Presentation on theme: "WHO Norms and Standards:"— Presentation transcript:
1WHO Norms and Standards: Blood Products & related BiologicalsDr Ana PadillaBlood Products & related BiologicalsQuality and Safety: MedicinesEssential Medicines and Pharmaceutical Policies DepartmentHealth Services and Systems ClusterWorld Health Organization
2Biological Standardization (*) Constitutional responsibility World Health OrganizationBiological Standardization (*) Constitutional responsibility28 March 2017WHO is mandated by it's Member States to "…develop, establish and promote international standards for biological products."In practice, biological products coverVaccinesBlood and blood productsIn vitro biological diagnostic devicesOther biological products(*) Expert Committee for Biological Standardization
3- implemented for more than 50 years - mandated by Member States International Biological Standardizationby WHO- implemented for more than 50 years - mandated by Member StatesWHO is expected to be both a driving forceand a key reference point on biologicalstandardization issues
4Implementation of strategic objective for quality of biologicals (WHO/HQ)
5Blood Products & related Biologicals World Health Organization28 March 2017Blood Products & related BiologicalsHuman blood derived productsBlood components (red cells, platelets, plasma)Blood Coagulation FactorsPolyvalent Immunoglobulins (IV, IM)Specific ImmunoglobulinsAnti-hepatitis BAnti-rabiesAnti-tetanusAnti-rhesus (anti-D)AlbuminAnimal- derived seraAnti-rabiesAnti-venoms (snake bites)Anti-tetanus toxinsAnti-diphteria toxinsAnti-botulism toxinsOther related products Anticoagulant & fibrinolysis biological therapeutic productsIn vitro biological diagnostic devices Priority: IVDs applied to the control of blood and blood products safety
6Quality Assurance and Safety: Blood Products and related biologicals World Health Organization28 March 2017Quality Assurance and Safety: Blood Products and related biologicalsWHO standard setting functions*:to establish WHO Biological Reference Preparationsto develop evidence based WHO Guidelines on Quality Assurance and Safety of specific productsto support implementation of WHO Norms and Standards: (strengthen technical/regulatory capacity of MRAs & NCLs)to support operational strategies to improve access to quality products(*) Expert Committee on Biological Standardization
7World Health Organization Blood Products & related Biologicals Strategic Plan (approved at 57th ECBS, 2006)28 March 2017WHO Essential Medicines List:Animal derived sera (IgS):Snake antivenom and anti-rabies immunoglobulinsHuman blood derived products:GMP production of plasma for fractionationWHO Biological Reference Standards for regulation and control of in vitro (biological) diagnostic testsStandardization of traditional and new technologies
8WHO Essential Medicines List (I) World Health OrganizationWHO Essential Medicines List (I)28 March 2017Animal derived blood productsSnake anti-venom immunoglobulinsAnti-rabies imunoglobulins
91 patient treated = 1 life saved or 1 permanent disability prevented The Meeting urged WHO to:Improve availability of antisera by building technical capacity and expertise of regulatory authorities and manufacturers creating a prequalification system. Improve management of diseases through adequate distribution and improved clinical guidance.coordinate collaboration and partnerships (resource mobilization)1 patient treated = 1 life saved or 1 permanent disability prevented
10Antivenom sera are essential to prevent long-term disability & death World Health Organization28 March 2017Antivenom sera are essential to prevent long-term disability & deathnBites by Bothrops species – fer de lance and lancehead in central & South AmericaCourtesy Prof D Warrell, Nuffield Department of Clinical Medicine, Oxford
11Component 1: Global Quality Assurance Guidance World Health OrganizationComponent 1: Global Quality Assurance Guidance28 March 2017Development of WHO Guidelines on the Production, Control and Regulation of animal plasma-derived immunoglobulins (encompassing e.g. control of starting materials and large-scale implementation and control of manufacturing steps)Elaborated in parallel to, and as a result of, WHO Regional and Bi-Regional Workshops
12Countries represented Jakarta, May 2008 World Health OrganizationCountries represented Jakarta, May 200828 March 2017SEAROWPROBangladeshIndiaIndonesiaNepalThailandAustraliaCambodiaJapanMalaysiaPapua New GuineaChinaPhilippinesVietnam
13Countries represented Addis Ababa, July 2008 World Health Organization28 March 2017Countries represented Addis Ababa, July 2008AFROEMROBenin, Cameroon, Côte d'Ivoire,Democratic Republic of CongoGhana, Guinea, KenyaMali, Niger, NigeriaSouth Africa, SenegalTanzania, UgandaZimbabweEgyptMoroccoPakistanSaudi ArabiaTunisia
14World Health Organization 28 March 2017Fragility of production systems in developing worldThe document has been discussed in the field:Bi-Regional Workshops in Aisa and Africa: Jakarta, May Addis Ababa, June 2008Global experts consultationAdoption requested to the 59th ECBS (2008)
15Antivenom Is the Only Specific Antidote to Snake Venom Most important decision in the management of a victim is whether or not to give antivenomFrom Dr Ariaratne, Sri Lanka
16Clinical Assessment: Need of Efficacy Test (reported by Dr Thapa, Nepal) 3 envenomed victims arrived in snakebite treatment center within half an hour but died during medication (Reported from Bharatpur Hospital during recent research)In Bhratpur Hospital, of the two cases, one with 98 ASV vials died but next with 94 vials survived (Pandey et al )
17Major issues about antivenom preparations Enormous doses, uncertain benefitReaction rates are very highTakes time to dissolve, frothChanging the tender for AVS supply by the authoritiesVery poor regulatory controlNo definite way reporting adverse reaction
18World Health Organization LiteratureWorld Health Organization28 March 2017
19World Health Organization LiteratureWorld Health Organization28 March 2017
20A - Collection of venoms PRODUCTION OF ANTIVENOM IMMUNOGLOBULINS:Technology in the public domain (not protected by intelectual property)A - Collection of venomsB – Horse ImmunizationProtocolsC – Starting material of animal derived seraD – Fractionation &Purification process
213 major instruments to inform about potency and efficacy of Antivenoms Pre-requisite: Preclinical assessment of all antivenoms, using local venoms or venoms likely to have close similaritiesClinical assessement: safety & efficacySafety (reaction rates)Dose finding studiesObservational prospective studiesRandomised control trials (when possible)Post-marketting surveillance
22a proposal to strenghten national capacities Capacity building for snake venoms production and antivenoms preclinical evaluation:a proposal to strenghten national capacities
23Venoms production: Basic problems Lack of adequate venom production: Venoms used for production need to have appropriate quality and to be representative of the snake populations.Lack of endogenous capacity to assess the neutralizing potency of antivenoms at the preclinical level.
24Consequences…The antivenoms produced using low quality, or non- representative venoms are deficient in terms of neutralizing potency and extent of coverage.The capacity to prepare high-quality venoms is a key component in any global strategy aimed at increasing the production and use of effective and safe antivenoms.
25Consequences…The lack of endogenous capacity in many countries to assess the preclinical efficacy of antivenoms results in the introduction of antivenoms which are not effective to neutralize the venoms of a particular country or region.
26Component 2: national/regional capacity building on venoms production To develop a programme to assist countries in the development of local snake venom production for antivenom manufacture, and in the development of local capacity for the preclinical assessment of antivenom efficacy using these venoms.
27Components of the WHO proposal (Proposed WHO Consultation, 2009) Assistance to identify in-country organisations to host snake venom production and preclinical testing of antivenoms;Mobilize international experts through regional workshops and via specific contracts for direct assistance in countries;Regional support for countries through funding of contracted, independent quality assurance services by recognised non- commercial laboratories;Training exchanges (i.e.: venom QA laboratory facilities, laboratories for preclinical testing of antivenoms);Assistance in leveraging funding support for snake venom production and preclinical assessment of antivenoms projects
28Expected outcomesA worldwide support in the availability of high-quality snake venom preparations for antivenom production and for preclinical assessment and quality control.Strenghtening of the endogenous national capacities to participate in antivenom production and control.
29WHO Essential Medicines List (II) World Health OrganizationWHO Essential Medicines List (II)28 March 2017Human derived blood plasma productsPlasma for FractionationBlood Coagulation Factors: FVIII, PCCHuman Normal Immunoglobulin (IV and IM)Anti-D immunoglobulinAnti-tetanus immunoglobulinBlood-derived medicinal products for the treatment of haemophilia and immune diseases are included in the WHO Model List of Essential Medicines
30Blood Plasma: a valuable human resource Medicinal products derived from human donations of blood and plasma play a critical role in health care
31World Health Organization 28 March 2017The ‘Achilles’ project:a WHO initiative to assure safety and availability of blood products in developing countries
32What is the global situation ? BackgroundBlood-derived products are often unavailable in developing countries: patients suffering from hereditary bleeding disorders or congenital and acquired immune diseases do not have access to treatmentThe global need for blood plasma products exceeds by far available supplyNo realistic possibility of generating surplus products in developed countries to meet developing countries needs and, even when available, would be unaffordable.
33What is the global situation ? BackgroundPlasma for fractionation available in industrialized countries meet their needs"Developing countries will only be able to create an affordable and sustainable supply of blood derived products by using blood plasma collected in their own blood establishments and from their own populations"Plasma fractionation can be performed through plasma contract fractionation programs
34What is the global situation ? What are the problems?Wastage of blood plasma in developing countries: (does not currently meet the standards required for product manufacture)Risk of transfusion-transmitted diseases and cross-border threats: (increasing internationally mobility of populations highlights need to strengthen quality assurance systems globally)Need to introduce a "plasma production culture" (GMP culture in blood establishments)Poor regulation of blood and blood products: (need for update of legal provisions and strengthen MRAs technical capacity)
35WHO “Achilles” project: Expected Outcomes The “Achilles” project: Project GoalsWHO “Achilles” project: Expected OutcomesIncrease availability of safe blood derived products by:Supporting implementation of national validated quality and safety standards for blood establishmentsRaising the manufacturing activities of blood establishments to international standardsUsing reliable regulatory systems able to "prequalify" blood establishments: adherence to WHO standards for the manufacture of plasma for fractionation and to WHO GMP for blood establishmentsUsing expertise and experience gained from developed countries
36World Health Organization Good Manufacturing Practices (GMP): an essential tool for improvement of safety28 March 2017GMP implementation in Blood/Plasma Establishments: a key element toQuality and safety of plasma for fractionationPlasma contract fractionation programsSupporting access to blood plasma products
37TRACEABILITY FROM DONOR TO PATIENT Blood/PlasmadonationPlasma forFractionationBloodComponentsPlasma-DerivedMedicinal ProductPatientsFRACTIONATIONVIRAL INACTIVATIONDONATIONINFORMATIONCOMPONENTS PREPARATIONTREATMENTGood Manufacturing Practices
38Plasma Contract Fractionation Programs (Need for GMP implementation) GMP- common principlesPLASMASUPPLIERFRACTIONATORNat.Reg.AuthorityLicensingGMPQuality Assurance ProgramGMPLicensingacross countries
39WHO “Achilles” project Action Plan (demonstration project) Development of comprehensive GMP guidelines to support training and inspection activities: GMP Guidelines for Blood Establishments (ECBS 2009)Development of Work Plans: upgrading quality assurance systems, regulatory expertise and national regulations initially in 2 pilot countries (ECBS 2009)Work Plans imply development of specific and measurable indicators to monitor success and progress with the pilot countries (e.g. regulations updated; BE GMP compliance; quality assurance officers trained; increase in plasma volume for fractionation…)(*) Demonstration project: First steps action plan 2009
40WHO “Achilles” project: Expected Outcomes Optimal use and benefit from donated blood plasmaUse of local plasma to improve supply of blood derived medicinal productsIncrease quality and safety of all blood products in blood establishmentsApply internationallly agreed standards for blood establishmentsSustainable and affordable blood plasma derived essential medicinesPotential application of QA and GMP principles to other medical disciplinesSubstantial contribution to public health programs
41WHO Biological Reference Preparations Global Measurement Standards
42WHO Biological Reference Preparations Global measurement standards World Health Organization28 March 2017WHO Biological Reference Preparations Global measurement standardsTool for comparison of biological measurement results worldwideTo facilitate transfer of laboratory science into worldwide clinical practiceTo support harmonization of international regulations of blood products and high risk IVDsTo accelerate transfer technology
43WHO Biological Reference Preparations Strategic Plan World Health OrganizationWHO Biological Reference Preparations Strategic Plan28 March 2017Impact of migrations: health safety/securityStandardization of in vitro biological diagnostic technologiesConvergence of regulatory policiesTrack and monitor blood safety"The battle against infections and the struggle for blood safety are closely interrelated!"
44WHO Biological Reference Preparations Blood Products and related Biologicals WHO Catalogue of Biological Reference Preparations:
45World Health Organization 28 March 2017Web site addresses
46Priority Projects for Biological Reference Preparations WHO Collaborating Centres' Meeting (29-30 January 2007)WHO Recommendations: Annex 2, WHO TRS, No 932, 2005ECBS200920082007HCV RNA (3rd)*Anti-Syphilitic (2nd)*Anti-HBs (2nd)*Anti-HBc*HIV-1 gt1 (2nd)**HIV-2 RNA*HBV gt2**Anti-HCV**Anti-T. cruzi**ConsultationFeasibility studiesCollaborative study*IS**Panel1the anti-HIV antibody panel will also be extended; 2two panels for HBsAg- and NAT-tests
47WHO IVD Standardization Priorities 2009 World Health OrganizationWHO IVD Standardization Priorities 2009World Health Organization28 March 201728 March 2017WHO Collaborating Centres Meeting in 2009Identify and coordinate needs/priorities within WHODisease oriented DepartmentsIHR-core laboratory capacityAnti-Trypanosma cruzi (Chagas) reference panelHBV genotype panel (DNA and HBsAg)H. Scheiblauer47
48Migration Flows from Latin America Chagas disease
49Technical capacity of National Regulatory Authorities Blood Products Regulations
50World Health Organization International Conference of Drug Regulatory Authorities (ICDRA): Recommendations, Bern 200828 March 2017Recognizing the need worldwide for blood products regulation to ensure availability of safe blood and blood products in the face of known and emerging threats, including emerging infectious diseases, WHO should:Take steps to further develop and strengthen national/regional blood regulatory authorities and to promote cooperationProvide harmonized "assessment criteria for blood regulatory systems" (BRN): convene a consultation of NRAs to review Draft assessment toolPrioritize development of Guidelines on GMP for Blood EstablishmentsPromote introduction of WHO recommended plasma standards by NRAs
51Essential Element of a public health system Quality Assurance & Safety: Blood Products and related Biologicals. Programme OverviewWHO standard setting functions for Biological Products (WHO Constitution ……….)Global Norms and Standards: Quality Assurance regulatory and biological standardization functionsExpert Committee on Biological StandardizationWHO Essential Medicines ListWHO Biological Standards for blood safety-related diagnostic testsEssential Element of a public health system
52World Health Organization 28 March 2017WHO Working GroupsNational/RegionalReg. AuthoritiesWHO ConsultationsExperts Partners& CollaborationsWHO CC for Biological Standards & Quality AssuranceWHO ECBSExpert Advisory PanelsIndustry:ManufacturersAssociationsResearch& Public HealthInstitutionsOther Standardsetting Organizations(e.g.BIPM, EDQM, ISO)Intnal ScientificSocieties(e.g. ISTH, ISBT, IFCC)
53World Health Organization 28 March 2017Web site addresses