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Co-funded by the European Commission

Health and Consumer Protection Directorate GeneralPublic Health and Risk Assessment Directorate

Grant Agreement No. 2004217

Manual

European standard operating procedure (SOP)methodology reflecting European best practicewithin the area addressing

the quality and safety of blood.

Published by the Project Participants: DRK-BSDBH, Germany;HBRK, Belgium; NBT, Bulgaria; MOH, Cyprus; VFN, Czech Republic;

EBS, Estonia; EFS, France; HNBT, Hungary; BTS, Iceland;NBTS, Ireland; ISS, Italy; IBT, Malta; IHBP, Poland; FMP, Romania;

Sanquin, The Netherlands; SNBTS and NBS, United Kingdom.

Standard Operating Procedure (SOP)

Editors: E. Seifried and C. Seidl,Frankfurt, Germany, Edition 1.0, 2007

English German


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European Standard Operating Procedure (SOP) Manual, Edition 1.0, 2007

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Publication notice:

This manual has been developed by the participants of the EU-Q-Blood SOP Project co-funded bythe European Commission, Health and Consumer Protection Directorate General, Public Health andRisk Assessment Directorate, Grant Agreement No. 2004217. (2006-2007)

The manual gives valuable information and guidance on the structure of documents related to quality

management systems. The content of this manual will therefore by included in the EU co-fundedproject on developing common criteria and standards for the inspection of blood establishments.

Further information on this manual including updated versions, national training courses or seminarsorganised by the project participants is available from the project Website of EUBIS (Europeanblood inspection system) (www.EUBIS-europe.eu).

Supported by the European Blood Alliance (EBA)

Disclaimer:

The content of this manual does not necessarily reflect the views of the EuropeanCommission. Neither the Commission nor any person acting on its behalf can beheld responsible for any use that may be made of the information in this report.

The editors and project participants assume no responsibility for the use to whichthis manual is made.

EuBISEuropean Blood Inspect ion SystemCo-funded by th e EC


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Red Cross Blood Donor Service Baden-Wrttemberg Hessia, University HospitalFrankfurt am Main, Germany

Editors / Herausgeber; Erhard Seifried and Christian Seidl

Edited in cooperation with the Project Participants / Herausgegeben gemeinsam mit den Projektteilnehmern

DRK-BSDBH Germany (ProjectCoordinator)

Deutsches Rotes Kreuz Blutspendedienst, Baden-Wrttemberg, Hessen (Red CrossBlood Donation Service)

BTS - Iceland Landspitalinn Hsklasjukrahs (Icelandic National University Hospital)

EBS - Estonia Phja-Eesti Verekeskus (North-Estonian Blood Centre)

EFS - France Etablissement Franais du Sang (French Blood Establishment)

FMP - Romania Universitatea de Medicina si Farmacie "Victor Babes" Timisoara (University ofMedicine and Pharmacy "Victor Babes" Timisoara)

HBRK - Belgium Het Belgische Rode Kruis (Belgian Red Cross)

HNBT - Hungary Orszgos Vrellt Szolglat (Hungarian National Blood Transfusion Service)

IBT - Malta Centru Nazzjonali ta't-Trafuzjoni tad-Demm (National Blood Transfusion Service)

IHBP - Poland Instytut Hematologii I Transfuzjologii (Institute of Hematology and Blood Transfusion)

ISS - Italy Istituto Superiore di Sanit

MOH - Cyprus - (Ministry of Health of the Republic of Cyprus - Medical and PublicHealth Services)

NBS - UnitedKingdom

The National Blood Authority (England and North Wales)

NBT - Bulgaria (NationalCenter of Hematology and Transfusiology)

NBTS - Ireland The Blood Transfusion Service Board

Sanquin - TheNetherlands Stiching Sanquin Bloedvoorziening (Sanquin Blood Supply Foundation)

SNBTS - UnitedKingdom

Scottish National Blood Transfusion Service

VFN - CzechRepublic

VSEOBECN FAKULTN NEMOCNICE V PRAZE and Vseobecn fakultn nemocnice(University Hospital of Prague)

Advisory Board (Martin Gorham, Jeroen de Wit, Magdalene Letowska, Angus Macmillan Douglas).

Supported by the European Blood Alliance (EBA) /mit Untersttzung der European Blood Alliance (EBA)

Copyright


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PREFACE

Ensuring the quality and safety of blood continues to be a major preoccupation within theframework of public health on the national and European level. The introduction ofadvanced technologies for the collection, processing and testing of blood during the lastdecade has resulted in extremely high quality and safety standards of blood and bloodcomponents. Increasing importance has been addressed to establish effective qualitymanagement systems for blood establishments. Those systems enable to optimise thecontrol and monitoring of the complex and sophisticated processes covered by modernblood establishments. A key element of quality systems is to define a common qualitypolicy, using standard process or operating procedures as an important tool fortransposition.

The objective of this manual is to set out a methodology for establishing such standardoperating procedures (SOPs) based on the European Commissions directiverequirements related to ensuring the quality and safety of blood. It is the result of acollaborative effort of representatives from 16 institutions participating in a project co-funded by the European Commission (Grant Agreement N 2004217) within theframework of its Public Health Programme (Decision N1786/2002/EC). Initiated and

coordinated by the Red Cross Blood Donor Service Baden-Wrttemberg Hessia inFrankfurt am Main, Germany, this project aimed to develop a manual that would assistblood services to implement or improve their standard operating procedures and thatwould reflect, in the view of project participants, European best practice.

It is hoped that this EU-SOP Manual will contribute to the understanding andmanagement of quality processes in blood services and assist blood establishments inpreparing for the inspection of their services related to the implementation of qualityrelevant elements required by European Union legislation. In this context, the manualincludes a master SOP template and SOP examples illustrating the structure and the

process to develop SOPs.The project coordinators herewith express their sincere appreciation to the participatinginstitutions and their representatives, as well as to the team of advisors, in particularMartin Gorham, Dr. Jeroen deWit, and Angus Macmillan Douglas for their continuedcooperation, collaboration and support throughout the life of this undertaking. Theirwillingness to share their expertise and experience at the national level on the use of themanual is gratefully acknowledged. The project participants also express their gratitudefor the constructive cooperation with the representatives of the European Commission,Tapani Piha and Dr. Eduardo Fernandez-Zincke as well as the support of Frances

Delaney. Finally, the project participants would like to acknowledge the support given bythe European Blood Alliance at present and in sustaining the future dissemination of theProjects deliverables and the continual development of its ideas.


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This 1st Edition of the manual is presented on behalf of the project participants. Anelectronic form can be ordered via the Project Website (www.EUBIS-europe.eu).

Prof. Dr. med. Erhard Seifried (Project Leader)

Prof. Dr. med. Christian Seidl (Project Coordinator)

On behalf of the Project Participants


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VORWORT

Die Sicherheit und Qualitt von Blut und Blutbestandteilen ist von groer Bedeutung frdas ffentliche Gesundheitswesen auf nationaler und Europischer Ebene. In denzurckliegenden Jahrzehnten hat die Einfhrung modernster Verfahren zur Gewinnung,Verarbeitung und Testung von Blut- und Blutbestandteilen zu einem hohen Qualitts- undSicherheitsstandards in diesem Bereich gefhrt. Eine zunehmende Bedeutung kommtder Etablierung von effektiven Qualittsmanagementsystemen innerhalb derBlutspendeeinrichtungen zu. Diese Systeme ermglichen die berwachung der teilweisekomplexen Ttigkeitsbereiche und Arbeitsablufe. Ein wichtiger Bestandteil solcherQualittsmanagementsysteme ist die Festlegung von einheitlichen Qualittszielen unddie Beschreibung der hierfr erforderlichen Vorgehensweisen in Form vonstandardisierten Verfahrens- und Arbeitsanweisungen.

Das vorliegende Handbuch soll einen praktischen Leitfaden geben fr die Etablierungvon Standardarbeitsanweisungen (engl. Standard operating procedure = SOP) inBlutspendeeinrichtungen basierend auf der durch die Europische Kommissionerlassenen Direktiven fr Blut und Blutbestandteile. An der Ausarbeitung waren Expertenvon Blutspendeeinrichtungen sowie Gesundheitsministerien aus 16 EU-Mitgliedslndernbeteiligt. Die Arbeitsgruppe war Teil eines durch die Europische Kommissiongefrderten Projektes (Grant Agreement N 2004217), das nach Initiative und unterLeitung des Blutspendedienstes Baden-Wrttemberg Hessen des Deutschen RotenKreuzes in Frankfurt am Main durchgefhrt wurde. Die Frderung hierfr erfolgte durchdas Aktionsprogramm der Europischen Gemeinschaft im Bereich der ffentlichenGesundheit (Beschluss N1786/2002/EG).

Vorrangiges Ziel des Handbuches ist es zu einem besseren Verstndnis von Qualitts-relevanten Prozesses auf Ebene von Arbeitsanweisungen in Blutspendeeinrichtungenzufhren sowie Blutspendeeinrichtungen die Mglichkeit zu geben, bestehendeArbeitsanweisungen an die Anforderungen der Europischen Direktiven anzugleichen. Indiesem Zusammenhang kann der vorliegende Leitfaden Blutspendeeinrichtungen auchbei der Vorbereitung auf Inspektionen entsprechend den Vorgaben der EuropischenDirektiven genutzt werden. Hierzu versucht das Handbuch anhand von Muster-SOPssowie mit praktischen Beispielen die Vorgehensweise zur Erstellung vonArbeitsanweisungen zu veranschaulichen.

Die von den Projektteilnehmern auf Basis langjhriger Erfahrungen mitQualittsmanagementsystemen erarbeiteten Empfehlungen verstehen sich somit alsHilfestellung zur Umsetzung einheitlicher Europischen Sicherheits- undQualittsstandard im Bereich von Blut und Blutbestandteilen wie sie in den Direktiven der

Europischen Kommission vorgegeben werden.


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Die Projektkoordinatoren mchten sich bei allen mitwirkenden Institutionen, denProjektteilnehmern sowie den Mitgliedern des Advisory Boards, insbesondere MartinGorham, Dr. Jeroen de Wit und Angus Macmillan Douglas, fr die hervorragendeZusammenarbeit, den konstruktiven Gedankenaustausche und die fortwhrende

Untersttzung der Projektarbeit bedanken. Im Namen der Projektteilnehmer mchten wiruns weiterhin fr die gute Zusammenarbeit mit den Vertretern der EuropischenKommission, Tapani Piha und Dr. Eduardo Fernandez-Zincke sowie der Untersttzungdurch Frances Delaney, bedanken. Unser Dank gilt auch der Untersttzung durch dieEuropean Blood Alliance in der bisherigen und zuknftigen Verbreitung der Projekt-Ergebnisse und der kontinuierlichen Weiterentwicklung der Projektinhalte.

Die vorliegende 1. Ausgabe des Handbuches wird im Namen der Projektteilnehmerverffentlich. Eine elektronische Version des Handbuches kann ber die Homepage(www.EUBIS-europe.eu) bestellt werden.

Prof. Dr. med. Erhard Seifried (Projektleiter)

Prof. Dr. med. Christian Seidl (Projektkoordinator)

im Namen der Projektteilnehmer


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Table of Contents / Inhaltsverzeichnis

PREFACE.............................................................................................................................. V

VORWORT.......................................................................................................................... VII

MANUA L VERSION 1.0 ENGLISH / ENGLISCH...................................................................1

CHAPTER 1 ...........................................................................................................................3

INTRODUCTION............................................................................................................................................................ 3

BACKGROUND............................................................................................................................................................. 3

PROJECT OBJECTIVES ................................................................................................................................................ 4

METHODOLOGY .......................................................................................................................................................... 5

BACKGROUND SUMMARY ............................................................................................................................................ 7

CHAPTER 2. QUALITY PRINCIPLES OF DIRECTIVE 2002/98/EC AND 2005/62/EC........8THE SOP MANUAL ................................................................................................................................................... 10

CHAPTER 3. DEVELOPMENT AND IMPLEMENTATION OF AN SOP.............................133.1. IDENTIFY THE OBJECTIVE AND SCOPE OF THE SOP AND DRAFT A TITLE (STEP 1)................................................. 15

3.2. IDENTIFY THE COMPETENT USER AND ASSIGN RESPONSIBILITY FOR WRITING (STEP 2)......................................... 16

3.3. USING THE MASTER SOP TO WRITE AN SOP (STEP 3) ..................................................................................... 17

3.4. DESIGN A FLOW CHART AND DESCRIBE EACH STEP OF THE WORK PROCESS (STEP 4).......................................... 18

3.5. INITIATE DOCUMENT CHANGE CONTROL (STEP 5)............................................................................................... 27

3.6. PERFORM TRAINING OF THE SOP (STEP 6)....................................................................................................... 32

CHAPTER 4. MASTER SOP AND EXAMPLES .................................................................354.1. STANDARD OPERATING PROCEDURE TEMPLATE................................................................................................ 35

Section A: Purpose / Scope / Role ............................................................................................................37

Section B: Authorisation and change control.............................................................................................37

Section C: Description of operating procedure........................................................................................... 39

Section D: Procedure for Non Conformance (Directive 2005/62/EC, Annex 9) ........................................40

Section E: Documentation ..........................................................................................................................41

Section F: Annex.........................................................................................................................................42

4.2. EUBIS MASTER SOP ....................................................................................................................................... 44

4.3. SPECIAL SOP FORMATS (TESTING AND EQUIPMENT).......................................................................................... 48

4.3.1. Standard test procedure (laboratory) using the EUBIS format.........................................................524.3.2. Standard equipment procedures using the EUBIS format................................................................56

4.4. SOP EXAMPLES COVERING CRITICAL QUALITY ACTIVITIES ................................................................................. 59

4.4.1. Labelling and donor identification at collection site ..........................................................................60

4.4.2. Blood group determination and compatibility testing........................................................................68

4.4.3. Collection and processing of platelet apheresis concentrates..........................................................74

4.4.4. Validation of temperature control areas for storage and transportation ...........................................85

ANNEXES ............................................................................................................................94ANNEX I TERMINOLOGY (DEFINITIONS) .................................................................................................................. 94

ANNEX II - PARTICIPATING INSTITUTIONS AND INDIVIDUALS ......................................................................................107 ANNEX III - REFERENCES ........................................................................................................................................111

ANNEX IV - PROJECT-PUBLICATIONS ...................................................................................................................... 113


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MANUAL VERSION 1.0 GERMAN / DEUTSCH.............................................................114

KAPITEL 1 .........................................................................................................................118EINFHRUNG ..........................................................................................................................................................118

HINTERGRUND ........................................................................................................................................................118

PROJEKTZIELE ........................................................................................................................................................120

ARBEITSPROGRAMM ...............................................................................................................................................120

ZUSAMMENFASSUNG DER PROJEKTZIELE ................................................................................................................123

KAPITEL 2. QUALITTSGRUNDSTZE - DIREKTIVEN 2002/98/EG / 2005/62/EG ......125Das SOP-Handbuch .................................................................................................................................128

KAPITEL 3. ENTWICKLUNG UND IMPLEMENTIERUNG EINER SOP...........................130

3.1. FESTLEGUNG DES AUFGABENBEREICHES DER SOP UND ENTWURF DES TITELS (SCHRITT 1)............................1323.2. ERMITTLUNG EINES GEEIGNETEN MITARBEITER ZUR SOP-ERSTELLUNG (SCHRITT 2)....................................... 133

3.3. EINSATZ DER MASTER-SOP ALS MUSTER ZUR ERSTELLUNG DER SOP (SCHRITT 3) ....................................... 134

3.4. ENTWURF EINES FLOW-CHARTS UND BESCHREIBUNG DER EINZELNEN SCHRITTE (SCHRITT 4)..........................136

3.5. DURCHFHRUNG EINES GELENKTEN DOKUMENTENAUSTAUSCHES (SCHRITT 5) ................................................ 144

3.6. SCHULUNG DER SOP (SCHRITT 6)..................................................................................................................150

KAPITEL 4. MUSTER-SOP UND BEISPIEL SOPS....................................................... 1534.1. MUSTER FR EINE STANDARD ARBEITSANWEISUNG ........................................................................................153

Teil A: Zielsetzung / Anwendungsbereich / Aufgaben.............................................................................155

Teil B: Autorisierung und gelenkter Dokumentenaustausch (change control) ......................................155Teil B: Freigabe und gelenkter Dokumentenaustausch (change control) .............................................156

Teil C: Beschreibung des Arbeitsprozesses ............................................................................................158

Teil D: Verhalten bei Abweichungen (Direktive 2005/62/EG, Anhang 9) ................................................158

Teil E: Dokumentation..............................................................................................................................160

Teil F: Anhang..........................................................................................................................................160

4.2. EUBIS MUSTER-SOP.....................................................................................................................................163

4.3. BESONDERE SOP FORMATE (LABORTESTUNG UND GERTE)...........................................................................167

4.3.1. Standard Test-SOP unter Verwendung des EUBIS-Formates....................................................... 171

4.3.2. Standard Gerte-SOP unter Verwendung des EUBIS-Formates................................................... 175

4.4. SOPS ZU QUALITTSRELEVANTEN ARBEITSPROZESSEN ...................................................................................178

4.4.1. Beschriftung und Spenderidentifikation im Rahmen der Blutspende............................................179

4.4.3. Gewinnung und Herstellung von Apherese-Thrombozytenkonzentraten.......................................197

4.4.4. Validierung der Temperaturberwachung fr Lagerung und Transport von Blutprodukten........... 207

ANHANG............................................................................................................................216ANHANG I BEGRIFFSBESTIMMUNGEN .................................................................................................................... 216

ANHANG II TEILNEHMENDE INSTITUTIONEN UND PERSONEN..................................................................................231

ANHANG III - REFERENZEN .....................................................................................................................................235

ANHANG IV - PROJEKT-BEZOGENE PUBLIKATIONEN.................................................................................................237


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Manual Version 1.0 English / Englisc h


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CHAPTER 1

In t roduct ion

This manual setting out a European standard operating procedure (SOP) methodologyis the outcome of a project entitled EU-Q-Blood SOP.1The project was co funded by theEuropean Commission under its 2003-2008 Programme of Community action in the fieldof public health2, which identified the enhancement of the quality and safety of blood andblood components as one of its actions and support measures. This SOP manual,developed by a consortium of blood establishments having considerable expertise inquality management systems, reflects, in the view of the project participants, Europeanbest practice for developing high standards of quality and safety for the collection,processing, storage and distribution of blood and blood components. Its aim is to provide

the tools by which a blood establishment can build up its own standard operatingprocedures (SOPs), as well as provide a logical framework which hopefully can be usedby all institutions in a variety of different logistical and functional situations.

Background

In 2002, the European Union established a legislative foundation for setting a high levelof quality and safety of human blood and blood components with the adoption of Directive2002/98/EC3. This was followed in 2004 and 2005 by three European Commission

Directives setting out the technical implementing measures for issues that are identified inthat Directive. The first deals with certain technical requirements for blood and bloodcomponents (2004/33/EC4), the second with traceability and the notification of seriousadverse reactions and events (2005/61/EC5) and the third with standards andspecifications related to a quality system for blood establishments in the European Union(2005/62/EC6).

Directive 2002/98/EC places a major obligation on Member States and their identifiedcompetent authorities to carry out regular inspections and control of all bloodestablishments on their territory (Article 8). In addition, it requires all blood establishments

to establish and maintain a quality system based on the principles of good practice(Article 11).

1Grant Agreement 2004217.2Decision No 1786/2002/EC of the European Parliament and of the Council of 23 September2002 adopting a programme ofCommunity action in the field of public health (2003-2008). OJ L271, 9.10.2002, p.13 Directive 2002/98/EC of the European Parliament and of the Council of 27 January 2003 setting standards of quality and safety forthe collection, testing, processing, storage and distribution of human blood and blood components and amending Directive2001/83/EC. Official Journal of the European Union, L33, 8/02/2003, p.30.4Commission Directive 2004/33/EC of 22 March 2004 implementing Directive 2002/98/EC of the European Parliament and of theCouncil as regards certain technical requirements for blood and blood components. Official Journal of the European Union, L91,30/03/2004, p.25.5Commission Directive 2005/61/EC of 30 September 2005 implementing Directive 2002/98/EC of the European Parliament and of the

Council as regards traceability requirements and notification of serious adverse reactions and events. Official Journal of the EuropeanUnion, L256, 1/10/2005, p.32.6Commission Directive 2005/62/EC of 30 September 2005 implementing Directive 2002/98/EC of the European Parliament and of theCouncil as regards Community standards and specifications relating to a quality system for blood establishments. Official Journal ofthe European Union, L256, 1/10/2005, p.41.


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Recognizing this obligation on blood establishments to implement quality systems, theEuropean Commission in its 2004 work plan included as one of its priority actions tosupport the development and implementation of quality management programmes to

improve the safety of blood donations to be carried out in the Community.7 Thesubsequent Call for Proposals8specified inter aliathat in the area of blood, priority wouldbe given to the development of tools that would provide practical guidance on how toinstall and maintain quality systems in blood establishments in the Member States(Section 2.2.4).

In response to this Call, a consortium of 16 blood establishments with considerableexpertise in quality management systems was brought together to develop a projectproposal for submission to the European Commission. Coordinated by the Red CrossBlood Donor Service (Deutsches Rotes Kreuz Blutspendedienst) of Baden-Wrttemberg

in Germany, the participating blood establishments involved EU member, acceding orEuropean Free Trade Association (EFTA) countries from Belgium (BE), the CzechRepublic (CZ), the Federal Republic of Germany (DE), Estonia (EE), France (FR), theRepublic of Ireland (IE), Italy (IT), Cyprus (CY), Hungary (HU), Malta (MT), TheNetherlands (NL), Poland (PL), the United Kingdom (UK), Iceland (IS), Bulgaria (BG) andRomania (RO) (Listed in Annex II).

The Consortium, fully aware of the importance of quality management systems in bloodservices, recognised that standard operating procedures SOPs are a key element in theimplementation of good practice and represent the basis of the classical quality

management systems document hierarchy. They provide a series of instructions to carryout an activity in order to demonstrate compliance with procedures. Therefore, theConsortium decided to submit a proposal to the Commission for co-funding to establish amethodology for the preparation of SOPs in blood establishments in the European Union.

Project Object ives

The specific objectives of the EU-Q-Blood-SOP Project were to:

1. assess the existence of SOP manuals and guidelines currently used in the 16blood services involved in the project in order to identify (a) international andnational SOP manuals already in place and (b) the current inspection practice;

2. develop a manual to assist blood establishments to develop and implement theirown SOPs;

3. test this new SOP methodology among the partner institutions;

4. distribute this manual to (a) the participating blood establishments and (b) todisseminate the results to any interested blood establishments throughout the

72004/192/EC: Commission Decision of 25 February 2004 adopting the work plan for 2004 for the implementation of the programmeof Community action in the field of public health (2003 to 2008), including the annual work programme for grants (Text with EEArelevance). Official Journal of the European Union L 60, 27.2.2004, p.58.8Community action in the field of public health (2003-2008). Work plan 2005.


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European Union, acceding or EFTA states using the participating bloodestablishments as national contact points.

Methodology

Following submission of the project proposal to the European Commission, its approval,and the completion of project negotiations, the Project coordinators prepared a surveyquestionnaire designed to find out the current status of SOPs, their structures and anymanuals or regulations already in place in the various participating institutions andcountries. It was divided into four different sections specifically addressing questionsrelated to (i) basic validation, (ii) principal management requirements, (iii) areas of work,where SOPs are in place, i.e. donor recruitment, testing, management, logistics, etc. and(iv) the way that risks are identified and managed. Specific questions sought theidentification of international and national SOP manuals already in place [e.g. AmericanAssociation of Blood Banks (AABB)], being used or legally required. One question soughtto determine whether the blood establishments have been inspected by governmentauthorities and at what intervals. The awareness of inspections as required by Directive2002/98/EC where relevant was also solicited.

Based on the results of the questionnaire, differences and commonalities in the approachto quality management and specific related aspects were identified and summarized in asurvey report (www.EUBIS-europe.eu). It identified some of the perceived high riskareas in blood collection, preparation, laboratory testing, storage and distribution with 7 of

15 (47%) participating blood establishments of the view that their present SOP systemrequired change in the light of the European blood legislation, These were mainlyparticipants from the Member States that joined the EU in 2004 and from the ApplicantCountries (Bulgaria and Romania joined the EU in 2007). Four of 15 (27%) participants (2from Applicant Countries and 2 from the 15 pre-2004 EU Member States) indicated thattheir blood establishments were not inspected by governmental authorities. Theresponses also led to the identification of critical areas in transfusion medicine thatneeded to be addressed by the projects working groups.

Following compilation of the responses to the questionnaire, a start-up meeting of the

project participants was convened at which the projects work plan was reviewed, thesurvey results discussed and agreed, and four working groups established to address theentire range of blood establishment responsibilities from the donor interview to logisticand managerial responsibilities in blood supply. Nominated experts from each of theparticipating blood establishments were assigned to each working group and in January2006 began their work. The structure of the working groups and their area of coverageare presented in Table 1.1.


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Table 1.1. Working group Structure

Working group 1 (WG 1): Donor recruitment and production

The Netherlands (Leader), Cyprus, Iceland, ItalySOP-Topic Identification of donors and labelling

Test site Cyprus

Areas ofInterest andRisk identified

- Blood Collection- Donor Identification- Donor acceptability/selection/interview- Disinfection and Sterility of blood components- Labelling and Identification

Working group 2 (WG 2): Testing (Immunohaematology, Molecular Diagnostics)

United Kingdom (Leader), Belgium, Bulgaria, Romania

SOP-TopicBlood Group determination and compatibility testing inemergency

Test site Bulgaria


- Testing of blood groups and labelling(Rhesus variants/ABO)

- Testing in emergencies- Donor registries (could be linked to Section IV)

Working group 3 (WG 3): Special blood component production

Germany (Leader), Czech Republic, Hungary, Malta, Poland

SOP-Topic Processing of platelet apheresis concentrates

Test site Malta


- Apheresis Concentrates (Platelets)- Pooled Platelet Concentrates- Granulocyte Concentrates- Paediatric Units

Working group 4 (WG 4): Logistics, storage, distribution and management

France (Leader), Estonia, Ireland, Scotland

SOP-TopicValidation of temperature control areas for storage andtransportation of blood components

AdditionalGuidelines

Change control of documents


- Transportation and temperature control- Validation of equipment- Central blood stock management and distribution- Blood component release and/or issuing- Storage and transport related to production


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Participating blood establishments agreed on the common quality elements for SOPs(Chapter 3). They emphasized that while the SOP level can be sufficient to describe workprocesses, they have to be incorporated in a quality management system in accordance

with the relevant requirements of Directive 2002/98/EC (Article 11(1) and Annex I Part B)(Figure 1.1). In several cases, blood establishments are also required to follow additionalrequirements according to specific regulations defined by good manufacturing practice(GMP) and/or the standards of the International Organisation for Standardisation (ISO) forsetting-up a quality manual (linked to ISO) or site-master-file (linked to GMP). In thesecases it will be advisable to cross-reference the directive requirements to those standardsin order to harmonize the quality management system.

Background Summ ary

The aim of the EU-Q-Blood-SOP project was not to provide an operating procedure to beused in an institution, but rather to provide the tools by which one can build a standardoperating procedure (SOP). The resulting product is an SOP-manual that provides amethodology for creating an SOP comprising the basic quality elements. It is intended toset out a practical template aimed at assisting blood establishments prepare forgovernmental inspections as required by Directive 2002/98/EC. It could also be used toadapt existing procedures to comply with current EU requirements. This SOPmethodology comprises precise quality requirements, requisites and quality terms linked

to the EU Directives and is based on GLP/GMP-standards that have to be specified(filled-out) in order to complete the documents. These quality requirements are presentedin a modular fashion, in order to tailor the SOPs to meet local circumstances.

The Manual aims to deliver practical guidance on the basic structure for preparingStandard Operating Procedures (SOPs). Example SOPs, drafted by the working groupsfocusing on selected areas that have been chosen from the areas of highest risk, arepresented in Chapter 4. These examples are intended to assist those who are aiming toadapt their local SOPs using the guidelines given in this manual. The aim is to provide alogical framework which can be used by all institutions in a variety of different logistical

and functional situations.


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CHAPTER 2. Quality principles of Directive 2002/98/EC and 2005/62/EC

Directive 2002/98/EC3 requires that each blood establishment must provide specifiedinformation to the competent authority in order to be designated, authorised, accredited orlicensed [Article 5(1)].

The required information related to a quality system is set out in its Annex I, Part B andhas to include:

1) Documentation, such as an organisation chart setting out staffing responsibilitiesand reporting relationships;

2) Documentation such as a site master file or quality manual describing the qualitysystem based on the principles of good practice;

3) Number and qualifications of personnel;4) Hygienic provisions;

5) Premises and equipment;

6) List of standard operating procedures (SOP) for

- Donor recruitment

- Retention and assessment of donors

- Processing and testing

- Distribution and recall of blood and blood components- Reporting and recording of serious adverse reactions and events.

Directive 2005/62/EC6 sets out the standards and specifications related to a qualitysystem for blood establishments, based on Directive 2002/98/EC, which will help toensure the safety of blood throughout the European Union. Recital 3 states that

A quality system for blood establishments should embrace the principles ofquality management, quality assurance, and continuous quality

improvement, and should include personnel, premises and equipment,documentation, collection, testing and processing, storage and distribution,contract management, non-conformance and self-inspection, quality control,blood component recall, and external and internal auditing. (refer toDirective 2005/62/EC)

A quality system for blood establishments is considered to be a key element in theimplementation of good practice.

A quality management system is used for the purposes of compliance with regulations

and guidelines. It should ensure a systematic approach towards quality and theimplementation and maintenance of a quality system. It should involve all persons and


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processes in the blood establishment (Annex 1.1) and lead to a system for the evaluationof processes and to continuous quality improvement.

There are no absolute criteria for framing the quality management system. In general, itcomprises a number of tools defined by the individual institution, in order to allow for the

flexibility to adjust to various regulations and guidelines. In meeting the requirements ofDirective 2005/62/EC, individual Member States must take into account their ownadditional specific regulations and guidelines.

According to Directive 2005/62/EC quality systems for blood establishments should bebased on good practice (GP).

In order to ensure the highest quality and safety for blood and bloodcomponents, guidance on good practice should be developed to support thequality system requirements for blood establishments taking fully intoaccount the detailed guidelines referred to in Article 47 of Directive2001/83/EC so as to ensure that the standards required for medicinalproducts are maintained. (Recital 5)

Such good practice guidelines for blood establishment are to be developed by theEuropean Commission (Article 2, Para 2) taking fully into account the principles andguidelines of Good Manufacturing Practice (GMP) (see terminology, Annex I)

Annex I requires that the quality system ensures that all critical processes are specified insuitable instructions. The system must be reviewed by management at regular intervals toverify its effectiveness and measures introduced if deemed necessary (Section 1.1 Para.

3).In order to fulfil these requirements, a blood establishment needs to establish adocumentation system. It should be organized at different levels of documentresponsibility with the top level being those legislative instruments (e.g. legislation andlaws), regulations and guidelines the individual blood establishment has to follow (refer tochapter 2, Figure 2.1). These regulations should be incorporated into the qualitymanagement system and be reflected throughout the entire quality documentationsystem.

A description of the quality system itself should be presented in the document leveldirectly below. Documentation on the manual and/or site-master file (See Definitions) hasto be in accordance with Article 11(1) of Directive 2002/98/EC9. In addition, standardoperating procedures (SOPs) have to be prepared by the blood establishment10. TheseSOPs are an important part of the quality system and have to cover all theestablishments critical activities.

9Annex I, Part B, indent 210Annex I, Part B, indent 6


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In preparing the site master file and the SOPs, the blood establishment needs to addressthe main aspects of the quality system standards and specifications set out in the Annexof Directive 2005/62/EC:

- General Principles (Part 1)

- Personnel and Organisation (Part 2)

- Premises (Part 3)

- Equipment and Materials (Part 4)

- Documentation (Part 5)

- Blood collection, testing and Storage (Section 6), including

6.1 Donor Eligibility, 6.2 Collection, 6.3 Laboratory testing, 6.4 Processing andvalidation, 6.5 Labelling, 6.6 Release of blood and blood components

- Storage (Section 7)

- Contract Management (Part 8)

- Non-Conformance (Part 9), including

9.1 Deviations, 9.2 Complaints, 9.3 Recall, 9.4 Corrective and preventive actions

- Self-inspection, audits and improvements (Part 10)

In order to ensure standardised practice across the blood establishment, it is advisable to

introduce general procedures to describe common processes. These procedures shouldcover operational activities (e.g. sample receipt, collection, etc.), support services (e.g.human resources, etc.) and management processes (e.g. objective setting, non-conformances, internal audit, etc.).

The Quality Manual or Site Master File should be established according to Annex I PartB, and Article 11(1) of Directive 2002/98/EC. They are the official documents describingthe overall function and quality policy of the blood establishment as required by the Annexof Directive 2005/62/EC (see above Part 1 Part 10).

The SOP Manu al

This manual provides a methodology for creating an SOP which comprises the basicquality elements. It is intended to set out a practical template for the preparation of SOPsand aims to assist blood establishments in preparing for governmental inspections underblood legislation. It could also be used to adapt existing procedures to comply withcurrent EU requirements.


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The SOP methodology is presented in the context of a quality management system. Itcovers the creation/writing of an SOP, its modification, review and authorization, and itsimplementation including the documented training of users and maintenance of records.

The developed SOPs must adhere to the quality principles set out in the quality manual or

site-master-file in keeping with good documentation practice. In order to be in line withthose principles it is essential to have procedures defining

- change control and

- training personnel on SOPs.

The requirements for these procedures are set out in Directive 2005/62/EC (Part 5 Documentation)

1. Documents setting out specifications, procedures and records covering eachactivity performed by the blood establishment shall be in place and kept up to

date.

2. Records shall be legible and may be handwritten, transferred to anothermedium such as microfilm or documented in a computerised system.

3. All significant changes to documents shall be acted upon promptly and shallbe reviewed, dated and signed by a person authorised to perform this task.

An SOP provides a series of instructions to carry out an activity. In order to demonstratecompliance with SOPs, records of these activities must be generated. Properlymaintained records provide the evidence of adherence to procedures.

Generally records fall into the following categories

- electronic records

- manually generated records

- hybrid record (combination of electronic and manual records)

The writing of SOPs is the responsibility of user departments. This should be carried outin cooperation with the quality function. A major aim in writing SOPs is to ensure that theyare comprehensive but clear, simple and user friendly.


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Figure 2.1: Document structure of the EU-Q-SOP-manual with SOP levels covered bythe Project manual. The figure represents the hierarchy of documents used by a quality

management system following good quality standards as defined by the Directive2002/98/EC and its technical annexes. The Quality Manual or Site Master File shouldbe established according to Annex I Part B, Art 11(1), Directive 2002/98/EC.

Quality Manual(Site Master File)

General/Operating Procedures (GP / OP)

Standard Operating Procedures (SOP)

Records (RP)

Guidelines on Document Change Control (GP/OP)

Regulations / Laws

Guidelines on Personnel Training (GP/OP)


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CHAPTER 3. Development and implementation of an SOP

A Standard Operating Procedure (SOP) can be prepared and formatted in a number ofdifferent ways. The ultimate goal is to create a document that is readable, useful for thosecarrying out the work and compatible with the whole Quality Management system of theinstitution concerned.

An SOP document describes a regularly recurring operation that affects the quality of theprocess. Its purpose is to ensure that the operations are carried out correctly and in aconsistent way. It should be readily available where the work is performed.

The original copy of the SOP must be retained in the Quality Management Department.Authenticated working copies should be available at the appropriate places of work. Thenumber and site of authenticated copies should be included in the SOP; alternatively, a

distribution list should be maintained. A labelling system must be implemented in order toauthenticate each copy of the SOP and to control the number of copies in existence. Thiscan be facilitated by using coloured stamps (e.g. green) to prevent the production ofunauthorized copies.

A standard format for the SOP layout should be defined and documented by theinstitution concerned. The document control process is managed by the qualityprofessional, in cooperation with the management / director of the institution. The personresponsible for writing an SOP must have received training in the design and use ofSOPs.

An SOP is a compulsory instruction. If deviations from an established SOP arenecessary, the entire process should be amended appropriately and the change(s) fullydocumented. This documentation should include a description of the corrective actionsand a clear identification of who had authorized them.

The development of an SOP is a multi-step process that involves preparation, writing,conclusion and training. These are reflected in the following table.


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Table 3.1. Multi-step process of writing an SOP

Step Action Description

Preparation Phase

1 Identify the objective and scope of the SOP and draft a title Chapter 3.1

2 Identify the competent user and assign responsibility forwriting the SOP

Chapter 3.2

Writing Phase

3 Use the Master SOP to write an SOP Chapter 3.3

4 Design a process flow chart and describe each step of thework process in this flow-chart

Chapter 3.4

Training and implementation Phase

5 Initiate document change control Chapter 3.5

6 Conduct training in the use of the SOP Chapter 3.6

This multi-step process can be understood by using an example.

Consider how the production department of a small / medium size local bloodestablishment would go about writing an SOP for the production of an erythrocyteconcentrate.

The director of the blood establishment, together with the departmental directors,identifies the need for and the objective of an SOP. This could be as a result of the

introduction of a new safety measure (e.g. leukocyte depletion of erythrocyte componentby filtration).

The director of the production department assigns responsibility for drafting the SOP to acompetent user. This would be phase 1 of the multi-step process.

The competent user drafts the SOP adhering to the format of the master SOP and he/sheensures the involvement of other workers in describing the production process (e.g.sterile multi-component-systems with integrated leukocyte filter systems). He considerswhether the drafting could benefit from consultation with an expert from the company

producing these filter-systems. The competent user also consults with the qualityprofessional, the director of the testing laboratory and other relevant professionals. Hecreates a process flow chart which helps in identifying critical points in collecting samples


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for testing the product quality (e.g. leukocyte count,) and the release parameters of theblood component to be included in the SOP. He involves the person responsible forstorage and logistics of blood components in order to ensure they make any changesrequired to their SOPs. He has completed the second phase.

Finally, the competent user puts in place a process to allow for a change to be made tothe SOP. This is known as the change control process and includes the training of staff inthe new procedure before it is implemented. The third phase has been completed.

3.1. Identify th e object ive and s cope of th e SOP and draft a tit le (Step 1)

Before drafting the SOP, its objective has to be defined. Then the area of activity coveredby the SOP (i.e. its scope) needs to be identified.

The objective and scope of the SOP must be compatible with the objective and structure

of the institution. This can be facilitated by using an organogram and job descriptions.

In a small blood establishment, simple hand drawn organogram can be used. In a largerinstitution, a computer software tool (e.g. Visio) may be used to develop theseorganogram. The organogram will help identify the activities covered by each SOP. It willalso help in the identification of the personnel responsible for drafting it (3.2). The linemanagement of the area concerned should work with the Quality professional in carryingout this process. Once the objective and scope of the SOP are clear, its drafting will beeasier.

Each SOP must fit into the quality system of the institution concerned. Modern qualitymanagement systems will use either a site master file and/or quality manual, incombination with SOPs, to describe general procedures, process procedures, testing oranalytical procedures, production procedures, donor recruitment procedures, bloodcomponent storage and issuing procedures, etc. These procedures can be classified asfollows:

- General / operational procedures(e.g. covering a department/unit or institution)

- Complex processes (e.g. blood component production and quality control, requiringmultidisciplinary drafting)

- Simple processes

General / operational procedures are very often used to describe the organization ofprocesses throughout a department or institution / blood establishment. These can beprocesses on the registration of samples or blood components entering the bloodestablishment, regulation for general hygienic conditions applied throughout theproduction department or regulations defined to handle non-conformance. These SOPsare often assigned to senior academic-level personnel and authorized by the departmentdirector and or institutional director.


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Complex procedures are characterized by processes that cover different areas of ablood establishment. Complex procedures can result from describing the productionprocess of erythrocyte concentrates including the quality control measurement points andthe sample collection plan involved. This can result in the need for cooperation between

the production department and the quality department on the appropriate steps indescribing the process. It will subsequently also lead to a co-authorization of this SOP bythe person responsible involved (e.g. director production department and director qualitydepartment and/or institutional director).

Simple processes are the classical SOPs describing in detail a small segment of theworking activities of a blood establishment. These simple SOPs can be written bycompetent personnel at the practical working level. For example, the method for testingthe donors ABO blood group (erythrocyte concentrate) can be written by the seniortechnician and authorized by the laboratory director. Examples of these simple SOPs are

given in Chapter 4.

3.2. Ident i fy the competent user and ass ign resp ons ibi l i ty for w ri t ing (Step 2)

The personnel who are authorized to write and sign SOPs should be defined in aprocedure on document writing and authorisation. The decision should be based on theSOP content and level of importance reflecting the hierarchy of the blood establishment.For example, an SOP describing the management structure of a blood establishmentshould be written by the senior management and should be authorized by the institution

director him/herself, while an SOP used to describe the testing procedure for ABO bloodgrouping can be written by the responsible senior laboratory technician and authorized bythe laboratory director.

The competent user is the person who works in the area covered by the SOP and who isadequately trained for this purpose. The identification of competent user will vary withrespect to the scope and purpose of the SOP (Table 3.2).


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Table 3.2 Identifying the competent user to write the SOP

Decision Making Level (Staff)

Level (Document)

Executive

Managerial

Department

Function

Operational

Quality Manual / Site Master File

General / Operational Procedures

Complex Procedures

Simple Procedures

Exceptions from this procedure are possible in cases where individual expertise isrequired to write the SOP. As an example, the writing of a GMP/GLP SOP related tohygienic regulations and/or cleaning procedures may be out-sourced to an independentconsultant who is a specialist in this subject. The same may occur for health and safetyregulations. In these cases, the writing of a SOP is carried out in cooperation with theperson authorized to issue the SOP.

3.3. Usin g the Master SOP to write an SOP (Step 3)

Drafting the SOP should provide a simple and precise description of the process.

First, choose a short and descriptive title for the SOP.

Second, use the EUBIS Master SOP in drafting the SOP. At least the following minimumrequirements must be included:

- SOP number

- Unique title (clear and descriptive)

- version number

- page number and total number of pages

- name and signature of author including date of signing

- name and signature of person who authorized the introduction of theSOP

- date on which the SOP or revision becomes effective

Include the number and location of authenticated copies in the SOP or alternatively

maintain a distribution list.


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Note: detailed information concerning the EUBIS Master SOP can be found in Chapter4.1 and 4.2.

Third, design a flow-chart (Chapter 3.4), where possible. This will identify working stepsand decision points and will assist in describing the work process consistently throughout

the document.Human nature dictates that people support what they help to create. A team-workapproach in writing SOPs can enhance the training process in their use. Managers orDepartment Directors should ensure there is input from those staff and relevant expertswho will be affected by the SOP. By enlisting the talents of their personnel and technicalexperts / senior consultants, the competence of relevant staff will be improved and betterSOPs produced. This will foster teamwork between personnel and managers / directors.This approach has been proven to be very effective. In small and medium bloodestablishments the whole team may be located at one site. But in large blood

establishments, the team may be situated on more than one site and the quality systemwill need to establish a more sophisticated training programme.

Fourth, validate the draft SOP using qualified personnel. In the case of general oroperational procedures, this validation could be carried out by senior management. Thisvalidation phase will allow for fine tuning and revisions can be introduced as required.Upon completion of the validation submit the SOP to the appropriate line manager forauthorization. When ever possible the drafting and authorization of an SOP should becarried out by at least two independent persons. The authorization process will includethe signature by the appropriate senior line manager. In addition, SOPs addressing

pharmaceutical blood products need authorization by a qualified person.

Standard operational proceedings (SOPs) need to follow strict guidelines in order tocontrol the precision and actuality of their content. Different types / categories of SOPshave to be integrated in a quality system in order to assist in consistency betweendocuments. The quality function / or quality management department itself (see alsoChapter 2), is responsible for ensuring that basic document standards are defined, thatall personnel responsible for writing SOPs are trained to these standards and that finallythese standards are fulfilled when SOPs are issued or revised.

These standards are described in general in an SOP by itself or are integrated in thedescription of the quality system included in the quality manual or site master file.

3.4. Design a f low chart and d escr ibe each step of th e work proc ess (Step 4)

Flow charts are an ideal way to describe step-wise a process including the criticaldecision points. Inclusion of the responsible persons for those decision points defines theaction performed under practical work conditions and ensures that best practice isfollowed throughout the various processes performed by blood establishments.


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The use of a standard set of symbols for drawing flow charts is highly recommended.These symbols are provided by standard commercial computer software11 or will beincluded in special software available for drawing flow charts12. The standard set ofsymbols is as follows:

The drawing of flow charts for the regular users (SOP writer) is most conveniently splitinto two

- 1: Map the process covered by the SOP

- 2: Draw the flow chart using symbols

11Microsoft Office Professional Business Edition, PowerPoint12Visio


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1: Map the process covered by the SOP

Mapping of the process is based on the information from identifying the purpose andobjective of the SOP. The writer (or writing team) has to define the main tasks (steps) toachieve the objective of the SOP (e.g. Testing request for blood component).

This is achieved most easily by starting with the most reasonable beginning point of theprocess. Subsequently one will put the main task into a logical order to get from thebeginning (input, e.g. test sample from customer) to the end point (output, e.g. testedblood component) of the procedure. The decision points that a worker will need to makeand the action that follow each decision should be marked. One should not try to beperfect with the first draft, because it is very likely that revisions will be required.

This first process map can be done by drawing down the process on paper. It should beensured that the process flows in one direction from the beginning to the end point. Thisshould include the choices and decision points including the personnel responsible fordeciding on the action. It will be important to define, if the main process depends onanother process or if there are certain tasks that are sub-processes. These processes /sub-processes should be cross referenced to the SOP. If the process map revealscomplex decision points or sub-processes involving responsible personnel from otherdepartments or locations of the blood establishment, one should invite these persons toreview the process map and clarify their function.

2: Drawing the flow chart using symbols

The process map will be used to draw the process steps and decision points usingstandard symbols. This can be easily done by PowerPoint or other software supportingthese symbols.

Flow charts are able to present processes to a high detail. However, the level of detailresulting from a flow chart needs also extended training of the personnel in understandingthese flow charts. Highly detailed flow chart may come close to electronic wiring mapsand this can lead to misinterpretation if the SOP user is not particularly trained. Thereforeeach institution should define the level of flow chart detail that is appropriate to supportbest practice.

An example of a flow chart using defined symbols is given in Figure 3.3.1. The upper partrepresents the main five steps covering the process (1. to 5.). The ending point is markedby the STOP symbol. Further details on each of these five steps can be given by usingadditional flow charts. The lower part of figure 3.3.1. gives an example on how to givefurther detail on the first step (1. Reception of request). All steps referring to thereception of request are indicated by using the main step number followed by analphabetic letter (1a, 1b, 1c, etc). At decision point 1c (Test sample?)the flow chart is re-directed to the main flow chart, step 2 - Testing or step 3 No testing. Similarlyadditional flow charts can be used for steps 4 and 5.


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Stop

2.

Testing

3.

No testing

4.

Selection

of units

5.

Issuing

units

1.

Reception

of request

1a.

Request

1b.

Registration

of request

1c. Test

sample?

2.

Testing

3.No testing

yes

no

Figure 3.3.1. Example of a flow chart using international symbols to describe the testingrequest for blood component.

Using this example it is also important to define in which direction flow charts are oriented(horizontal or vertical). There are no official recommendations and this decision will be

based on the personal practicability of flow charts used by each blood establishments.Most users prefer to use a vertical orientation of flow charts since it allows to line-up moresteps on a single page and may facilitate to cross-reference sub-processes.

In order to facilitate the reading of these flow charts by the SOP user, it is helpful toinclude a brief description of the action represented in each step and to link this to theresponsible person for this action.


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Using the example in figure 3.3.1, this could be done as follows:

Procedure

Step Action Responsibility

1 Reception of request technician1a Check if the request is complete and valid

- address of the customer- type of test requested- testing material and labelling

1b Register the sample information in your technicianlaboratory information system (LIMS)

1c In case all information is complete proceed to step 2, technicianif the request/test material/sample identification is

incomplete go to step 3

2 Start to perform the analytical test technician

3 No testing performed. technician +Document the type of non conformance and physicianreturn relevant information to the customer

The ability to describe complex processes using standard flow chart symbols is presentedby another example using the SOP describing the process on how the produce a plateletapheresis concentrate (Table 3.3.1). The example includes the guidelines and standardsfor writing a SOP that have been set-up in the EUBIS master SOP (Chapter 4.1). Criticaldecision points to be used for risk analysis are marked by red dots ( ).

This SOP has been worked-out by the working group 3 of the Project (Chapter 4.4.3).


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Table 3.3.1: Example on how to translate a flow chart (working group 3 Apheresis) tointernational symbols._______________________________________________________________________

Start

by including the requirements set-out by the EU blood legislation

Table 3.3.1: continued_______________________________________________________________________

StopDonation /Apheresis

BloodComponentprocessing andtesting

PatientDonorSelection

A B C2C1

2002/98/EC, Art 18 Eligibility of donors2004/33/EC, Art 3 Information required from the donor

Art 4 Eligibility of donors2005/61/EC, Art 2 Traceability2005/62/EC complete


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Table 3.3.1: continued_______________________________________________________________________

A

Donor-Selection

Deferral

ConsentYes/no Pos/

Neyesno

Predonationtesting

A.1

no

pos

neg

yesno

yes

Donation


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Log-books

BatchRecall

Document

Yes/NoYes/No

Yes/No

ApheresisE ui ment

no

yes

Donation /Apheresis

Collection Set/Medicinalcomponents

no

yes

Phlebo-tomyYes/No

A.1B RepairService

yes

no

no

yes

Donor-Discharge

Disconnect /DischargeDonor

ProductTestsamples

StoC1 C2

Log-books


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Table 3.3.1: continued_______________________________________________________________________

no

Testsamples

MandatoryTesting- Blood Group- Infectiousdisease markers

C.2

C.1

no

Product

Product process

Yes/No

Additional Test(e.g. HLA/HPA)

yes

Specification/Qualiy

blood componentsnot released

Sample

archiving

Additional Process required- irradiation- Plasma reduction

-washing-- small volume components

Component release

Issuance / Distribution

Post quarantine Storage

Refer to specific SOP(s)SOPSORefer to specific SOP(s)SOPSO

blood componentsnot released

Quarantine Storage


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3.5. Ini t iate doc um ent change con trol (Step 5)

Change control of SOPs is a principle requisite for a proper functioning quality

management system. The guidelines for document change control are therefore part ofthe quality manual or site master file of the system and have to be followed by allpersonnel involved in the institution. These guidelines have to be used for all documentsrelated to the quality management system (Figure 3.5.1).

Figure 3.5.1: Structure of a controlled document system

The objectives of a change control system are:

To have a standard protocol for issue, revision, distribution and disposal ofcontrolled documents,

To prevent the inadvertent use of obsolete documents.

The responsibilities are:

The document control system is under the responsibility of the qualitymanagement department (or quality management officer).

The users are responsible for implementation of controlled documents.

Forms are considered as documents and the same requirements apply. Recordsmanagement should be properly described in a separate procedure or as part of thechange control general procedure.

The change control system has to differentiate between two different types of documents.

QUALITY MANUAL (Policies)

PROCESSES (General procedures :operational, support, management)

RECORDS

SOP Standard Operating Procedure

REGULATIONS


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Internal documents:

They are included in the scope of this procedure.

o Master document: is the original signed documento Controlled documents: they are distinguished and they are copies of the master

document (in a paper based system)

o Information / uncontrolled copies: they must be clearly identified (in a paperbased system or electronic system)

o Obsolete documents: they must be clearly identified

o Forms / records: must be under control

External documents:

They must be controlled and the control system formally described in a specificprocedure.

External documents comprise all relevant national or international legislation, norms orguidelines referred to by the quality management system. These external documentsshould be controlled using a document record list including the respective documentidentification.

External documents are :o Legislation and regulations: Commission Directive 2005/62/EC, Directive

2002/98/EC, others..

o Standards (ISO 9000, 9001, 9004-2000; ISO 15189:2003, )

o Volume 85, supplement 1, August 2003, The International Journal ofTransfusion Medicine, Vox Sanguinis : ISBT Guidelines for validation andmaintaining the validation state of automated systems in blood banking.

o ISBT Guidelines for Information Security in Transfusion Medicine Version 1.0.

The change control system has to incorporate the following quality elements

o Change control procedure

o SOP compiling procedure

o Auditing procedure

o Training procedure

o Records and archive procedure


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The following flow-chart describes the decision-making structure of a change controlsystem.

2. Initiate change control system

1. Need to create / modify aprocedure in agreement with

users / manager

6.Review / approval of the document

5. Elaboration of the document

4. Registration of the document(in the quality system)

users

users / quality /relevant manager

users


document controller

change control committee3. Approval ofthe change

quality

quality

users / document controller

users

7. Signature

8. Making controlled document

available with an effective date

9. Retrieval of obsolete documentswhere appropriate

10. Storage

11. Training

document controller

14. Archive / disposal

13. Audit

12. Implementation

End

users

quality

no

yes

yes

no


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Description of critical control points (flow-chart)

Step Activity Responsibility

1 Need to create / modify a procedure in agreement

with managerBy discussion between the user and the manager, theproposal is accepted or not.

users / manager

2 Initiate change control system

The user who wants to raise a change request has to fillin a change control form.

The manager has to approve or reject the changerequest in order to avoid duplication and to assurecompleteness.

users

3 Approval of the change

The change control committee must include qualityrepresentatives and concerned managers. Itscomposition depends on the significance of the change.

The change control approval must include regulatoryrequirements are met.

change controlcommittee

4 Registration of the document (in the quality system)

Each quality document has to be uniquely identifiedlogged and tracked.

A current master list of controlled document should beavailable.

documentcontroller

5 Elaboration of the document

The user writes the document by using the documenttemplates and defined procedure.

Validation is required for some processes prior todevelopment of documentation.

users

6 Review / approval of the document

All documents should be written and reviewed byrelevant personnel (users / quality / relevant manager).Quality is responsible for ensuring the completeness andstandardisation of the documents.

An effective date must be assigned to controlleddocuments.


7 Signature users / quality /

relevant manager


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Continued - Description of critical control points (flow-chart)

Step Activity Responsibility

8Making controlled document available with aneffective date

Approved document must be communicated anddistributed to users, on electronic form or paper form orboth, in a timely manner. There must be a formal systemto issue controlled document.

documentcontroller

9 Retrieval of obsolete documents where appropriate

The aim of this step is to insure that only current versionof the controlled document is available for users. Index

(extraction of the master list) must be up to date.

users /

documentcontroller

10 Storage

All controlled documents must be stored appropriatelydepending on the storage media, to insure integrity of thedocuments.

quality

11 Training

Depending on validation requirements, training on draftcould occur early in the process.

Training has to be formally documented.

users

12 Implementation

Each concerned department must ensureimplementation of controlled document.

Changes in the described process must be evaluated todetermine whether modification of the document isnecessary.

All controlled documents must be reviewed within a

defined period. The review must be recorded.

users

13 Audit

Independent audit of the effective implementation of thedocument must be carried out at appropriate intervals.

quality

14 Archive / disposal

Obsolete master documents are retained and storedappropriately for the defined period.

Obsolete controlled documents are destroyed.

quality


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Documentation

Key forms and templates for document control system:

change control form

current master list of controlled document training registration form

document templates(description of the form, content and paragraphs),

see Chapter 4.1.

3.6. Perform trainin g of the SOP (Step 6)

After completion of the writing and review process of the SOP document,authorization / approval of this document does not automatically imply that the SOP canbe effectively used by the relevant personnel. A very important step in implementing thenew or revised document will be training of the relevant personnel. This last step in theSOP development process is often neglected. Training and retraining of all personnel isthe only mechanism to ensure that the SOP and the quality relevant criteria it contains will

secure best practice in the blood establishment. Even with very detailed flow charts andprocess descriptions, it is necessary to train all personnel. Otherwise, individuals willinterpret the meaning of procedures in different ways, leading to inconsistency in workroutines and performance.

The European blood legislation13requires that

- All personnel in blood establishments shall receive initial and continued trainingappropriate to their specific tasks. Training records shall be maintained.Training programmes shall be in place and shall include good practice.

- The contents of training programmes shall be periodically assessed and thecompetence of personnel evaluated regularly.

Formally this requires that a system of basic information is given to each individual whenstarting to work in the blood establishment. This basic training should include the qualitypolicy of the institution, theory and practice of the EU blood directives, GoodManufacturing Practice as well as Good Laboratory Practice. The basic training mustinclude training appropriate to the specific work processes based on the job description ortask12.

13 Directive 2005/62/EC, Article 2, Para 1, referring to Annex 2, recitel 3 and 4.


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The periodical training may be best achieved using a training plan and a record forevaluation. Training plans can be organized on different working levels, e.g. a workingteam, the department or the institution. In all cases it should be approved either by thedepartment/institution head or the head of quality.

Training courses are an ideal tool to share between the personnel involved the logic whyprocedures must be performed correctly not just what to do or how to do it. Thesecourses should be used to explain the overall quality policy reflected by these documents.It should be the ultimate goal to convince personnel that these SOPs are not only writtenpaper-work taking off their time, rather that these SOPs are intended to help thepersonnel work according to the best quality standards. This will result in optimal bloodproducts issued for the therapeutic use in patients and/or optimal diagnostics to save-guard patients from infections transmitted by blood products. Personnel involved intransportation and storage should be trained since they are a key element in the process

chain of blood component production. It will be important for the success of the trainingthat despite the limited content of individual SOPs the personnel is able to understand theintegration of this content in the overall operational procedure of the blood establishment.

The trainer has the important function to explain and demonstrate both why and howeach step in the SOP is performed. This can be combined with a practical demonstration,where the personnel will get the change to practice the procedure under the supervisionof the trainer. People are much more likely to follow procedures exactly, when theyunderstand why they are important. In some cases, e.g. change of production processfrom standard component production to leukocyte depleted component production, it will

be helpful to include an external expert, e.g. from the filter-blood-bag company, inassisting the training course.

The training programme should also reflect the idea that training SOPs will improve theprofessional competence of the individual and enhance his or her personal jobqualification including the ability to contribute to future procedure improvements. Thetrainer will provide positive feedback as the learner masters parts of the procedure andpatiently revisits those parts that need improvement.

Training records should be kept and archived. The training record must include thenames and signatures of the personnel present. The record should also contain the

content of the training. This can be realized be including the SOP number of the traineddocument, additional presentation material (e.g. PowerPoint slides, hand-outs) usedand/or a written summary by the trainer. SOPs should be only released after the trainingof the personal is documented. All personnel not present during the initial training have tobe trained before using the SOP. The latter will require a reliable system indocumentation. Very often a training matrix is used for this purpose, whereby informationis interchanged between the working department and the employment department tomonitor the presence of personal.


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A training matrix for SOP documents could be set up as follows:

Department SOP Document-Code

Personal

(Names)

Documentation of individual training

Following the appropriate training, the respective trainees need to be certified competentin the particular SOP procedure by the authorized staff of the blood establishment.Competence also needs to be documented, so that an individual may gradually build upthe competence level.


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CHAPTER 4. Master SOP and examples

This chapter presents the proposed standard operating procedure EUBIS Master SOP.This standard format has been designed by the participants in order to give a practicalexample on how a SOP may be designed. It is based on the essential elements to beaddressed when setting-up a format and writing an SOP.

4.1. Standard Operat ing Procedure template

The following basic standards for documents should / must be included in each SOP:

Section A: Purpose / Scope / Role

- Title (Objective and Purpose)- Scope (Area of application)- Roles covered by the SOP

Section B: Authorization and change control

- Document number (see also EUBIS Document-Code)- Version (see also EUBIS Document-Code)- Page number- Distributor (Number of copies)- Document category (see also EUBIS Document-Code)(e.g. WP Working procedure; PP Production procedure, TP Testing procedure, EP

Equipment procedure, WS Worksheet, RF Registration form, GP General procedure,

OP Operational procedure, QM Quality manual)- written/revised by1

- written/revised date- Effective date- Expiration date2 - reviewed by1

- reviewed date- Authorization date- authorized by1 - authorization date- Changes Description: (compared to the previous version)

1 name and signature of responsible person(s)

2 the maximum interval between revisions should not exceed 2 years


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Section C: Description of operating procedure

- Process Flow-Chart- Description of the work activities

Section D: Procedure for Non Conformance

Section E: Documentation

Section F: Annex

- Literature- References

- Definitions (Terminology)- related SOP documentsrelated worksheets or files

These basic elements comprise principle requirements included in an SOP (Figure 4.1).An example ( EUBIS Master Document) for the practical use of these elements instructuring a SOP are given at the end of this chapter or can be downloaded from theProjects Website (www.EUBIS-europe.eu).

The use of flow-charts is important in order to define a certain process or topic that hasto be described in an SOP. These flow-charts should be flexible enough to allow for localadaptation. However, important specific requirements should be used in order toharmonize the procedure to be used in a quality management system. These are definedas follows:

- usage of international symbols to describe flow-charts

- flow charts should be made as a first step in a simplified manner in order todefine the key decision points in an overall work process. In a later stepimportant decision point have to be elaborated using additional flow-charts.

- This approach should also be used to define, if the process should bedescribed in a single SOP or if it would be more convenient to use severalSOPs linked to each other to cover the process.

-

Explanations on setting-up appropriate flow-charts are given in Chapter 3.4. Thefollowing paragraph gives explanations on how to use the basic elements of the SOPmaster template summarised above.


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