Log In
Or create an account ->
Imperial Library
Home
About
News
Upload
Forum
Help
Login/SignUp
Index
Cover image
Title page
Table of Contents
Copyright
Contributors
Proverb
Preface
Section I: Healthcare and Biopharma Industry, Products and Processes
Chapter 1: Disease and Healthcare Priorities
Abstract
1.1 Introduction
1.2 Status and Measurement of Global Health
1.3 The World is Changing—Demographic Transition
1.4 The World is Changing—Disease Challenge Transition
1.5 Prevention—Health Risks and Their Mitigation
1.6 Priorities for Medicine Development
1.7 Additional Drivers and Challenges in Healthcare
Chapter 2: Brief Review of the Biopharmaceutical and Vaccine Industry
Abstract
2.1 Industrial Context
2.2 Brief History of the Biopharma Industry
2.3 Business Summary
2.4 Biopharma Business Challenges
2.5 Biopharma Pipeline—The Promise
Chapter 3: Selected Biotherapeutics Overview
Abstract
3.1 Introduction
3.2 Marketed Biopharmaceuticals by Molecule Category
3.3 Brief Business Review of Biopharmaceutical Therapeutics
3.4 Current R&D Pipeline of Biotherapeutics and Vaccines
3.5 Basic Processing Characteristics of Biotherapeutics
Chapter 4: Process Capability Requirements
Abstract
4.1 Introduction
4.2 Regulatory Requirements
4.3 Producing the Required Quality
4.4 Producing the Required Quantity
4.5 Product Yield
4.6 Pre-Clinical, Phase I to III Manufacturing, and Regular Production
Section II: Upstream Processes Principles and Methods
Chapter 5: Upstream Bioprocessing: Basic Concepts
Abstract
5.1 Introduction
5.2 Kinetic Models
5.3 A General Mass Balance
5.4 Cell Growth
5.5 Cell Death
5.6 Metabolic Concepts
5.7 Glucose, Glutamine, Lactate and Ammonia
5.8 Oxygen
5.9 Carbon Dioxide
5.10 Product Formation
5.11 Appendix
Chapter 6: Host Cells
Abstract
6.1 Cells in Biopharmaceutical Production
6.2 Animal Cell Culture
6.3 Microbial Systems
6.4 Other Production Systems
6.5 Outlook and Perspective
Appendix I The Hybridoma Technology and Humanization of Antibodies
Chapter 7: Cell Line Development
Abstract
7.1 Introduction
7.2 Generation of Stable CHO Cell Lines
7.3 Host Cell Engineering
7.4 Conclusions and Future Perspectives
Appendix I Biosafety Analysis for Cell Banks
Appendix II Transient Transfection
Chapter 8: Cell Culture Media in Bioprocessing
Abstract
8.1 Introduction
8.2 Cell Culture Media
8.3 Cell Culture Media Components and Supplements
8.4 Serum-Free Media Selection, Development and Optimization
8.5 Manufacturing and Supply of Cell Culture Media
8.6 Quality Systems for Cell Culture Media
8.7 Outsourcing Versus In-House Development and Manufacturing of Cell Culture Media
8.8 Summary
Section III: Recovery Processes, Principles, and Methods
Chapter 9: Industry Review of Cell Separation and Product Harvesting Methods
Abstract
9.1 Introduction
9.2 E. coli System
9.3 Future Developments
Chapter 10: Overview of Alternative Separation Methods in Relation to Process Challenges
Abstract
10.1 How To Become Knowledgeable of Alternative Separations in One Hour
10.2 Overview of Alternative Bioprocessing Operations
10.3 General Comparison of Alternative Separation Methods
10.4 Alternative Separation Operations
10.5 Acknowledgements, Notices, and Disclaimers
Chapter 11: Alternative Separation Methods: Flocculation and Precipitation
Abstract
Acknowledgments, Notices, and Disclaimers
11.1 Introduction
11.2 Clarification and Primary Recovery Challenges
11.3 Cell Debris Reduction and Clarification
11.4 Precipitation and Flocculation of Target
11.5 Examples of Contaminant Precipitation
11.6 Sequential and Continuous Precipitation
11.7 Process Economics Notes
11.8 Conclusions
Chapter 12: Alternative Separation Methods: Crystallization and Aqueous Polymer Two-Phase Extraction
Abstract
Acknowledgements, Notices, and Disclaimers
12.1 Introduction
12.2 Crystallization
12.3 Aqueous Polymer Two-Phase Extraction
12.4 Crystallization and ATPE—Summing Up
Chapter 13: Expanded Bed Adsorption
Abstract
13.1 Introduction and Background
13.2 Principles of Operation
13.3 Adsorbents for EBA
13.4 Columns for EBA
13.5 Examples
13.6 Cleaning and Sanitization
13.7 Capabilities and Challenges
Chapter 14: Filtration Principles
Abstract
14.1 Introduction
14.2 Types of Filters and MaterialS of Construction
14.3 Nominally-Rated Filters
14.4 Sterilizing-Grade Filters
14.5 Microfiltration Versus Ultrafiltration
14.6 Retention
14.7 Fouling
14.8 Modeling of Filtration Operations
14.9 Summary
Chapter 15: Filtration Methods for Use in Recovery Processes
Abstract
15.1 Introduction
15.2 Normal-Flow Filtration
15.3 Cross-Flow Filtration
15.4 Summary
Section IV: Purification Processes, Principles and Methods
Chapter 16: Introduction to Preparative Protein Chromatography
Abstract
16.1 Introduction
16.2 Chromatographic Principles
16.3 Chromatography Stationary Phase: Properties, Classification, and Basic Concepts
16.4 Mass Transfer Effects in Protein Chromatography
16.5 Modes of Chromatography Operations
16.6 Performance Descriptors for Preparative Protein Chromatography
16.7 Scale-up of Preparative Chromatography
16.8 Economy of Preparative Chromatography
16.9 Purification Strategies
16.10 Introduction to Process Development and Optimization
16.11 Multicolumn Operations
16.12 Conclusions
Chapter 17: Affinity Chromatography
Abstract
17.1 Application Areas
17.2 Examples
17.3 Standard Methods
17.4 Buffers
17.5 CIP
17.6 PD Workflow
17.7 Scale-Up
17.8 Critical Process Parameters
17.9 Economy
17.10 Future
Notes
Chapter 18: Ion Exchange Chromatography
Abstract
18.1 Introduction
18.2 Application Areas
18.3 Examples
18.4 IEC Principle and Standard Methods
18.5 Buffers
18.6 Cleaning in Place and Sanitization
18.7 Process Development Workflow
18.8 Critical and Key Process Parameters
18.9 Methodology
18.10 Optimization
18.11 Productivity and Economy
18.12 Future
Chapter 19: Hydrophobic Interaction Chromatography
Abstract
19.1 Application Areas
19.2 Examples
19.3 Standard Methods
19.4 CIP
19.5 PD Workflow
19.6 QbD Perspective
19.7 Methodology
19.8 Economy
19.9 Productivity
Chapter 20: Multimodal Chromatography
Abstract
20.1 Application Areas
20.2 Examples
20.3 Standard Methods
20.4 Buffers
20.5 CIP/SIP
20.6 PD Workflow and Optimization
20.7 Critical Process Parameters
20.8 Economy and Productivity
20.9 Future
Chapter 21: Size Exclusion Chromatography (SEC)
Abstract
21.1 Introduction
21.2 Basic Theory
21.3 Application Areas
21.4 Examples
21.5 Standard Methods
21.6 Buffers
21.7 CIP/SIP
21.8 Process Development (PD) Workflow
21.9 Critical and Key Process Parameters (CPP and KPP)
21.10 Methodology
21.11 Economy/Optimization
21.12 Productivity
21.13 Future
Chapter 22: Reversed Phase Chromatography
Abstract
22.1 Application Areas (Goals and Objectives)
22.2 Example: Insulin Purification
22.3 Standard Methods
22.4 CIP/SIP
22.5 Process Development Workflow
22.6 Critical and Key Process Parameters
22.7 Methodology
22.8 Economy
22.9 Productivity
Chapter 23: Filtration Methods for Use in Purification Processes (Concentration and Buffer Exchange)
Abstract
23.1 Application Areas
23.2 Process Development
23.3 Examples
23.4 Advanced Methods
23.5 Critical Process Parameters (CPP)
23.6 Key Process Parameters
23.7 Economy/Optimization
23.8 Future
Section V: Bioprocessing Equipment
Chapter 24: Upstream Processing Equipment
Abstract
24.1 Introduction
24.2 Common Design Aspects in Bioprocessing Equipment
24.3 The Bioreactor
24.4 Available Bioreactor Technology
24.5 Vessels for Adherent Processes
24.6 High-Throughput Process Development Bioreactors
24.7 Modeling and Simulation
Chapter 25: Downstream Processing Equipment
Abstract
25.1 Introduction
25.2 Critical Aspects of the User Requirement Specification
25.3 Common Components in Equipment for Bioprocessing
25.4 System Flow Path
25.5 Pumps
25.6 Valves
25.7 In-Line Filtration (Sterile Filtration and Particle Filtration)
25.8 Engineering Documents
Chapter 26: Chromatography Columns
Abstract
26.1 Introduction
26.2 Column Design
26.3 Column Packing
26.4 Assessing Column Performance: Efficiency Testing
26.5 Conclusions and Outlook
Chapter 27: Simplification of Buffer Formulation and Improvement of Buffer Control with In-Line Conditioning (IC)
Abstract
Acknowledgments
27.1 Introduction
27.2 Buffers for Downstream Processing
27.3 In-Line Dilution (ILD)—Addressing the Footprint Issue
27.4 In-Line Conditioning—Controlled Production of Any Buffer
27.5 Testing and Verifying the IC Buffer Preparation Capabilities
27.6 Straight-Through Processing (STP), an Extension of IC Use
Chapter 28: Continuous Capture of mAbs—Points to Consider and Case Studies
Abstract
28.1 Introduction
28.2 The Rationale for Continuous Processing in Biopharma
28.3 Technical Options for Continuous Purification
28.4 Systems for Continuous Purification
28.5 Process Development Guidance
28.6 Case Studies—Capture and Polishing
28.7 Selected Economic Considerations
28.8 Acknowledgments
Chapter 29: Single Use Technology and Equipment
Abstract
29.1 Introduction
29.2 Overview of Single Use Technologies
29.3 Single Use Material of Construction, Componentry, Assembly, Sterilization, Integrity and Use
29.4 Description of SU Unit Operations and General User Requirement Specifications for a Typical Monoclonal Antibody Suspension Cell Process
29.5 Gaps and Disadvantages of SUT
29.6 Conclusions and the Future of Single Use Technologies
Chapter 30: Process Control and Automation Solutions
Abstract
30.1 Introduction
30.2 Instruments and Input & Outputs
30.3 Automation Hardware
30.4 Programmable Logic Controller & Supervisory Control and Data Access
30.5 Distributed Control System
30.6 The ISA-88 Standard for Batch Control
30.7 Exception Handling
30.8 Computer System Validation
30.9 System Backup, Archival and Disaster Recovery
30.10 Data Historian
30.11 Other Automation Standards
30.12 Further Reading
Section VI: Industrial Process Design
Chapter 31: The Upstream Process: Principal Modes of Operation
Abstract
31.1 Introduction
31.2 Process Development
31.3 Principal Modes of Operation
31.4 The Seed Train
31.5 Process Intensification
31.6 Discussion and Outlook
Chapter 32: Downstream Process Design, Scale-Up Principles, and Process Modeling
Abstract
32.1 Introduction
32.2 Process Design Landscape
32.3 The Core Elements of Process Design
32.4 A Process Design Framework
32.5 Downstream Process Design Methodologies and Tools
32.6 Combining Steps for an Efficient Process
32.7 Scale-up as Part of Process Design
32.8 Downstream
32.9 Process Modeling and Optimization
32.10 Summary
Chapter 33: Cleaning-in-Place and Sanitization
Abstract
33.1 Introduction
33.2 Basic Considerations
33.3 Cleaning and Sanitization of Hardware
33.4 Cleaning and Sanitization of Chromatography Resins
33.5 Cleaning and Sanitization Validation
33.6 Preventive Steps and Bioburden Management
33.7 Economic and Environmental Aspects
Chapter 34: The Search for Process Intensification and Simplification: Alternative Approaches versus Current Platform Processes for Monoclonal Antibodies
Abstract
Acknowledgments
34.1 Overview
34.2 Discussion/Conclusions
Chapter 35: Single-Use Technology Implementation For Biologics and Vaccines Production
Abstract
Acknowledgments
35.1 Summary
35.2 Benefits of Implementing Single-Use Technology
35.3 Designing and Implementing a Single-Use Technology Process
35.4 Case Studies of Next Generation Processes Enabled by SUT
35.5 Future State Summary
Chapter 36: Points to Consider for Design and Control of Continuous Bioprocessing
Abstract
36.1 Introduction
36.2 Development and Implementation
36.3 Design of Unit Operations
36.4 Integration of Unit Operations
36.5 Summary
Chapter 37: Perfusion N-1 Culture—Opportunities for Process Intensification
Abstract
37.1 Introduction
37.2 N-1 Perfusion Seed Culture
37.3 Available Technology
37.4 Bioreactor Types
37.5 Perfusion Filtration Systems
37.6 Process Development
37.7 Use of Process Analytical Technology (PAT)
37.8 Conclusions
37.9 Future Prospects
Chapter 38: Process Development and Intensification for a Recombinant Protein Expressed in E.coli
Abstract
Acknowledgments
38.1 Introduction
38.2 Microbial (E. coli) Expression System and Culture Process Overview
38.3 Cell Line Development
38.4 Culture Process Development and Optimization
38.5 Microbial (E. coli) Downstream Process Overview
38.6 The Baseline Downstream Process and Process Intensification Goals
38.7 Downstream Process Intensification and Improvement
38.8 Summary
38.9 Materials and Methods
Chapter 39: Next-Generation Process Design for Monoclonal Antibody Purification
Abstract
Acknowledgments
39.1 Introduction
39.2 Current Practices and Emerging Process Alternatives for Downstream Unit Operations
39.3 Enabling Technologies for Next-Generation Manufacturing Facilities
39.4 Concluding Remarks
Chapter 40: Process Development and Manufacturing of Antibody-Drug Conjugates
Abstract
40.1 Introduction
40.2 Process Development and Manufacturing Considerations
40.3 ADC Conjugation Equipment
40.4 Conclusions
Chapter 41: Process Design for Bispecific Antibodies
Abstract
41.1 Introduction
41.2 Process Designs for Bispecific Antibodies
41.3 Conclusion
Chapter 42: Current Manufacturing of Human Plasma Immunoglobulin G
Abstract
42.1 Introduction
42.2 Plasma Fractionation Technologies
42.3 Processing Technologies to Assure Viral Safety
42.4 Low level Plasma Protein Impurities in Immunoglobulin Products
42.5 Formulation
42.6 Conclusions
Chapter 43: Modern Production Strategies in the Vaccine Industry
Abstract
43.1 Introduction
43.2 Outline
43.3 Whole-Organism Vaccines
43.4 Bacterial Vaccines
43.5 Parasite Vaccines
43.6 Subunit Vaccines
43.7 Polysaccharide and Protein-Polysaccharide Conjugate Vaccines
43.8 Nucleic Acid Vaccines
43.9 Influenza Vaccines
43.10 Vaccine Economics
43.11 Closing Remarks
Chapter 44: Bioprocesses for Cell Therapies
Abstract
44.1 Introduction
44.2 Cell Therapy Bioprocess Economics
44.3 Bioprocess Flowsheet Variations Across Cell Therapies
44.4 Culture Strategies for Cell Therapies
44.5 Differentiation of hPSCs
44.6 Genetic Engineering of Cells for Cell Therapies
44.7 Downstream Processing of Cell Therapies
44.8 Integrated and Continuous Bioprocess Strategies for Cell Therapies
44.9 Manufacturing and Distribution Models for Cell Therapies
44.10 Concluding Remarks
Section VII: Facility Design and Operation
Chapter 45: Facility Design and Process Utilities
Abstract
45.1 Introduction
45.2 The Manufacturing Landscape
45.3 Capacity Planning
45.4 Facility Functional Needs
45.5 cGMP Facility Design
45.6 Multiproduct Manufacturing
45.7 Process Support Functional Considerations
45.8 Planning for the Facility Support Systems on Site
45.9 Facility Construction
45.10 Summary: Considerations When Planning a New Facility
Appendix A
Chapter 46: Points to Consider in Manufacturing Operations
Abstract
46.1 Introduction
46.2 Non-GMP Manufacturing
46.3 GMP Manufacturing
46.4 Economics
46.5 Outsourcing
Section VIII: Analytics, Regulatory, Quality, and Safety Aspects
Chapter 47: Analytical Methods
Abstract
47.1 CQA
47.2 Analytical Control Strategy
47.3 Analytical Method Development and Qualification
47.4 Analytical Methods
47.5 Analytical Support of Process Development
47.6 Cost of Operating a Modern, High-Throughput Analytical Laboratory
Chapter 48: Implementation of QbD for Manufacturing of Biologics—Has It Met the Expectations?
Abstract
Acknowledgments
48.1 Introduction
48.2 What is QbD?
48.3 Framework for Assessing the Benefits of QbD Application in Manufacturing of Biologics
48.4 Impact of QbD on Biopharmaceutical Life Cycle
48.5 Summary
Chapter 49: Pathogen Safety
Abstract
49.1 Introduction
49.2 Raw Material
49.3 Starting Material
49.4 Capacity of the Manufacturing Process to Inactivate and Remove Pathogens
49.5 Transmissible Spongiform Encephalopathy
49.6 Cleaning and Sanitization of Equipment and Material
49.7 Assessment of Risk of Virus Transmission
49.8 Conclusion
Glossary
Chapter 50: Chemistry, Manufacture and Control
Abstract
50.1 Introduction
50.2 Part A: Planning
50.3 Part B: Tech Transfer
50.4 Part C: Execution
50.5 Part D: Common Technical Document
Glossary
Chapter 51: Post-Licensure Purification Process Improvements for Therapeutic Antibodies: Current and Future States
Abstract
Acknowledgments
51.1 Introduction
51.2 History and Current Status of Therapeutic mAb Production and Purification
51.3 Strategies of Post-Licensure Changes
51.4 Case Studies
51.5 Future Embodiments and Options
51.6 Conclusions
Chapter 52: Navigating the Regulatory Maze Upon Process Changes
Abstract
52.1 Introduction: What is Fragmentation?
52.2 Why Changes Happen: The Business Case for Changes to Approved Processes
52.3 Lack of Common Practice: Impact of Divergent Regulations
52.4 A Call to Action: Against Future Fragmentation
Chapter 53: Security of Bioprocess Consumables Supply
Abstract
53.1 Introduction
53.2 Material and Product Selection
53.3 Supplier Selection
53.4 Risk Management
53.5 Communication
53.6 Conclusion
Section IX: Financial Management and Process Economics
Chapter 54: Basics of Financial Management
Abstract
54.1 Finance Management Principles & Terminology
54.2 Financial Goals and Objectives of Business Enterprises
54.3 Explanation of Financial Key Terms
54.4 Measuring Success
Chapter 55: Management of Process Economy—Case Studies
Abstract
Acknowledgments
55.1 Introduction
55.2 Billion-Dollar Questions
55.3 The Objective, the Baseline, and the Return of Improvements
55.4 Facility and Process Cost Break-Down, Outlining the Options
55.5 Million-Dollar Questions
55.6 Financial Analysis—Consider Bias and Transparency
55.7 Conclusions
Section X: Appendices
Chapter 56: Appendix 1—The Ideal-World Research Portfolio
Abstract
Chapter 57: Appendix 2—History of Biomedical Research
Abstract
Chapter 58: Appendix 3—Marketed Biotherapeutics
Abstract
Index
← Prev
Back
Next →
← Prev
Back
Next →