Assurance qualité des produits sanguins et autres produits biologiques
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Transcript of Assurance qualité des produits sanguins et autres produits biologiques
Assurance qualité des produits sanguins Assurance qualité des produits sanguins et autres produits biologiqueset autres produits biologiques
Dr Ana Padilla Assurance Qualité des Médicaments
Médicaments Essentiels et Produits de SantéOrganization Mondiale de la Santé
HSS/EMP/QSM: Séminaire francophone 20112 |
Web site addressesWeb site addresses
http://www.who.int/bloodproducts
http://www.who.int/bloodproducts/snakeantivenoms
http://www.who.int/bloodproducts/catalogue
HSS/EMP/QSM: Séminaire francophone 20113 |
Blood Products & related BiologicalsBlood 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 In vitro biological diagnostic devices (IVDs): Priority: Support of international regulations In vitro biological diagnostic devices (IVDs): Priority: Support of international regulations
Other biological products Anticoagulant & fibrinolysis biological therapeutic products
Other biological products Anticoagulant & fibrinolysis biological therapeutic products
HSS/EMP/QSM: Séminaire francophone 20114 |
Blood Products & related BiologicalsBlood Products & related Biologicals Mission (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 quality and their rational use by prescribers and consumers
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Blood Products & related BiologicalsBlood 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
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Blood Products and related BiologicalsBlood Products and related Biologicals Target AudienciesTarget 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
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National/Regional Reg. Authorities
Other Standardsetting Organizations
(e.g.EDQM; ISO)
Blood Establishments Representation
Industry: ManufacturersAssociations
Intnal Scientific Societies
(e.g. ISBT, ISTH, IFCC)
Research& Public Health
Institutions
WHO ECBSBlood Products and
IVD Track
WHO Working Groups
WHO Collaborating
Centres
WHO Consultations
Produits Sanguins d'origine HumainProduits Sanguins d'origine Humain
Human Blood Derived ProductsHuman Blood Derived Products
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Blood Plasma: a valuable human resourceBlood Plasma: a valuable human resource
Medicinal products derived from human donations of blood and plasma play a critical role in health care
HSS/EMP/QSM: Séminaire francophone 201110 |
Blood Products: Life-Saving MedicinesWHA Resolution 63.12
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
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WHO List of Essential Medicines 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
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TRACEABILITYTRACEABILITY FROM DONOR TO PATIENTFROM DONOR TO PATIENT
TRACEABILITYTRACEABILITY FROM DONOR TO PATIENTFROM DONOR TO PATIENT
COMPONENTS PREPARATION
DONATIONINFORMATION
FRACTIONATIONVIRAL INACTIVATION
TREATMENT
Good Manufacturing Practices
Blood/Plasma donation
Plasma for Fractionation
Blood Components
Plasma-Derived Medicinal Product
PatientsPatients
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GMP implementation in Blood/Plasma Establishments: a key element to
Quality and safety of plasma for fractionationPlasma contract fractionation programs
Supporting access to blood plasma products
Good Manufacturing Practices (GMP)*: an essential tool for improvement of safety
*Proposed WHO Guidelines: Final document for submission at ECBS 2010
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Plasma Contract Fractionation Programs(Need for GMP implementation)
Plasma Contract Fractionation Programs(Need for GMP implementation)
GM
PL
ice
ns
ing GM
PL
ice
ns
ing
Quality Assurance Program
across countries
PLASMASUPPLIER FRACTIONATOR
Nat.Reg.Authority
Nat.Reg.Authority
GMP- common principles
The ‘Achilles’ project*: The ‘Achilles’ project*:
A WHO initiative to assure safety and A WHO initiative to assure safety and availability of blood products in availability of blood products in
developing countries developing countries
*WHA Resolution 63.12 on "Availability, quality and safety of blood products" (adopted May 2010)
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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
Overall Goals (WHA Resolution 63.12) The “Achilles” project
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The “Achilles” project What do we have?
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
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WHO Guidelines and RecommendationsWHO Guidelines and Recommendationshttp://www.who.int/bloodproducts/en/
WHO Guidelines and RecommendationsWHO Guidelines and Recommendationshttp://www.who.int/bloodproducts/en/
WHO Guidelines on viral inactivation and removal procedures intended to assure the viral safetyof human blood plasma products
WHO Recommendations for the production, controland regulation of human plasma for fractionation
WHO Guidelines on good manufacturing practices for blood establishments
Préparations de Référence Préparations de Référence Internationale (Étalons Internationals) Internationale (Étalons Internationals)
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Definition of Biologicals (WHO) Definition of Biologicals (WHO) Definition of Biologicals (WHO) Definition of Biologicals (WHO)
Biological sourcesCrude, semi purified extracts or purified fractions
of microbial, animal or human tissues
Produced by biological processesProduced by biological processes Traditional/ Recombinant DNA/
Other biological technologies
- Complex molecular structure- Cannot be characterized by physicochemical criteria alone
Biological assay Biological assay
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WHO Biological Reference Standards*WHO Biological Reference Standards*Global measurement standardsGlobal 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
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WHO Biological Reference Preparations
A tool for comparison of results worldwide
WHOIS/IRP
2ndary Ref. Material
Regulatory
Authorities
Manufacturers
and Blood Establishments
Product Users
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WHO Biological Reference PreparationsBlood Products and related Biologicals
WHO Biological Reference PreparationsBlood Products and related Biologicals
0
20
40
60
80
100
120N
um
ber
of
pre
par
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ns
In vitro Diagnostic Tests 55 13 10 78
Therapeutic products 0 25 11 36
Blood Safety and General Hematology
Coagul.Factors/ Thrombolytic Agents
Immunological Reagents
Total
WHO Catalogue of Biological Reference Preparations: www.who.int/bloodproductsWHO Catalogue of Biological Reference Preparations: www.who.int/bloodproducts
60% of total IS or Ref Panels
established between 1999-2009
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DocumentsDocuments
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WHO Biological Reference Standards*WHO Biological Reference Standards*Development & EstablishmentDevelopment & Establishment
WHO Biological Reference Standards*WHO Biological Reference Standards*Development & EstablishmentDevelopment & Establishment
1. Selection of candidate materials
2. Characterization of candidate materials
3. Dilution of materials (dilution matrix)
4. Inactivation (if needed)
5. Freeze-drying
6. Feasibility studies
7. Characterization of final product
8. Stability studies (incl. statistical analysis)
9. WHO international collaborative study (incl. statistical analyses)
10. WHOCC & Working Groups
11. Report to ECBS and decision
12. Storage and distribution *Recommendations for the preparation, characterization and establishment
of international and other biological reference standards (revised 2004); Annex 2, WHO TRS, No 932, 2005.
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In vitro diagnostic devices (IVDs)*Medical devices used in vitro for the examination of human specimens
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
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ECBS: HIV (IVD Technologies) http://www.who.int/bloodproducts/en/
ECBS: HIV (IVD Technologies) http://www.who.int/bloodproducts/en/
WHO International Standard or Reference Panel
TestCurrentUsersSerologyHIV-1 p24 antigen, 1st IS (IU)
Test developers, manufacturers, regulators, blood establishments,fractionators ,
reference laboratories, diagnostic laboratories
Anti-HIV, 1st Ref Panel (no unitage)(HIV-1 subtypes: A, B, C, CRF_01, O; HIV-2)
NATHIV-1 RNA 2nd IS (IU)
HIV-1 RNA Genotype 1st Ref Panel (no unitage)(A,B,C,D, AE, F, G, AG-GH, groups N & O)
HIV-2 RNA 1st IS (IU) -
HSS/EMP/QSM: Séminaire francophone 201129 |
ECBS: Hepatitis Viruses (IVD Technologies) http://www.who.int/bloodproducts/en/
ECBS: Hepatitis Viruses (IVD Technologies) http://www.who.int/bloodproducts/en/
WHO International Standard or Reference Panel
TestCurrentUsersSerologyHepatitis B surface antigen, 2nd IS (IU) - adw2 Test developers,
manufacturers, regulators, blood establishments,
fractionators, reference laboratories, diagnostic laboratories
Anti-Hepatitis B virus core antibodies (IU)HBsAg genotype reference panel
NATHepatitis A virus RNA 1st IS (IU)
Hepatitis B virus DNA 2nd IS (IU) – genotype A2Hepatitis B virus DNA Genotype 1st Reference Panel
Genotypes A, B, C, D, E, F, G (no unitage) -
Hepatitis C virus RNA 2nd IS (IU)
Current IS both for HBsAg and HBV DNA are genotype A2: 1% of HBV infections worldwide
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How do we work?
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
Immunoglobulines d'origine animal Immunoglobulines d'origine animal Produit thérapeutique d'origine animalProduit thérapeutique d'origine animal
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WHO Essential Medicines List WHO Essential Medicines List
Animal derived blood products
– Snake anti-venom immunoglobulins
A - Collection of venoms
B – Horse ImmunizationProtocols
C – Starting material of animal derived sera
D – Fractionation &Purification process
SNAKE ANTIVENOM IMMUNOGLOBULINS VERY POOR REGULATORY CONTROL: Technology in the public domain
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WHO Guidelines and RecommendationsWHO Guidelines and RecommendationsWHO Guidelines and RecommendationsWHO Guidelines and Recommendations
ANIMAL DERIVED BLOOD PRODUCTSANIMAL 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)
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WHO Database: Medically Important Snakes Distribution maps, pictures & antivenoms
WHO Database: Medically Important Snakes Distribution maps, pictures & antivenoms
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)
Red or orange question marks(?) )Indicates expected presence not
yet confirmed due to lack of exploration
www.who.int/bloodproducts/snakeantivenoms
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WHO Guidelines
WHO Database: Medically Important Snakes Distribution maps, pictures & antivenoms
www.who.int/bloodproducts/snakeantivenoms
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WHO web site: Target AudiencesWHO 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.
HSS/EMP/QSM: Séminaire francophone 201138 |
Web site addressesWeb site addresses
http://www.who.int/bloodproducts
http://www.who.int/bloodproducts/snakeantivenoms
http://www.who.int/bloodproducts/catalogue
E-mail addresses: [email protected]; [email protected]