Process scale purification of antibodies / edited by Uwe Gottschalk.

Format:

Book

Contributor:

Gottschalk, Uwe, editor.

Language:

English

Subjects (All):

Monoclonal antibodies.

Monoclonal antibodies--Purification.

Physical Description:

1 online resource (754 pages) : illustrations

Edition:

Second edition.

Place of Publication:

Hoboken, New Jersey : Wiley, 2017.

Summary:

Promoting a continued and much-needed renaissance in biopharmaceutical manufacturing, this book covers the different strategies and assembles top-tier technology experts to address the challenges of antibody purification. • Updates existing topics and adds new ones that include purification of antibodies produced in novel production systems, novel separation technologies, novel antibody formats and alternative scaffolds, and strategies for ton-scale manufacturing • Presents new and updated discussions of different purification technologies, focusing on how they can address the capacity crunch in antibody purification • Emphasizes antibodies and innovative chromatography methods for processing

Contents:

Intro

TITLE PAGE

COPYRIGHT PAGE

CONTENTS

PREFACE

LIST OF CONTRIBUTORS

CHAPTER 1 DOWNSTREAM PROCESSING OF MONOCLONAL ANTIBODIES: CURRENT PRACTICES AND FUTURE OPPORTUNITIES

1.1 INTRODUCTION

1.2 A BRIEF HISTORY OF CURRENT GOOD MANUFACTURING PROCESS mAb AND INTRAVENOUS IMMUNOGLOBULIN PURIFICATION

1.3 CURRENT APPROACHES IN PURIFICATION PROCESS DEVELOPMENT: IMPACT OF PLATFORM PROCESSES

1.4 TYPICAL UNIT OPERATIONS AND PROCESSING ALTERNATIVES

1.5 VLS PROCESSES: TON-SCALE PRODUCTION AND BEYOND

1.6 PROCESS VALIDATION

1.7 PRODUCT LIFE CYCLE MANAGEMENT

1.8 FUTURE OPPORTUNITIES

1.9 CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 2 THE DEVELOPMENT OF ANTIBODY PURIFICATION TECHNOLOGIES

2.1 INTRODUCTION

2.2 PURIFICATION OF ANTIBODIES BY CHROMATOGRAPHY BEFORE PROTEIN A

2.3 ANTIBODY PURIFICATION AFTER 1975

2.4 ADDITIONAL TECHNOLOGIES FOR ANTIBODY PURIFICATION

2.5 PURIFICATION OF mAbs APPROVED IN NORTH AMERICA AND EUROPE

2.6 CURRENT ANTIBODY PROCESS TECHNOLOGY DEVELOPMENTS

CHAPTER 3 HARVEST AND RECOVERY OF MONOCLONAL ANTIBODIES: CELL REMOVAL AND CLARIFICATION

3.1 INTRODUCTION

3.2 CENTRIFUGATION

3.3 MICROFILTRATION

3.4 DEPTH FILTRATION

3.5 FLOCCULATION

3.6 ABSOLUTE FILTRATION

3.7 EXPANDED BED ADSORPTION CHROMATOGRAPHY

3.8 HARVESTING IN SINGLE‐USE MANUFACTURING

3.9 COMPARISON OF HARVEST AND CLARIFICATION UNIT OPERATIONS

CHAPTER 4 NEXT-GENERATION CLARIFICATION TECHNOLOGIES FOR THE DOWNSTREAM PROCESSING OF ANTIBODIES

4.1 INTRODUCTION

4.2 IMPURITY PROFILES IN CELL CULTURES

4.3 PRECIPITATION

4.3.1 Acid Precipitation

4.3.2 Caprylic Acid Precipitation

4.3.3 PEG Precipitation

4.3.4 Cold Ethanol Precipitation

4.4 AFFINITY PRECIPITATION

4.5 FLOCCULATION

4.5.1 Anionic Flocculation.

4.5.2 Cationic Flocculation

4.5.3 Multimodal Flocculation

4.6 TOXICITY OF FLOCCULANTS AND PRECIPITANTS AND THEIR RESIDUAL CLEARANCE

4.7 DEPTH FILTRATION

4.7.1 Improvements in Depth Filtration Technology

4.7.2 Impurity Removal by Depth Filtration

4.7.3 Virus Clearance by Depth Filtration

4.8 CONSIDERATIONS FOR THE IMPLEMENTATION OF NEW CLARIFICATION TECHNOLOGIES

4.9 CONCLUSIONS AND FUTURE PERSPECTIVES

CHAPTER 5 PROTEIN A-BASED AFFINITY CHROMATOGRAPHY

5.1 INTRODUCTION

5.2 PROPERTIES OF PROTEIN A AND COMMERCIALLY AVAILABLE PROTEIN A RESINS

5.2.1 Protein A Structure

5.2.2 Protein A-Immunoglobulin G Interaction

5.2.3 Stoichiometry of Protein A-IgG Binding

5.2.4 Protein A Stability

5.2.5 Commercial Protein A Resins

5.2.6 Static Capacity

5.2.7 Dynamic Binding Capacity

5.2.8 Leaching

5.2.9 Production Rates

5.3 PROTEIN A CHROMATOGRAPHY STEP DEVELOPMENT

5.3.1 Loading/Binding

5.3.2 Wash Development

5.3.3 Elution

5.3.4 Stripping

5.3.5 Regeneration and CIP

5.4 ADDITIONAL CONSIDERATIONS DURING DEVELOPMENT AND SCALE‐UP

5.4.1 Controlling HMW Aggregate Formation

5.4.2 Removal of Soluble HMW Contaminants

5.4.3 Turbidity

5.5 VIRUS REMOVAL/INACTIVATION

5.5.1 Virus Removal

5.5.2 Low-pH Inactivation

5.5.3 Prion Clearance

5.6 VALIDATION AND ROBUSTNESS

5.6.1 Validation

5.6.2 Robustness

5.7 CONCLUSIONS

ACKNOWLEDGMENT

CHAPTER 6 PURIFICATION OF HUMAN MONOCLONAL ANTIBODIES: NON-PROTEIN A STRATEGIES

6.1 INTRODUCTION

6.2 INTEGRATED PROCESS DESIGN FOR HUMAN MONOCLONAL ANTIBODY PRODUCTION

6.3 PURIFICATION PROCESS DESIGNS FOR HuMabs

6.3.1 Protein A Purification Schemes

6.3.2 Non-Protein A Purification Schemes

6.3.3 Host Cell Protein Exclusion Approach for IEX Purification Schemes.

6.3.3.1 Primary Recovery

6.3.3.2 Optimization of CEX Capture Chromatography

6.3.3.3 Two-Column Nonaffinity Purification Processes

6.4 CONCLUSIONS

CHAPTER 7 HYDROPHOBIC INTERACTION CHROMATOGRAPHY FOR THE PURIFICATION OF ANTIBODIES

7.1 INTRODUCTION

7.2 HIC WITH mAbs

7.2.1 Stationary Phases

7.2.2 Dynamic Binding Capacities

7.2.2.1 Salts and Electrolytes

7.2.2.2 Buffer pH

7.2.2.3 Dual Salt Mixtures

7.2.2.4 Resin Screening

7.2.3 Selectivity and Impurity Removal

7.2.4 Antibody Capturing

7.2.5 Aggregate Removal

7.2.6 mAb Fragments and Other Formats

7.2.7 Antibody-Drug Conjugates

7.2.8 Analytical HIC for mAbs

7.3 HIC WITH MEMBRANE ADSORBERS

7.4 FUTURE PERSPECTIVES

CHAPTER 8 PURIFICATION OF MONOCLONAL ANTIBODIES BY MIXED‐MODE CHROMATOGRAPHY

8.1 INTRODUCTION

8.2 A BRIEF HISTORY

8.3 PREREQUISITES FOR INDUSTRIAL IMPLEMENTATION

8.4 MECHANISMS, SCREENING, AND METHOD DEVELOPMENT

8.5 CAPTURE APPLICATIONS

8.6 POLISHING APPLICATIONS

8.7 SEQUENTIAL CAPTURE/POLISHING APPLICATIONS

8.8 FUTURE PROSPECTS

CHAPTER 9 ADVANCES IN TECHNOLOGY AND PROCESS DEVELOPMENT FOR INDUSTRIAL-SCALE MONOCLONAL ANTIBODY PURIFICATION

9.1 INTRODUCTION

9.2 AFFINITY PURIFICATION PLATFORM

9.2.1 Overview

9.2.2 Standard Purification Sequence

9.2.3 Challenges and Opportunities

9.3 ADVANCES IN THE PURIFICATION OF mAbs BY CEX CHROMATOGRAPHY

9.3.1 Overview

9.3.2 High-Capacity CEX

9.3.3 An Exclusion Mechanism in IEX Chromatography

9.3.4 Factors Affecting the Critical Conductivity

9.3.5 Advances in mAb CEX Process Development

9.4 HIGH-PERFORMANCE TANGENTIAL FLOW FILTRATION

9.4.1 Overview

9.4.2 Advances in HPTFF

9.5 A NEW NONAFFINITY PLATFORM

REFERENCES.

CHAPTER 10 ALTERNATIVES TO PACKED‐BED CHROMATOGRAPHY FOR ANTIBODY EXTRACTION AND PURIFICATION

10.1 INTRODUCTION

10.2 INCREASING THE SELECTIVITY OF HARVEST PROCEDURES: FLOCCULATION AND FILTER AIDS

10.2.1 Flocculation

10.2.2 Filter Aids

10.3 SOLUTIONS FOR ANTIBODY EXTRACTION, CONCENTRATION, AND PURIFICATION

10.3.1 Extraction and Concentration by Precipitation

10.3.2 Extraction and Concentration by Liquid-Phase Partitioning

10.3.3 Concentration by Evaporation

10.4 ANTIBODY PURIFICATION AND FORMULATION WITHOUT CHROMATOGRAPHY

10.4.1 Crystallization

10.4.2 Controlled Freeze-Thaw

10.4.3 Lyophilization

10.5 MEMBRANE ADSORBERS

10.6 CONCLUSIONS

CHAPTER 11 PROCESS-SCALE PRECIPITATION OF IMPURITIES IN MAMMALIAN CELL CULTURE BROTH

11.1 INTRODUCTION

11.2 PRECIPITATION OF DNA AND PROTEIN-OTHER APPLICATIONS

11.3 A COMPREHENSIVE EVALUATION OF PRECIPITANTS FOR THE REMOVAL OF IMPURITIES

11.3.1 Protocol

11.3.2 Ammonium Sulfate Precipitation

11.3.3 Polymer Precipitation

11.3.4 Precipitation with Ionic Liquids

11.3.5 Precipitation with Cationic Detergents

11.3.6 Ethacridine Precipitation

11.3.7 Caprylic Acid Precipitation

11.4 INDUSTRIAL-SCALE PRECIPITATION

11.5 COST OF GOODS COMPARISON

11.6 SUMMARY

CHAPTER 12 CHARGED ULTRAFILTRATION AND MICROFILTRATION MEMBRANES FOR ANTIBODY PURIFICATION

12.1 INTRODUCTION

12.2 CHARGED UF MEMBRANES

12.3 CONCENTRATION POLARIZATION AND PERMEATE FLUX

12.4 STAGNANT FILM MODEL

12.5 SIEVING COEFFICIENT

12.6 MASS TRANSFER COEFFICIENT

12.7 MASS BALANCE MODELS

12.8 SCALE-UP STRATEGIES AND THE CONSTANT WALL CONCENTRATION (Cw) APPROACH

12.9 MEMBRANE CASCADES

12.10 PROTEIN FRACTIONATION USING CHARGED UF MEMBRANES

12.11 CASE STUDY

12.11.1 Methods

12.11.2 Results.

12.11.3 Discussion

12.12 CHARGED MF MEMBRANES

12.13 VIRUS CLEARANCE

12.14 SALT TOLERANCE

12.15 CONCLUSIONS

CHAPTER 13 DISPOSABLE PREPACKED-BED CHROMATOGRAPHY FOR DOWNSTREAM PURIFICATION: FORM, FIT, FUNCTION, AND INDUSTRY ADOPTION

13.1 INTRODUCTION

13.2 DEVELOPMENT-SCALE PREPACKED COLUMN APPLICATIONS

13.2.1 Resin and Condition Scouting

13.2.2 Process Development

13.2.3 Process Optimization and Troubleshooting

13.2.4 Virus Titer Reduction Validation

13.3 PROCESS-SCALE PREPACKED COLUMN APPLICATIONS

13.3.1 Overview

13.3.2 Prepacked Columns-Form

13.3.3 Prepacked Columns-Design Considerations

13.3.4 Prepacked Columns-Function

13.4 BASIC TECHNICAL DATASETS

13.4.1 Scale-Up and Basic Chromatography

13.4.2 Column Cycling

13.4.3 Column Cleanability

13.4.4 Shelf Life

13.4.5 Extractables and Leachables

13.4.6 Shipping and Handling

13.5 INDEPENDENT INDUSTRY ASSESSMENTS OF "FIT FOR PURPOSE"

13.6 CASE STUDY 1: CATION-EXCHANGE POLISHING CHROMATOGRAPHY

13.7 CASE STUDY 2: PREPACKED COLUMNS FOR PILOT-/LARGE-SCALE BIOPROCESSING

13.8 PREPACKED COLUMNS-FIT

13.8.1 Manufacturing Operations for Toxic Products

13.8.2 Single-Use/Disposable Facilities

13.8.3 Clinical Manufacturing Operations

13.8.4 Contract Manufacturing

13.8.5 Distributed Commercial Manufacturing

13.9 THE ECONOMICS OF PREPACKED COLUMN TECHNOLOGIES

13.10 THE IMPLEMENTATION OF DISPOSABLE PREPACKED COLUMNS

13.10.1 Cross‐Functional Alignment

13.10.2 Project and Process Fit

13.10.3 Risk Analysis and Risk Mitigation

13.10.4 Enabling Future Processes

13.10.5 Technological Pros and Cons

13.11 CONCLUSIONS

CHAPTER 14 INTEGRATED POLISHING STEPS FOR MONOCLONAL ANTIBODY PURIFICATION

14.1 INTRODUCTION

14.2 POLISHING STEPS FOR ANTIBODY PURIFICATION.

14.2.1 Ion-Exchange Chromatography.

Notes:

Includes bibliographical references at the end of each chapters and index.

Description based on print version record.

ISBN:

9781119126935

1119126932

9781119126942

1119126940

OCLC:

972640364