Biopharmaceutical Production Technology

PREFACE

Volume 1

PART ONE: Upstream Technologies

STRATEGIES FOR PLASMID DNA PRODUCTION IN ESCHERICHIA COLI
Introduction
Requirements for a Plasmid DNA Production Process
Structure of a DNA Vaccine Production Process
Choice of Antigen
Vector DNA Construct
Host Strains
Cultivation Medium and Process Conditions
Lysis/Extraction of Plasmid DNA
Purification
Formulation
Conclusions

ADVANCES IN PROTEIN PRODUCTION TECHNOLOGIES
Introduction
Glycoengineering for Homogenous Human-Like Glycoproteins
Bacteria as Protein Factories
Mammalian Cell Technology
Yeast Protein Production
Baculovirus - Insect Cell Technology
Transgenic Animal Protein Production
Plant Molecular Farming
Cell-Free Protein Production
Future Prospects

PART TWO: Protein Recovery

RELEASING BIOPHARMACEUTICAL PRODUCTS FROM CELLS
Introduction
Cell Structure and Strategies for Disruption
Cell Mechanical Strength
Homogenization
Bead Milling
Chemical Treatment
Cellular Debris
Conclusions

CONTINUOUS CHROMATOGRAPHY (MULTICOLUMN COUNTERCURRENT SOLVENT GRADIENT PURIFI CATION) FOR PROTEIN
PURIFI CATION
Introduction
Overview of Continuous Chromatographic Processes
Principles of MCSGP
Application Examples of MCSGP
Enabling Features and Economic Impact of MCSGP
Annex 1: Chromatographic Process Decision Tree

VIRUS-LIKE PARTICLE BIOPROCESSING
Introduction
Upstream Processing
Downstream Processing
Analysis
Conclusions
Nomenclature

THERAPEUTIC PROTEIN STABILITY AND FORMULATION
Introduction
Protein Stability
Formulation and Materials
Screening Methods
Accelerated and Long-Term Stability Testing
Analytical Techniques for Stability Testing
Conclusions

PRODUCTION OF PEGYLATED PROTEINS
Introduction
General Considerations
PEGylation Chemistry
PEGylated Protein Purification
Conclusions

PART THREE: Advances in Process Development

AFFINITY CHROMATOGRAPHY: HISTORICAL AND PROSPECTIVE OVERVIEW
History and Role of Affinity Chromatography in the Separation Sciences
Overview of Affinity Chromatography: Theory and Methods
Affinity Ligands
Affinity Ligands in Practice: Biopharmaceutical Production
Conclusions and Future Perspectives

HYDROXYAPATITE IN BIOPROCESSING
Introduction
Materials and Interaction Mechanisms
Setting up a Separation
Separation Examples
Conclusions

MONOLITHS IN BIOPROCESSING
Introduction
Properties of Chromatographic Monoliths
Monolithic Analytical Columns for Process Analytical Technology Applications
Monoliths for Preparative Chromatography
Enzyme Reactors
Conclusions

MEMBRANE CHROMATOGRAPHY FOR BIOPHARMACEUTICAL MANUFACTURING
Membrane Adsorbers - Introduction and Technical Specifications
Comparing Resins and Membrane Adsorbers
Membrane Chromatography Applications and Case Studies
Conclusions

MODELING AND EXPERIMENTAL MODEL PARAMETER DETERMINATION WITH QUALITY BY DESIGN FOR BIOPROCESSES
Introduction
QbD Fundamentals
Process Modeling and Experimental Model Parameter Determination
Process Robustness Study
Conclusions
Nomenclature

Volume 2

PART FOUR: Analytical Technologies

BIOSENSORS IN THE PROCESSING AND ANALYSIS OF BIOPHARMACEUTICALS
Introduction
Principles and Commercial Applications of Biosensors
Use of Biosensors in Biopharmaceutical Production and Processing
Conclusions

PROTEOMICS TOOLKIT: APPLICATIONS IN PROTEIN BIOLOGICAL PRODUCTION AND METHOD DEVELOPMENT
Introduction
Applications of Proteomics
Myths and Misconceptions - Perceived Drawbacks of Proteomics
Critical Factors for Industrialization of Proteomics
Case Studies
Conclusions

SCIENCE OF PROTEOMICS: HISTORICAL PERSPECTIVES AND POSSIBLE ROLE IN HUMAN HEALTHCARE
Science of 'Omics'
Major Advances in Biology That Led to the Sciences of 'Omics'
Mendel's Principles of Inheritance
One Gene/One Enzyme Concept of Beadle and Tatum
Watson - Crick Structure of DNA
Development of Different Technologies Responsible for the Emergence of Genomics and Proteomics
Genomics
Proteomics
Interactomics: Complexity of an Organism Based on the Interactions of Proteins
Relation between Diseases, Genes, and Proteins: Diseasome Concept
Proteins as Biomarkers of Human Diseases
Metabolomics
Proteomics and Drug Discovery
Current and Future Benefits of Proteomics in Human Healthcare

PART FIVE: Quality Control

CONSISTENCY OF SCALE-UP FROM BIOPROCESS DEVELOPMENT TO PRODUCTION
Inhomogeneities in Industrial Fed-Batch Processes
Effects of Conditions in Industrial-Scale Fed-Batch Processes on the Main Carbon Metabolism
Effects of Conditions in Industrial-Scale Fed-Batch Processes on Amino Acid Synthesis
Scale-Down Reactors for Imitating Large-Scale Fed-Batch Process Conditions at the Laboratory Scale
Improved Two-Compartment Reactor System to Imitate Large-Scale Conditions at the Laboratory Scale
Description of the Hydrodynamic Conditions in the PFR Part of the Presented Two-Compartment Reactor
Description of Oxygen Transfer in the PFR Part of the Two-Compartment Reactor
E. coli Fed-Batch Cultivations in the Two-Compartment Reactor System
Future Perspectives for the Application of a Two-Compartment Reactor

SYSTEMATIC APPROACH TO OPTIMIZATION AND COMPARABILITY OF BIOPHARMACEUTICAL GLYCOSYLATION THROUGHOUT THE DRUG LIFE CYCLE
Costs of Inconsistent, Unoptimized Drug Glycosylation
Scheme 1: Traditional Approach to Comparability of Drug Glycosylation
Scheme 2: Comparability of Drug Glycosylation Using QbD DS
Scheme 3: Enhanced QbD Approach to Comparability of Drug Glycosylation
Conclusions

QUALITY AND RISK MANAGEMENT IN ENSURING THE VIRUS SAFETY OF BIOPHARMACEUTICALS
Introduction
QRM and Virus Safety
Pillars of Safety
Committee for Proprietary Medicinal Products Guidelines for Investigational Medicinal Products - Risk Management in Practice
Developing a Robust Risk Minimization Strategy - What Is the Correct Paradigm?

ENSURING QUALITY AND EFFI CIENCY OF BIOPROCESSES BY THE TAILORED APPLICATION OF PROCESS ANALYTICAL TECHNOLOGY AND QUALITY BY DESIGN
Introduction
PAT and QbD in Bioprocessing - Engineering Meets Biology
Aspects of Biological Demands - Selected Examples
Technical and Engineering Solutions
Conclusions

PART SIX: Process Design and Management

BIOPROCESS DESIGN AND PRODUCTION TECHNOLOGY FOR THE FUTURE
Introduction
Analysis of Biomanufacturing Technologies
AAC: Anything and Chromatography
Process Integration
Process Design and QbD
Package Unit Engineering and Standardization
Downstream of Downstream Processing
Conclusions

INTEGRATED PROCESS DESIGN: CHARACTERIZATION OF PROCESS AND PRODUCT DEFINITION OF DESIGN SPACES
Introductory Principles
Original Process Development Paradigm
The Essential QbD Concepts
Conclusion

EVALUATING AND VISUALIZING THE COST-EFFECTIVENESS AND ROBUSTNESS OF BIOPHARMACEUTICAL MANUFACTURING STRATEGIES
Introduction
Scope of Research on Decision-Support Tools for the Biotech Sector
Capturing Process Robustness Under Uncertainty
Reconciling Multiple Conflicting Outputs Under Uncertainty
Searching Large Decision Spaces Efficiently
Integrating Stochastic Simulation with Multivariate Analysis
Conclusions

PART SEVEN: Changing Face of Processing

FULL PLASTICS: CONSEQUENT EVOLUTION IN PHARMACEUTICAL BIOMANUFACTURING
FROM VIAL TO WAREHOUSE
Increased Demand, Reduced Volumes, and Maximum Flexibility - Driving Force to Plastic Devices
Plastic - The Flexible All-Round Replacer: From Material to Function
Pollution with Plastics: Leachables and Extractables
Plastics for Storage: Vial and Bag
Plastics for Cultivation: Flask, Tube, and Unstirred and Stirred Bioreactor
Plastics for Purification: Column and Membrane
Case Study: Comparability of Plastic Bag-Based Bioreactors in Cultivation Processes
Conclusions and Prospects

BIOSMB - TECHNOLOGY: CONTINUOUS COUNTERCURRENT CHROMATOGRAPHY ENABLING A FULLY DISPOSABLE PROCESS
Introduction
Continuous Chromatography in Biopharmaceutical Industries
Process Design Principles
Case Studies
Conclusions

SINGLE-USE TECHNOLOGY: OPPORTUNITIES IN BIOPHARMACEUTICAL PROCESSES
Current Single-Use Technologies
Future Single-Use Operations
Automation Requirements in Single-Use Manufacturing
Qualification and Validation Expectations
Operator Training

SINGLE-USE BIOTECHNOLOGIES AND MODULAR MANUFACTURING ENVIRONMENTS INVITE PARADIGM SHIFTS IN BIOPROCESS DEVELOPMENT AND BIOPHARMACEUTICAL MANUFACTURING
Introduction
Paradigm Shift at Crucell
Conclusions and General Outlook