european public health programme: the eu-q-blood-sop manual

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


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


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 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)


- 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


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


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.

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


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