Upstream Industrial Biotechnology, 2 Volume Set E-Book

Michael C. Flickinger

• Herausgeber: John Wiley & Sons
• Kategorie: Fachliteratur
• Sprache: Englisch

Seitenzahl: 5556

Veröffentlichungsjahr: 2013

Beschreibung

Biotechnology represents a major area of research focus, and many universities are developing academic programs in the field. This guide to biomanufacturing contains carefully selected articles from Wiley's Encyclopedia of Industrial Biotechnology, Bioprocess, Bioseparation, and Cell Technology as well as new articles (80 in all,) and features the same breadth and quality of coverage and clarity of presentation found in the original. For instructors, advanced students, and those involved in regulatory compliance, this two-volume desk reference offers an accessible and comprehensive resource.

Leseprobe

Table of Contents

Title Page

Copyright

Preface

Contributors

Volume I: Expression Systems & Process Development

Part I: Introduction

Introduction

Part II: Industrial Cell Growth and Gene Expression Systems

Chapter 1: Animal Cells, Suspension Culture

1.1 Introduction

1.2 Types Used for Large-Scale Production in Suspension Culture

1.3 Suspension Culture Reactors

1.4 Operating Modes for Reactors

1.5 Process Monitoring and Control

1.6 Culture Media for Suspension Culture

1.7 Conclusions

References

Further Reading

Chapter 2: Baculovirus Expression Systems

2.1 Introduction

2.2 Baculovirus Structure and Replication

2.3 Production of Recombinant Baculoviruses

2.4 Baculovirus Transfer Vectors

2.5 Modifying the Baculovirus Genome to Improve Protein Production

2.6 Insect Cell Culture

2.7 Baculoviruses for Gene Expression in Mammalian Cells

2.8 Conclusion

References

Chapter 3: Baculovirus Kinetics, Insect Culture

3.1 History and Challenge

3.2 Baculovirus

3.3 Cell Yield Concept

3.4 Kinetic Model of Viral Infection: Synchronous Infection

3.5 Kinetic Model of Viral Infection: Asynchronous Infection

References

Chapter 4: Cell Culture, Aseptic Techniques

4.1 Introduction

4.2 Aseptic Technique: General Considerations

4.3 Aseptic Technique: Basic Procedures

4.4 HEPA Filtration

4.5 Hoods and Cabinets Employing HEPA Filtration

4.6 Working Within Unidirectional Airflow Cabinets and Microbiological Safety Cabinets

4.7 Testing of Class I and Class II Microbiological Safety Cabinets

4.8 Cleanrooms for Cell Culture Use

References

Chapter 5: Cell Cycle in Bioprocesses

5.1 Introduction

5.2 The Cell Cycle

5.3 Methods for Describing the Cell Cycle

5.4 Importance of the Cell Cycle in Process Biotechnology

References

Chapter 6: Cell Growth and Protein Expression Kinetics

6.1 Introduction

6.2 Batch Culture Kinetics

6.3 Continuous Culture Kinetics

6.4 Fed-Batch and Perfusion Cultures

6.5 Conclusions

Nomenclature

References

Chapter 7: Cell Viability Measurement

7.1 Introduction

7.2 Permeability Assays

7.3 Functional Assays

7.4 Flow Cytometry

7.5 Physical Methods

References

Chapter 8: Contamination Detection in Animal Cell Culture

8.1 Introduction

8.2 Historical Perspectives

8.3 Regulatory Issues

8.4 Manufacturing and Safety Testing Standards

8.5 Examples of Viral Contaminants

8.6 Detection of Viral Contaminants in Cell Lines

8.7 Testing Raw Materials

8.8 Detection of Mycoplasmas

8.9 Bacteria and Fungi

8.10 Oxygen Uptake Rate

8.11 Endotoxin Detection

8.12 Statistical Analysis

8.13 Detection of Prions

8.14 Summary

References

Chapter 9: Culture Collections and Biological Resource Centers (BRCs)

9.1 Introduction

9.2 Culture Collection Funding

9.3 Operation

9.4 Quality Management

9.5 Services

9.6 Summary

References

Further Reading

Chapter 10: Culture Preservation

10.1 Introduction

10.2 Culture and Preservation of Bacteria

10.3 Culture and Preservation of Fungi and Yeast

10.4 Culture and Preservation of Cell Cultures

References

Chapter 11: Expression and Secretion of Heterologous Proteins, Bacillus and Other Gram-Positive Bacteria

11.1 Introduction

11.2 Major Industrial Strains

11.3 Bacillus Megaterium

11.4 Protocols for Bacillus Megaterium

References

Chapter 12: Gene Expression in Human Cells

12.1 Background

12.2 The Safety and Regulatory Aspects of Using Human Cell Lines for Gene Expression

12.3 Gene Expression in Human Cell Lines

12.4 Scale-Up of Recombinant Human Cell Lines Cultivation

12.5 Concluding Remarks

References

Chapter 13: Gene expression in Pichia and other methylotroph yeast

13.1 Introduction

13.2 Background

13.3 Strategies for Optimization of Protein Expression

13.4 Fermentation Process

13.5 Conclusions and Future Perspectives

13.6 Media Compositions

13.7 Glossary of P. Pastoris Strains

References

Further Reading

Chapter 14: Gene Expression in Recombinant Animal Cells and Transgenic Animals

14.1 Introduction

14.2 Overview

14.3 Plasmid Expression Vectors for Animal Cells

14.4 Other Direct Transfer Vectors

14.5 Direct DNA Transfer

14.6 Transfection Methods

14.7 Viral Expression Vectors

14.8 Expression Parameters And Optimization—Vector And Insert Sequences

14.9 Expression Parameteroptimization—Consequences of Transgene Integration

14.10 Recombination-Based Methodology and Gene Inhibition Strategy

14.11 The Production of Transgenic Mammals from Manipulated Cells

14.12 Uses for Transgenic Animals

14.13 Nuclear Transfer Technology

References

Chapter 15: Inoculum Expansion Methods, Animal Cell Lines

15.1 Introduction

15.2 Inoculum Expansion Processes

15.3 Impact of Cell Banks on Inoculum Expansion

15.4 Current Trends in Inoculum Expansion

15.5 Technology Transfer

15.6 Conclusion

15.7 Product Websites

References

Further Reading

Chapter 16: Insect Cell Culture

16.1 Introduction

16.2 Insect Cell Lines

16.3 Viruses

16.4 Baculovirus Gene Expression

16.5 Construction of Recombinant Baculoviruses

16.6 Posttranslational Processing

16.7 Applications

16.8 Large-Scale Processing: Cell Culture or Larval Production

16.9 Conclusion

References

Chapter 17: Kinetics of Microbial Growth

17.1 Introduction

17.2 Growth Stoichiometry

17.3 Kinetics of Chemical and Enzyme Reactions

17.4 Simple Models of Microbial and Cell Growth

17.5 Structured Models

17.6 Population Dynamics (Mutations, Autoselection, Plasmid Transfer)

17.7 Microbial Growth in Various Cultivation Systems

References

Chapter 18: Microalgae, Mass Culture Methods

18.1 Introduction

18.2 Bioreactors for Microalgae Mass Cultures

18.3 MAJOR FACTORS GOVERNING THE PRODUCTION OF MICROALGAE

18.4 Tubular Photobioreactors Design

18.5 Photosynthetic Efficiency in Microalgal Mass Cultures

18.6 Operational Considerations

18.7 Concluding Remarks

Nomenclature

References

Chapter 19: Microbial Growth Measurement

19.1 Introduction

19.2 Direct Particle Counts

19.3 Colony Counts Equal Viable Counts

19.4 Direct Biomass Measurements

19.5 Biomass By Light Scattering

19.6 Sampling

References

Chapter 20: Microbial Media Composition

20.1 Introduction

20.2 Essential Nutritional Requirements

20.3 Physical Parameters

20.4 Media Design and Composition

20.5 Media Sterilization

20.6 Media Storage

References

Chapter 21: Microscopic Characterization of Cells

21.1 Introduction and Perspective

21.2 Developments and Milestones in Microscopy

21.3 Light Microscopy

21.4 Laser Tweezers and Scissors

21.5 Scanning-Probe Near-Field Microscopes

21.6 Video Microscopy and Image Processing

21.7 Electron Microscopes

21.8 Summary

21.9 Web Sites

References

Chapter 22: Mycoplasma Contamination Of Cell Cultures

22.1 Biology and Nomenclature of Mycoplasmas

22.2 Mycoplasma Contamination of Cell Cultures

22.3 Detection of Mycoplasma Contamination

22.4 Elimination of Mycoplasma Contamination

22.5 Working Protocols for Detection, Elimination, and Prevention of Mycoplasma Contamination

References

Chapter 23: Protein Glycosylation: Analysis, Characterization, and Engineering

23.1 Introduction

23.2 Overview of Protein Glycosylation

23.3 Effects of Glycosylation on Proteins

23.4 Techniques for Analyzing Glycoproteins, Glycopeptides, and their Attached Glycans

23.5 Glycosylation of Recombinant Protein Therapeutics

23.6 Conclusions

References

Chapter 24: Secretion of Heterologous Proteins, Gram Positive Bacteria

24.1 Protein Secretion Via the General Export Pathway in Gram-Positive Bacteria

24.2 Secretion of Heterologous Proteins in L. Lactis

24.3 Expression Systems

24.4 Protein Secretion in L. Lactis

24.5 Conclusion

References

Chapter 25: Soluble Protein Expression in Bacteria

25.1 Introduction

25.2 Altering Growth Conditions to Increase Soluble Expression

25.3 Altering the Host Strain and Vector to Direct Soluble Expression

25.4 Altering the Protein Sequence for Solubility

25.5 Growth Conditions and Variables That Affect Yields of Soluble Protein

25.6 Conclusions and Outlook

References

Further Reading

Part III: Media, cell lines and process development

Chapter 26: Animal Cell Culture Media

26.1 Introduction

26.2 Nutrients in Cell Culture Media

26.3 Basal Medium Development

26.4 Feed Medium Development

26.5 Product Quality

26.6 Use of Appropriate Small-Scale Model and High Throughput Systems

26.7 Industrial Considerations for The Optimization and Implementation of Basal and Feed Media

26.8 Concluding Remarks

References

Chapter 27: Animal Cell Culture, effects of Osmolality and Temperature

27.1 Effect of Osmolality of the Cellular Microenvironment

27.2 Effects of Temperature Perturbations on Cellular Physiology and Performance in Bioprocess Systems

27.3 Conclusions

References

Chapter 28: Animal Cell Stability

28.1 Factors That Affect Genetic Stability of Endogenous Genes

28.2 Genotypic and Phenotypic Stability of Recombinant Cell Lines

28.3 Consequences of Genetic Instability on Recombinant Protein Quality

28.4 Genotypic Characterization and Validation of Genetic Stability

References

Chapter 29: Animal Cell Types, Hybridomas

29.1 Introduction

29.2 Antibody Production by Animal Cells In Vitro

29.3 New Methods for Human Antibody Production (In Vitro Immunization, Artificial Lymph Node Systems)

29.4 Alternatives to Antibodies for Use in Human Beings

29.5 Outlook

References

Further Reading

Chapter 30: Antibody Production, Human Recombinant

30.1 Introduction

30.2 Why Recombinant Antibody Selection and Production?

30.3 Making Hybridoma-Derived Antibodies More Human

30.4 Obtaining Human Recombinant Antibodies

30.5 Production of Recombinant Antibodies

30.6 Recombinant Antibody Variants

30.7 Applications of Recombinant Antibodies

30.8 Outlook

Further Reading

Reviews

Remark: this chapter is based on and/or contains materials derived from of other chapters written by the same author in detail:

Chapter 31: Antifoams and Pluronic Polyols, Cell Protection

31.1 Introduction

31.2 Properties of Pluronic Polyols

31.3 Protective Effects of Pluronic Polyols

31.4 Application

References

Chapter 32: Biominiaturization of Bioreactors

32.1 Introduction

32.2 Bioreactor Monitoring Tools

32.3 Static Bioreactor Systems

32.4 Microfabricated Reactors

32.5 Shaken Bioreactor Systems

32.6 Stirred Bioreactor Systems

32.7 Bioreactors

32.8 Other Methods Of Convective Mixing

32.9 Conclusion

References

Chapter 33: Inoculum Preparation

33.1 Introduction

33.2 Culture Storage

33.3 Stock Culture

33.4 Culture Assessment

33.5 Inoculum Development

33.6 Inoculation/Seed Transfer Criteria

33.7 Inoculum Preparation Studies

33.8 Inoculum Development Summary

References

Chapter 34: Microcarrier Culture

34.1 History and Development

34.2 Cell Cultivation

34.3 Microcarriers in Vaccine Production

34.4 Microcarriers in Recombinant Protein Production

34.5 Future Directions in Microcarrier Culture

34.6 Conclusions

References

Chapter 35: Monoclonal Antibody Production, Cell Lines

35.1 Introduction

35.2 Role of The Cell Line

35.3 Properties Of Most-Commonly Used Mammalian Cell Lines and Vector Systems

35.4 Other Host Platforms

35.5 Closing Comments

References

Chapter 36: Plant Cell Culture, Laboratory Techniques

36.1 Introduction

36.2 Laboratory Facilities

36.3 Plant Cell Culture Media

36.4 Cell Culture Systems

36.5 Summary

References

Further Reading

Chapter 37: Scale-Up of Biotechnological Processes

37.1 Introduction

37.2 Dimensional Analysis

37.3 The Pi Theorem

37.4 Determination of a Pi Set by Matrix Calculation

37.5 Fundamentals of the Theory of Models and of Scale-Up

37.6 Further Procedures to Establish A Relevance List

37.7 Short Summary of the Essentials of the Dimensional Analysis and Scale-Up

37.8 Treatment of Variable Physical Properties by Dimensional Analysis

37.9 Dimensional Analytical Treatment of Heat Transfer Processes

37.10 DIMENSIONAL ANALYTICAL TREATMENT OF MASS TRANSFER PROCESSES

References

Volume II: Equipment, Process Design, Sensing, Control, and cGMP Operations

Part IV: Bioreactor design, engineering, process sensing and control

Chapter 38: Aeration, Mixing, and Hydrodynamics in Animal Cell Bioreactors

38.1 Introduction

38.2 Aeration

38.3 Mixing

38.4 THE RELATIONSHIP OF ANIMAL CELLS TO HYDRODYNAMIC FORCES

38.5 Summary

References

Chapter 39: Biocatalytic Membrane Reactors

39.1 Introduction

39.2 Fundamentals

39.3 Membrane Reactor Configurations

39.4 Applications

39.5 Other membrane bioreactor applications

39.6 Conclusions

References

Chapter 40: Bioreactor Scale-Down

40.1 The Scale-Down Approach

40.2 Regime Analysis

40.3 Simulation

40.4 Optimization and Modeling

40.5 Application

40.6 Scale-Down Studies in Microbial Fermentations

40.7 Experimental Configurations for Scale-Down Studies

40.8 Simulation of Substrate or pH Gradients

40.9 Simulation of Simultaneous Environmental Gradients

Nomenclature

References

Chapter 41: Bioreactor Scale-Up*

41.1 Introduction

41.2 Aspect Ratio, Homogeneity, and Gradients

41.3 Heating and Cooling

Nomenclature

References

Chapter 42: Bioreactors: Airlift Reactors

42.1 Introduction

42.2 Fluid Dynamics

42.3 Mass Transfer

42.4 Heat Transfer

42.5 Multiphase Airlift Bioreactors

42.6 Selection and Design

42.7 Models

42.8 Bioprocesses

42.9 Summary

List of Abbreviations

Nomenclature

References

Chapter 43: Bioreactors, Continuous Culture of Plant Cells

43.1 Introduction

43.2 Assumptions in Continuous Culture Theory and their Pitfalls

43.3 The Practical Setup of a Continuous Culture

43.4 Mathematical Description of Continuous Culture

43.5 Applications of the Continuous Cultivation of Plant Cells

Nomenclature

References

Chapter 44: Bioreactors, Fluidized-Bed

44.1 History and Introduction

44.2 Plant Conception and Operation

44.3 Scale-Up Considerations

44.4 Modeling and Simulation

44.5 Praxis Examples

Nomenclature

References

Chapter 45: Bioreactors, Gas-Treatment

45.1 Introduction

45.2 Microorganisms and Applications

45.3 Bioreactor Types

45.4 Bioreactor Design

Nomenclature

References

Chapter 46: Bioreactors, Perfusion

46.1 Introduction

46.2 Cell Retention Based on Filtration

46.3 Cell Retention Based on Sedimentation

46.4 Conclusion

References

Chapter 47: Bioreactors: Rotating Biological Contactors

47.1 Introduction

47.2 Background

47.3 Conclusions and Prospects

References

Chapter 48: Bioreactors, Stirred Tank for Culture of Plant Cells

48.1 Products From Suspended Plant Cell Cultures

48.2 Properties of Suspended Plant Cell Cultures: Implications for Bioreactor Engineering

48.3 Suitability of Stirred Bioreactors for Suspended Plant Cell Culture

48.4 Stirred Tank Equipment and Operating Characteristics

48.5 Plant Cell Culture in Stirred Bioreactors: Experimental Findings

48.6 Plant Cell Culture in Stirred Bioreactors: Theoretical Analysis

48.7 Conclusions

Nomenclature

References

Chapter 49: Cell Immobilization, Engineering Aspects

49.1 Introduction

49.2 Internal Mass Transport

49.3 External Mass Transport

49.4 Reaction and Diffusion

References

Chapter 50: Fermenter/Bioreactor Design

50.1 Introduction

50.2 Safety and Regulatory Compliance

50.3 Design Basis and Other General Considerations

50.4 Process Requirements: Basics

50.5 Mechanical Design

50.6 Conclusion

References

Chapter 51: Gas-Holdup in Bioreactors

51.1 Basic Definitions

51.2 Biotechnological Relevance

51.3 What determines gas holdup?

51.4 Physico-chemical effects

51.5 Measurement Techniques

References

Chapter 52: Immobilization of Proteins and Enzymes, Mesoporous Supports

52.1 Introduction

52.2 Immobilization of Proteins on Mesoporous Silicas and Carbons

52.3 Conclusions and Outlook

References

Chapter 53: Immobilized Cells

53.1 Introduction

53.2 Cell Immobilization: Carriers and Techniques

53.3 Microencapsulation of Cells

53.4 Requirements for Cell Immobilization

53.5 Biomaterials for Cell Immobilization

53.6 Techniques for Cell Immobilization

53.7 Effects of Immobilization on Cells

53.8 Reactor Design

53.9 Conclusions

References

Further Reading

Chapter 54: Immobilized Enzymes

54.1 Introduction

54.2 Immobilized Enzymes as Catalysts of Industrial Chemical Processes

54.3 Current Industrial Applications of Immobilized Enzymes

54.4 Immobilization Protocols

54.5 Adsorption of Industrial Enzymes on Ionic Exchangers

54.6 Selective Adsorption of Lipases on Hydrophobic Supports

54.7 Bioaffinity Immobilization

54.8 Covalent Immobilization

54.9 Immobilized Enzymes Without Supports

54.10 Improvement of Enzyme Properties by Immobilization Techniques

54.11 Modulation of Selectivity of Lipases by Using Different Immobilization Methods

54.12 Future Prospects: Immobilization of Enzymes Acting on Insoluble Substrates

54.13 Concluding Remarks

References

Chapter 55: Impeller Selection, Animal Cell Culture

55.1 Introduction

55.2 The Most Important Aspects Impacting Impeller Selection

55.3 Oxygen Transfer Considerations

55.4 “Shear Sensitivity” To Impeller-Generated Fluid Dynamic Stresses

55.5 Other Parameters Dependent on Agitation and Bioreactor Configuration: Implications for Impeller Selection

55.6 Important Parameters Not Related to Impeller Selection

55.7 Selection of Impeller/Geometry, Scale-Up, and Operational Strategy

Nomenclature

References

Chapter 56: Mammalian Cell Bioreactors

56.1 Introduction

56.2 Basic Reactor Operation and Kinetics

56.3 Cell Support for Mixing Vessels

56.4 Cell Culture Bioreactors

56.5 Concluding Remarks

References

Chapter 57: Mammalian Cell Culture Reactors, Scale-Up

57.1 Introduction

57.2 Background

57.3 Reactors for ADCs

57.4 Reactors for Suspension Cells

57.5 High-Cell-Density Bioreactors

57.6 Comparisons, Conclusions, and Future Developments

References

Chapter 58: Mass Transfer

58.1 Introduction

58.2 Diffusion Coefficient or Diffusivity

58.3 Gas–Liquid Mass Transfer

58.4 Liquid–Liquid Mass Transfer

58.5 Solid–Liquid Mass Transfer

58.6 Mass Transfer Behavior

Nomenclature

References

Chapter 59: Oxygen Transfer Rate Determination Methods

59.1 Introduction

59.2 Experimental Determination of kLa

59.3 Comparison of kLa Values Obtained by Different Methods

59.4 Correlation of kLa Values

59.5 A General Method for OTR Prediction

59.6 OTR in Miniature Bioreactors (Mini- and Micro- Devices)

59.7 Conclusion

Nomenclature

References

Chapter 60: Photobioreactors

60.1 Introduction

60.2 Photobioreactor Categories

60.3 Large Scale Commercial Photobioreactors

60.4 Concluding Remarks and Prospects

60.5 Conclusions

References

Chapter 61: Rheological Behavior of Fermentation Fluids

61.1 Introduction

61.2 Rheological Models

61.3 Rheometry

61.4 Exo-Biopolymer Fermentations

61.5 Mycelial Fermentations

61.6 Mixing

61.7 Conclusion

Nomenclature

References

Chapter 62: Rheology of Filamentous Microorganisms, Submerged Culture

62.1 Introduction

62.2 Rheological Measurements in Filamentous Fermentation Broths

62.3 Rheological Models

62.4 Viscosity as an Engineering Problem in Filamentous Fermentations

62.5 Viscosity as a Function of Suspension Characteristics

62.6 Control of the Rheological Properties of Filamentous Fermentation Broths

62.7 Equipment Used for Measuring Rheological Properties of Non-Newtonian Broths

62.8 Conclusion

Nomenclature

References

Chapter 63: Sampling and Sample Handling for Process Control

63.1 Sampling

63.2 Chemical Means

63.3 Physical Means

63.4 Chemical Means

63.5 Sampling from Gas Phase

63.6 Representative Samples

63.7 Reproducibility in Sampling

63.8 Sample Handling

63.9 Noninvasive Monitoring Methods

63.10 Integrated Processes

63.11 Commercial Systems

63.12 Conclusion

References

Chapter 64: Solid State Fermentation, Kinetics

64.1 Introduction

64.2 Aims of This Chapter

64.3 Organization and Scope

64.4 Description of Key Features of Solid-State Fermentation

64.5 Modeling of Microbial Phenomena

64.6 Modeling of Local Transport Phenomena

64.7 Modeling of Bulk Transport Phenomena

64.8 Parameter Estimation

64.9 Summary and Needs for the Future

References

Chapter 65: Solid Substrate Fermentation, Automation

65.1 Introduction

65.2 Measurement and Control of Critical Operating Variables

65.3 Automatic Control Strategies for Commercial-Scale Ssf Bioreactors

65.4 Case Study: Automation of a Pilot Packed Bed Bioreactor with Periodic Mixing

References

Further Reading

Chapter 66: Stainless Steels

66.1 The Nature of Stainless Steels

66.2 Types of Stainless Steels

66.3 Corrosion Mechanisms

66.4 Corrosion Susceptibility of Stainless Steels

66.5 Forms of Localized Corrosion

66.6 Factors Contributing to Localized Corrosion

66.7 Prevention of Localized Attack

66.8 Remedial Measures

66.9 Standard Operating Procedures

References

Chapter 68: Static Mixing, Fermentation Processes

67.1 Introduction

67.2 Structural Types and Construction

67.3 Effects of Static Mixers on Momentum Transfer

67.4 Mass Transfer in Presence of Static Mixers

67.5 Heat Transfer Using Static Mixers

67.6 Scale-up Considerations

67.7 Concluding Remarks

Nomenclature

References

Chapter 68: Transfer Phenomena in Multiphase Systems

68.1 Introduction

68.2 Description of the Modified Rushton Turbine Agitators

68.3 Multiphase System Hydrodynamics

68.4 Mass Transfer

68.5 Performance of the Modified Agitators in Biosynthesis of Antibiotics

References

Part V: Process analytical technologies (PAT)

Chapter 69: Bioprocess and Fermentation Monitoring

69.1 Introduction

69.2 General Aspects of Sensors and Monitoring

69.3 Methods of Monitoring

69.4 Sensor, Devices, and Technologies

69.5 Conclusion

References

Chapter 70: Flow Injection Analysis in Industrial Biotechnology

70.1 Introduction

70.2 Fundamentals of Flow Injection Analysis

70.3 SELECTED BIOANALYTICAL APPLICATIONS EXPLOITING FI

70.4 The Role of FI for Process Analysis/Monitoring

70.5 Fundamentals of Sequential Injection Analysis

70.6 Microfluidic Devices: Lab-on-Valve

70.7 Selected Bioanalytical Applications Exploiting SI-LOV

70.8 Conclusion and Perspectives

References

Chapter 71: Fluorescence Techniques for Bioprocess Monitoring

71.1 Introduction

71.2 Principles of On-Line Fluorescence Sensors for Bioprocess Monitoring

71.3 Application of On-Line 2D Fluorescence Spectroscopy

71.4 Conclusion

References

Chapter 72: Off-Line Analysis in Animal Cell Culture

72.1 Introduction

72.2 Analysis of Cell Density

72.3 Analysis of Medium Components

72.4 Analysis of Metabolic End Products

72.5 Analysis of Other Substances and Parameters

72.6 Analysis of Proteins

72.7 Analysis With Clinical Analyzers

Service Information

References

Chapter 73: Process Analytical Technology: Strategies For Biopharmaceuticals

73.1 Introduction

73.2 Pat Applications for Upstream Operations

73.3 Pat Applications in Harvest Operations

73.4 Pat Applications in Downstream Operations

73.5 Pat Applications in Drug Product Operations

73.6 Pat and Rapid Microbiological Methods

73.7 Applications of Chemometrics in Pat

73.8 Case Studies on Implementation of Pat

73.9 Conclusion and Future Perspective

References

Chapter 74: Vent Gas Analysis

74.1 Introduction

74.2 Methods of Vent Gas Analysis

74.3 Installation and Operation

74.4 Parameter Calculation

References

Part VI: Upstream cGMP operations

Chapter 75: Antibody Manufacture, Disposable Systems

75.1 Introduction

75.2 Single-Use Devices in Antibody Production Processes: An Overview

75.3 Disposable Bioreactors in MAb Production Processes

75.4 Conclusions and Apparent Trends

References

Chapter 76: Bioreactor Operations

76.1 Preparation

76.2 Sterilization

76.3 Charging

76.4 Culture Initiation

76.5 Harvesting

References

Chapter 77: Bioreactors, Cell Culture, Commercial Production

77.1 Introduction

77.2 Design of Bioreactors

77.3 Process Operations

77.4 Process Scale-Up for Production

77.5 Conclusions

Nomenclature

References

Chapter 78: Biotransformation, Process Optimization

78.1 Introduction

78.2 Whole Cells or Isolated Enzymes?

78.3 Classification of Different Reactors

78.4 Process Development Step by Step

78.5 Examples

References

Chapter 79: Foam Formation and Control in Bioreactors

79.1 An Overview of the Mechanisms of Foam Formation in Bioreactors

79.2 Description of the Foam at the Microscopic Level: Molecular Mechanisms at the Interfaces

79.3 Description of the Foam at the Macroscopic Level: Gas–Liquid Dispersion in the Reactor

79.4 Methods used to Evaluate the Foaming Properties of a Solution

79.5 Detection and Regulation of Foam in Bioprocesses

79.6 Chemical Methods Used to Prevent Foam

79.7 Physical Methods used to Prevent or Reduce Foam Formation in Bioreactors

79.8 Impact of Foam Formation and Prevention

79.9 Foam in Biotechnological Processes: Present Knowledge and Future Prospects

References

Chapter 80: Pilot Plants, Design and Operation

80.1 Introduction

80.2 Operational Concepts and Processing Requirements

80.3 Design

80.4 Operation

References

Chapter 81: Shear Sensitivity

81.1 Introduction

81.2 Shear Forces in Bioreactors

81.3 Response to Shear

81.4 Concluding Remarks

Nomenclature

Greek Symbols

References

Chapter 82: Sterilization and Decontamination, Bioprocess Equipment

82.1 Introduction

82.2 Sterilization by Heat

82.3 Filtration

82.4 Fumigation

82.5 Gamma Irradiation

82.6 Ultraviolet Light

82.7 Liquid Disinfectants

82.8 Virus Testing and Elimination from Biological Products

82.9 Prions

82.10 Regulatory and Safety Issues

References

Index

Copyright © 2013 by John Wiley & Sons, Inc. All rights reserved

Published by John Wiley & Sons, Inc., Hoboken, New Jersey

Published simultaneously in Canada

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, scanning, or otherwise, except as permitted under Section 107 or 108 of the 1976 United States Copyright Act, without either the prior written permission of the Publisher, or authorization through payment of the appropriate per-copy fee to the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, [phone], fax [phone], or on the web at www.copyright.com. Requests to the Publisher for permission should be addressed to the Permissions Department, John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, [phone], fax [phone], or online at http://www.wiley.com/go/permission.

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 may 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 author shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages.

For general information on our other products and services or for technical support, please contact our Customer Care Department within the United States at [phone], outside the United States at [phone] or fax [phone].

Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic formats. For more information about Wiley products, visit our web site at www.wiley.com.

Library of Congress Cataloging-in-Publication Data:

Upstream industrial biotechnology / edited by Michael C. Flickinger.

v. cm

nIcludes bibliographical references and index.

Contents: volume 1. Expression Systems and Process Development- volume 2. Equipment, Process Design, Sensing, Control and cGMP Operations.

ISBN 978-1-118-13123-7 (set : hardback) 1. Biotechnology. I. Flickinger, Michael C., editor of compilation. II. Encyclopedia of industrial biotechnology. Selections.

TP248.2.U675 2013

660.6--dc23

2012030697