact country data lacking, or less frequently implicated in these countries) www.who.int/bloodproducts/snakeantivenoms

36. WHO Database: Medically Important Snakes Distribution maps, pictures & antivenoms www.who.int/bloodproducts/snakeantivenoms WHO Guidelines

37. WHO web site: Target Audiences Central information source for data on the current availability of antivenoms for specific species. Aimed at a wide audience, that includes: National Regulatory Agencies Ministries of Health Antivenom Manufacturers Medical Professionals, Health Workers Procurement Personnel in Industry and NGO’s Objective is to use the web site to distribute accurate data that can be used to plan improvements to existing supply and distribution.

38. Web site addresses http://www.who.int/bloodproducts http://www.who.int/bloodproducts/snakeantivenoms http://www.who.int/bloodproducts/catalogue E-mail addresses: padillaa@who.int; greenoughl@who.int