Applying lean six sigma in the pharmaceutical industry

171 Pages·2014·5.012 MB·English

by  Chatterjee, Bikash

Applying Lean Six Sigma
in the Pharmaceutical Industry
This book is dedicated to my dear friend Cordell
whose support has always been behind my success in this business
and to my wife Debbie
whose spirit has always been behind my success in life.
Applying Lean
Six Sigma in the
Pharmaceutical
Industry
BIkASh ChAtterjee
© Bikash Chatterjee 2014
All rights reserved. No part of this publication may be reproduced, stored in a retrieval
system or transmitted in any form or by any means, electronic, mechanical, photocopying,
recording or otherwise without the prior permission of the publisher.
Bikash Chatterjee has asserted his right under the Copyright, Designs and Patents Act, 1988,
to be identified as the author of this work.
Published by
Gower Publishing Limited Gower Publishing Company
Wey Court East 110 Cherry Street
Union Road Suite 3-1
Farnham Burlington, VT 05401-3818
Surrey, GU9 7PT USA
England
www.gowerpublishing.com
British Library Cataloguing in Publication Data
A catalogue record for this book is available from the British Library.
ISBN: 978-0-566-09204-6 (hbk)
ISBN: 978-1-4724-2521-8 (ebk – ePDF)
ISBN: 978-1-4724-2522-5 (ebk – ePUB)
Library of Congress Cataloging-in-Publication Data
Chatterjee, Bikash, author.
Applying lean six sigma in the pharmaceutical industry / by Bikash Chatterjee.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-0-566-09204-6 (hardback) -- ISBN 978-1-4724-2521-8 (ebook) -- ISBN 978-1-4724-
2522-5 (epub)
I. Title.
[DNLM: 1. Technology, Pharmaceutical--standards. 2. Drug Discovery--organization &
administration. 3. Efficiency, Organizational. 4. Technology, Pharmaceutical--organization &
administration. 5. Total Quality Management--methods. QV 778] RS100
338.4'76151--dc23
2013042257
III
Printed in the United Kingdom by Henry Ling Limited,
at the Dorset Press, Dorchester, DT1 1HD
Contents
List of Figures vii
List of Tables ix
List of Abbreviations xi
Preface xv
1 The Product Lifecycle and Quality Philosophy 1
2 Trouble in Paradise and Catalyzing Change 27
3 Lean in the Product Development Environment 45
4 Applying Lean in the Analytical Laboratory 63
5 Applying Lean in the Pilot Plant 81
6 Applying Lean Six Sigma on the Manufacturing Floor 101
7 Lean and Six Sigma as a Framework for Process Analytical
Technology 125
Index 147
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List of Figures
1.1 Product development lifecycle 3
1.2 Pharmaceutical QMS framework 9
2.1 Process understanding through QbD 32
2.2 ICH Q9 risk management framework 33
2.3 FTA analysis of a contaminated autoclave batch 35
2.4 HAZOP risk matrix 38
2.5 HAZOP analysis for a chemical reaction vessel 38
2.6 Example of FMEA 41
3.1 The pharmaceutical Lean organization 46
3.2 TPDS triumvirate 47
3.3 Lean R&D implementation roadmap 58
3.4 R&D organizational force field diagram 60
4.1 Applying Lean in the laboratory 66
4.2 Symbols used for VSM 69
4.3 The eVSM summary for the Phase 1 and Phase 2 stability VSM 70
4.4 Lab scheduling visual status board 78
5.1 2L Pilot Plant cVSM 86
5.2 12-month throughput performance—2L manufacturing 87
5.3 2L Miniferm processing success rate 93
5.4 Breakdown rates for causes of failed lots 94
5.5 Correlation plot between Miniferm contamination incidence
and number of runs 95
5.6 Incidence of errors/month 95
5.7 Regression plot of number of lots and error rate 96
5.8 Equipment-related operational issues for the past 12 months 97
5.9 Regression plot of equipment issues and number of runs 98
6.1 Shewart Cycle/PDCA Cycle 104
6.2 LSS and PDCA Cycle 105
6.3 Project charter template 107
6.4 Six Sigma program and team structure 108
6.5 Hybrid LSS project team structure 109
6.6 Transdermal manufacturing line area layout 111
6.7 Downtime Pareto analysis 111
6.8 Line utilization and throughput Ishikawa diagram 113
viii AppLying LeAn Six SigmA in the phArmAceuticAL induStry
6.9 Changeover time by shift 113
6.10 Setup time by shift 114
6.11 Rapid changeover methodology 115
6.12 Quality inspection/line clearance current work flow analysis 118
6.13 Quality inspection/line clearance optimized work flow analysis 120
6.14 Quality inspection/line clearance cleaning zones 121
6.15 Heat sealing Pareto analysis 123
7.1 Lean Sigma roadmap 129
7.2 Controlled release tablet process flow 133
7.3 Lean DFSS models 136
7.4 Design for LSS model applied to PAT 137
7.5 Process understanding through QbD 140
7.6 Process capability curve for eight-hour tablet dissolution
timepoint 144
List of Tables
2.1 Compression operation HACCP 37
2.2 HAZOP Guide Word table 37
2.3 Severity ranking table 40
2.4 Occurrence ranking table 40
2.5 Detection ranking table 41
4.1 Rhythm Wheel by analyst 67
4.2 Baseline metrics for the current operation 71
4.3 5S evaluation criteria 74
4.4 Rhythm Wheel for PDQC laboratory 77
4.5 Resulting metrics at the end of the Lean exercise 79
5.1 Results of the value stream exercise 85
5.2 Overall process cycle efficiency—2L operation 86
5.3 Throughput-driven estimated cycle time reduction opportunities 89
5.4 Breakdown rates for causes of failed lots 93
5.5 Increasing trends in error 96
5.6 Quality and reliability-driven estimated capacity increase
opportunities 98
7.1 Comparison of a traditional NDA filing and a PQAS filing 128
7.2 Lot to lot tablet lubricant content 142
7.3 Analytical method comparison 143