Quality Assurance and Safety of Blood Products and related Biologicals

1. Quality Assurance and Safety of Blood Products and related Biologicals Dr Ana Padilla Blood Products & related Biologicals Quality Assurance and Safety: Medicines Essential Medicines and Pharmaceutical Policies Health Systems and Services World Health Organization

2. OUTLINE OUTLINE • General background • Need for blood regulation: WHA Resolution 63.12 • WHO Biological Reference Preparations • WHO snake antivenoms website

3. 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

4. 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

5. WHA63.12: "Blood Products" definition "Any therapeutic substances derived from human blood, including whole blood, labile blood components and plasma-derived medicinal products"

6. 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

7. 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

8. The Need for Blood Regulation: the WHA Resolution 63.12 Dr Ana Padilla Blood Products & related Biologicals Quality Assurance and Safety: Medicines Health Systems and Services World Health Organization

9. The Need for Blood Regulation • The inherent risks of blood and the complexity of providing adequate, timely and equitable access to safe blood products require an organized national or regional blood system. • Within that system, a competent blood products regulatory authority assures that appropriate standards are met for production of blood products and monitoring of blood safety. (*) Blood Products are defined as: therapeutic substances derived from human blood, including whole blood, labile blood components and plasma-derived medicinal products (WHA Resolution 63.12 on availability, quality and safety of blood products).

10. The Need for Blood Regulation: WHAR63.12, May 2010 • WHA resolution 63.12 recognized that: • “stringent regulatory control is vital in assuring the quality and safety of blood products…” and • urged Member States to “update their national regulations … in order to ensure that regulatory control in the area of quality and safety of blood products across the entire transfusion chain meets internationally recognized standards.” • Strengthening regulatory systems for blood products and building technical capacity of national and regional blood regulatory authorities is recognized as a fundamental need to assure global availability of safe blood products

11. TRACEABILITYFROM DONOR TO PATIENT Blood/Plasma donation Blood Components Patients Plasma-Derived Medicinal Product Plasma for Fractionation • COMPONENTS PREPARATION, e.g. • production process • testing • process control • release • storage & transport • DONATION • INFORMATION • donor population • donor selection • donor protection • collection process • FRACTIONATION, e.g. • production process • viral inactivation • QC & release • storage & transport

12. The Need for Blood Regulation: WHO ECBS/WHOBRN/WHOCC • Consistent with WHA Resolution 63.12, WHO adopts: • WHO assessment criteria for national blood regulatory systems (2011) • WHO Guidelines on GMP for blood establishments (2010) • WHO Guidelines on Production, control & regulation of plasma for fractionation (2007) • Establishment of Biological reference materials for the control of blood products and blood safety IVDs (on-going)

13. The Need for Blood Regulation:Assessment criteria for national blood regulatory systems (ECBS 2011)* To identify essential control functions that should be undertaken by an effective/functional NRA to assure the quality, safety and efficacy of blood and blood products as well as IVDs and associated drugs To establish standard indicators for these functions in order to allow NRAs to assess their performance in the regulation of blood and blood products *Developed by the WHO BRN and global consultation process 13

14. An example 46th ECSPP Meeting, Oct. 2011 62nd meeting ECBS, Oct. 2011

15. The Need for Blood RegulationICDRA 2010: Blood and Blood Products Workshop WHO should focus oncapacity buildingfor implementation of Quality Assurance Systems for blood and blood products through development of independent regulatory authorities Primary attention should be placed on strengthening regional regulatory networks Education and training are needed to make best use of the GMP Guidelines and Assessment Criteria for national blood regulatory systems

16. TRACEABILITYFROM DONOR TO PATIENT Blood/Plasma donation Blood Components Patients Plasma-Derived Medicinal Product Plasma for Fractionation • COMPONENTS PREPARATION, e.g. • production process • testing • process control • release • storage & transport • DONATION • INFORMATION • donor population • donor selection • donor protection • collection process • FRACTIONATION, e.g. • production process • viral inactivation • QC & release • storage & transport

17. 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

18. WHA 63.12: Availability, quality and safety of blood products 2. REQUESTS the Director-General: 2. (4) to ensure sustainable development and provision of WHO International Biological Reference Preparations for use in the quality control and regulation of blood products and related in vitro diagnostic devices; (5)to improve access by developing countries to WHO International Biological Reference Preparations and to the scientific information obtained in their validationin order to assure appropriate use of these preparations

19. WHO Biological Reference Preparations*Global measurement standards (IS) • Tool for comparison of biological measurement results worldwide • Facilitate transfer of laboratory science into worldwide clinical practice • Underpin apropriate clinical dosage • Support regulatory convergence of international regulations (e.g. blood products; IVDs – infectious agents) *Established by the Expert Committee on Biological Standardization

20. 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

21. HIV (IVD Technologies)

22. Hepatitis Viruses (IVD Technologies)

23. Therapeutic Products: Blood coagulation factors, Inhibitors, Anticoagulants and Fibrinolytic agents • Antithrombin concentrate • Blood Coagulation factors concentrates (FVIII, FIX, FII&X) • Fibrinogen concentrate • Albumin • Plasmin and plasminogen activator inhibitor 1 • Protein C, plasma and concentrate • Protein S • Streptokinase • Tissue Plasminogen Activator • Unfractionated and LMW Heparin • Urokinase (HMW)

24. Human Immunoglobulins • Anti-D (Rh0) • Hepatitis A • Hepatitis B • Rabies • Rubella • Tetanus • Varicella Zoster

25. WHO Biological Reference Preparations A tool for comparison of results worldwide Regulatory Authorities WHO IS/IRP 2ndary Ref. Material Manufacturers Product Users (e.g. blood establishments, clinical labs etc.)

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. Coordination of standards setting activities • WHO CC plans of work in the development of IVD IRPs • Updates on emerging/re-emerging pathogens • New test strategies & emerging technologies • WHO Collaborative studies • WHO disease control programmes (infectious diseases): Overview of global epidemiological data • Collaboration of Regional Offices: participating laboratories and identification of candidate materials • Coordination with other standard setting organizations and international organizations (ISBT, ISTH, EDQM, EC,….)

28. 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

29. Documents

30. WHA 63.12: Availability, quality and safety of blood products. What is next? WHO is requested to report back in May 2014 to the WHA (through the Executive Board) on actions taken by Member States and WHO to implement this resolution

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

32. 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