Bioprocessing
Bioprocessing Owen P. Ward SPRINGER SCIENCE+BUSINESS MEDIA, LLC
First published in 1991 by Copyright Owen P. Ward 1991 Originally published by Van Nostrand Reinhold in 1991 Softcover reprint ofthe hardcover lst edition 1991 AII rights reserved. No part of this work covered by the copyright hereon may be reproduced or used in any form or by any means - graphic, electronic, or mechanical, including photocopying, recording, taping, or information storage and retrieval systems - without written permission from the publisher. U.S.A. Edition Library of Congress Catalog Card Number 91-10022 16 15 14 13 12 II 10 9 8 76543 2 I Library of Congress Cataloging-in-Publication Data Ward, Owen P., 1947- Bioprocessing I Owen P. Ward. p. cm. Includes bibliographical references and index. ISBN 978-1-4613-6745-1 ISBN 978-1-4615-3914-8 (ebook) DOI 10.1007/978-1-4615-3914-8 1. Biotechnology - Technique. 1. Title. TP248.24.W37 1991 660'.6 - dc20 91-10022 CIP
Contents Preface Acknowledgements Vlll IX CHAPTER 1 CHAPTER 2 CHAPTER 3 Introduction: Biomaterials and Bioprocessing l.l Raw materials 1.2 Cell cultivation 1.3 Enzymes 1.4 Product purification 1.5 Further reading Bulk Bioprocessing Operations 2.1 Agitation and mixing 2.2 Heat transfer 2.3 Size reduction and enlargement 2.4 Solid-liquid separations 2.5 Solid-solid separations 2.6 Further reading Bioreactors in Bioprocessing 3.1 Microbial bioreactors 3.2 Non-microbial cell culture systems 3.3 Bioreactor sterilization and sterility main tenance 1 2 5 9 10 14 15 15 20 25 30 35 35 37 37 43 47
vi 3.4 Bioreactor control 3.5 Enzyme bioreactors 3.6 Further reading Bioprocessing 48 49 53 CHAPTER 4 CHAPTER 5 CHAPTER 6 Biochemical Separations 4.1 Precipitation 4.2 Crystallization 4.3 Membrane processes 4.4 Chromatographic methods in bioprocessing 4.5 Liquid-liquid extraction 4.6 Supercritical fluid extraction 4.7 Process scale continuous electrophoresis 4.8 Lyophilization 4.9 Further reading Sterilization and Preservation in Bioprocessing 5.1 Dry-heat sterilization 5.2 Steam sterilization 5.3 Gas sterilization 5.4 Ionising radiation 5.5 Other sterilants 5.6 Filtration 5.7 Food preservatives and stabilizers 5.8 Stabilizers of other biological solutions 5.9 Further reading Bulk Processing of Animal and Plant Materials 6.1 Cereal processing 6.2 Baking 6.3 Fruits and vegetables 6.4 Coffee and tea 6.5 Chocolate and cocoa products 6.6 Sugar production 6.7 Milk processing 6.8 Meat processing 6.9 Egg processing 6.10 Animal blood processing 6.11 Fats and oils - manufacture and processmg 6.12 Further reading 55 55 57 57 60 64 67 67 69 71 73 73 74 76 76 76 76 77 79 80 81 82 87 88 91 92 94 96 101 102 103 105 108
Contents CHAPTER 7 CHAPTER 8 Purification of Fine Chemicals from Non-microbial Sources 110 7.1 Extraction of plant products 110 7.2 Fish by-products 113 7.3 Animal by-products 113 7.4 Human products lis 7.5 Further reading 120 Fermentation and Cell Culture Processes 121 8.1 Examples of microbial fermentation processes 122 8.2 Animal cell culture 130 8.3 Plant cell culture 134 8.4 Further reading 135 vii CHAPTER 9 Recovery of Cell Products 137 9.1 Downstream processing steps 139 9.2 Examples of recovery processes 140 9.3 Further reading 149 CHAPTER 10 Enzyme Bioprocessing Applications 151 10.1 Bulk industrial enzymes lsi 10.2 Biotransformations 159 10.3 Concluding remarks 166 10.4 Further reading 168 CHAPTER 11 Waste Treatment 170 11.1 Waste water treatment 170 11.2 Trickling filters 174 11.3 Rotating biological contactors 174 11.4 Activated sludge 174 1I.5 Sludge processing 175 11.6 Composting 175 11.7 Micro-organisms and enzymes as waste treatment processing aids 175 11.8 Further reading 177 CHAPTER 12 Good Manufacturing 178 12. I Further reading 181 Index 182
Preface Methods for processing of biological materials into useful products represent essential core manufacturing activities of the food, chemical and pharmaceutical industries. On the one hand the techniques involved include well established process engineering methodologies such as mixing, heat transfer, size modification and a variety of separation and fermentation procedures. In addition, new bioprocessing practices arising from the exciting recent advances in biotechnology, including innovative fermentation cell culture and enzyme based operations, are rapidly extending the frontiers of bioprocessing. These developments are resulting in the introduction to the market place of an awesome range of novel biological products having unique applications. Indeed, the United States Office of Technology Assessment has concluded that 'competitive advantage in areas related to biotechnology may depend as much on developments in bioprocess engineering as on innovations in genetics, immunology and other areas of basic science'. Advances in analytical instrumentation, computerization and process automation are playing an important role in process control and optimization and in the maintenance of product quality and consistency characteristics. Bioprocessing represents the industrial practice of biotechnology and is multidisciplinary in nature, integrating the biological, chemical and engineering sciences. This book discusses the individual unit operations involved and describes a wide variety of important industrial bioprocesses. I am very grateful to Sanjay Thakur who assisted me in the collection of material for this book. A very special acknowledgement is due to my colleague, Val Butler, who played a major role in production of the manuscript, including word processing and layout of text and figure and table design. Owen Ward * Commercial Biotechnology: An International Analysis (Washington D.C. US Congress, Office of Technology Assessment, OT A-BA-218, 1984).
Acknowledgements I wish to thank the following publishers and organisations for granting permission to reproduce original or copyright material. Biotage Inc., Charlottesville, VA: Figure 4.5. BioITech~logy, New York. Figure 8.9 from Posillico, E.G. (1986). Microencapsuliitjon technology for large-scale antibody production, Bioi Technology 4, 114-117. Butterworths Heinemann, US: Table 10.4 from Dordick, ].S. (1989). Enzyme catalysis in monophasic organic solvents. En;:yme and Microbial Technology 11, 194-211. CRC Press, Boca Raton, FI: Table 5.1 from Chichester, D.F. and Tanner, F.W. (1972). Antimicrobial Food Additives. In Handbook of Food Additives, Ed. Furia, T.E. pp. 115-184. Dekker, New York: Figure 8.7 from Seaver, S.S. (1987). Culture method affects antibody secretion of hybrid om a cells. In Commercia.( Production of Monoclonal Antibodies, Ed. Seaver, S.S. pp. 93-118. Figure 8.8 from Lebherz III, W.E. (1987). Batch production of monoclonal antibodies in large-scale suspension culture. In Commercial Production of Monoclonal Antibodies, Ed. Seaver, S.S. pp. 93-118. Figure 8.10 from Von Wedel, R.]. (1987). Mass culture of mouse and human hybridoma cells in hollow-fibre culture. In Commercial Production of Monoclonal Antibodies, Ed. Seaver, S.S. pp. 159-173. Ellis Horward, Chichester: Table 3.1 from Kennedy,j.F. and White, C.A. (1985). Principles of immobilization of enzymes. In Handbook of En;:yme Biotechnology, 2nd ed., Ed. Wiseman, A. pp. 147-207. Society for General Microbiology: Figure 4.8 from Lambe, GA. (1986). Continuous electrophoresis for production-scale purification. In Bioactive Microbial Products 3: Downstream Processing, Ed. Stowell,].D., Bailey, P.]. and
x Bioprocessing Winstanley, P.J. pp. 191-203. London Academic. Figure 7.6 from Low, D.K. T. (1986) Chromatographic methods. In Bioactive Microbial Products 3: Downstream Processing, Ed. Stowell, ].D., Bailey, P.J. and Winstanley, P.]. pp. 121-145. London Academic. Figure 8.6 from Atkinson, T., Barstow, D.A., Court,]., Minton, M.P., Sharp, R.]. and Sherwood, R. (1986). High level microbial expression and purification of recombinant proteins. In Bioactive Microbial Products 3: Downstream Processing, Ed. Stowell,].D., Bailey, P.J. and Winstanley, P.J. pp.27-43. London Academic. Wiley, New York: Figure 4.9 from Snowman, ].W. (1988). Lyophilization techniques, equipment and practice. In Downstream Processing, Equipment and Techniques. Ed. Mizrahi, A., pp. 315-351. New York, A.R. Liss. Figure 8.4- from Ryu, D.D.Y. and Hospodka,]. (1980). Quantitative physiology of Penicillium chryosogenum in penicillin fermentation. Biotechnol. Bioeng. 20, 289-298.