Bioprocessing. Owen P. Ward SPRINGER SCIENCE+BUSINESS MEDIA, LLC

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1 Bioprocessing

2 Bioprocessing Owen P. Ward SPRINGER SCIENCE+BUSINESS MEDIA, LLC

3 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 II I Library of Congress Cataloging-in-Publication Data Ward, Owen P., Bioprocessing I Owen P. Ward. p. cm. Includes bibliographical references and index. ISBN ISBN (ebook) DOI / Biotechnology - Technique. 1. Title. TP W '.6 - dc CIP

4 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

5 vi 3.4 Bioreactor control 3.5 Enzyme bioreactors 3.6 Further reading Bioprocessing 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

6 Contents CHAPTER 7 CHAPTER 8 Purification of Fine Chemicals from Non-microbial Sources Extraction of plant products Fish by-products Animal by-products Human products lis 7.5 Further reading 120 Fermentation and Cell Culture Processes Examples of microbial fermentation processes Animal cell culture Plant cell culture Further reading 135 vii CHAPTER 9 Recovery of Cell Products Downstream processing steps Examples of recovery processes Further reading 149 CHAPTER 10 Enzyme Bioprocessing Applications Bulk industrial enzymes lsi 10.2 Biotransformations Concluding remarks Further reading 168 CHAPTER 11 Waste Treatment Waste water treatment Trickling filters Rotating biological contactors Activated sludge 174 1I.5 Sludge processing Composting Micro-organisms and enzymes as waste treatment processing aids Further reading 177 CHAPTER 12 Good Manufacturing I Further reading 181 Index 182

7 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).

8 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, Butterworths Heinemann, US: Table 10.4 from Dordick, ].S. (1989). Enzyme catalysis in monophasic organic solvents. En;:yme and Microbial Technology 11, 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 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 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 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 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 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

9 x Bioprocessing Winstanley, P.J. pp 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 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 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 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,

Flexible Food Packaging. Questions and Answers

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