training course quality management - edqm · 2019. 4. 8. · programme 7 trainers 14 list of...

1st European Training Course

QUALITY MANAGEMENT

for Blood Establishments

BLOOD-QUALITY MANAGEMENT WORKING

GROUP (B-QM WG)

EDQM, Strasbourg, FranceTrainee Toolkit 14 - 17 April 2015

PROCEEDINGS

B-QM Programme

Direction européennede la qualité du médicament& soins de santé

European Directoratefor the Quality

of Medicines& HealthCare

1st EUROPEAN TRAINING COURSE: QUALITY MANAGEMENT For Blood Establishments

2015

European Directorate for the Quality of Medicines

& HealthCare (EDQM)

Council of Europe, EDQM

These proceedings are published by the European Directorate for the Quality of Medicines & HealthCare (EDQM) of the Council of Europe.

All rights conferred by virtue of the International Copyright Convention are specifically reserved to the Council of Europe and any reproduction or translation requires the written consent of the Publisher.

Director of the publication: Dr S. Keitel

Page layout and cover: EDQM Cover illustration: ©Shutterstock

European Directorate for the Quality of Medicines & HealthCare (EDQM) Council of Europe 7 allée Kastner, CS 30026 F-67081 StrasbourgFrance

Website: www.edqm.eu For accessing the publication: https://register.edqm.eu/freepub FAQs & EDQM HelpDesk: www.edqm.eu/hd

© Council of Europe, 2019

This training course was organised by the EDQM in the frame of the Blood Quality Management Programme, an activity carried out with funding by the European Union and by the Council of Europe. This document was produced with financial assistance by the European Union. The views expressed herein can in no way be taken to reflect the official opinion of the European Union.

Contents FOREWORD AND WELCOME ADDRESS 4

PROGRAMME 7

TRAINERS 14

LIST OF PARTICIPANTS 15

PURPOSE OF THE TRAINING COURSE 17

PRESENTATIONS 18

OPENING SESSION 18

MODULE A–REGULATORY FRAMEWORK AND QUALITY MANAGEMENT 33 EUROPEAN REGULATORY FRAMEWORK FOR THE QUALITY AND SAFETY OF BLOOD COMPONENTS

34

FOCUS ON QUALITY STANDARDS USED IN BLOOD ESTABLISHMENTS 41

QUALITY- WHAT IT IS 52

MODULE B–MANAGEMENT PROCESSES 60

ORGANIGRAM – ORGANISATIONAL CHART 61

MANAGEMENT OF QUALITY DOCUMENTATION 69

TRAINING IN QUALITY MANAGEMENT SYSTEMS 82

MODULE C–SUPPORT PROCESSES 94

RISK IN PERSPECTIVE 95

INTRODUCTION TO RISK MANAGEMENT TOOLS 103

QUALIFICATION: A RISK-BASED APPROACH 114

MODULE D–REALISATION PROCESSES 124

KEY PERFORMANCE INDICATORS IN BLOOD ESTABLISHMENTS 125

QUALITY CONTROL & STATISTICAL PROCESS CONTROL 131

MODULE E–CONTINOUS IMPROVEMENT 143

MANAGEMENT OF NON-CONFORMITIES 144

CHANGE CONTROL 152

HAEMOVIGILANCE 164

INTERNAL AUDIT 174

MANAGEMENT REVIEW 185

LIST OF DEFINITIONS 191

LIST OF ACRONYMS 194

LIST OF AUTHORS 195

Page 3

Foreword

ounded in 1949, the Council of Europe is the oldest and largest of all European institutions and now numbers 47 Member States (MSs) 1 . One of its founding principles is increasing cooperation between Member States to improve the quality of life of all Europeans.

Within this context of intergovernmental co-operation in the field of health, the Council of Europe has consistently worked on ethical problems. The most important such ethical issue relates to the non-commercialisation of human substances, i.e. blood, organs and tissues.

With regard to blood transfusion, co-operation among MSs started in the 1950s. Through its activities in the blood transfusion area, the Council of Europe has been actively contributing to the implementation of high standards for the protection of public health and the promotion of human rights and human dignity.

Blood and blood components are essential for healthcare in Europe as they are used to provide treatment to citizens. They are essential in major surgery. Furthermore, treatments of traumas, acute bleeding and also several chronic diseases such as thalassemia rely on the availability of blood.

Since the 1950s, the Council of Europe has elaborated a number of agreements and recommendations2 covering ethical, social, scientific and training aspects of blood transfusion. Whereas agreements are binding for the States that ratify them, recommendations are policy statements to governments proposing a common course of action to be followed.

Work in the field of Quality Assurance (QA) started in the 1980s. The major recommendations in this field include Recommendation No. R (95) 15 and its technical Appendix, which has now become the Guide to the preparation, use and quality assurance of blood components” referred hereafter as the “Guide”. The purpose of the Guide is to provide blood establishments with a set of standards and principles relating to the preparation, use and quality assurance of blood components. The Guide covers all blood components that will be prepared at a blood establishment but does not cover plasma products obtained by fractionation. In respect of plasma-derived products, technical matters are addressed by the European Pharmacopoeia whereas the European Union has a substantial body of legislation including plasma-derived products.

On 27 January 2003 the European Union adopted Directive 2002/98/EC on setting standards of quality and safety for the collection, testing, processing, storage and distribution of human blood and blood components.

1 Albania, Andorra, Armenia, Austria, Azerbaijan, Belgium, Bosnia and Herzegovina, Bulgaria, Croatia, Cyprus, Czech

Republic, Denmark, Estonia, Finland, France, Georgia, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Liechtenstein, Lithuania, Luxembourg, Malta, Republic of Moldova, Monaco, Montenegro, Netherlands, North Macedonia, Norway, Poland, Portugal, Romania, Russian Federation, San Marino, Serbia, Slovak Republic, Slovenia, Spain, Sweden, Switzerland, Turkey, Ukraine, United Kingdom.

2 http://www.edqm.eu/en/blood-transfusion-recommendations-resolutions-71.html

F

Page 4

As regards technical requirements to be set under Article 29 of the said Directive, the European Commission and the Council of Europe work closely together to ensure that these requirements are compatible with the Guide.

Whereas blood establishments in EU Member States are required to comply with legislation derived from the European Commission Directives, the Guide is intended to facilitate ongoing improvements in the preparation, use and quality assurance of blood components through education and the provision of non-binding recommendations.

The Guide therefore provides additional information and guidance on best practices consistent with current scientific knowledge and expert opinion. Implementation of these recommendations may vary among MSs and individual blood transfusion establishments, and alternative procedures, practices and standards may be in place.

In 2007, the Secretariat with responsibility for activities related to blood transfusion was transferred to the European Directorate for the Quality of Medicines & Healthcare (EDQM) of the Council of Europe.

In 2010, as a result of cooperation with the Commission of the European Union, and with a view to improving the safety of labile blood products and of patients undergoing blood transfusion, the EDQM implemented the Blood Proficiency Testing Scheme (B-PTS)3, an External Quality Assessment (EQA) programme dedicated to European blood establishments.

The EDQM realised over time that, with the complexity of available standards in the field of blood transfusion, European blood establishments did encounter difficulties in implementing a comprehensive and integrated Quality Management System (QMS). For this reason, the EDQM decided to further develop its activities in the field of Quality Management. In 2012, the Blood Quality Management (B-QM) activity was set up. As an assistance and educational activity, it includes the provision of on-site training courses, visits and an audits scheme4. The decision was taken in 2013 to complement these activities with learning activities, and therefore to organise a Training Course on Quality Management for European blood establishments.

This Quality Management programme has been elaborated with the input of experts working in blood establishments. Special thanks should be given to all these experts for their contributions, efforts and commitment, in particular to:

Alina Dobrota, Director, Regional BTC, Romania Beate Rothe, Head of Department, Klinikum Wolfsburg, Germany Mariëlle Van Roosmalen, Compliance Officer, Sanquin, Netherlands Alex Aquilina, Director, NBTS, Malta Jan Ceulemans, Quality Manager, HBRC-Flanders, Belgium Oliver Kürsteiner, Head of Quality Management, SRK, Switzerland Martin Pisacka, Head of Immunohematology Department, UHKT, Czech Republic

The members are also grateful to the European Committee on Blood Transfusion (Partial Agreement) (CD-P-TS) members who support the B-QM Working Group (B-QM WG) and the EDQM in the implementation of these recent activities.

These proceedings reproduce the presentations with the kind permission of the trainers. Their preparation and publication was co-ordinated by Marie-Laure Hecquet, Scientific Officer responsible for the B-PTS and B-QM activities, with the assistance of Nevena Kojic and Béatrice Barth.

3 https://www.edqm.eu/en/blood-proficiency-testing-scheme-b-pts 4 https://www.edqm.eu/en/blood-quality-management-programme-b-qm

Page 5

Welcome Address Dear Colleagues, Dear Friends,

The concept of Quality Management has evolved greatly over the last decade while European blood establishments have constantly had to implement new regulatory requirements. Transfusion is a medical procedure that carries an intrinsic component of risks and implementation of a Quality Management system (QMS) in blood establishments is the key to managing risks and ensuring the efficacy, quality and safety of blood components.

Implementation of a QMS is required by EU Directives and prescribed in the Council of Europe Guide to the Preparation, Use and Quality Assurance of Blood Components. However, while it is a means of ensuring that quality and risks are under control, it is often regarded as a burden and a complicated process. Hence the need for a training course on Quality Management.

The EDQM Blood Quality Management Working Group (B-QM WG) has worked to set up a training course on Quality Management that meets the needs of European Blood Establishments.

We do believe that common knowledge of implementing a QMS would promote mutual confidence across European countries.

The 1st European Training Course on Quality Management for Blood Establishments is organised by the European Directorate for the Quality of Medicines & HealthCare (EDQM).

We are pleased to welcome all of you in Strasbourg and do hope that you will have fruitful discussions and exchanges.

Marie-Laure Hecquet Responsible Scientific Officer, DBO

“Quality Management system (QMS) in blood establishments is the key to managing risks and ensuring the efficacy, quality and safety of blood components”

Page 6

Programme 14 APRIL 2015 – MORNING SESSION

9:00-9:45 Opening & Welcome Address M.-L. Hecquet, Scientific Officer, EDQM

Introduction of the trainers and the participants - Ice Breaker M. Pisacka

9:45-10:15 INTRODUCTION TO THE TRAINING COURSE

10:15-10:45 MODULE A - REGULATORY FRAMEWORK FOR QUALITY MANAGEMENT SYSTEMS IN EUROPEAN BLOOD ESTABLISHMENTS

10:15-10:30 Lecture 1 - European Regulatory Framework for Quality Management Systems M.-L. Hecquet

10:30-10:45 Lecture 2 - Focus on Quality Standards used in Blood Establishments M.-L. Hecquet

11:20-12:15 Exercise 1: Gap Analysis- Audit report M. v. Roosmalen

12:15-12:30 Plenary Session- Exercise 1 A. Aquilina

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13:30-17:00 MODULE B - MANAGEMENT PROCESSES

13:30-13:50 Lecture 4 - Why is an organigram useful? A. Aquilina

13:50-14:10 Exercise 2: Elaboration of the organigram of vBC A. Aquilina

14:10-14:20 Plenary Session - Exercise 2 A. Dobrota

14:20-14:50 Exercise 3: Role and Responsibilities within a BE Interactive Exercise – Quiz B. Rothe

15:05-16:05 Exercise 4: Process Mapping M.-L. Hecquet

16:05-16:40 Plenary Session - Exercise 4 J. Ceulemans

16:40-17:00 Sum-up Day 1 M.-L. Hecquet

14 APRIL 2015 – AFTERNOON SESSION

Page 8

15 APRIL 2015- MORNING SESSION

9:00-11:10 MODULE B - MANAGEMENT PROCESSES

9:00-9:10 Exercise 5: Are you Awake? Interactive Exercise - Quiz M. Pisacka

9:10-9:50 Exercise 6: “Spot the errors” B. Rothe

9:50-10:05 Plenary Session - Exercise 6 A. Aquilina

10:05-10:30 Lecture 5 - Management of Quality Documentation M.-L. Hecquet

10:45-11:10 Lecture 6 - Training in QMS M. v. Roosmalen

11:10-12:00 MODULE C - SUPPORT PROCESSES

11:10-11:30 Lecture 7 - Risk in Perspective A. Aquilina

11:30-12:00 Lecture 8 - Introduction to Risk Analysis Tools J. Ceulemans

Page 9

15 APRIL 2015- AFTERNOON SESSION

13:20-16:00 MODULE C - SUPPORT PROCESSES

13:00-14:00 Exercise 7: Do I have a risk? A. Aquilina/J. Ceulemans

14:00-14:30 Plenary Session - Exercise 7 B. Rothe

9:50-10:05 Plenary Session - Exercise 6 A. Aquilina/J. Ceulemans

14:45-15:10 Lecture 9 - Qualification and Validation A. Aquilina

14:45-15:30

Exercise 8: How to qualify/validate an equipment/method? J. Ceulemans

15:30-16:00 Plenary Session- Exercise 8 A. Aquilina

16:00-16:20 Exercise 9: What a wonderful day! Interactive Exercise - Quiz A. Dobrota

Page 10

16 APRIL 2015- MORNING AND AFTERNOON SESSIONS

11:30-13:00 MODULE D - REALISATION PROCESSES

11:30-12:30 Exercise 10: Process under Control? B. Rothe/M. Pisacka

12:30-12:50 Plenary Session - Exercise 10 M. Pisacka/B. Rothe

12:50-13:00 Lecture 10 - Introduction to Quality Indicators/KPIs J. Ceulemans

14:00-14:30 MODULE D - REALISATION PROCESSES

14:00-14:15 Lecture 11 - Quality Control and Statistical Process Control A. Aquilina/J. Ceulemans

14:15-14:35 Exercise 11: Quality Control and Statistical Process Control Interactive Exercise J. Ceulemans/A. Aquilina

14:35-14:45 Plenary Session- Exercise 11 A. Aquilina /J. Ceulemans

14:45-18:00 MODULE E - CONTINUOUS IMPROVEMENT

14:45-15:05 Lecture 12 - Management of Non-Conformities M.-L. Hecquet

15:20-15:50 Exercise 12: Root-Cause Analysis of a Non-Conformity M.-L. Hecquet

15:50- 16:05 Plenary Session- Exercise 12 M. v. Roosmalen/A. Dobrota

16:05 -16:20 Lecture 13 - Change Management M. v. Roosmalen

16:20-17:00 Exercise 13: Change Management M. v. Roosmalen/J. Ceulemans

17:00-17:20 Plenary Session- Exercise 13

17:20-17:40 Lecture 14 – Haemovigilance B. Rothe

Page 11

17:40-17:50 Sum-up Day 3

M.-L. Hecquet

18:00-18:15 Welcome Address S. Keitel, EDQM Director

Page 12

17 APRIL 2015 -MORNING SESSION

9:00-10:00 EXAM

10:15-12:00 MODULE E - CONTINUOUS IMPROVEMENT

10:15-10:35 Lecture 15 - Management of Internal Audits J. Ceulemans

10:35-10:55 Lecture 16 - Management Review A. Dobrota

10:55-11:30 GENERAL DISCUSSION - ADDITIONAL QUESTIONS

11:30-11:45 CONCLUDING REMARKS - ATTESTATION OF PARTICIPATION

Page 13

Trainers

AQUILINA Alexander National Blood Transfusion Service, Director Malta CEULEMANS Jan Flemish Red Cross, Quality Manager Belgium DOBROTA Alina Mirella Regional Blood Transfusion Centre, Director Romania

HECQUET Marie-Laure European Directorate for the Quality of Medicines & HealthCare (EDQM), Council of Europe, Scientific Officer

France

KUERSTEINER Oliver Interregionale Blutspende SRK AG, Head of Quality Management Switzerland

PISACKA Martin Institute of Haematology and Blood Transfusion, Head of Immunohematology Department

Czech Republic

ROTHE Beate Institute of Clinical Chemistry, Laboratory and Transfusion Medicine - Klinikum Wolfsburg, Head of Department

Germany

VAN ROOSMALEN Marielle Sanquin Blood Supply, Compliance Officer Netherlands

This training course was organised by the EDQM and in the frame of the Blood Quality Management Working Group (B-QM) WG programme. The B-QM WG is a technical committee nominated by the European Committee on Blood Transfusion (Partial Agreement) (CD-P-TS).

Page 14

List of Participants

BROISE Frédéric European Directorate for the Quality of Medicines & HealthCare (EDQM)

France

CADERAS BOSCHETTI

Doina Interregional Blood Transfusion Src Ltd Switzerland

ELDEMIR Sibel Turkish Red Crescent General Directorate of Blood Services

Turkey

ERAKOVIC Nela Institute for Blood Transfusion of Montenegro Montenegro ESPADA MARTIN Raquel JACIE Spain GHIAZZA Paola AOU Città della Salute e della Scienza di Torino Italy GLOCK Barbara Austrian Red Cross, Blood Donation Center for

Vienna, Lower Austria and Burgenland Austria

HERMUNDSTAD Brita Akershus University Hospital Norway IVANOVA Elena Regional Blood Establishment/Rcth Bulgaria JOVANOVIC Radmila Blood Transfusion Institute of Vojvodina Serbia KAVANAGH Margaret Irish Blood Transfusion Service Ireland KOK Lotte Region Zealand, Tissue and Transfusion

Services Denmark

KORKOLAINEN Mirja Finnish Red Cross Blood Service Finland KRYZAUSKAITE Lina Vilnius University Hospital Santariskiu Klinikos

Blood Centre Lithuania

LABANCA Luciana Blood Component Production Centre A.O.U. Città della Salute e della Scienza

Italy

LJUBICIC Julijana Croatian Institute for Transfusion Medicine Croatia LOPEZ Dulce Spanish Medicines Agency Spain LOPEZ FRAGA Marta European Directorate for the Quality of

Medicines & HealthCare (EDQM) France

LUND Merete Eis Odense University Hospital Denmark MALVAUX Nicolas Red Cross Luxembourg Luxembourg MARTINIS Georges Alexandroupolis University General Hospital,

Transfusion Centre Greece

NILSSON Maria Department of Laboratory Medicine Sweden PEREIRA Paulo Portuguese Institute of Blood and

Transplantation Portugal

PHILIPPUS Frans Military Blood Bank Netherlands PISACKA Martin Institute of Haematology and Blood

Transfusion Czech Republic

RASOVIC Gordana Institute for Blood Transfusion of Montenegro Montenegro RICHARD Arnaud European Directorate for the Quality of

Medicines & HealthCare (EDQM) France

RILEY Marie National Blood Transfusion Service Malta RISTIMAE Raili North Estonian Medical Centre Blood Centre Estonia ROCHA Cristina Directorate General of Health Portugal SNYKERS Philippe Belgian Red Cross Belgium SREDZINSKI Dariusz Regional Blood Center of Bialystok Poland STONIENE Laimute National Blood Centre Lithuania URAN Apolonija Blood Transfusion Center of Slovenia Slovenia

Page 15

VARDY Stephen National Health Service Blood and Transplant (NHSBT) - Leeds

United Kingdom

VELKOVA Emilija Institute of Transfusion Medicine North Macedonia VOLAKA Natalja National Blood Service of Latvia Latvia

Page 16

Purpose of the Training Course Implementation of a Quality Management System (QMS) is required by the EU legislation prescribed in the Council of Europe Guide to the Preparation, Use and Quality Assurance of blood components and the newly developed Good Practices Guidelines (GPG).

However, the concept of Quality Management has evolved greatly over the last decade while European blood establishments have constantly had to implement new regulatory requirements.

In 2012, the EDQM performed a survey which showed that European blood establishments encountered difficulties in implementing a QMS and understanding its concept. In addition, the use of standards varies between countries and even within countries.

While a QMS is a means of ensuring that quality and risks are under control, it is often regarded as a burden, and a complicated process.

This prompted the EDQM to initiate an appropriate Training Course with the aim of supporting European blood establishments in setting up, developing and further improving their QMS.

The EDQM wishes to harmonise QMS practices and provide a common and uniform knowledge and approach for developing a QMS in a sustainable way. We do believe that this should ultimately promote mutual confidence across European countries and contribute to ensuring the quality and safety of blood components.

In this course, participants acquired advanced knowledge on quality management and how to implement an integrated QMS in a blood establishment.

The topics of process mapping, management of a quality documentation system, the concepts of validation and qualification and risk management, CAPA management and continuous improvement were tackled by experts in the field.

The course comprised a series of lectures and practical exercises, including active learning and discussions.

A Certificate of attendance was issued at the end of the course. Acquired knowledge was evaluated at the end of the course with a written exam. Candidates performing well in the exam received an exam certificate.

The course was also an excellent opportunity to meet experts in the field, exchange best practices and initiate collaboration between all the participants.

The Training Course was intended for quality managers or those with responsibility for quality in a European Blood establishment.

Page 17

Presentations

OPENING SESSION

14 April 2015

- Opening & Welcome Address, M. Wierer & M.-L. Hecquet

- Ice Breaker, M. Pisacka

- EDQM Mission & Activities in the Field of Blood Transfusion, M.-L. Hecquet

- Setting-up the Scene

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1st European Training Course

QUALITY MANAGEMENT FORBLOOD ESTABLISHMENTS

14 - 17 April 2015EDQM, Strasbourg, France

B-QM WG©2015 EDQM, Council of Europe. All rights reserved. Training Course - April 2015 2

WELCOME ADDRESS

Dr M. Wierer, Deputy Head of DBO

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ICE BREAKER

Introduction of the trainers and the participants

M. Pisacka

4

EDQM MISSION & ACTIVITIES IN THE FIELD OF BLOOD TRANSFUSION

M.L Hecquet

B-QM WG©2015 EDQM, Council of Europe. All rights reserved. Training Course - April 2015

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THE COUNCIL OF EUROPE (CoE)

Founded in 1949Intergouvernmental organisationHeadquarters in Strasbourg47 Member States

Primary Objectives: create a common democratic and legal area and ensure fundamental values: human rights, democracy and the rule of law

Driving Bodies: the Committee of Ministers of Foreign Affairs and the Parliamentary Assembly


DO NOT GET CONFUSEDCoE - Different roles but shared values- EU

Agree on minimum legal standards with the primary concern of developing and spreading the awareness on these values

Refers to theses values in a deeper political and economic integration processes

D

E MOC

R

A

C

Y

HUM N RIGHTS

RUL OF LAW

European Union27 Member States

500 Million of Citizens

Council of Europe47 Member States

800 Million of Europeans

B-QM WG©2015 EDQM, Council of Europe. All rights reserved. Training Course- April 2015

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THE EUROPEAN DIRECTORATE FOR THE QUALITY OF MEDICINES & HEALTHCARE (EDQM)

7

A Directorate of the Council of EuropeCreation in 1964: activities based on the Convention on the Elaboration

of a European Pharmacopoeia37 Member States Partial agreement

MISSION: Contribute to the basic human right of access to good quality medicines and healthcare and to promote and protect human and animal health

How do we work?Experts, nominated by the Member States, provide the technical and scientific expertise to elaborate standards and provide input in various programmes.


8

EDQM ACTIVITIES

Sharing Expertise

High Quality Standards

Quality Controls

CollaborationBlood

TransfusionOrgan, Tissue &

Cells, Transplantation

Pharmaceuticals

Cosmetics

Anticounterfeiting medicines


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EDQM BLOOD TRANSFUSION ACTIVITIES

Non-commercialisation of substances of human origin Voluntary and non-remunerated donation

Self-sufficiencyProtection for both the donors & the

recipients

Wor

king

G

roup

s –

Tech

nica

l ex

pert

ise

GTS

B-P

TS A

G

B-Q

M

CD-P-TSEuropean Committee on Blood Transfusion(Steering Committee)

OUTCOMES: Recommendations, Resolutions, Annual reports, Guides, Quality Managament Programme

……

..


Legal status: Annex to Recommendation(95)15 of the Committee of Ministers of theCouncil of Europe i.e. non binding legalinstrument as such but possibility to use it as areference in national binding legal instrumentsSections:Standards: minimum requirementsPrinciples: additional advance informationCurrently:17th Edition

GUIDE TO THE PREPARATION, USE AND QUALITY ASSURANCE OF BLOOD COMPONENTS

Quality and Safety Standards to be used by the Blood Transfusion Establishments


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B-QM WG©2015 EDQM, Council of Europe. All rights reserved. Training Course- April 201511

GOOD PRACTICE GUIDELINESIdentifies the quality system elements that must be met by blood establishmentsand hospital blood to comply with EU Directive 2005/62/EC (Article 2):

- quality system standards and specifications of Directive 2005/62/EC

- quality system Standards and Principles derived from the Guide to the Preparation, Use and Quality Assurance of Blood Components (17th edition)

- quality system elements derived from the detailed principles of GMP

12

ACTIVITIES REPORTS: Examples

Report of the survey on Blood supply management in member and observer states (2012)

Trend & observations on the collection, testing and use of blood and blood components in Europe (2001-2008)


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BLOOD-PROFICIENCY TESTING SCHEME

Method for measuring the performance of laboratories basedon interlaboratory comparisons.

AIM: B-PTS provides Blood Establishments (BEs) with anobjective mean of assessing that the testing results (Viralmarkers e.g HIV, HBV, HCV; ABO Rhesus) for blooddonations are reliable.

(1) Dedicated to European BEs(2) Programme unique in Europe

Participation in PTS required by Blood EU Directive2002/98/EC & prescribed by the Council of EuropeGuide to the Preparation, Use and Quality Assuranceof Blood Components.

Proposed B-PTS: tests required in the Directive


BLOOD-QUALITY MANAGEMENT PROGRAMME

AIM: Assistance/Educational Programme to help BEs inestablishing, developing a comprehensive and integratedQuality Management System (QMS) & improving it.

(1) Dedicated to European BEs(2) Programme unique in Europe

Implementation of a QMS required by Blood EU Directive2002/98/EC & prescribed by the Council of Europe Guide tothe Preparation, Use and Quality Assurance of BloodComponents.

NEED- Existing norms/guidelines in European BEs variesbetween countries and even between BEs within a samecountry;- BEs seeking for help to develop and build anintegrated QMS.

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Learning QMS Tools

QMS Manual

(Ongoing)Training Course

On site Monitoring QMS Tools

B-TV B-MJV B-MJA

B-QM PROGRAMME (2)

Blood Training Visit (B-TV): On-site visit educate staff ontechnical & QMS topics;

Blood Mutual Joint Visit (B-MJV): Observe the QMS underdevelopment and give recommendations/advice for improvementand/or implementation of the QMS;

Blood Mutual Joint Audit (B-MJA): check compliance of theQMS with CoE Guide/relevant standards implemented final compliance assessment

“On-site” schemes take into account specificities of the bloodtransfusion field; tailor-made auditing/training schemes take intoaccount all applicable Norms/Guidelines;

Auditors: experts from European BEs bring & shareexperience/knowledge;

Less expensive than general accreditation provided by private bodies;

Impetus to implement EU Blood & Cross Border Directives;

Harmonisation of QM Practices in Europe ultimate goal of agreeingon a common approach in the implementation of QMS;

Improve Mutual Confidence between European BEs;

Increase Exchange of Blood Components between countries.

B-QM PROGRAMME: VALUES

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INTRODUCTION TO THE TRAINING COURSE

M.L. Hecquet


TRAINING COURSE PROGRAMME

- BASED ON THE PROCESS APPROACH;

- LEARN HOW TO SET UP A QMS REFLECTING ON PROCESSES AND QUALITY ELEMENTS;

- 5 MODULES – STRUCTURAL APPROACH:

- MODULE A (RED): REGULATORY FRAMEWORK & QUALITY

- MODULE B (BEIGE): MANAGEMENT PROCESSES- MODULE C (GREEN) SUPPORT PROCESSES- MODULE D (BLUE): REALISATION PROCESS- MODULE E (YELLOW): CONTINUOUS IMPROVEMENT

IN EACH MODULE: LECTURES & EXERCISES

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TRAINING COURSE CONTENT: LECTURES- LECTURES:

MA- L1

Module A –Lecture 1


TRAINING COURSE CONTENT: EXERCISES

FLOW OF LEARNING:- CASE STUDY- QUIZ

- Individual Exercises- Group Exercises- Interactive Exercises

A 31

Module A – page 31

Time

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TRAINING COURSE CONTENT: TOOLKIT (1)

- BINDER:

- GENERAL INFORMATION- EXERCISES ORDERED ACCORDING TO THE LETTER &

COLOUR OF THE MODULES

DURING THE COURSE:

- HANDOUTS OF LECTURES

- MODEL ANSWERS TO EXERCISES (BLUE PAPER)

- Reflect trainer’s view- Example of answers


TRAINING COURSE CONTENT: TOOLKIT (2)

- BINDER:

- ANNEXES:- ANSWERS TO PRE-ASSESSMENT QUESTIONNAIRE- ABBREVIATIONS- DEFINITIONS - SOCIAL INFORMATION

- CoE Guide 17th Ed.- Compilation of Standards (Directives, GPG, PIC/S)

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PRACTICAL ISSUES- Coffee Breaks (2 per day);- Lunches (EDQM cafeteria – Buffet);

- Social Event: No-Host Dinner on Wednesday 15 April - (Further information to be provided on day 2);

- Visit at the French Blood Establishment on Thursday 16 April (morning);

- (Further information to be provided on day 2);

- Administrative issues: Nevena & Beatrice

B-QM WG©2015 EDQM, Council of Europe. All rights reserved. Training Course- April 2015 23


FINAL EXAM: FRIDAY 17 APRIL at 9:00

- BE ON TIME: 8h50 in Room 100

- DURATION: 1h15 min

- 15 questions:- Open questions;- Multiple Choice Questions;- Based on Exercices & Lectures (except Lectures

provided on day 4)

- LISTEN & PARTICIPATE!

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STARTING POINT OF THE TRAINING COURSE

- vBC: VIRTUAL BLOOD CENTER

- vBC Factsheet: information on the BE- Audit report (EDQM audit)

LEARNING STYLE: KOLB THEORY

B-QM WG©2015 EDQM, Council of Europe. All rights reserved. Training Workshop - April 2015 26

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AND ESSENTIAL KEY FACTORS


- Humour (with a minimum of seriousness);

- Experience sharing;

- Collegial Atmosphere;

- Be open , don’t be shy, do not hesitate to askquestions;

- Be happy :-) and Enjoy!


QUESTIONS

Page 32

MODULE A- GENERAL REGULATORY FRAMEWORK

14 April 2015

- Lecture 1, European Regulatory Framework for the

Quality and Safety of Blood Components, M.-L. Hecquet

- Lecture 2, Focus on Q-Standards Used in Blood Establishments, M.-L. Hecquet

- Lecture 3, Quality- What It Is? M.-L. Hecquet

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EUROPEAN REGULATORY FRAMEWORK FOR THE QUALITY AND SAFETY OF BLOOD COMPONENTS

Trainer: M-L HecquetLecture 1 –Day 1

Mod

ule

A:R

egul

ator

yFr

amew

ork

-Lec

ture

1


TEACHING AIM

Understand European regulatory framework for blood establishments;

EU Directives, CoE guide, GMP, PIC/S, ISO Standards; QMS level among CoE Member States.

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BLOOD COMPONENTSALLOGENIC TRANSPLANTINTRINSIC IRREMOVABLE COMPONENTS OF RISKS, e.g:

- Biological risk (blood type differences/immunologicalinteraction);- Transmission of diseases;- Adverse events (medical intervention/recipients’equilibrium)- Errors during testing, processing, storage;- Administrative errors: identification, mislabelling……..


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BLOOD COMPONENTDEFINITION: « Therapeutic constituent of blood (red cells, white cells,platelets, plasma) that can be prepared by various methods »(EU Directive 2002/98/EC)

WHY A REGULATORY FRAMEWORK ?


HEALTH PROTECTION & IMPROVEMENT

QUALITY & SAFETY

INTRINSIC RISKS

AVAILABILITY OF BLOOD DONORS/CITIZENS

RECIPIENTS& CITIZENS

BLOOD

PROCESSED BLOOD

ALL RECIPIENTS& CITIZENS

CONFIDENCE , EQUIVALENT & LEVEL OF SAFETY & QUALITY

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EU TREATY PROVISIONS

Article 168- Treaty of the Functioning of the European Union (TFUE)« A High level of human health protection shall be ensured in the definition and implementation of all union policies and activities »« measures setting high standards of quality and safety »


EU Directives

28 Countries

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EU BLOOD DIRECTIVES


2002/98/EC of the EP & of the Council of 27/01/2003 setting standards of qualityand safety for the collection, testing, processing, storage and distribution ofhuman blood and blood components and amending Directive 2001/83/EC

Mother Directive

2004/33/EC of 22/03/2004 implementing Dir. 2002/98/EC as regards certain technical requirements for blood and blood components.

Tech. Directive 2005/62/EC of 30/09/2005 implementing Dir. 2002/98/EC as regards Community standards and specifications relating to a quality system for blood establishments.

2005/61/EC of 30/09/2005 implementing Dir. 2002/98/EC as regards traceability requirements & notification of serious adverse reactions and events.

IMPLEMENTATING MEASURES

Techn. Directive Techn. Directive

http://europa.eu/legislation_summaries/public_health/threats_to_health/c11565_en.htm

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REGULATORY FRAMEWORK FOR BLOOD


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BLOOD ESTABLISHMENT FRACTIONATORB

LOO

D

Pharmaceutical Legislation 2001/83/EC2003/94/EC - GMP

Blood Legislation 2002/98/EC & Technical Directives

GMP

EUC

oE

CoE Guide & Good Practice Guidelines

Nat

iona

lVo

lunt

ary

ISO Standards

ISO Standards

National LegislationNational LegislationNational LegislationNational Legislation

SURVEY AMONG CoE MS: QMS LEVELSURVEY – 2012: 186 ANSWERS/BEs – 33 COUNTRIES


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MA-L1SURVEY AMONG CoE MS: USED STANDARDS


MA-L1SURVEY AMONG CoE MS: MANDATORY STANDARDS

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MA-L1SURVEY AMONG CoE MS: STANDARDS USED- PLASMA FOR FRACTIONATION

SUMMARY/CONCLUSION

Blood legislation is complex; Level of implementation varies between countries, although some

legislation is mandatory; Use/implementation of standards in Europe varies from one

country to another; Use/Implementation of standards in Europe varies within the

same countries; Difficulties to implement legislation and standards; Need for assistance programme EDQM B-QM Programme; Need for a training course on how to elaborate a QMS in this

context.


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USEFUL LINKS/READINGS

http://europa.eu/legislation_summaries/public_health/threats_to_health/c11565_en.htmhttp://ec.europa.eu/health/documents/eudralex/vol-4/index_en.htmhttps://www.edqm.eu/en/blood-transfusion-guides-1608.html


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FOCUS ON Q-STANDARDS USED IN BLOOD ESTABLISHMENTS

Trainer: M-L HecquetLecture 2 – Day 1

Mod

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A:R

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amew

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2

- Process and management review.

ELEMENTS OF A QMS


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- Quality system: management, quality policy, objectives

- Personnel and organisation;- Premises, material, Equipment;- Documentation, record keeping;- Collection;- Testing and Processing;- Storage and Distribution;- Quality Monitoring & Control;- Quality indicators/KPI;- Contract Management;- Change Control; - Risk management;- Non-Conformities and CAPA management;- Haemovigilance; - Internal and external auditing;

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COMMONALITIES BETWEEN STANDARDS (1)


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ELEMENTS

EU D

IR.

CoE

G.

GM

P

PIC

/S

ISO

900

1

ISO

151

89

QM: management, leadership, quality policy, objectivesPersonnel and organisation

Premises, material, Equipment

Documentation, Record keeping

Collection

Testing

Processing

Storage and Distribution

Quality Monitoring & Control

Quality indicators/KPI

Absent

Implicit, or slight reference

Explicit, Description or more generalExplicit, substantial description

COMMONALITIES BETWEEN STANDARDS (2)


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ELEMENTS

EU D

IR.

CoE

G.

GM

P

PIC

/S

ISO

900

1

ISO

151

89

Contract Management

Change Control

Risk management *Non-Conformities and CAPA management

Haemovigilance

Internal and external auditing

Process and management review

Absent

Implicit, or slight reference

Explicit, Description or more generalExplicit, substantial description

* ISO 9001:2015

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30Total Responses

Complete Responses: 30Blood Establishments: 28

PRE-ASSESMENT QUESTIONNAIRE PART 2 (QMS IN BE)- RESULTS

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Q16: Which of the following quality standards does your Blood Establishment have to follow?Answered: 28 Skipped: 2

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Q17: Which of the following quality standards does your Blood Establishment follow on a voluntary basis?Answered: 26 Skipped: 4

Inconsitent withprevious resultsInconsitent withprevious results

Q18: In your Blood Establishment, do you haveAnswered: 28 Skipped: 2

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Q19: Do you have a procedure on qualification/validation of equipment/methods in place?Answered: 28 Skipped: 2

Q20: Have you been already inspected by a Health Authority/National inspection body?Answered: 28 Skipped: 2

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Q21: Are self-inspections/internal audits performed?Answered: 28 Skipped: 2

Q22: Do you have a haemovigilance system or adverse reactions/adverse events system in place? If yes, please indicate whether the system is national- or local-based?Answered: 28 Skipped: 2

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Q23: Do you have system to manage non-conformances/non-conformities (e.g. anomalies, deviations, out of specifications, complaints) in place?Answered: 28 Skipped: 2

Q24: Do you have a system for corrective and preventive actions?Answered: 28 Skipped: 2

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Q25: Do you have a recall procedure in place?Answered: 28 Skipped: 2

Q26: Do you have a procedure for managing changes?Answered: 28 Skipped:2

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Q27: Do you have outsourced activities ?Answered: 27 Skipped: 4

Q28: Do you have a regular management review?Answered: 28 Skipped: 2

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Q29: Do you have a procedure for training and qualifying employees?Answered: 28 Skipped: 2

Q30: Do you have job description for key personnel?Answered: 28 Skipped: 2

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SUMMARY/CONCLUSION

EU directives do have to be implemented in EU countries; Not all BEs are inspected yet by national authorities; Not all QMS elements are in place; Standards to be regarded as complementary; Gap between standards and implementation which might only be

filled in by appropriate tools such as training and audits


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QUALITY….. OH MY GOD….LET’S GO BACK HOME

Trainer: M-L. HecquetLecture 3 - Day 1

Mod

ule

A:Q

ualit

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Lect

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3

TEACHING AIM

Understand quality concepts; Understand the process approach.

2B-QM WG©2015 EDQM, Council of Europe. All rights reserved. Training Course - April 2015

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QUALITY, THIS IS……

Who is willing to give a definition?

1) Quality of the product

N T NLY !

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BUT ALSO ………….

2) Quality of the processes which are carried out to produce a product or to provide clients/patients with a service

Direct your organisation and processes towards quality;

Ensure all processes are consistent, under control and are continuously improved;

e.g. - good management processes;- good recruitment, training processes;- good validation/qualification of equipment;- good reagents; - good premises;- good quality documentation etc…

BUT WHAT DOES “GOOD” MEAN?

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PLAN and write “What to do”: describe your processes , sub-activities and tasks and responsible personnel;

In accordance with applicable standards, internal policies and other requirements (hospitals, recipients etc…);

Trained personnel Procedures, so that they can implement “What to do” (procedure) in a consistent way;

DO what is written; Records outputs/critical data of your processes: temperature, raw

data, interpreted data…..Traceability!!! CHECK whether the data/results meet process and products

specifications; Use the outputs/results to improve process : update what you

have written and ACT.

HOW TO ACHIEVE « GOOD » PROCESSES?

PLAN

DO

CHECK

ACT


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ACT Apply actions for

improvement. Review all steps (Plan, Do,

Check, Act) and update processes to improve them

before next implementation.

ITERATIVE 4 STEPS QM METHOD: PDCA PLAN Establish quality policy, objectives and processes (Process mapping, procedures, forms) necessary to deliver results in accordance with the specifications.

ContinuousImprovement

DOImplement processes as planned and written

CHECKMonitor, evaluate processes/

results/outputs against objectives/specifications and

records

PLAN

DOCHECK

ACT


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QUALITY- “Degree to which a set of inherent characteristics fulfils requirements” (ISO 9001)

Specifications for blood products are fulfilled; Quality Control Testing.

QUALITY ASSURANCE- Implement procedures so that requirements for a product/service are fulfilled

Procedures in place for the transfusion chain processes; Quality assurance function.

LET’S TALK THE SAME LANGUAGE (1)


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QUALITY MANAGEMENT SYSTEM

- System level: Organisational structure, processes, proceduresQuality Manager function;

- Management level: - To direct and control an organisation towards quality- Top-down Management- Quality policy and quality objectives

Independent from the Norms/guidelines implemented in the BE or from what your are doing in your organisation

LET’S TALK THE SAME LANGUAGE (2)


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Quality

QualityAssurance

QualityManagement System

Total QualityManagement


EVOLUTION OF QUALITY

Product

Product

Product

Processes

ProcessesOrganisation

REACTIVE

PRO-ACTIVE

- Quality policy & objectives

- Leadership- Personnel

implication- Customers focus

& interestedparties

- ContinuousImprovement

- Product requirements

- Quality control

- Procedures

- Strategic planning

- Quality cost and productivity(Lean, 6 Sigma)

ProductProcesses

Organisation

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BUILDING A QMS


APPROACH “STANDARDS/CHAPTERS” APPROACHFollow the structure of a standard (chapter, sections….)

- Structured- Easy elaboration

- Incompatibility if more than2 standards to follow

- Rigidity- No interaction betweenunit- Redundancy

“FUNCTIONAL OR SERVICE “ APPROACHGrouped by entities/responsibilities (Laboratory, Quality Unit, Processing unit)

- Structured- Easy elaboration

- Rigidity- No interaction betweenunit- Redundancy

PROCESS APPROACHBased on activities and commonalities

- Structuredand Integrated- Takes into account interactions

betweenprocesses and personnel

- Management, continousimprovementand support processes taken into account

- Compatibility withotherstandards

- No redundancy- Long term life

- Requiresgrouping requirementsof different standards for a givenprocess

- Requiresgood knowledgeof all applicable standards

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QMS IN BLOOD ESTABLISHMENTS – PROCESS APPROACH

MANAGEMENT PROCESSES

EU DIRECTIVES, CoE GUIDE, PIC/SEU GMP

SELECTION DONORS COLLECTION TESTING PREPARATION RELEASE DISTRIBUTION/

ISSUING

REALISATION/CORE PROCESSES

SUPPORT PROCESSESVALIDATION/QUALIFICATION EQUIPMENT/ MAINTENANCE/ PURCHASING/

MEA

SUR

E/

IMPR

OVE

MEN

T

IMPL

EMEN

T ISO 9001

* Not restrictiveISO 15189

INTEGRATED QUALITY MANAGEMENT SYSTEM STANDARDS: SYSTEM & TECHNICAL TRANSVERSAL APPROACH

Piloting: Management of Q-Documentation/ Management staff …..

Improvement: Management of non-conformance, Management of audits

11

MA-L3

PROCESS: WHAT IS IT?


PROCESSINPUTINPUT OUTPUTOUTPUT

- Products- Results achieved

- Requirements- What is needed

DEFINITION: Process is anyset of interrelated or

interacting activities whichtransforms inputs into

outputs (ISO 9000:2005)

FEEDBACK

RESOURCES: PERSONNEL, DOCUMENTATION, EQUIPMENT….

An output of an upstream process often becomes the input for a downstream process INTERNAL CLIENTS

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CATEGORIES OF PROCESSES


Management/piloting processes include planning, strategical, management, overseen activities directing processes towards quality;

Realisation/core processes include direct customers/patients relatedprocesses such as collection, processing, testing;

Support processes are assisting processes such as maintenance, validation of equipment.

MA-L3

SUMMARY/CONCLUSIONAdopting the process approach allows: Managing and controlling processes;

Managing interactions between processes;

Understanding the importance of your work for your collaborators;

Integrating, aligning and linking processes effectively to achieve planned goals and objectives;

The organisation to focus on improving processes, effectiveness and efficiency;

It also:

Facilitates the involvement and empowerment of people and the clarification of their responsibilities;

Promotes the smooth and transparent flow of operations within the organisation.


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ISO 9000 Standard – QM TerminologyISO 9001 Standard – as a System/QM Standard

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MODULE B- MANAGEMENT PROCESSES

14 April 2015

- Lecture 4, Organigram – Organisational Chart, A. Aquilina

15 April 2015

- Lecture 5, Management of Quality Documentation, M.-L. Hecquet

- Lecture 6, Training in QMS, M. v. Roosmalen

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ORGANIGRAM -ORGANISATIONAL CHART

Trainer: Alex AquilinaLecture 4 - Day 1

Mod

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B:

Man

agem

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Proc

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TEACHING AIM

Understand the goal of an organigram; Get knowledge on how to elaborate an organigram.


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Directive 2002/98/EC – Annex I

Information to be provided to the CA for the purposes of designation, authorisation, accreditation or licensing in accordance with article 5(2):

Part B: Documentation such an organisation chart, including responsibilities of responsible persons and reporting relationship.

CoE Guide

There must be an organisation chart showing the hierachical structure and withclear delineation of lines of responsibilities

EU GMP – Chapter 2

2.2. The manufacturer must have an organisation chart.

ISO 9001

Top management shall ensure that responsibilities and authorities are defined andcommunicated within the organisation.

REGULATIONS


MB-L4

WHAT IS AN ORGANIGRAM?Organisational structure is an important part of any organisation.

It helps you:- to understand the communication and reporting flow (who reports to

whom) within the organisation;- to understand the line of responsibilities.

Organigram is:

A diagram (visual display) that shows the structure of an organisation and the relationships and relative ranks of its parts and positions/jobs.

Relationship: - one official/person to another;

- one department to another;

- one function to another.


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DID YOU KNOW?

Egyptians First people to use charts to illustrate the division of labour employed for large projects like the building of the Pyramids


MB-L4

WHY ?ORGANISATION CHART- Effective way to communicate organisational, employee and

enterprise information;- Makes it easier for personnel to comprehend and digest large

amounts of information as a visual picture (rather than as a table of names and numbers);

- Provide the greatest value when used as a framework for managing change and communicating current organisational structure.


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USE OF OC- Organisational and supervisory communication;- Workforce planning;- Departmental or team planning;- Framework for managing change; Managing change becomes much

easier once everyone is able to visualize the organization;- Communicate operational information across the organisation;- Decision making about resources for managers;- Job analysis: quick visualisation of the organisation with access to

salary, gender and tenure information needed for decision-making purposes;

- Organisational restructuring or redesign.


MB-L4

HOW SHOULD IT BE?


• Invaluable tool for managementClear and Concise

• Facilitate Team organisationClear responsibilities,

titles and lines of authority

• Communication of valuable organisational information to all employees

• Sharing organisation strategic vision and responsibilities, dependecies and relatiosnhip

Distributing and sharing

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LIMITATIONS- If done/updated manually: OC quickly become out-of-date (especially in

large organisations with regular staff turn over);

- Show "formal relationships“ only ; no pattern of human (social) relationships; No horizontal relationships;

- No information about the managerial style adopted (e.g. "autocratic", "democratic" or other);

- In some cases, an organigraph more appropriate, particularly if wish to show non-linear, non-hierarchical relationships in an organisation;

- Does not include customers.


MB-L4

TYPE OF OC (1)1) TEAM BASED/HIERARCHICAL;


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TYPE OF OC (2)2) MATRIX


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TYPE OF OC (2)

3) FLAT


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Administrative Council

Medical director

Secretariat

Quality Manager

IH Lab

TTI Lab

Preparation Laboratory and distribution

LP preparation DeptDept for QC

Dept for Distribution

Collection LabDept for mobile

collectionDept for donor advise

Dept for pre-collection

Internal Audit Dept

HR

Accounting & Finance

Transport, procuring

Technical -Maintenance

Archive

Public Purchasing

EXAMPLE 1 (B-MJV) MB-L4


EXAMPLE 2 MB-L4

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SUMMARY/CONCLUSION

You know everything about OC now! OC is essential in organisation! Basis for communication, management and setting-up a

QMS……because QM is management and communication after all! For achieving a successful QMS, the structure of the organisation

should be clearly defined and this should be reflected in an OC with clear alignment of responsibilities.


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USEFUL LINKS

http://knowhownonprofit.org/organisation/orgdev/structure-and-culture/structure


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MANAGEMENT OF QUALITY DOCUMENTATION


Mod

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Man

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1


TEACHING AIM

Understand the different kind of quality documentation; Management of the quality documentation

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2

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Directive 2002/98/EC

Information to be provided by blood establishment to the competent authority forthe purposes of designation, authorisation, accreditation or licensing in accordance witharticle 5(2):

- Documentation, such as an organisation chart, including responsibilities ofresponsible persons and reporting relationships;- Documentation such as site master file or quality manual describing the qualitysystem in accordance with Article 11(1);- Number and qualifications of personnel;- Hygiene provisions;- Premises and equipment;- List of standard operating procedures for recruitment, retention and assessment ofdonors, for processing and testing, distribution and recall of blood and blood componentsand for the reporting and recording of serious adverse reactions and events.

MB-L5REGULATIONS (1)

33



Documents setting out specifications, procedures and records covering each activityperformed by the blood establishment shall be in place and kept up to date

- Personnel and Organisation; Premises ; Equipment and Materials; Documentation; Blood collection, testing and Storage including Donor Eligibility, Collection, Laboratory testing, Processing and validation, Labelling, Release of blood and blood components; Storage; Contract Management; Non-Conformance including deviations, Complaints, Recall, Corrective and preventive actions; Self-inspection, audits and improvements

Records must be legible and may be handwritten, transferred to another medium such as microfilm or documented in a computerised systemAll significant changes to documents must be acted upon promptly and must be reviewed, dated and signed by a person authorised to perform this task

MB-L5REGULATION (2)

4

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MB-L5REGULATION (3)

5

Guide to the preparation, use and quality assurance of bloodcomponents, 17th edition

A document control system, defined in a written procedure, must beestablished for review, revision history and archiving of documents, includingSOP.

Each activity that may affect the quality and/or safety of the blood andblood components must be described in an SOP and recorded.

The records system must ensure continuous documentation of theprocedures performed, from the blood donor to the recipient, i.e. eachsignificant step must be recorded in a manner that permits a component orprocedure to be traced, in either direction, from the first step to final use ordisposal.

Records must be retained for a period according to local, national or EUrequirements, as appropriate.

Good Practices Guideline

Whole section 5

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QUALITY DOCUMENTS? WHAT DID YOU SAY?QUALITY DOCUMENT……WHAT IS IT?- Every document that you need to write, and/or which describes in a

standardised way processes, which ultimately lead to the quality of the processes and product/service ;

- Every document that prove the quality of the process and product/service and show that your process is under control!

A Quality Document should be an Help to reach Quality

But not a Burden!

Q-DOCUMENT= SAY WHAT YOU DO

MB-L5


CATEGORIES OF DOCUMENTS

I

II

III

IV

V

Figure 1. Structure of a controlled document system

I. Laws/Standard (External

V. Supporting Documentation Worksheets, forms, templates, labels Records to support the procedures & processes =proof)

II. Quality Manual - Policies and Objectives – Express the highest level of goal/intent of the BE.

III. General Procedures - Describes flow of activities, decision points, responsibilities of departments & acceptance criteria to accomplish a given course of action ref to specific OPs.

IV. Operational Procedures- Detailed step by step instructions to accomplish a task.


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HOW TO START?

Do you know whythey follow me?


MB-L5

9

1. QUALITY MANAGER

- Keep track of the elaboration/revision of the Q-documents.

- Motivates staff;

- Builds trust within the team;

- Leader;

- Overview of the quality management;

- Incentive to write/revise quality documents to facilitate your work and improve quality;


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10

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MANDATORY

- National law- EU directives- CoE Guide 17th (depending on the national law)

NON MANDATORY (At your own discretion)

- ISO 9001, ISO 15189- GMPs- PIC/S

2. IDENTIFICATION OF STANDARDS


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IMPORTANT NOTE

Quality documentation is not just a copy/paste of requirements & standards

11


MB-L53.1. PROCESSES MAP/CARTOGRAPHY

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MB-L53.2. MICRO-CARTOGRAPHY FOR DOCUMENTATION

Instruction (I) or Operational procedure (OP) e.g

Forms

M2: Management of Q-Documentation

General ProcedureP/M2: General procedure describing the life cycle of a quality document from elaboration to implementation

I/M2.02: Instruction « approval of a Q-document »

I/M2.03: Instruction « revision of a Q-document »

F/M2.01: Request for new Q-document

13

I/M2.01: Instruction for elaboration of a Q-Document


MB-L53.2. MICRO-CARTOGRAPHY FOR DOCUMENTATION

14

I/M3.01: instruction for recruitment

Forms

M3: Management of Staff: Recruitment and training

I/M3.02: instruction « initial training »

I/M3.03: Instruction « continuous training »

F/M3.01: Check list« new arrival »

F/M 3.03: Assessment of training

General ProcedureP/M3: General procedure describing the process of management of staff fromrecruitment, initial training, continuous training to end of contract

F/M 3.02: trainings needchecklist

Instruction (I) or Operational procedure (OP) e.g

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Quality Manager Leader

Organigram Responsibilities defined

Mapping processes List of Quality Documents

Attribute the elaboration/revision of documents to the staff responsible (competent user) of the activity.


MB-L5IN BETWEEN SUMMARY

15

4.1. PREPARATION PHASE

- Identify the objective, scope of the document and title ;- Identify the competent user and assign responsibility for writing the document;

4.2. WRITING PHASE

- Use a model/template;- Design a process flow chart and describe each step of thework process; Think about the criticality of the process;

MORE GUIDANCE: EU-Q-SOP PROJECT

MB-L54. WRITING PHASE


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MB-L5


MB-L5EU-Q-SOP PROJECT: GUIDANCES Template Flowcharting

Identification of competent users

- SOP number and unique number;- Title: clear and descriptive;- Version number;- Page number and total number of pages;- Name and signature of author + Signature date;- Name and signature of person who authorised the introduction

of the document + Signature date;- Effective date, date on which the document/revised version become

effective;- Consistent structure;- Note on the changes included.


MB-L5Q-DOCUMENT: KEY POINTS

18

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1. Objective;

2. Area of application/scope;

3. Definitions/abbreviations;

4. Roles covered by the document;

5. Description of the process or activity/logigram;

6. Related documents;

7. References to external documents/related Q-Documents;

8. Annexes.


MB-L5Q-DOCUMENT: CONTENT

19

MB-L55. DOCUMENT CHANGE CONTROL & IMPLEMENTATION (1)


AIM OF A DOCUMENT CHANGE CONTROL SYSTEM

Control any changes in the life of a Q-Document: issue, revision, distribution, disposal, archiving, destruction;

Prevent use of obsolete document.

Formal process used to ensure that changes to Q-Documents are introduced in a controlled and coordinated manner

Standardised Procedure on document change control

20

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2. Initiate the change

3. Approval of 3. Approval of the change

YES

NO

4. Registration of the document

5. Elaboration

6. Review

7.Approval & 7.Approval & signatures

NO

YES

1. Identification of need for a new Q-document or revision

(e.g. form to befilled-in)

(e.g. approvalform)

(e.g. SOPsregistry)



9. Retrieve obsolete version and make itunavailable to personnel

10. Appropriate and controlled storage

8. Make document available to users with an effective date and in a controlled way

7.Approval & 7.Approval & signatures

YES

11. Appropriate Training (before effective date)

12. Implementation (effective date)

13. Audit

END

-Archiving of original document

-Destruction of controlled copies

(e.g. list of controlleddocuments)

(e.g. list of archiveddocuments)

(e.g. Training form)

(e.g. Audit plan & report)

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- List of Q-Documents Keep track of revision, date of revision, effective date & responsible person;

- Relevant versions of applicable documents available at points of use!

- Documents of external origin identified and their distribution controlled;

- Prevent unintended use of obsolete documents;

- Completed & Readable forms.;

- Corrections to a document/record: to be signed, initialled & dates. - Correction must permit the reading of original information- Reason for correction to be recorded, when appropriate

- Period of retention/archiving period;


MB-L5LAST REMARKS BEFORE THE END

SUMMARY/CONCLUSION

Q-Documentation shall be elaborated on a risks based approach; It ensures that work is performed the same way « Standardised

Operating Procedure » Proof of your work; Traceability Purpose; Documentation: an initial huge effort, which becomes worth in the

long run.

WRITE WHAT YOU DO & DO WHAT YOU WRITE


MB-L5

24

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EU-Q-SOP Manual - http://www.eubis europe.eu/blood_manual_details.php?ausgabe=sop


MB-L5

25

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TRAINING IN QMSWithout a well-trained workforce,high quality work becomes an impossibletask

Trainer: M. v. RoosmalenLecture 6 - Day 2

Mod

ule

B:

Man

agem

ent

Proc

esse

s-L

ectu

re6


TEACHING AIM

Understand the relevance of training in QMS Be able to set up and implement a training programme

MB-L6


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Directive 2005/62/EC – Annex 2

1. Personnel shall be available in sufficient numbers to carry out the activities […] and be trained and assessed to be competent for their tasks.

2. Personnel shall have up to date job descriptions which clearly set out their tasks and responsibilities.

3. Personnel shall receive initial and continued training appropriate to their specific tasks. Training records shall be maintained. Training programmes shall be in place and shall include good practice.

4. The contents of training programmes shall be periodically assessed and the competence of personnel evaluated regularly.

REGULATIONS (1)

3B-QM WG©2015 EDQM, Council of Europe. All rights reserved. Training Course - April 2015 3

REGULATIONS (2)

Guide to the preparation, use and quality assurance of bloodcomponents, 17th edition

References to EU Directive 2005/62/EC

And multiple references in several chapters:

Qualification: ……the calibration, cleaning, preventative maintenance, operating procedures and operator training procedures and records should be documented. Documentation: Procedures should be designed, developed and validated, and personnel should be trained, in a consistent manner.

Good Practice Guidelines

References to EU Directive 2005/62/ECTraining should be provided for all personnel whose duties take them intopreparation area or into laboratories.

MB-L6


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There are competent and appropriately qualified personnel in sufficient numbers.

Senior management should provide adequate resources.

The responsibilities of all staff should be clearly understood and recorded.

All personnel receive initial and continuing training relevant to their needs.

Practical effectiveness should be assessed periodically

Only trained staff are authorised to carry out that procedure/enter certain areas.

Training should be structured and continuous.

Training records should be kept

Training programmes should be available

REGULATIONS (3) MB-L6


PICS/S for Blood establishments

There should be an adequate number of personnel.The responsibilities of personnel should be described. There should be an organisation chart showing the hierarchical structure of the BE.Personnel should receive initial and continuous training to ensure that they have the skills to perform their assigned tasks. Records should be maintained to demonstrate compliance to training requirements. The effectiveness of the programmes should be regularly assessed.Personnel should have relevant knowledge of basic transfusion medicine, microbiology, hygiene and GMP.Personnel in key areas of responsibility should have appropriate qualifications, experience, and specific training to discharge their responsibilities. Delegation should only be given to appropriately qualified and authorised individuals who have been trained for the task. Delegation should be in written form.

REGULATIONS (4) MB-L6


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WHY IS TRAINING IMPORTANT? (1)

ORGANISATION- Fundamental to quality and safety;- To ensure good process control (less variation);- Higher employee satisfaction/morale Team Spirit same

goals.

INDIVIDUAL- Increased knowledge and skills;- Increased awareness of responsibilities within the process.

MB-L6


The organisation benefits from having a skilled and motivated workforce: - Improved quality, reduced errors;- Fewer safety/quality incidents/NC;- Less equipment damage;- Less complaints;- Higher efficiency;- Increased production;- Cost-reduction.

MB-L6WHY IS TRAINING IMPORTANT? (2)


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GOOD TRAINING = A MAJOR CHALLENGE

An indicator for the extent of this challenge can be withdrawn from analysing the type and ranking of FDA findings:

- For biologics the most frequent causes of findings (105/191): procedures not always maintainedand followed (data taken from: www.fda.gov/ICECI/Inspections (2013);

- Data compliance with procedures and documentation are major source for findings;

For the stability of the QMS, the success of training is very important.

MB-L6


PERSONAL AWARENESS

- Personnel in regulated environment need to know why they have additional demands placed upon their performance;

- The reason should go beyond “ because you have to…, it’s the law”;- Without a personal value for (GMP) compliance, a compliant operation

will be very difficult to achieve!;

- Value must come from the realisation that:- they need to ensure the blood quality and safety and;- that each individual performance has the potential to affect this.

MB-L6


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RESPONSIBILITIES FOR TRAININGDevelop organised training programme that includes:

- Employees are trained for the tasks they perform;- Developed training programme comprising:

- Training/Qualification of new employees;- Re-Qualification of existing employees;

- Training identification, prioritisation and schedule (WHO should be trained, on WHICH tasks/job, by WHEN (date) and HOW);

- Assessment of training effectiveness;- Documentation/recording: Training procedure for initail and

continuous training, training plan/programmes, training content, assessment;

- Improvement, when necessary.

MB-L6


TRAINING PROCESS MB-L6

Training needs & requirementsassessment

Develop training Programme

Training Implementation

Training Evaluation Authorisation

TRAINING DOCUMENTATION


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- Review job requirements (job description!);- New and existing employees (experience, background);- Identify the categories of staff;- Perform tasks analysis of job (through interview, direct observation);- Identify required skills to perform the job;- Determine gap between current and required skills;- Define level of competence for each job function;- Regulatory requirements (hygiene, GMP).

MB-L6



STEP 1. ASSESS


STEP 2. DEVELOP

- Allocate resources (budget, time of personnel to be trained, trainers, equipment, space, materials);

- Define who and what should be included in the training;- Define purpose, outcome objectives;- Decide on training content / method;- How will the competence be evaluated;- Determine criteria for certification;- Define validity;- Design forms for recordkeeping of training;- Define qualifications of the trainer.

MB-L6





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EXAMPLE

OUTCOME OBJECTIVE

CONTENT METHOD EVALUATION (measurable behavior to

outcome objective)

CERTIFICATION

1. Operate the processing centrifuge

References SOP Operator’s Manual

Topics Centrifuge partsTimeTemperatureBalanceProgramTroubleshooting

Review SOP

Show centrifuge parts

Use SOP to practice

Employee …

Successfully performs operation of centrifuge according to SOP

A minimum of 5 times in succession under observation by an experienced staff member who has been identified as trainer

MB-L6


STEP 3. IMPLEMENT

- Training material had been developed;- Validate training (try-out in small group) and revise training if necessary;- Develop an agenda;- Schedule days, times, places;- Schedule trainings, trainers, personnel.

MB-L6






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STEP 4. EVALUATE

- What is evaluated:- Components and process ;- Transfer of knowledge (written test, performance of practical exercises,

observation);- Trained personnel: achievement of objectives, feedback;- Trainer: organisation, feedback of personnel;- Manager: effectiveness of return on training investment.

Feedback used to increase quality and effectiveness of training!

MB-L6




Training Implementation Training Evaluation Authorisation


LONG TERM EVALUATION

Standards/Requirements-related performance compared BEFORE and AFTERtraining

- Product failures;

- Non-conformities statistics;

- Audit results;

- Operational efficiency.

MB-L6


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DOCUMENTATION/ RECORDS

If not documented: it is not done !- Assessment of training needs of employees;- Training plan;- Training sheet: Employee name, department name, trainer’s name, training date;- Attendance list;- Evaluation sheets; Competences/knowledge areas successfully completed (specific

training course, SOP);- Sign off training/qualification by employee, trainer and manager Authorisation;- Keep records and make sure it remains up-to-date;- List employees authorised for a specific job and those who still need to take/ renew

training DATABASE WITH ALL INFO

MB-L6




Training Evaluation Authorisation


RECORD SOP TRAINING: EXAMPLE MB-L6


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TRAINING – DEVELOPMENT CYCLE

DESIGN

IMPLEMENT

EVALUATE

ASSESS

MB-L6


SUMMARY/CONCLUSION

Training is essential for promoting and establishing a QMS;

Despite potential drawbacks (time, resources), training provides both the organisation & employees with benefits that make cost and time a worthwhile investment.

MB-L6


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USEFUL LINKS/READINGS MB-L6


http://www.who.int/bloodsafety/publications/qmp_toolkit/en/

Page 93

MODULE C- SUPPORT PROCESSES

15 April 2015

- Lecture 7, Risk in Perspective, A. Aquilina

- Lecture 8, Introduction to Risk Management Tools, J. Ceulemans

- Lecture 9, Qualification: A Risk-based Approach, A. Aquilina

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RISK IN PERSPECTIVE

Trainer: A. AquilinaLecture 7 –Day 2

Mod

ule

C:

Supp

ort

Proc

esse

s-L

ectu

re7


TEACHING AIM

Understand Risk Management; Why is it important to manage/assess risks.

MC-L7

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DEFINITIONS (1)

RISKDEFINITION: « Effect of uncertainty on objectives » RISK MANAGEMENT DEFINITION: something that “ aids decision making by taking account of uncertainty and its effect on achieving objectives and assessing the need for any actions”(ISO 31 000:2009- « Risk management—Principles and guidelines on implementation)


MC-L7

DEFINITIONS (2)

RISKDEFINITION: « The combination of the probability of occurrence of harm and the severity of harm » QUALITY RISK MANAGEMENTDEFINITION: « A systematic process for the identification, assessment and control of risks to the quality of pharmaceutical product across the product lifecycle »

(ICH Q9 - « Quality Risk Management”)


MC-L7

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APPLICATION TO THE BLOOD FIELD

RISK IN BLOOD TRANSFUSIONProbability of the occurrence of a ultimate harm on the donor/recipient and its severity

RISK MANAGEMENT Eliminate or minimise the occurrence of this harm and the severity of the harm on the donor/recipient

LET’S START WHO HAS AN EXAMPLE OF RISK IN THE BLOOD FIELD?


MC-L7

EXAMPLES PLEASE?


MC-L7

DonorSelection

Blood Collection

Processing Testing

Release

Storage

Transport

Documentation

Human resourcesmanagement

Equipment management

Qualification/ Validation

Material management

Suppliercontrol

Financial management

…….

Audits

Complaints

Haemovigilance

DeviationsRecalls

Management review

CAPA

Management & Support

Monitoring & ImprovementRealisation/Core activities

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RISK MANAGEMENT IS NOT NEW!


“Premises including mobile sites shall be adapted and maintained to suit the activitiesto be carried out. They shall enable the work to proceed in a logical sequence so as tominimise the risk of errors, and shall allow for effective cleaning and maintenance inorder to minimise the risk of contamination.”

“Blood collection procedures shall minimise the risk of microbial contamination”.

EU GMP – Annex 15 – Qualification and Validation

“A risk assessment approach should be conducted to determine the scope andextent of validation”


MC-L7

But implicit?

IMPORTANCE OF RISK MANAGEMENT

USEFUL TOOL TO:- Implement, maintain and continuously improve a QMS in a resource

effective manner;- Create awareness and influence the factors/hazards;- Critical processes are under control; provide thus confidence;- Incentive to implement preventive actions;- Recognise risks at desired level zero risk does not exist.

RISK MANAGEMENT IS A DISCIPLINE


MC-L7

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RISK MANAGEMENT PROCESS (1)


MC-L7

Initiate QRM Process

Risk identification

Risk Analysis

Risk EvaluationR

isk

Asse

ssm

ent

Ris

kC

ontr

ol Risk Reduction

Risk Acceptance

Output/result of the QRM Process

Review Events

Ris

kR

evie

w

CO

MM

UN

ICAT

ION

RIS

KS

MAN

AGEM

ENT

TOO

LS

unacceptable

RISK MANAGEMENT TOOLS (2)


MC-L7

Initiate QRM Process

Risk identification

Risk Analysis

Risk Evaluation

Ris

kAs

sess

men

tR

isk

Con

trol Risk Reduction

Risk Acceptance

RIS

KS

MAN

AGEM

ENT

TOO

LS

Identify the source of risks: Brainstorming, Cause & Effectassignements (Fishbone/Ishikawa), Flow charts, Fault tree analysis,

Analyse the causes and source of risks and the likelihood to occurRisk Ranking, FMEA, FMECA HACCP

Determine whether risks to beadressed/treated

Determine Strategies to mitigates/control the riskSPC, Process sensors, indicators

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RISK MANAGEMENT PROCESS (3)


MC-L7

REDUCTION, ACCEPTANCE, WHAT ELSE ?


MC-L7

Consider also…….

Avoiding Risks- Why installing a temperature sensitive automate in a area known as being hot and where no air conditioning can beinstalled?

Transfer Risks- Outsourcing of testing

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MC-L7

SUMMARY/CONCLUSION

QRM does not eliminate risks but is a tool to manage them (identification/assessment/monitoring/prioritisation…..)

RM is a discipline Focus not on objectives but on the risks to achieve the objectives 4Ps: Proactive-Preventive-Predictive-Preemptive


MC-L7

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8


http://www.ich.org/products/guidelines/quality/q9-briefing-pack.htmlhttp://www.researchgate.net/publication/229602150_Quality_risk_management_a_valuable_tool_in_implementing_maintaining_and_improving_a_quality_management_system (Agoston et. Al, ISBT Science Series (2011) 6, 52-55)


MC-L7

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INTRODUCTION TO RISK MANAGEMENT TOOLS

Trainer: J. CeulemansLecture 8–Day 2

Mod

ule

C:

Supp

ort

Proc

esse

s-L

ectu

re8


TEACHING AIM

Understand basic tools for risk management; Aid to get more knowledge; Be able to use tools.

MC-L8

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2

METHODS AND TOOLS

Guidance; Tools to be adapted to the risks/to every situation No one tool is « all inclusive »! The list provided is not exhaustive.


MC-L8

METHODS & TOOLS - OVERVIEW


MC-L8

1. Initiate QRM Process

2. Risk identification

3. Risk Analysis

4. Risk Evaluation

Ris

k As

sess

men

tR

isk

Con

trol 5. Risk Reduction

6. Risk Acceptance

RIS

KS

MAN

AGEM

ENT

TOO

LS

Identify the source of risks: Brainstorming, Cause & Effectassignements (Fishbone/Ishikawa), Flow charts, Fault tree analysis, Mind Map

Analyse the causes and source of risks and the likelihood to occurDetermine whether risks to beadressed/treatedRisk Ranking, FMEA, FMECA HACCP

Determine Strategies to mitigates/control the riskSPC, Process sensors, Indicators

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INITIATION QRM

ALLOCATE RESPONSABILITIES & INITIATE QRM1.1. Interdisciplinary team – experts from appropriate areas(Quality unit, production, legal…and experts knowledgeable about risk)

1.2. Decision Makers - Take responsability for the coordination of the QRM

1.3. Initiate - objectives, define problem/risk question

- assemble background information/define the context

- develop a plan, timeline, deliverables

- records to be kept


MC-L81

RISK IDENTIFICATION (1)

QUESTION:WHAT MIGHT GO WRONG?

Use of information (Historical data, theoretical analysis, concerns of Hospitals);Identification of possible consequences;Identification of possible causes;


MC-L82

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MC-L82

TOOLS FOR RISK IDENTIFICATION

BRAINSTORMING: Internal and external brainstorming (involvement of suppliers, subcontracting parties)

ISHIKAWA:

+ Policies+ Procedures+ Plant+ Budget/Cost

ProblemStatement = Risk

Causes

MIND MAP



MC-L82

ISHIKAWA – EXAMPLES 1. RISK= delayed flight departures

2. RISK= Tea not available during the training course break

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MC-L82

MIND MAP – EXAMPLE PROCESS MAPPING – EXAMPLE

DonorSelection

Blood Collection

Processing Testing

Release

Storage

Transport

Causes

RISK RANKINGQuantitative

RISK ANALYSIS & EVALUATION (1)


MC-L8

LIK

ELYH

OO

D

SEVERITY

TOOLS

3 & 4

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6

RISK RANKINGQualitative


MC-L8

SEVERITYLI

KEL

YHO

OD

TOOLS

RISK ANALYSIS & EVALUATION (2)3 & 4

FAILURE MODE EFFECTS ANALYSIS (FMEA)

RISK ANALYSIS & EVALUATION (3)

- SEVERITY – Table in Annex- PROBABILITY - Table in Annex- DETECTION - Table in Annex


MC-L8

TOOLS

3 & 4

Item/Process Potential Failure Cause

Potential effect of failure

Potential Causes S P D RPN

1. Set up of an automate

Insufficient cleaning of equipment

Fail to start Cleaning procedure not up to date

4 5 8 160

4x5x8 = 160Recommended Action S P D RPNChange cleaning procedure 4 3 4 48

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RISK CONTROL (1)

DECISION MAKING - To reduce/accept risk to an acceptable level;- Benefit/cost analysis;- Amount of effort used for risk control proportional to the significance

of the risk.

QUESTIONS:- Is the risk above an acceptable level?

- What can be done to reduce or eliminate the risk?- What is the appropriate balance among benefits, risks and resources?


MC-L85 & 6

RISK CONTROL (2)

RISK REDUCTION- Action to mitigate severity and probability of harm;- Processes that improve detectability of risks; Are new risks introduced as a result of the identified risks being

controlled? New risks Risk Assessment


MC-L85 & 6

RISK ACCEPTANCE- Decision to accept the risk and residual risks .

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RISK CONTROL (3)


MC-L85 & 6

STATISTICAL CONTROL- Control charts- Pareto charts

TOOLS

QUALITY INDICATORSe.g. number of non-conformities for a given process

PROCESS SENSORSe.g. Temperature data logger

SUMMARY/CONCLUSION

Various tools for Quality Risk Management; Adapt tools to the situation; Combination of tools is possible: Quality Risk Management: pro-active approach for identifying and

controlling quality issues.


MC-L8

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http://www.ich.org/products/guidelines/quality/q9-briefing-pack/briefing-pack.html


MC-L8


MC-L8

Risk Controlled Mountain Bike Riding

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ANNEX 1


MC-L8

Rating Description Potential Failure Rate10 Very High: Failure is

almost inevitable.More than one occurrence per day or a probability of more than three occurrences in 10 events.

9 High: Failures occur almost as often as not.

One occurrence every three to four days or a probability of three occurrences in 10 events .

8 High: Repeated failures. One occurrence per week or a probability of 5 occurrences in 100 events .

7 High: Failures occur often.

One occurrence every month or one occurrence in 100 events .

6 Moderately High:Frequent failures.

One occurrence every three months or three occurrences in 1,000 events .

5 Moderate: Occasional failures.

One occurrence every six months to one year or five occurrences in 10,000 events .

4 Moderately Low: Infrequent failures.

One occurrence per year or six occurrences in 100,000 events .

3 Low: Relatively few failures.

One occurrence every one to three years or six occurrences in ten million events .

2 Low: Failures are few and far between.

One occurrence every three to five years or 2 occurrences in one billion events .

1 Remote: Failure is unlikely.

One occurrence in greater than five years or less than two occurrences in one billion events .

FMEA - Occurrence Rating Scale

ANNEX 2


MC-L8

FMEA – Severity Rating ScaleRating Description Definition (Severity of Effect)

10 Dangerously high Failure could injure the customer or an employee.9 Extremely high Failure would create noncompliance with federal regulations.

8 Very high Failure renders the unit inoperable or unfit for use.7 High Failure causes a high degree of customer dissatisfaction.6 Moderate Failure results in a subsystem or partial malfunction of the product.

5 Low Failure creates enough of a performance loss to cause the customer to complain.

4 Very Low Failure can be overcome with modifications to the customer’s process or product, but there is minor performance loss.

3 Minor Failure would create a minor nuisance to the customer, but the customer can overcome it without performance loss.

2 Very Minor Failure may not be readily apparent to the customer, but would have minor effects on the customer’s process or product.

1 None Failure would not be noticeable to the customer and would not affect the customer’s process or product.

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ANNEX 3


MC-L8

FMEA – Detectability Rating Scale

Rating Description Definition10 Absolute Uncertainty The product is not inspected or the defect caused by failure is not detectable.

9 Very Remote Product is sampled, inspected, and released based on Acceptable Quality Level (AQL) sampling plans.

8 Remote Product is accepted based on no defectives in a sample.7 Very Low Product is 100% manually inspected in the process.6 Low Product is 100% manually inspected using go/no-go or other mistake-proofing

gauges.

5 Moderate Some Statistical Process Control (SPC) is used in process and product is final inspected off-line.

4 Moderately High SPC is used and there is immediate reaction to out-of-control conditions.

3 High An effective SPC program high.2 Very High All product is 100% automatically inspected.1 Almost Certain The defect is obvious or there is 100% automatic inspection with regular

calibration and preventive maintenance of the inspection equipment.

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QUALIFICATION: A RISK BASED APPROACH

Trainer: A. AquilinaLecture 9 –Day 2

Mod

ule

C:

Supp

ort

Processes-L

ecture

9


TEACHING AIM

Understand the concept of qualification and validation; Understand the qualification/validation cycle;

MC-L9

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2

QUALIFICATION- For the inspector?

- For the Quality Manager?

- For the patient?

Qualification is not for the Inspector or the Quality Managerit is

FOR SAFETY REASONS (PATIENT & DONOR )


MC-L9

DEFINITIONS

QUALIFICATIONDEFINITION: “Provision of evidence that a specific equipment, facility or system is fit/ready for intended use/that predefined requirements for a specific equipment, facility or system are fulfilled” (Own definition)

VALIDATIONDEFINITION: “Provision of evidence that requirements for a specific intended use are fulfilled” (ISO 9000:2005)“Provision of objective evidence that pre-defined requirements for a specific procedure or process can be consistently fulfilled” (CoE Guide)


MC-L9

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3

POLICY


Process

Production

Transport

Disinfection

Assays

Serological assays

Molecular Biological assays

Quality control assays

Computer Systems

Software

Hardware

Fixes, Updates

Equipment / Infrastructure

Premises

Equipment

Systems

Process validation

Method validation

Computer system validation Qualification

MC-L9

REGULATIONS


Guide to the preparation, use and quality assurance of blood components, 17th edition All validated processes must use qualified equipment. Qualificationresults must be documented.Facilities and equipment need to be qualified prior to implementation.Systems, processes and tests all need to be validated.

EU-GMP Critical steps of manufacturing processes and significant changes to theprocesses are validated.(e.g. Annex 15: Qualification and Validation in revision)

PICS/S for Blood establishments Equipment for collection, preparation and storage of blood and bloodcomponents should be dedicated to its use. New and repairedequipment should meet qualification requirements when installed andauthorised before use. Qualification results should be documented.

MC-L9

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GENERAL PROCEDURE


Definitions:URS: User requirements specificationRA: Risk assessmentDQ: Design qualificationIQ: Installation qualificationOQ: Operational qualificationPQ: Performance qualificationReQ: Re-Qualification

Formal documentationURS: separate documentRA: risk assessment has to be documented

DQ, IQ, OQ, PQ: • Plan: Definition of acceptance criteria's, test

procedures• Records: raw data• Report: Evaluation whether criteria's are met,

deviations, changes to the test plan• All documents have to be approved by QM

MC-L9

EXAMPLES


Example 1 Example 2

MC-L9

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5

URS (USER REQUIREMENT SPECIFICATION) / LASTENHEFT


The URS defines the specifications for your equipment /premises. The URS is your reference document throughout the qualification life cycle.

Example 1: Example 2:

MC-L9

URS - EXAMPLES


MC-L9

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RISK ASSESSMENT


The risk assessment helps to define the critical elements of your equipment and to establish the qualification parameters. The risk assessment defines the content of the qualification.

Possible general risk bases approach:• Each equipment is categorised with predefined qualification parameters

MC-L9


MC-L9

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DESIGN QUALIFICATION


During the DQ the compliance of design with your specifications and GMP is demonstrated and documented.

Example 1: Example 2:• Floor plan with details• Offers from builders with indications for

the materials planned to be used, installations, alarms

• Technical documentation (wiring, P&ID Schema)

MC-L9

DEFINITION: The documented verification that the proposed design of the facilities, systems and equipment is suitable for the intended purpose.

INSTALLATION QUALIFICATION


During the IQ the verification of the correct installation is performedExample 1: Example 2:

• Verification of construction (no damages, correct materials used, doors are tight, …)

• Temperature- and alarm-monitoring correctly installed

• Operating and working instructions are available

• Calibration of sensors

MC-L9

DEFINITION: The documented verification that the facilities, systems and equipment, as installed or modified, comply with the approved design and the manufacturer’s recommendations

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OPERATIONAL QUALIFICATION


During the OQ the verification of the correct function is performed

Example 1: Example 2:• Equipment file and SOP is available

including cleaning procedures• Temperature monitoring: empty,

loaded (with monitoring including hot spots, cold spots)

• Alarm system testing• Open door tests• Shortage of power

MC-L9

DEFINITION: The documented verification that the facilities, systems and equipment, as installed or modified, perform as intended throughout the anticipated operating ranges.

PERFORMANCE QUALIFICATION


During the PQ the verification of the correct function during routine conditions is performed.

Example 1: Example 2:• Temperature monitoring during one

week under real conditions• Alarm monitoring: False alarms?

MC-L9

DEFINITION: The documented verification that the facilities, systems and equipment, as connected together, can perform effectively and reproducibly, based on the approved process method and product specification.

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VALIDATION MASTER PLAN (VMP)- All qualification and validation activities should be planned and take the life cycle

of equipment, process and product into consideration;

- Validation activities to be performed by suitably trained personnel;- The key elements of the site validation programme should be clearly defined and

documented in a validation master plan (VMP) or equivalent document.

- Validation policy;- Organisational structure of validation activities;- Summary of the facilities, systems, equipment, processes on site and the currentvalidation status;- Template formats to be used for protocols and reports;- Planning & scheduling;- Change control;- Acceptance criteria;- Reference to existing documents;- Resources required.


MC-L9

SUMMARY/CONCLUSION

Qualification of equipment in blood establishments should be seen as an excellent tool to gain confidence in your equipment and procedures rather than a burden;

A risk based approach can standardise and minimise your qualification work to a useful and reliable extend;

Sample size to be based on statistical rationale; Qualification is not for the Inspector or the Quality Manager.

It is

FOR SAFETY REASONS (PATIENTS / DONORS)


MC-L9

Page 122

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10


GMP Annex 15 - http://ec.europa.eu/health/files/gmp/2014-02_pc_draft_gmp_annex.pdf

ISBT Guidelines for Validation of automated Systems in Blood Establishments http://www.isbtweb.org/fileadmin/user_upload/guidelines-Validation-Automated-Systems-in-Blood-Establishments.pdf


MC-L9

Page 123

MODULE D- REALISATION PROCESSES

16 April 2015

- Lecture 10, Key Performance Indicators in Blood Establishments, J. Ceulemans

- Lecture 11, Quality Control & Statistical Process Control, J. Ceulemans/A. Aquilina

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KEY PERFORMANCE INDICATORS IN BLOOD ESTABLISHMENTS

Trainer: Jan CeulemansLecture 10 – Day 3

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TEACHING AIM

Introduction to KPI; Sensitisation to the use of KPI.


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KPI

Key Performance IndicatorHelps an organisation define and measure progress toward organisational goals;Quantifiable measurements, agreed to beforehand, that reflect the critical success factors.


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STRATEGIC PLAN


Mission

Vision

Goals

Objectives

Measures

Why we exist

What we want to be

Indicators and Monitors of success

Desired level of performance and timelines

Planned Actions to Achieve Objectives

O1 O2

AI1 AI2 AI3

M1 M2 M3

T1 T1 T1

Specific outcomes expressed in measurable terms (NOT activities)

Strategic Plan

Action Plans

Evaluate Progress

Targets

Initiatives

What we must achieve to be successful

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MEASUREMENTS

- Measure your milestones – short-term outcomes at Action Item level;

- Measure the outcomes of your objectives;- Try to keep your measures one per objective;- May want to include lead and lag measures to depict cause-effect

relationships if you are uncertain about driving (leading) the desired outcome;

- Establish measures using a template to capture critical data elements.


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EXAMPLES OF MEASUREMENTS


Average time to initiatecustomercontact:

Shorter timeBetter

customerservice

Averageresponse

time to incident:

Belowaverage

responsetimes

Increasedeffectiveness

in dealingwith incident

Facilities that meet facility quality A1

rating

improved operational readiness for meeting

customer needs

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TARGETS

- For each measurement, at least one target;- Bring the organisation to higher levels of performance;- Incremental improvements over current performance;- Put focus on your strategy;- Successfully executed your strategy when targets reached;- KPI need to be smart:

- Specific;- Measurable;- Achievable;- Realistic;- Time based.


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EXAMPLES OF TARGETS


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SANITY CHECK

Make sure everything is linked and connected for a tight end-to-end model for driving strategic execution.


INITIATIVE

Employee Productivity

Improvement Program

Employee Satisfaction

Survey Rating

90% favorable

overall

Measure

Target

Target Actual

90%

45%

Perc

ent S

atis

fact

ion

gap

MEASURE / TARGET

OBJECTIVEImprove Employee

Satisfaction

ACTION PLAN

Identify issues per a company wide

survey

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SUMMARY /CONCLUSION

Help to measure organisational performance; Help to measure process performance; KPI linked to organisational goals; Focus on a few critical KPI rather than on many trivial ones.


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QUALITY CONTROL & STATISTICAL PROCESS CONTROL

Trainer: J. Ceulemans/A. AquilinaLecture 11 –Day 3

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TEACHING AIM

Learn more about Quality Control (QC) and Statistical Process Control (SPC);

Understand the value of SPC;

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DEFINITIONS

QUALITY CONTROLDEFINITION: « part of a quality system focussed on fulfilling qualityrequirements »(Directive 2005/62/EC)STATISTICAL PROCESS CONTROLDEFINITION: « Tool that enables an organisation to detect changes in theprocesses and procedures it carries out by monitoring data collected overa period of tile in a standardised fashion »(CoE Guide/Appendix 3)« Statistical process control’ means a method of quality control of a product or a process that relies on a system of analysis of an adequate sample size without the need to measure every product of the process »(Directive 20004/32/EC)


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REGULATIONS (1)


The quality system encompasses quality management, quality assurance, continuousquality improvement, personnel, premises and equipment, documentation,collection, testing and processing, storage, distribution, quality control, bloodcomponent recall, and external and internal auditing, contract management, non-conformance and self-inspection.

CoE guide (Blood components Monographs)

- Quality Control Requirements

- Frequency of sampling for all measurements shall be determined using statistical process control


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CoE Guide & Good Practice Guidelines What does Quality Control encompass?

- Defined specifications- Validation of QC procedures- QC Results evaluated, Statistical Process Control- Standard procedure/documentation for QC in place- QC according to a Sampling plan- Assays in accordance with kit instructions- Proficiency testing scheme (PTS)- Records


REGULATIONS (2) MD-L11

EU-GMP Guide, Part 1, Chapter 6 Quality control- General (Responsibilities, Personnel)- Good Quality Control Laboratory (GQCL)Practices- Documentation- Sampling- Testing- (on-going stability programme)- (technical transfer of testing methods)


REGULATIONS (3) MD-L11

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HOT TOPICS IN QC

• CE–marked kits• Not CE-marked kits

Validation of QC methods

• Sampling planSampling

• What is an OOS?• OOS investigation

Out-Of-Specification (OOS)

B-QM WG©2015 EDQM, Council of Europe. All rights reserved. Training Couse - April 2015 7

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VALIDATION OF QC METHODS

CASE 1: QC METHOD IS CE-MARKED Testing with CE-marked assays should be done according to manufacturers recommendations/instructions- Validation approach

- Eligibility of the method in your laboratory• Different technicians• Different days• Different lots of the kits• Different equipments (if applicable)• …


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CASE 2: QC method is an in-house assay (non CE-markedassays)- The testing should comply with the ICH guidance Q2B „Validation of

analytical methods: Methodology“(CPMP/ICH/281/95)- Validation approach


VALIDATION OF QC METHODS MD-L11

SAMPLING PLAN- Standardised Procedure describing:

- The method of sampling;- The amount of samples to be taken (frequency, blood bag system…);- Instructions for any sub-division of the sampling (if required);- Identification of the containers sampled (or the segment);- Storage conditions;

- Samples should be representative:- Maybe include samples for critical steps (after starting a new process,

equipment, …)


SAMPLING MD-L11

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OUT OF SPECIFICATION (OOS)Product Quality Control Results outside of the given specification,

= OOS- Each OOS needs an investigation:

- Laboratory;- Production.

- The investigation summaries the root cause of an OOS:- Laboratory failure (retesting);- Sampling failure (resampling, reanalysing);- Production failure (material, processing, storage, …);- Others root causes;


OOS (1) MD-L11

OUT OF SPECIFICATION – LABORATORY INVESTIGATION- Investigation about the sample and the sampling;- Investigation of the testing procedure;

- Method validated?- Equipment qualified?- Internal controls valid?- Staff trained?- Reagents and references ok?.....

- If no failure in the testing is found OOS-result is confirmed;- If a testing failure is found, a retesting might be conducted (Need Q-approval)


OOS (2) MD-L11

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OUT OF SPECIFICATION CONFIRMED – QUALITY INVESTIGATION- Donation process;- Transport process;- Processing process;- Material and equipment;- Qualification, training, maintenance …;- Trends, malfunctions…

Responsible person has to decide about the release of an OOS-product!


OOS (3) MD-L11

STATISTICAL PROCESS CONTROL (SPC)CoE GuideAppendix 3

AIM- Is my process stable?

- Free of confounding factors?- I recognise trends and changes in advance and can react!- Pre-requisites:

- Commitment of staff and training;- Representative sampling (statistical sampling and frequency);- Known specifications.


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ZOOM ON SPC SAMPLINGNUMBER AND FREQUENCY-Trigger an appropriate response (e.g. investigation or re-validation)

- Tolerance of failure: Target failure rate (failure rate that should not beexceeded); e.g. maximum 5% of RBC with residual WBC content abovethe limit (<5.0 x 106);

- Confidence level; e.g. 95 %, 95 %Chance that QC testing will detect the problem

- Frequency based on complexity of the system e.g.- Number of sites, operators;- Number of collection/processing system;- Use of multiple reagents lots;- Donor related variables;- Public health issues;Overall production volume;


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Risk based sampling

METHODS –EXAMPLE 1: CONTROL CHART (1)

Control chart maps samples of a product characteristic over time to identifywhen a process might be out of control


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Central line= average value

Upper and lower control values

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Control chart, but- Statistically are 3 of 1000 results out of 3 SD within a controlled process;- The probability of a “3 SD” result is 0.27% (rare event);

Different kinds of charts- Run chart

- Documentation of results over time, without specification;- Control charts

- Limits are based on statistical and representative data.


METHODS –EXAMPLE 1: CONTROL CHART (2)

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WECO Rules – Distinguish unnatural patterns from natural patterns

- The absence of points near the centerline (identified as a mixture pattern);

- The absence of points near the control limits (identified as a stratification pattern);

- The presence of points outside the control limits (identified as an instability pattern);- Other unnatural patterns (systematic (auto correlative), repetition, trend patterns


CoE Guide - Appendix 3 - Rules - Occurrence of a changes:

- Any point outside of control limits- 7 consecutive points all above/below the average line- 7 consecutive points all increasing/decreasing

DECISION RULES FOR OUT OF CONTROL OR NON RANDOM CONDITIONS (1)

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WECO RULESThe zone rules are designed to detect process instability. There are four basic rules that deal with appraising runs of observations within the various zones:



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WECO RULES



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METHODS – EXAMPLE 2: SCAN STATISTICS

- Suitable model for determining frequency of control testing;- Determine the number of non-conforming test results in a fixed sample

size- Sample = window of observations moving progressively

Example- Allowed failure rate for a conforming process: 0.1%- 1200 tests/year (100 tests/month)- Moving window of 120 consecutive tests non-conform process if at least

3 non-conform results- False positive rate: 0.7%


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METHODS –EXAMPLE 2: SCAN STATISTICS

22

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Allo

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Num

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ts in

“u

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Minimum failure rate of a non-conforming process

detectable at > 80% power in any single “window”

Min

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“targ

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rate”

for

ano

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25%400 30 16 2.5% 63% 81.9%

60 26 2.9% 50% 81.7%

1 200 30 17 2.0% 66% 81.3%60 27 3.8% 52% 83.0%

10% 400 30 9 3.5% 40% 82.4%60 14 2.7% 30% 83.8%

1 200 30 10 2.8% 43% 81.1%

5% 400 30 6 3.7% 29% 81.0%60 9 2.3% 21% 83.7%

1 200 30 7 2.2% 33% 82.3%

1%400

30 3 1.0% 18% 81.4%60 4 0.9% 11% 80.3%

1 200 60 4 2.7% 11% 80.3%

0.1%400

30 1 1.1 % 10% 81.6%60 1 2.0% 5% 80.8%

1 20030 1 3.2% 10% 81.6%

120 2 0.7% 4.6% 80.7%

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SUMMARY/CONCLUSION

Performance of QC are a requirement Ensure process are under control and product of quality SPC allows to think upstream any changes/potential deviations

might happen SPC can show how an improvement to a process has achieved a

desired result SPC enables decision making based on rational/scientific basis


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Appendix 3 (SPC) - Guide to the preparation, use and quality assurance of blood components


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MODULE E- CONTINOUS IMPROVEMENT PROCESSES

17 April 2015

- Lecture 12, Management of Non-conformities, M.-L. Hecquet

- Lecture 13, Change Control, M. v. Roosmalen

- Lecture 14, Haemovigilance, B. Rothe

- Lecture 15, Internal Audit, J. Ceulemans

- Lecture 16, Management Review, A. Dobrota

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MANAGEMENT OF NON CONFORMITIES


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TEACHING AIM

Understand the concept of NC/CAPA Management; Be able to perform a root cause analysis Be able to implement an action plan

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Annex 9.1, 9.2 & 9.3 about deviations, complaints and recall

Annex 9.4. A system to ensure CAPA on blood component non-conformity and qualityproblems shall be in place. Data shall be routinely analysed to identify qualityproblems that may require corrective action or to identify unfavourable trends thatmay require preventive action. All errors and accidents shall be documented andinvestigated in order to identify system problems for correction.

Good Practices Guidelines

As in the Directive

EU GMP – Chapter 8 –Complaints and Recall

ISO 9001 – Chapter 8.5 Improvement

The organisation shall continually improve the effectiveness of the QMS through theuse of the quality policy, objectives, audit results, analysis of data, corrective andpreventive actions and management review.

REGULATIONS


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DEFINITIONS


NON-CONFORMANCEDEFINITION: « Non-fulfillment of a requirement »CORRECTIONDEFINITION: « Action to eliminate a detected non-conformity » e.g.repair, rework or adjustementCORRECTIVE ACTIONDEFINITION: « Action to eliminate the cause of an existing non-conformity »PREVENTIVE ACTIONDEFINITION: « Action taken to eliminate the cause of a potential non-conformity(ISO 9000:2005)

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CORRECTION, CA OR PA?


Replacing the label on the blood bag that had a wrong labelapplied?

Revising process parameters in response to complaints?

Revising equipment maintenance procedures to reduce drift inprocess specifications?

Auditing all technicians of testing process after a quality issuewith one technician had been indentified?

Rewelding a contact that does not meet visual inspectionrequirements?

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NON-CONFORMANCES


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Requirement, SOP, Specification

TYPES:

Deviations: e.g. volume in a tube Out of specifications: e.g fridge temperature: 15 °C (Specification: 4-8°C)Complaint: e.g Surgeon complaint that the tubing of the bag was leakyAudit finding: e.g training was not performed against SOP 151Trending quality review: e.g trend analysis of product quality – leucocytes concentrationRecall: e.g recipient with fever after transfusion of platelets -> recall of associated comonents : FFP and EC

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THE CAPA PROCESS


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• Deviations• OOS• Audit findings• Complaints• Trending• Recall

NON-CONFORMANCE

• Identification & Data Analysis

• Risk assessment• Immediate action

(correction)• Root cause

Investigation• Action Plan• Implementation

& follow up

PROCESS

• Change control• Dissemination of

information• Document

change• Training

CAPA

INPUT

OUTPUT

1. IDENTIFICATION


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Non-conformance need to be clearly defined:

- Collect all available information- Use the 6 W’s: What?, When?, Where?, Who?, Which?, Why?- Summarise in a detailed and concise description

A well documented non-conformance is a non-conformance which can be solved

Example:: The stability of product XWY failed: The assay result of the 24 months stability testing of batch 126543 of product XWY is Out of Specification. Specification: 95.0 % -105.0%, Result: 93.4%

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2. RISK ASSESSMENT


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Evaluation to determine the need for immediate, corrective andpreventive actions and level of action required based on impact andrisks:

- Potential impact;

- Risks to patients, related to the safety and quality of the product,staff, blood establishments;

- Risks to donors;

- Immediate action that might be required.

4. IMMEDIATE ACTION


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Immediate action is necessary, when the quality, efficacy or safetymay be compromised

Example of immediate actions:

- Product Recall;- Blockage stock of a blood component due to bacterial contamination;- Interruption of the processing (i.e. until the problem is assessed and

fixed).

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5. ROOT CAUSE INVESTIGATION


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Systematic approach to be applied toensure no root cause is missed:

• Common sense;• Multi disciplinary teams;• Keep open mind for different opinions.

ISHIKAWA/5M’s:

+ Policies+ Procedures+ Plant+ Budget/Cost+ Measurement+ Management

ProblemStatement

Causes

6. ACTION PLAN


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- Summary of root cause analysis;

- Document the quality decision:e.g. no impact of the deviation on the product quality –product can be released;

- Action plan: All tasks assigned to correct the problem andprevent the reoccurence are identified

- Assignements of responsibilities and due dates- Details about required action and expected outcome

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7. IMPLEMENTATION & FOLLOW-UP


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- Execution of action plan;

- Document the action taken;

- Appropriateness & effectiveness of action evaluated ofresponsibilities and due dates;

- Closure of CAPA after sucessfull implementation, approved byQM.

NC MANAGEMENT FLOWCHART


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NC MANAGEMENT FLOWCHART


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SUMMARY/CONCLUSION


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NC/CAPA management need to be clearly defined; Implementation of Root Cause Analysis should eliminate

recurrence of NC; NC/CAPA management is part of continuous improvement

of a QMS.

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CHANGE CONTROLEverything is changing…. Why should we control it?

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Trainer: M. v. RoosmalenLecture 13 - Day 3

Understand the concept of change control; Learn all relevant aspects to implement and/or improve your change

control system; Know the whole process from initiation to implementation;.


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TEACHING AIM

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WHY CHANGE CONTROL?

• Guarantee that all changes are evaluated for their effect on product quality and validation status

• To ensure that changes are introduced in a controlled and coordinated manner

• To identify and reduce risks• Uncontrolled changes carry significant risks of loss of the

validated status


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CHANGE CONTROLDEFINITION: « A formal system by which qualified representatives of appropriate disciplines review proposed or actual changes that might affect a validated status of facilities, systems, equipment or processes. The intent is to assess the impact and risks and to determine the need for action that would ensure and document that the system is maintained in a validated state»(CoE Guide)KEY WORDS: Formal system, qualified representatives, changes, affect

validated status, impact & risks, actions, maintained.


ME-L13DEFINITIONS

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No explicit requirement of a CC system

All procedures, premises and equipment that have an influence on the quality andsafety of blood and blood components must be validated prior to introduction and bere-validated at regular intervals determined as a result of these activities

CoE Guide

All modifications, enhancements or additions to validated systems and equipment mustbe managed through the blood establishment's change control procedure. The effect ofeach change to the system or equipment, and its impact on quality and safety, must bedetermined in order to identify the extent of revalidation that is required.

REGULATIONS


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1.2.12.

A formal change control system must be in place to plan, evaluate and document all changes that may affect the quality, traceability, availability or effect of components or safety of components, donors or patients.

The potential impact of the proposed change must be evaluated and the degree of re-validation or additional testing, qualification and validation needed must be determined.

4.5.

Change control procedure should ensure that sufficient data are generated todemonstrate that revised process results in a product of the desired quality, consistentwith the approved specifications;Written procedure should be in place to describe the actions taken when a change isproposed;Changes should be formally requested, documented and accepted;Impact should be evaluated, including a risk analysis;Need for re-qualification and re-validation should be determined;Some changes may require notification to, or license amendment from, a nationalregulatory authority.


ME-L13REGULATIONS

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No explicit requirement of a CC systemSignificant changes to the [manufacturing] process have to be validated [chapter 1.2 (ii)

Changes carried out to the processes or analytical methods have to be reviewed regularly [chapter 1.4 (v), on PQR]

EU GMP – Annex 15

Written procedures [no. 43]

All changes treated formally, impact to be evaluated, need of revalidation to be determined [no. 44]

PICS/S for Blood establishments

A formal change control system should be in place to evaluate and document all changes that may effect the collection, preparation, storage, dispatch, quality control and quality assurance of blood and blood components.

The potential impact of the proposed change on the quality of the blood component should be evaluated.

Scientific judgement should determine what additional testing and validation studies are needed to justify a change in a validated process.


ME-L13REGULATIONS

CHANGES WILL HAPPEN

- Proactively due to business or technical reasons (e.g. new supplier, new equipment…)- Reactively driven as part of CAPA (e.g. due to deviations, OOS, trend analysis, audit observations)


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EXAMPLES REQUIRING CC

- New products, processes, critical materials, software, hardware, buildings, installations, specifications- Process changes (process times, storage times, storage temperatures, test methods, software)- Changes of critical materials, or supplier- Changes of critical equipment or parts or supplier- Changes regarding (collection) facilities (move, reconstruction)


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WHAT SHOULD YOU THINK ABOUT?

- What do you want to change and why- Who is involved?- What are the consequences?- What are the risks?- What can you do to reduce or to eliminate the risks?- When are you going to do what (planning, time-schedule)?


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CHANGE CONTROL PROCESS


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Change Request Assessment Change Plan

Change plan

approval

Executionof action

items

Change implementation

approvalChange closed


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Change plan

approval

Executionof action

items



STEP 1: CHANGE REQUEST

- Formal request (standardized form)- Description of old versus new situation- Reason for change, rationale- Planned implementation date- Request approved by manager

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STEP 2: ASSESSMENT

- Which departments are involved?- What is the impact of the change?- What are the risks?- What can you do to eliminate or reduce the risk?- Review assessment


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Change plan

approval

Executionof action

items



STEP 3: CHANGE PLAN

- Identify action items;- When are you going to do what (planning, time-schedule)? - Assign action items.


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Change plan

approval

Executionof action

items



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STEP 4: CHANGE PLAN APPROVAL

- Who should evaluate and approve the change plan?

- Change Control Board

– Process owner/manager– Other relevant managers– Responsible Person– Quality Manager


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Change plan

approval

Executionof action

items



STEP 5: EXECUTION OF ACTION ITEMS

- Execution of action items (qualification/validation, documentation, training, communication)

- Regularly update of status

- Project leader verifies completion of actions described


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Change plan

approval

Executionof action

items



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STEP 6: IMPLEMENTATION APPROVAL

- Evaluation and approval for implementation by CCB;

- CCB is the same as for authorization of change plan.


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Change plan

approval

Executionof action

items



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STEP 7: CLOSURE OF CHANGE

- Effective date

- Effectiveness check

- Closure by QA

- Records archived.


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Change plan

approval

Executionof action

items



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EXAMPLE OF FLOW CHART CC (1/2)

Change Control Init iated

Init iat ive Change Control

Approved

Assessment review ed

Assessment Made

Yes

No

Action items made (Change

Plan)

Change Plan (Act ion items)

Approved

Impact on other departments?

Assessment Performed

Change Plan (Act ion items)

Approved


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EXAMPLE OF FLOW CHART CC (2/2)

Effectivenesscheck made

Changecontrol

checked

Act ion itemsperformed

Change Plan(Action items)

Approved

ChangeApproved

ChangeApproved

Effectivenesscheck needed?

ChangeClosed

Yes

No

Effectivenesscheck

performed

Result ofaction items

approved


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DOCUMENTATIONCC requires a written procedure including:

- What type of changes should follow the CC procedure?- Who can suggest/initiate changes?- How are changes requested (forms, communication)?- How are measures for carrying out the change determined? Who compiles the

directions required?- Who is responsible for the execution and monitoring of all necessary actions?- What is the minimum documentation required before implementation

(completed risk analysis, validation protocol/report, new/revised SOP, evidence of training)?

- Who are included in the CC Board; what are the responsibilities of the CCB?- How is the change documented (format, content, storage)?- Who is responsible to close the change?


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EXAMPLE: CHANGE IN BLOOD BAG SYSTEM FROM HARD TO SOFT HOUSE FILTER

Action items- Validation of new blood bag system- Stock inventory- Set transition date and communicate- Arrange transport for new and old bag between collection facility and warehouse- Decide what to do with remaining old batches- Instruction memo- Training- Change SOPs- Check “tarra”- Introduce the new system in blood bank system- Check whether all old batches are removed- Set stock of old batch in blood bank system to zero.


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SUMMARY/CONCLUSION

Change Control is a process on its own; Makes sure no unnecessary changes are made, services are not

disrupted and resources are used efficiently; Is a risk based approach.


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http://www.fdanews.com/ext/resources/files/The_Food_And_Drug_Letter/2013/Pharma-Change-Control-Peither-ExecSeries.pdf

http--apps.who.int-prequal-trainingresources-pq_pres-workshop_China_November2009-english-1-4_ChangeControl.ppt


ME-L13USEFUL LINKS/READINGS

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1

Trainer: Beate RotheLecture 14 – Day 3

HAEMOVIGILANCE

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TEACHING AIM

Understand why haemovigilance is important; Be able to set up a haemovigilance system in BE.


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Directive 2002/98/EC – Chapter V on Haemovigilance

Directive 2005/61/EC as regards traceability requirements and notification of serious and adverse reactions and events

REGULATIONS (1)

3


Guide to the preparation, use and quality assurance of blood components,17th editionChapter 10 on haemovigilance

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DEFINITIONSHAEMOVIGILANCE

DEFINITION: « Organised surveillance procedures relating to serious adverse orunexpected events (SAE) or reactions (SAR) in donors or recipients, and theepidemiological follow-up of donors ».

SERIOUS ADVERSE REACTION

DEFINITION: « An unintended response in donor or in patient associated with thecollection or transfusion of blood and blood components that is fatal, life- threatening,disabling, incapacitating, or which results in, or prolongs, hospitalisation or morbidity.

SERIOUS ADVERSE EVENT

DEFINITION: « Any untoward occurrence associated with the collection, testing,processing, storage and distribution, of blood and blood components that might leadto death of life-threatening, disabling or incapacitating conditions for patients orwhich results in or prolongs, hospitalisation or morbidity”.

(2002/98/EC Directive and CoE Guide)


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HAEMOVIGILANCE: WHY?

WHO says:

"Haemovigilance is required to identify and prevent occurrence or recurrence of transfusion related to unwanted events, to increase the safety, efficacy and efficiency of blood transfusion, covering all activities of the transfusion chain from donor to recipient”.

Accumulation of Data on

Complications

Accumulation of Data on

Complications

Preventive / Corrective

Actions

Preventive / Corrective

Actions

No/lessrecurrence of complications

No/lessrecurrence of complications

ME-L14

HAEMOVIGILANCE NETWORK


National Competent Authority

ClinicalDepartment

Hospital/ HBB

Shared responsibilities

BE BE BE BE

Notification Feed-back & communication

Notification

Monitoring

LOCAL BE DATABASE

NATIONAL DATABASE

Notification

Feed-back & communication

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LOCAL BE DATABASE

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7

PRE-REQUISITE: TRACEABILITY (1) Ensuring traceability of blood and blood components

Within the processes

DONOR PRODUCT RECIPIENT OUTCOME OF TRANSFUSION

BLOOD ESTABLISHMENTSHOSPITALS OR CLINICS (FACILITIES)

Selection, Eligibility

Collection

ProcessingTestingStorageDistribution

Blood transport/ ReceptionTransfusion prescriptionIH testingCompatibility testingBlood issuing

Bedside checkBlood transfusionMonitoring and follow-up

Look-backBlood utilisation review

RecordsRecords

ME-L14

Unique identification of donorsUnique Identification of donations

Unique Identification of blood unit & blood components

)

Unique identification of donorsUnique Identification of donations

Unique Identification of blood unit & blood components

)


8

Seriouseffect in

recipient(s)

Donor‘s infectivity/production

process incident

PRE-REQUISITE: TRACEABILITY (2) Ensuring traceability of blood and blood components

Between donor and recipients

RRData linked todonor & recipient

DO

NO

R

RECIPIENT

Look-backTrace-back

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(e.g Notification of all recipients of blood from an HIV-infected donor)

(e.g. Identification of the HIV-infected source donor, after an HIV-infected recipient of blood cites transfusion as a risk for infection)

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HAEMOVIGILANCE PROCESS: HOW? (2)

MONITORING

IDENTIFICATION

NOTIFICATION/REPORTING

INVESTIGATION & ANALYSIS

- Without traceability no haemovigilance process cycle is possible- Procedures in place

Part A: Rapid Notification

Part B: Imputability level

Part C:Confirmation

Part D: annualnotification

SARSAE

SAR

SAR

SAE

SAE

SAE

SAR

SAR

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REPORTING: SAE/SAR RISK EVALUATION

Number of recipients transfused

Num

bero

fblo

odun

itsis

sued

Num

bero

fblo

oddo

nors

/don

atio

n

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SAR & SAE REPORTING

PROMPT REPORTING Opportunity to:

Stop transfusion of other blood components of a same donor or; Stop production process and; Stop issuing other units.

QUESTIONExamples of adverse reactions in patients or donors that shouldbe monitored by a haemovigilance system?


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Adverse Reactions in patients or donors:Transfusion reaction (haemolytic, febrile, urticaria, anaphylaxis, bacterial contamination, TRALI, TACO, DHTR, viral transmission, allo-immunisation).Drop in blood pressure, nausea or vomiting, muscle cramps, slow blood flow…..

Adverse Events:Incorrect ABO typing, labelling mistake, patient identification mistake, non-detection of infectious agents, non-performed irradiation…..


12

SAR & SAE EXAMPLES ME-L14

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SAR – IMPUTABILITY LEVELS


13

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TRACE-BACK/LOOK-BACK

Rapid and secure identification of transfused blood units, and related blood components, and donor(s) if a SAR in recipients is noted.

Rapid identification of recipient(s) if a SAE associated with collection, testing, processing, storage and distribution, is noted.

Only possible with completed documentation and traceability!


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RECALL

- Personnel authorised to inititiate the recall: to be independantof the production & sales management

- Establishments to which components were distributed should bepromptly informed;

- Recalled components to be identified and stored separately;- Progress of recall to be recorded and final report issued, including

reconciliation of the delivered and recovered quantities.


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ISBT GUIDELINES

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ISBT GUIDELINES

ISBT Working Party on Haemovigilance 2013

Severity?

Association withtransfusion?

Standard definitions enable evaluation ofdata

SUMMARY/CONCLUSION

Systematic surveillance of the transfusion chain relating to SAR/SAE;

Importance of post-donation information to donor; Important steps in this process is “ Look-back” and “Trace back” Traceability! Ultimate Goal: Prevention of transfusion associated risks and safe

blood


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Useful links


- International haemovigilance network www.ihn-org.com(Members are national haemovigilance systems);

- International Society of Blood Transfusion(ISBT): www.isbtweb.org/nc/working-parties/haemovigilance

- UK haemovigilance: www.shotuk.org- Germany: www.pei.de/Hämovigilanz- German Medical Association: Cross-Sectional Guidelines for

Therapy with Blood Components and Plasma Derivatives

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INTERNAL AUDIT

Trainer: Jan CeulemansLecture 15 – Day 3

Mod

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TEACHING AIM

Introduction to Internal Audit


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DEFINITIONS

AUDITDEFINITION: “A systematic, independent and documented process forobtaining audit evidence and evaluating it objectively to determine theextent to which audit criteria are fulfilled"(ISO 9000:2005)AUDIT PROGRAMMEDEFINITION: “ A systematic and independent examination to determinewhether quality activities and related results comply with planned arrangements and whether these arrangements are implementedeffectively and are suitable to achieve objectives.(CoE Guide)


ME-L16


A quality system for blood establishments should embrace the principles of qualitymanagement, quality assurance, and continuous quality improvement, and shouldinclude [..] and external and internal auditing.

Annex 1.1.2

Annex 10.1. Self-inspection or audit systems shall be in place for all parts of theoperations to verify compliance with the standards set out in this Annex. They shall becarried out regularly by trained and competent persons in an independentway according to approved procedures.

CoE Guide and Good Practices Guidelines

Annex 1.1.2 of 2005/62/EC

Annex 10.1 of 2005/62/EC

REGULATIONS (1)


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EU GMP – Chapter 9 –Self Inspection

Self inspections should be conducted in order to monitor the implementation andcompliance with Good Manufacturing Practice principles and to propose necessarycorrective measures.

9.1 Personnel matters, […..all processes] should be examined at intervalsfollowing a pre-arranged programme in order to verify their conformity with theprinciples of Quality Assurance.9.2 [……]in an independent and detailed way by designated competentperson(s) from the company.9.3 All self inspections should be recorded. [……]

ISO 9001

[……]conduct internal audits at planned intervals [……] An audit program shall beplanned, taking into consideration the status and importance of the processesand areas to be audited, as well as the results of previous audits. The auditcriteria, scope, frequency and methods shall be defined. The selection of auditorsand conduct of audits shall ensure objectivity and impartiality of the audit process.Auditors shall not audit their own work.

A documented procedure shall be established [……] Records of the audit [……].ensure that any necessary corrections and corrective actons [……] Follow-upactivities shall include the verification of the actions [……]

REGULATIONS (2)


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INTERNAL AUDIT


ME-L15

Why? When?

How? Who?

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WHY?The purpose of internal auditing is to ensure that the QMS is being operated correctly and effectively, by performing planned and documented checks, designed to ensure that:- The QMS documentation adequately defines the needs of the blood

establishment and requirements to be fulfilled;- The documented procedures and work instructions are practical,

understood and implemented;- All required processes (e.g validation) are performed and

performed as described;- The training of employees is adequate to allow them to perform

their tasks;- The QMS is continually improved.


ME-L15

IN BRIEF

- Check that:- What the establishment should do is documented;- What is documented is done.

Purpose of internal audits is:- not to search for the guilty;- or to find fault with individuals' performance.

The system is being audited - not the individuals! Based on continuous improvement


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HOW


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• Audit plan• Documentation review• Standards/Documents to be taken into

accountPlan and prepare

• Risk based auditIdentify criticalpoints - Checklist

• What should I look at?• What should I look for?Ask

• Observations, non conformities• Points to improve, strong pointsReport

• CAPA• Effective implementation

Action plan and follow up

STANDARDS AND DOCUMENTS

EU DirectivesDirective 2002/98/EC, 2005/62/EC (Quality Management), 2004/33/EC (Technical requirements) and 2005/61/EC (Haemovigilance).Local legislation including indirect legal requirements e.g. data protection, consumer rights.Other standards: GMP, PIC/S, CoE Guide, EDQM, ...BE Q-Documentation: Quality manual, procedures, process plans and work instructions.


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PRE-REQUISITE

- Procedure on internal audit management;

- Auditors should be trained for auditing;


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PLAN

- Audit plan should cover all activities;- Opening meeting: scope, presentation of auditors an and auditees,

plan;- Closing meeting;overall summary of the audit, including audits

findings;- Allow for ‘unexpected ‘ circumstances;- Be realistic;- Perform risk analysis (e.g. based on previous findings, CAPA…)

Risk-based audit; and risk-based frequency of internal audits- Audit plan to be disseminated.


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SCHEDULE

For each audit, the schedule should define:- The scope and location;- The auditors;- The auditees;- The date (at the planning stage information about the month for the

audit is sufficient, as the time approaches the auditor will set adefinite date with the auditees)


ME-L15

AUDITORS (1)

They shall:- Make use of standard auditing techniques to collect objective

information concerning the subject being audited;- Not respond to rumour and hearsay;- Avoid confrontational situations and arguments;- Makes notes as an aid to draft the audit report.


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They shall:- Collect documentary/factual evidences of conformity or non-

conformity;Auditing is not to look for non-conformity but check for compliance;

- Note where current procedures could be improved;- Keep the auditees informed as to the progress of the audit and any

findings.- Discuss audit findings with auditees to ensure that finding are

understood and accepted;


ME-L15AUDITORS (2)

FINDINGS CLASSIFICATION

EuBis ClassificationCritical deficiency: Any deficiency in a process or a written procedure that directly affects the safety of the donor or patientMajor deficiency: A serious inadequacy in a process or a written procedure, but would not on its own affect the safety of the donor or patient.Other deficiency: An inadequacy in a system or processObservation : An inadequacy in a system or process that is not a failure to comply with a standard


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AUDIT REPORT

- The names of the auditor, auditees, observers;- The scope of the audit;- Location of the audit;- Date of the audit.

OBSERVATIONS/NON-CONFORMITIES- Record only factual evidences (not hearsay, facts);- Clearly identifies the areas where corrective actions are

required.


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FOLLOW UP

PDCA cycle- Action plan (CAPA)

• Who ? • What ? • When ?• How?


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QUALITY RECORDS CONCERNING AUDITS

To be kept: Audit plan, Audit programme, Audit reportsCompleted audit records are stored as quality records Important functions:- Demonstrating that the audit system exists, is functioning and

effective;- Analysing responses and correction times (action plan);- Allowing analysis of types of problems and identifying the most

common problems so that CAPA can be taken;- Allowing auditors to prepare for audits N+1 by reviewing the past

reports for that area or function;- Providing valuable summary for use in Management Reviews


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EXAMPLES OF AUDIT REPORTS


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Internal audits have the ultimate goal to improve your QMS; Does not aim at blaming people;


SUMMARY/CONCLUSION ME-L15

EuBIS INITIATIVE

http://www.eubis-europe.eu/


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MANAGEMENT REVIEW

Alina DobrotaLecture 16 - Day 4

Mod

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TEACHING AIM

Understand the goal of a Management Review; Get knowledge on how to practice it and make it relevant


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Annex 1.1.3. Management shall review the system at regular intervals to verify itseffectiveness and introduce corrective measures if deemed necessary.


1.2.14 = Annex 1.1.3 of 2005/62/EC

1.2.15. There should be periodic management review and monitoring of itseffectiveness, with the involvement of executive management , of the operation of theQS to identify opportunities for continual improvement of blood and blood components,processes and the system itself.


1.6 There should be periodic management review, with the involvement of seniormanagement, of the operation of the Pharmaceutical Quality System to identifyopportunities for continual improvement of products, processes and the system itself.

ISO 9001

Top management shall review the organisation QMS at planned intervals to ensure itscontinuing suitability, adequacy and effectivenesss. This review shall include assessingopportunities or improvement and the need for changes to the QMS, including thequality policy and quality objectives.

REGULATIONS


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DEFINITIONS

REVIEWDEFINITION: « Activity undertaken to determine the suitability, adequacy and effectiveness of the subject matter (here management) to achieve established objectives »(ISO 9000:2005)


KEY WORDS: Planned, assessment of suitability, adequacy, and effectivess, opportunities for improvement and need for changes

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INPUTS AND OUPUTS OF A MR


• Non-conformities: productand process related;

• CAPA customers feedback;• Audits outcomes;• Process performance

(indicators);• Outcomes of process

reviews;• Follow-up actions from

previous management reviews;

• Changes that might affect the QMS;

• Recommendations for improvement.

• QMS improvement eg. Revisions of qualitypolicy and objectives;

• Process improvement;• Product improvement;• Resources needs• Request for changes

OUTPUTS

ANAL

YSIS

ANAL

YSIS

DEC

ISIO

NS

& A

CTIO

NS

DEC

ISIO

NS

& A

CTIO

NS

INPUTS PROCESS

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ACT Evaluate whether QMS effective

Evaluate whether improvements/changes effective (MR n-1);

MR AS PART OF THE PDCAPLAN Policy and objectives planning Planning QMSPlanning of improvements (MR n-1) Planning of changes (MR n-1)

ContinuousImprovement

DOImplement QMSImplement changes and improvements and related training if needed (MR n-1).

CHECKMonitor and analyse QMS;

Check, analyse implementation of changes/improvements (MR n-1) ;

PLAN

DOCHECK

ACT


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MAKE IT RELEVANT!


PRODUCT REVIEW

PROCESS REVIEW

MANAGEMENT REVIEW

R1 R2 R3 R4 R5

ProductsProducts Products

S1 S2 S3

M1 M2

FREQUENCY OF MR: RISK BASED !

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PERFORM A MR


Procedure on Management Review Participants: Top Management, QM, staff representing processses

and staff involved in quality issues. ResponsibilitiesTop Management:

- Conduct the meeting & ensure adequate attendance;- Review QMS and all inputs;- Decide on actions; - Approve decisions and actions Action plan;

Quality Manager:- Organise meeting (date, agenda, notification)- Compile inputs;- Elaborate MR report.

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MR PROCESS FLOWCHART


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• Non-conformities: product and process related;

• CAPA customers feedback;• Audits outcomes;• Process performance (indicators);• Outcomes of process reviews;• Follow-up actions from previous

management reviews;• Changes that might affect the QMS;• Recommendations for

improvement.

• QMS improvement eg. Revisions of quality policy and objectives;

• Process improvement;• Product improvement;• Resources needs;• Request for changes.

MR AGENDA & REPORT

QMS EVALUATION

• Adequacy: Compliance withstandards & requirement;

• Suitability: resources adapted;• Effectiveness: produce intended

results.

REVIEW INPUTS

AGENDA

REPORTREVIEW OUPUTS

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SUMMARY/CONCLUSION

Management Review is designed to:

Review QMS, processes and product adequacy, suitability and effectiveness;

All quality related issues are reviewed at highest possible level;

All levels of management involved in quality are made aware of changes, updates, revisions and policies;

Support to continuously improve the QMS


ME-L16

USEFUL LINKS

ISO 9001 Standard – as a System/QM Standard


Page 190

List of Definitions Audit

A systematic, independent and documented process for obtaining audit evidence and evaluating it objectively to determine the extent to which audit criteria are fulfilled. (ISO 9000:2005)

Audit programme

A systematic and independent examination to determine whether quality activities and related results comply with planned arrangements and whether these arrangements are implemented effectively and are suitable to achieve objectives. (CoE, Guide)

Blood

Whole blood collected from a single donor and processed either for transfusion or further manufacturing. (CoE, Guide)

Blood component

Therapeutic components of blood (red cells, white cells, platelets, plasma) that can be prepared by centrifugation, filtration and freezing using conventional blood bank methodologies. (CoE, Guide and Directive 2002/98/EC)

Blood establishment

Any structure or body that is responsible for any aspect of the collection and testing of human blood or blood components, whatever their intended purpose, and their processing, storage and distribution when intended for transfusion. This does not include hospital blood banks. (CoE, Guide)

Change control

A formal system by which qualified representatives of appropriate disciplines review proposed or actual changes that might affect the validated status of facilities, systems, equipment or processes. The intent is to determine the need for action that would ensure and document that the system is maintained in a validated state. (CoE, Guide)

Corrective action

Action to eliminate the cause of an existing non-conformity. (ISO 9000:2005) Haemovigilance

Organised surveillance procedures related to serious adverse or unexpected events or reactions in donors or recipients, and the epidemiological follow-up of donors. (CoE, Guide)

Non-Conformity

Non fulfilment of a requirement. (ISO 9000:2005)

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Preventive action Action taken to eliminate the cause of a potential non-conformity. (ISO 9000:2005)

Process Set of interrelated or interacting activities, which transforms inputs into outputs. (ISO 9000:2005)

Qualification Provision of evidence that a specific equipment, facility or system is fit for intended use/that predefined requirements for specific equipment, facility or system are fulfilled.

Quality Assurance Part of quality management focused on increasing the ability to fulfil quality requirements. (ISO 9000:2005)

Quality Control Part of quality management focused on fulfilling quality requirements. (ISO 9000:2005)

Quality Management Coordinated activities to direct and control an organisation with regards to quality. (ISO 9000:2005)

Quality Management System Management system to direct and control an organisation with regard to quality. (ISO 9000:2005)

Quality Manual Document specifying the quality management system of an organisation. (ISO 9000:2005)

Quality Objective Something sought, or aimed for, related to quality. (ISO 9000:2005)

Quality Policy Overall intentions and direction of an organisation related to quality as formally expresses by top management. (ISO 9000:2005)

Review Activity undertaken to determine the suitability, adequacy and effectiveness of the subject matter to achieve established objectives. (ISO 9000:2005)

Risk Effect of uncertainty on objectives. (ISO 31000:2009) The combination of the probability of occurrence of harm and the severity of harm (ICH-Q9)

Risk Management Aid to decision making by taking account of uncertainty and its effect on achieving objectives and assessing the need for any actions (ISO 31000:2009) A systematic process for the identification, assessment and control of risks to the quality of pharmaceutical product across the product lifecycle (ICH-Q9)

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Serious Adverse Event Any untoward occurrence associated with the collecting, testing, processing, storage and distribution of blood and blood components that might lead to death or life-threatening, disabling or incapacitating conditions for donors or recipients or which results in, or prolongs, hospitalisation or morbidity. (CoE, Guide and Directive 2005/61/EC)

Serious Adverse Reaction Unintended response in donor or in recipient associated with the collection or transfusion of blood or blood components that is fatal, life-threatening, disabling, incapacitating, or which results in, or prolongs hospitalisation or morbidity. (CoE, Guide and Directive 2005/61/EC)

Statistical Process Control Tool that enables an organisation to detect changes in the processes and procedures it carries out by monitoring data collected over a period of time in a standardised fashion. (CoE Guide)

Validation Provision of evidence that requirements for a specific intended use are fulfilled. (ISO 9000:2005) Means the establishment of documented and objective evidence that the pre-defined requirements for a specific procedure or process can be consistently fulfilled. (CoE, Guide)

Validation Plan A description of validation activities, responsibilities and procedures. It describes specifically how a certain validation is to be done. (CoE, Guide)

Page 193

List of Acronyms and Other Abbreviations

BE Blood Establishment

CD-P-TS European Committee on Blood Transfusion

CAPA Corrective and Preventive Action

EC European Commission

EDQM European Directorate for the Quality of Medicines and HealthCare

EU European Union EuBIS European Blood Inspection

Project GMP Good Manufacturing Practices GPG Good Practice Guidelines ISBT International Society for Blood

Transfusion ISO International Organisation for

Standardisation DQ Design Qualification IQ Installation Qualification NC Non-Conformity/Non-

Conformance

OQ Operational Qualification PIC/S Pharmaceutical Inspection

Convention and Pharmaceutical Inspection Co-operation Scheme

PQ Performance Qualification QC Quality Control QA Quality Assurance QM Quality Management QMS Quality Management System TQM Total Quality Management SAE Serious Adverse Event SAR Serious Adverse Reaction SOPs Standard Operating Procedures SPC Statistical Process Control WHO World Health Organisation

Page 194

Authors

HECQUET Marie-Laure EDQM/Council of Europe 7 Allée Kastner - CS 30026 FR - 67081 STRASBOURG [email protected]

KOJIC Nevena EDQM/Council of Europe 7 Allée Kastner - CS 30026 FR - 67081 STRASBOURG [email protected]

AQUILINA Alexander National Blood Transfusion Service Guardamangia Hill MT - PTA1314 PIETA [email protected]

CEULEMANS Jan Rode Kruis-Vlaanderen Wilrijkstraat 8 BE - 2650 EDEGEM [email protected]

DOBROTA Alina Mirella Regional Blood Transfusion Centre Str. Nicolae Iorga nr 85 Constanta County RO - 900587 CONSTANTA [email protected]

KUERSTEINER Oliver Rehhagstrasse 79 3018 BERN SWITZERLAND [email protected]

PISACKA Martin Interregionale Blutspende SRK AG, U nemocnice 1 128 20 PRAGUE CZECH REPUBLIC [email protected]

ROTHE Beate Institute of Clinical Chemistry, Laboratory and Transfusion Medicine Klinikum Wolfsburg Sauerbruchstraße 7 DE - 38440 WOLFSBURG [email protected]

VAN ROOSMALEN Mariëlle Sanquin Bloedbank Geert Grooteplein Zuid 34 6525 GA NIJMEGEN NETHERLANDS [email protected]

Page 195

The Council of Europe is the continent’s leading human rights organisation. It comprises 47 member states, including all members of the European Union. The European Directorate for the Quality of Medicines & HealthCare (EDQM) is a directorate of the Council of Europe. Its mission is to contribute to the basic human right of access to good quality medicines and healthcare and to promote and protect public health.

www.edqm.eu

ENG

B-QM Programme

Direction européennede la qualité du médicament& soins de santé

European Directoratefor the Quality

of Medicines& HealthCare