Industrial Scale Suspension Culture of Living Cells E-Book

Hans-Peter Meyer

• Herausgeber: Wiley-VCH
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 1244

Veröffentlichungsjahr: 2014

Beschreibung

The submersed cultivation of organisms in sterile containments or fermenters has become the standard manufacturing procedure, and will remain the gold standard for some time to come. This book thus addresses submersed cell culture and fermentation and its importance for the manufacturing industry. It goes beyond expression systems and integrally investigates all those factors relevant for manufacturing using suspension cultures. In so doing, the contributions cover all industrial cultivation methods in a comprehensive and comparative manner, with most of the authors coming from the industry itself. Depending on the maturity of the technology, the chapters address in turn the expression system, basic process design, key factors affecting process economics, plant and bioreactor design, and regulatory aspects.

Leseprobe

CONTENTS

Cover

Related Titles

Title Page

Copyright

Foreword

Preface

List of Contributors

The History and Economic Relevance of Industrial Scale Suspension Culture of Living Cells

Part I: Suspension Culture of Bacteria, Yeasts, and Filamentous Fungi

Chapter 1: Bacterial Suspension Cultures

1.1 Introduction

1.2 Organisms, Cells, and their Products

1.3 Bioprocess Design Aspects for Recombinant Products

1.4 Basic Bioreactor Design Aspects

1.5 Single Use Bioreactors for Microbial Cultivation

1.6 Quality by Design: Vision or Threat for Twenty-First Century Pharmaceutical Manufacturing

1.7 Process Economics

References

Chapter 2: Yeast Suspension Culture

2.1 Introduction

2.2 Yeast Species Used in Biotechnology and their Products

2.3 Basic Process Design Aspects

2.4 Basic Bioreactor Design Aspects

2.5 Key Factors Related to Process Economics

2.6 Regulatory Aspects

2.7 Summary and Outlook

References

Chapter 3: Filamentous Fungi Fermentation

3.1 Introduction

3.2 Products and Organisms in the Industry

3.3 Filamentous Fungi as a Production Platform

3.4 Fermentation of Filamentous Organisms

3.5 Process Scaling

3.6 Regulatory Aspects

3.7 Economic Aspects

3.8 Conclusions and Perspectives

References

Part II: Suspension Culture of Algae and Plant Cells

Chapter 4: Microalgae Grown under Heterotrophic and Mixotrophic Conditions

4.1 Eco-physiology and Genetics of Biotechnologically Relevant Species

4.2 Products from Microalgae Grown in the Absence of Light

4.3 Bioreactor Design

4.4 Process Design: Culture Media and Process Control Strategies

4.5 Process Economics

4.6 Commercialization of Microalgae-Derived Products and Regulatory Aspects

References

Chapter 5: Recombinant Protein Production with Microalgae

5.1 Organisms, Cells, Expression Systems, Products

5.2 Production of Recombinant Therapeutics in Microalgae: Process Design Aspects

5.3 Regulatory Aspects

5.4 Summary and Outlook

References

Chapter 6: Suspension Culture of Microorganisms (Algae and Cyanobacteria) Under Phototrophic Conditions

6.1 Introduction

6.2 Basic Process Design Aspects

6.3 Large-Scale Cultivation Systems

6.4 Photobioreactors – Technology Overview

6.5 Conclusion/Outlook

References

Chapter 7: Suspension Culture of Plant Cells Under Heterotrophic Conditions

7.1 Introduction

7.2 In Vitro Initiation and Maintenance of Plant Cell Suspension Cultures

7.3 Characteristics of Heterotrophic Plant Suspension Cells and Resulting Process Design

7.4 Suitable Bioreactors

7.5 Commercial Manufacture of Plant Cell-Derived Cosmetics and Therapeutics under Additional Consideration of Economic and Regulatory Aspects

7.6 Conclusion

References

Chapter 8: Suspension Culture of Plant Cells Under Phototrophic Conditions

8.1 Introduction

8.2 BryoTechnology™: Production of Biologics with Moss (Physcomitrella patens)

8.3 The LEX-System: Production of Biologics with Duckweed (Lemna minor)

8.4 Key Factors Related to Process Economics

8.5 Regulatory Aspects

References

Part III: Suspension Culture of Protozoa, Insect Cells, Avian Cells, and Mammalian Cells

Chapter 9: Suspension Culture of Protozoan Organisms

9.1 Introduction

9.2 Ciliates

9.3 Flagellates

9.4 Regulatory Aspects of Protozoan Production Organism

9.5 Summary and Outlook

References

Chapter 10: Industrial Large Scale of Suspension Culture of Insect Cells

10.1 History

10.2 Concepts in Insect Cell Culture

10.3 Regulatory Hurdles for Insect Derived Human Products

10.4 What Comes Next?

References

Chapter 11: Avian Suspension Culture Cell Lines for Production of Vaccines and Other Biologicals

11.1 Development of Cell Culture for the Production of Vaccines and Biologicals

11.2 Avian Cell Lines

11.3 Potential of Avian Cell Lines for the Manufacture of Vaccines and Biologicals

11.4 Development of Avian Cell Lines

11.5 Basic Process Design Aspects

11.6 Basic Bioreactor Design Aspects

11.7 Key Factors Related to Process Economics

11.8 Regulatory Aspects

11.9 Summary and Outlook

References

Chapter 12: Large Scale Suspension Culture of Mammalian Cells

12.1 Introduction to Mammalian Cell Culture1

12.2 Cell Lines and Expression Technologies2

12.3 Bioreactor Design3

12.4 Process Operation4

12.5 Process Economics of Mammalian Cell Culture5

12.6 Regulatory Aspects6

12.7 Summary and Outlook7

References

Part IV: Suspension Culture for Special Products

Chapter 13: Pillars of Regenerative Medicine: Therapeutic Human Cells and Their Manufacture

13.1 Introduction

13.2 Autologous Therapies

13.3 Allogeneic Therapies

13.4 Downstream Processing

13.5 Key Factors Towards Economic Success

13.6 Regulatory Considerations

13.7 Summary and Outlook

Acknowledgements

References

Chapter 14: Virus Production Under Suspension Conditions

14.1 Introduction

14.2 Adherent versus Suspension Culture for Virus Production

14.3 Polio Virus/Vaccines

14.4 Influenza Virus/Vaccines

14.5 Modified Vaccinia Ankara (MVA) Production in Suspension Cell Lines

14.6 Production of Viruses for Gene Therapy Purpose

14.7 Other Viruses

14.8 Concluding Remarks

References

Chapter 15: Cultivable Marine Organisms as a Source of New Products

15.1 Introduction

15.2 Substances of Interest Isolated from Archaea and Prokaryotes

15.3 Substances of Interest Isolated from Unicellular Eukaryotes

15.4 Substances of Interest Isolated from Microorganisms Associated with Pluricellular Organisms

15.5 Substances of Interest Produced by Sponge Cell Culture

15.6 Substances of Interest Isolated by Culture of Macroorganisms

15.7 Conclusion and Future Prospects

References

Index

End User License Agreement

List of Tables

Table 1.1

Table 1.2

Table 1.3

Table 1.4

Table 1.5

Table 1.6

Table 1.7

Table 1.8

Table 1.9

Table 1.10

Table 1.11

Table 1.12

Table 1.13

Table 1.14

Table 2.1

Table 2.2

Table 2.3

Table 2.4

Table 2.5

Table 2.6

Table 2.7

Table 2.8

Table 2.9

Table 2.10

Table 2.11

Table 2.12

Table 3.1

Table 3.2

Table 4.1

Table 4.2

Table 6.1

Table 6.2

Table 6.3

Table 6.4

Table 6.5

Table 7.1

Table 7.2

Table 7.3

Table 8.1

Table 8.2

Table 9.1

Table 9.2

Table 9.3

Table 9.4

Table 9.5

Table 10.1

Table 10.2

Table 10.3

Table 11.1

Table 11.2

Table 11.3

Table 12.1

Table 12.2

Table 12.3

Table 12.4

Table 12.5

Table 12.6

Table 12.7

Table 13.1

Table 13.2

Table 13.3

Table 14.1

Table 14.2

Table 14.3

Table 14.4

Table 14.5

Table 14.6

Table 15.1

Table 15.2

Table 15.3

Table 15.4

Table 15.5

Table 15.6

Table 15.7

Table 15.8

List of Illustrations

Figure 1.1

Figure 1.2

Figure 1.3

Figure 1.4

Figure 1.5

Figure 1.6

Figure 1.7

Figure 1.8

Figure 1.9

Figure 1.10

Figure 1.11

Figure 1.12

Figure 1.13

Figure 1.14

Figure 1.15

Figure 1.16

Figure 1.17

Figure 1.18

Figure 2.1

Figure 2.2

Figure 2.3

Figure 2.4

Figure 2.5

Figure 2.6

Figure 2.7

Figure 2.8

Figure 3.1

Figure 3.2

Figure 3.3

Figure 3.4

Figure 3.5

Figure 3.6

Figure 3.7

Figure 3.8

Figure 3.9

Figure 3.10

Figure 3.11

Figure 3.12

Figure 4.1

Figure 4.2

Figure 4.3

Figure 4.4

Figure 5.1

Figure 6.1

Figure 6.2

Figure 6.3

Figure 6.4

Figure 7.1

Figure 7.2

Figure 7.3

Figure 7.4

Figure 7.5

Figure 7.6

Figure 7.7

Figure 7.8

Figure 7.9

Figure 7.10

Figure 7.11

Figure 7.12

Figure 7.13

Figure 7.14

Figure 8.1

Figure 8.2

Figure 8.3

Figure 8.4

Figure 8.5

Figure 8.6

Figure 8.7

Figure 8.8

Figure 8.9

Figure 8.10

Figure 8.11

Figure 9.1

Figure 9.2

Figure 9.3

Figure 9.4

Figure 9.5

Figure 9.6

Figure 9.7

Figure 9.8

Figure 9.9

Figure 9.10

Figure 9.11

Figure 9.12

Figure 9.13

Figure 9.14

Figure 9.15

Figure 9.16

Figure 10.1

Figure 10.2

Figure 11.1

Figure 11.2

Figure 12.1

Figure 12.2

Figure 12.3

Figure 12.4

Figure 12.5

Figure 12.6

Figure 12.7

Figure 12.8

Figure 13.1

Figure 13.2

Figure 13.3

Figure 13.4

Figure 13.5

Figure 13.6

Figure 14.1

Figure 14.2

Figure 14.3

Figure 14.4

Figure 15.1

Figure 15.2

Figure 15.3

Figure 15.4

Figure 15.5

Figure 15.6

Figure 15.7

Figure 15.8

Figure 15.9

Figure 15.10

Guide

Cover

Table of Contents

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Industrial Scale Suspension Culture of Living Cells

Edited by

Hans-Peter Meyer

Diego R. Schmidhalter

Limit of Liability/Disclaimer of Warranty: While the publisher and author have used their best efforts in preparing this book, they make no representations or warranties with respect to the accuracy or completeness of the contents of this book and specifically disclaim any implied warranties of merchantability or fitness for a particular purpose. No warranty can be created or extended by sales representatives or written sales materials. The Advice and strategies contained herein may not be suitable for your situation. You should consult with a professional where appropriate. Neither the publisher nor authors shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages.

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© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Boschstr. 12, 69469 Weinheim, Germany

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Foreword

Biotechnology has the potential to move our economy to prosperity and sustainability. Today, this “bioeconomy” is estimated to be worth over 2 trillion euros, providing over 20 million jobs and accounting for 9% of the European Union's total employment. And as the editors of this volume point out, the industrial-scale suspension culture already has global annual sales of over $250 billion, with products ranging from pharmaceuticals, cosmetics, chemicals, industrial enzymes, food, dietary supplements, and feed products.

Especially in the context of climate change, the world's growing population will need a safe and secure supply of food, water, and energy. We must move toward processing systems that can produce more with fewer inputs, less environmental impact, and reduced greenhouse gas emissions. Bio-based industries can play a significant role in this transition toward a more resource-efficient society.

The bioeconomy can only thrive within an environment of intense basic and applied research and efficient innovation. Challenges include scaling up processes and improving quality control, taking into account both risks and benefits. Process standardization, harmonization of standards, and regulation are essential to support the creation of new markets and opportunities. This volume is a welcome contribution to this endeavor.

The scale up of production traditionally lies outside the research portfolio of universities and has to be taken up by the relevant industries. Of course, the large-scale suspension culture is old and well established; after all beer and wine have been around for thousands of years, and the Reinheitsgebot of 1487 defining beer production is probably the oldest biotechnology regulation. Yet academia has a critical role to play in developing cutting-edge technologies for the large-scale suspension culture. Harnessing the astonishing chemical creativity of plants to produce structurally complex metabolites and bioplastics and developing new protein expression systems (in insect, avian, or protozoan cells) are currently budding areas of research. Synthetic biology, until recently a futuristic dream, has now become a toolbox that will soon be central to manufacturing.

Stem cell technology is another recent development. But to become relevant in the clinic, issues involving scalability, safety, and cost of production still have to be settled. The same can be said about the production of vaccines and viral vectors for gene therapy. Moving forward, innovation in processing technology and bioreactor design for scalable, fully-controlled manufacturing processes will be paramount, and there is ample room for collaboration between industry and academia.

Until now, suspension culture has utilized bacteria, yeast, and filamentous fungi. In the twenty-first century, the biotechnology revolution will broaden its scope, benefitting many people around the world.

Lausanne, March 2014

Patrick Aebischer

President of Swiss Federal Institute of Technology in Lausanne (EPFL)

Preface

Why did we decide to edit this book? Both of us have been active in the biotechnology industry for more than 30 years. We have experienced exciting times, and have been personally involved in the production of recombinant proteins and other products using many different eukaryotic and prokaryotic organisms. During our professional careers, the commercial importance of biotechnology has probably grown by at least an order of magnitude, and it is still growing. Biotechnology affects practically all areas of our lives. Biotechnology can also provide sustainable solutions for many problems that a growing global population is facing today and will face tomorrow. We both have often wondered, how the industry looks in detail, and how it will develop in the future.

The idea for the book actually came from a book chapter we wrote together on the relevance of “microbial expression systems and manufacturing from a market and economic perspective.” We compared different expression systems and realized how little is known about which systems manufacturing industry is using, and how they value the different suspension culture methods. At least 95% of all applications use large-scale cell suspension culture, the remaining 5% are mainly genetically engineered crops. During one of our opulent monthly brainstorming lunches, which always comes with an excellent bottle of wine, we decided to try to assemble a group of industrial and academic authors who would be prepared to share their views with us. It was not an easy task, but we believe we have succeeded, and it was a pleasure to see how the academic and industrial contributors finally struggled constructively together in writing industrially relevant chapters.

Submersed production of organisms in sterile containments or fermenters has become the standard manufacturing process and it will remain the gold standard for quite some time to come. This book therefore addresses submersed cell culture and fermentation, and its importance for the manufacturing industry. It goes beyond expression systems and integrally investigates all those factors relevant for manufacturing using suspension cultures. One of the key features of the book is that it covers all suspension cultivation methods in a comprehensive and comparative manner in a single volume.

The book focuses on the industrial and manufacturing world, with a majority of contributing authors coming from industry. To make reading easier, each chapter has a similar structure. Depending on the maturity of the technology, the chapters address in turn the expression system, basic process design, key factors affecting process economics, plant and bioreactor design, and regulatory aspects.

After an introduction on the history and economic relevance of industrial scale suspension culture of living cells, the chapters are separated into four groups:

Suspension culture of bacteria, yeast, and filamentous fungi

Suspension culture of algae and plant cells

Suspension culture of protozoa, insect cells, avian cells, and mammalian cells

Suspension culture for special products

An important feature of the book is that the majority of the authors are from the industry itself. The reader therefore gets a “real picture” of what is going on in the manufacturing world.

The book should serve as an overview and guidance for advanced students and other academics interested in industrial aspects of cell and microbial cultivation, and for product developers and others interested in different modes of sterile suspension cultures and fermentations of industrial or commercial interest. We really hope you will enjoy the book as a valuable contribution and we would appreciate any constructive comments you might have.

Lonza AG, Switzerland, March 2014

Hans-Peter Meyer

Diego R. Schmidhalter

List of Contributors

Patrick Aebischer

President of EPFL

École Polytechnique Fédérale de

Lausanne

Centre Est, Station 1

1015 Lausanne

Switzerland

Richard M. Alldread

National Biologics Manufacturing Centre

Centre for Process Innovation (CPI)

Wilton Centre, Wilton

Redcar

Cleveland, TS10 4RF

UK

Paula Alves

ITQB-UNL

Av. República-EAN

2780-157 Oeiras

Portugal

and

IBET

Apartado 12

2781-901 Oeiras

Portugal

Wilfried A.M. Bakker

Intravacc – Institute for Translational Vaccinology

Antonie van Leeuwenhoeklaan 9

Bilthoven, 3721 MA

The Netherlands

P. Noel Barrett

Baxter Bioscience

Vaccine R&D

Uferstrasse 15

2304 Orth/Donau

Vienna

Austria

Peter Bergmann

Environmental Biotechnology and Bioprocess Engineering