10th European Haemovigilance SeminarFrankfurt, Germany 28.02. – 01.03.2008
European Public Health Programme: The EU-Q-Blood-SOP manual for implementing quality management systems following the blood directives.
Prof. Dr. Christian Seidl
Institute of Transfusion Medicine and ImmunohematologyRed Cross Blood Service (Frankfurt - Germany)
Session IV : EU Directives
with kind permission from Th. Bregeon, European Commission 2007
with kind permission from Th. Bregeon, European Commission 2008
EU-Q-Blood-SOPMethodology for standard operational proceduresCo-funded by the EC GA2004217
EuBISEuropean Blood Inspection SystemCo-funded by the EC – GA No. 2006202
Optimal Donor DOMAINEManagement(2007)
16 Participants from
EU member states: BE, CZ, DE, EE, FR, IE, IT, CY, HU, MT, NL, PL, UK
(acceding) new member states:BG, RO
EFTA states:IS
Public Health & Risk Assessment, Directorate General, DG SANCO
EU-Q-Blood-SOP Project
Develop a Manual describing a methodology based on good practice that will
(1) assist blood establishments to implement or expand their standard operating procedures (SOPs).
(2) contribute to the understanding and management of quality processes in blood services.
(3) assist blood establishments in preparing for the inspection of their servicesrelated to the implementation of quality relevant elements required by the EU directive 2002/98/EC.
Project objectives
EU-Q-Blood-SOPMethodology for standard operational proceduresCo-funded by the EC GA2004217
Directive 2002/98/EC and its technical annexes.
Directive 2005/62/EC Quality Management
‚the European blood legislation requirements‘
Article.2: … the Commission shall take fully into account the detailedprinciples and guidelines of Good manufacturing practice (GMP),as referred to in Article 47 of Directive 2001/83/EC.
Directive 2004/33/EC – Tech. Requirements
Directive 2005/61/EC – Traceability and SAR / SAE
1 General Principles
2 Personnel and Organisation
3 Premises
4 Equipment and Materials
5 Documentation
6 Blood collection, testing and processing
6.1 Donor eligibility
6.2 Collection of blood and blood components
6.4 Processing and validation
6.5 Labelling
6.6 Release of blood and blood components
7 Storage and distribution
8 Contract Management
9 Non-Conformance
9.1 Deviations
6.3 Laboratory testing
9.2 Complains
9.4 Corrective and preventive actions (CAPA)
9.3 Recall
10 Self-inspection, audits and improvements
Directive 2005/62/EC Quality Management
Annex
http://www.eu-q-blood-sop.deEU - Survey report
D1. Questionnaire on current SOP structurein 16 blood services of the participating members representing 17 EU member, acceding and EFTA member states.
The questionnaire covers 4 sections- Section I: Basic validation- Section II: Principle management
requirements- Section III: Working areas (technical)- Section IV: Areas of interest and risk
(referred to the 4 working areas) 27% of blood establishments indicated demand for improvedinspection system by governmental authorities
47% of blood establishments require improvement of SOPsrelated to the European blood legislation
Quality Management System
QMS Document System
Quality Manual
General / Operating Procedures (GP / OP)
General description of quality policy by the management (linked to GP)
Description of standard procedures that are applied at all locations ofthe blood establishment
- sampling and labelling, - equipment operation, - maintenance and cleaning; - validation; - cleaning of premises and environmental control; - Self-inspection; - QMS (change control, internal audits, continuous improvement).
1 General Principles
2 Personnel and Organisation
3 Premises
4 Equipment and Materials
5 Documentation
6 Blood collection, testing and processing
7 Storage and distribution
8 Contract Management
9 Non-Conformance
10 Self-inspection, audits and improvements
SOP Format – Structured / Flexible
Standard Working Procedure (WP)
Standard Test Procedure (TP)
Blood Component ProductionProcedure (PP)
Equipment Operating Procedure (EP)
Flexible
Structured according to specific quality relevant elements
Documentation Records (DR) Flexible
Quality managementdocumenation Records (QM-DR)
Structured according to QM system requirements
EU-Q-Blood-SOP Manual1 - Background and Objectives
2 - Quality principles linked to the Directive 2002/98/EC and 2005/62/EC
3 – Development and Implementation of an SOPDivided into 6 steps (Chapters 3.1-3.6):1 Identify the objective and scope of the SOP and draft a title2 Identify the competent user and assign
responsibility for writing the SOP3 Use the Master SOP to write an SOP4 Design a process flow chart and describe each step
of the work process in this flow-chart5 Initiate document change control6 Conduct training in the use of the SOP
4 - SOP Master and Examples (WG1-4) covering critical quality activities
Annex – Terminology , References and Participants http://www.eu-q-blood-sop.de
EU-Q-Blood-SOPMethodology for standard operational proceduresCo-funded by the EC GA2004217
EU SOP - Master
1. Objective
4.1 Process Flow Chart
4. Description Operating Procedure
5. Procedure for Non Conformance (Commission Directive 2005/62/EC - Art. 9)
Directive 2002/98/ECQuality manual*Site Master File*
*According to Annex I Part B, Art 11(1), Directive 2002/98/EC
Commission Directive 2004/33/ECCommission Directive 2005/61/EC
Commission Directive 2005/62/EC
Guidelines
National legislation
2. Area of application
3. Roles covered by the SOP (job description, personnel responsibilities)
4.2 Define Critical Points (Risk analysis) – Chapt. 2
6. Documentation
7. Annex (Literature / References / Terminology)
4.3 Description of the work activities
EU SOP - Master
http://www.eu-q-blood-sop.de
Chapter 3 – Development and Implementation of an SOP
Special SOP formats – Quality relevant information
Laboratory testing procedures Laboratory equipment
- Analytic Parameter and Abbreviation- Test Method and Test Principle- Reference Range- Measuring Range- Units and if appropriate Conversion Factor
or Formula- Test Material- Minimum Sample Volume- Minimum Test Sample Volume- Pre-analytic Requirements- Calibration- Sample Storage before Analysis
Laboratory testing procedures
- Equipment relevant for the Method (Test)- Reagents
(including Manufacturer/Ordering Number or Source)
- Detailed Test Procedure(optional Tables/Figures and Flow Charts)
- Sources of Variability- Suitability of Test (Indications)- Criteria for Technical Authorisation- Procedures for Non Conformance /
Corrective and Preventive Action - Interpretation and Documentation- Sample Storage after Analysis- Test Validation Records- Quality Control (Internal / External)
Special SOP formats – Quality relevant information
- Name and Type of Equipment- Manufacturer and Address- Serial Number- Inventory Equipment Number- Premises / Room - Construction Year- Purchase Date- Installation Protocol and Training of
Personnel by Manufacturer- Delivery Condition- Service- Service Contract (Emergency Failure
Service)- Responsible Person(s)
- Principle of Function- Measuring Principle- Measuring Range- Precision- Calibration and Adjustability- Operation Instruction- Regularly Service Instructions
(internal/external) - Procedures for Non Conformance /
Corrective and Preventive Action- Documentation (e.g. Log Book)- Validation (Qualification)- References / Annex
Equipment procedures
Special SOP formats – Quality relevant information
EU-Master-SOP and Sample SOPs
WG1 - Donor recruitement, collection, production, testingIdentification of donors and labelling
WG2- Immunohematology, molecular diagnosticsBlood Group determination and compatibility testing in emergency
WG3 - Special blood componentsProcessing of platelet apheresis concentrates
WG4 - Logistics, storage, distribution, managementValidation of temperature control areas for storage and transportation of blood components
Validation (Test Sites)Bulgaria - Cyprus – France – Malta - Germany
EuBIS - General Objectives(1) define requirements for quality management systems of blood
establishments based on the Directive 2005/62/EC.
(2) develop pan European standards and criteria for the inspection of blood establishments based on GMP guidelines to assist national inspections in implementing the Directive 2002/98/EC and its technical annexes.
(3) establish a common benchmark system for continual improvement. This benchmark system should develop practical assistance and advice to optimise processes based on good practice among blood establishments.
(4) develop a training programme for inspectors
EuBISEuropean Blood Inspection SystemCo-funded by the EC – GA No. 2006202
The general objective of the Project is to address the scope define in Area 2.2.4 of the work plan 2006 of the Public Health Programme ensuringEquivalent recognition of inspections of blood establishments among all Member States through the development and implementation of commonly accepted criteria and standards leading to comparable quality systems and inspection procedures.
with kind permission from Th. Bregeon, European Commission 2007
European Commission – Directorate CDr. Tapani Piha (DG Sanco)Mr. Thomas Bregeon (DG Sanco)Ms. Ann Thuvander (Project Officer-PHEA)
Project Structure
Project Coordination (DE): Prof. Dr. C. Seidl and Prof. Dr. E. Seifried (Leader)
Participants from 19 Member / Acceding / EFTA states:
AT, DE, MT, HU, CZ, NL, CY, IT, UK, BE, BG, RO, FR, EE, IE, PL, LU, SLO, IS
EuBISEuropean Blood Inspection SystemCo-funded by the EC – GA No. 2006202
EU Legislation
National Transposition National Transposition National Transposition
Competent Authority(ies)
Clinical Governance of the ‚vein-to-vein-process‘ – Blood Establishment
Donor Patient
GMP
Inspection Evaluation
0%
20%
40%
60%
80%
100%
GMP ISOstandards
used
CoE GLP nationalstandards /guidelines
WHO
ISO certified or accredited
ISO certification or accreditation in process
EuBIS Survey – Common standards
%Activity_________________________________________________________________
88Autologous blood components
56Cryoprecipitate
75Source Plasma for Fractionation
50Lymphocytes
69Granulocytes
31Cord blood
Related preparations
75Apheresis Fresh Frozen Plasma
100Apheresis Erythrocyte / Platelet concentrates
Apheresis component preparation
94Fresh Frozen Plasma (whole blood)
100Cellular (Erythrocyte and / or Platelet concentrates
Blood component preparation
_________________________________________________________________
EuBIS Survey – Activity profile
EuBIS Inspection manual
Common Standards
Common Criteria
EU-GMPPIC/S for BECoE guide(ISO)
Inspection standards
Defining the inspection processOrganisational requirementsEvaluation system for deviations
Linked to EMEA / PIC/SEUSTITE / JACIE
Eu Directives Legislation
European Commission
2005/62/ECQuality System
2002/98/EC2004/33/ECTechnical Requirements
2005/61/EC –Haemovigilance
WG 3
WG 4
WG 2
WG 1
Cross reference to ‚good practice‘following the EU-Directives
CoE
EUBIS-MANUAL
PICS-INSPECTION
BE
C
H
E
C
K
L
I
S
T
S
EU-GMP
2002/98/EC – Cap. II, Art 8 - Inspection and control measures
Chapter 1: Quality system (standards-cross reference)
Chapter 2: Organisational requirements of a CA / BE- Qualification and training of inspectors- Inspection Master Plan (Schedule)- Number of inspectors (staff) to cover the task
Chapter 5: Inspection checklists
Chapter 3: Inspection process of BE (external by CA)- Type of inspection- Inspection team- Information provided by the BE to CA before inspection- Documents/Lists of SOP (optional)- Information available on site during the inspection by CA- Inspection report- Evaluation system for deviations
Chapter 4: Self-Inspection process (internal by BE)- Quality policy (Management)- Type of inspections- Responsiabilities- Inspection team (e.g Peer-inspection process)- Internal inspection report- Evaluation system for deviations and continuous improvements
EuBIS Inspection Manual
www.eubis-europe.eu
Project Participantseu-q-blood-sop.de / Eubis-europe.eu
Erhard Seifried, RCBDS, (Germany)Christian Seidl, RCBDS (Germany)Walid Sireis, RCBDS (Germany)Veronika Brixner, RCBDS (Germany)Thea Müller-Kuller, RCBDS (Germany)Wiebke Siegel, RPDA (Germany)Margarethe Heiden, PEI (Germany)Helga-Marie Huber, PEI (Germany)Alain Beauplet, EFS (France)Claudine Hossenlopp, EFS (France) Leslie Sobaga, EFS (France) Alan Slopecki, NHSBT (United Kingdom)Mark Nightingale, NHSBT (United Kingom)Martin Gorham, EBA (United Kingdom)Petra van Krimpen, Sanquin (The Netherlands) Jan Peter van Galen, Sanquin (The Netherlands) Jeroen de Wit, Sanquin and CoE (The Netherlands) Jan Ceulemans, HBRK (Belgium)Inge Buyse, HBRK (Belgium)Philippe Vandekerckhove, HBRK (Belgium)Marie o`Connel, IBTS (Ireland)William Murphy, IBTS (Ireland)Patrick Costello, IMB (Ireland)Guiliano Grazzini, ISS (Italy)Hamisa Jane Hassan ISS (Italy)Adele Giampaolo, ISS (Italy)Valentina Hafner, WHO (Denmark)
Svetla Bakalova NCHT (Bulgaria)Andrey Andreev, NCHT (Bulgaria)Petr Turek, GTH (Czech Republic)Zuzana Cermakova, FNPO (Czech Republic)Renata Zimova, SUKL (Czech Republic)Klára Barótine-Tóth, HBTS (Hungary)Eszter Miskovits, HBTS (Hungary)Elzbieta Lachert IHBT (Poland)Magdalena Letowska, IHBT (Poland)Virgil Paunescu, BCT (Romania)Carmen Tatu, BCT (Romania)Dan Poenaru, BCT (Romania)Antoaneta Dragoescu, MoH (Romania)Harald Schennach, ABTS (Austria)Tatjana Plahova NEBC (Estonia)Riima Niidas NEBC (Estonia)Zoe Sideras MoH (Cyprus)Sveinn Gudmundsson IBTS (Iceland)Ina Björg Hjalmarsdotir (Iceland)Alex Aquilina NBTS (Malta)Richard Zammit MoH (Malta)Frances M. Delaney, FMD (Luxembourg)Angus McMillan Douglas, AMD (Scotland)Ian Franklin, SNBTS (Scotland)Brian McClelland, SNBTS (Scotland)Dragoslav Domanovic, BTCS (Slovenia)Irena Razborsek, BTCS (Slovenia)Andrijana Tivadar, JAZMP (Slovenia)
Tapani Piha, EC, DG Sanco(Belgium)Thomas Bregeon, EC, DG Sanco(Belgiun)Eduardo Fernandez-Zincke, EC, DG Sanco (Belgium)Ann Thuvander, EC, PHEA (Luxembourg)
Thank you
http://www.eu-q-blood-sop.de
http://www-eubis-europe.eu