Continuous Processing in Pharmaceutical Manufacturing E-Book

Ganapathy Subramanian

• Herausgeber: Wiley-VCH
• Kategorie: Fachliteratur
• Sprache: Englisch

Seitenzahl: 920

Veröffentlichungsjahr: 2014

Beschreibung

With contributions from biotechnologists and bioengineers, this ready reference describes the state of the art in industrial biopharmaceutical production, with a strong focus on continuous processes.
Recent advances in single-use technology as well as application guidelines for all types of biopharmaceutical products, from vaccines to antibodies, and from bacterial to insect to mammalian cells are covered. The efficiency, robustness, and quality control of continuous production processes for biopharmaceuticals are reviewed and compared to traditional batch processes for a range of different production systems.

Leseprobe

CONTENTS

Cover

Related Titles

Title Page

Copyright

List of Contributors

Preface

Chapter 1: Proteins Separation and Purification by Expanded Bed Adsorption and Simulated Moving Bed Technology

1.1 Introduction

1.2 Protein Capture by Expanded Bed Technology

1.3 Proteins Separation and Purification by Salt Gradient Ion Exchange SMB

1.4 Conclusion

References

Chapter 2: BioSMB Technology as an Enabler for a Fully Continuous Disposable Biomanufacturing Platform

2.1 Introduction

2.2 Integrated Continuous Bioprocessing

2.3 Multicolumn Chromatography

2.4 BioSMB Technology

2.5 Fully Disposable Continuous Processing

2.6 Case Studies

2.7 Regulatory Aspects

2.8 Conclusions

References

Chapter 3: Impact of Continuous Processing Techniques on Biologics Supply Chains

3.1 Introduction

3.2 Chromatography Techniques Used in Downstream Purification of Biomolecules

3.3 Next-Generation Biologic Products – Bispecific Monoclonal Antibodies

3.4 Improving the Downstream Processing of Bispecific Mabs by Introduction of MCSGP in the Value Chain

3.5 Conclusion

3.6 Further Research

Acknowledgments

3.A Appendix/Additional Information

References

Chapter 4: Integrating Continuous and Single-Use Methods to Establish a New Downstream Processing Platform for Monoclonal Antibodies

4.1 Introduction

4.2 Harvest and Clarification

4.3 Capture

4.4 Polishing

4.5 Cost of Goods Analysis

4.6 Summary

References

Chapter 5: Modeling of Protein Monomer/Aggregate Purification by Hydrophobic Interaction Chromatography: Application to Column Design and Process Optimization

5.1 Introduction

5.2 Mathematical Model

5.3 Experimentation

5.4 Results and Discussion

5.5 Conclusion

Acknowledgments

References

Chapter 6: Continuous Animal Cell Perfusion Processes: The First Step Toward Integrated Continuous Biomanufacturing

6.1 Introduction

6.2 The Basics of Perfusion Processes

6.3 Cell Banking and Inoculum Development in the Context of Perfusion Processes

6.4 Culture Conditions

6.5 Cell Retention Devices

6.6 Integrated Perfusion–Purification Processes for Continuous Biomanufacturing

6.7 Concluding Remarks

References

Chapter 7: Perfusion Process Design in a 2D Rocking Single-Use Bioreactor

7.1 Introduction

7.2 Production Costs

7.3 Equipment Requirements for a Single-Use Perfusion Process

7.4 Testing Results Single-Use Perfusion Process

7.5 Simplified Seeding Process

7.6 Future Outlook

References

Chapter 8: Advances in the Application of Perfusion Technologies to Drosophila S2 Insects Cell Culture

8.1 Introduction

8.2 Case Study 1: Acoustic Separation

8.3 Case Study 2: ATF-Based Cell Retention

8.4 Final Remarks

Acknowledgments

References

Chapter 9: Single-Use Systems Support Continuous Bioprocessing by Perfusion Culture

9.1 Introduction

9.2 Potential Advantages in Continuous Processing

9.3 Challenges in Adoption of Continuous Processing

9.4 Continuous Biomanufacturing

9.5 Single-Use Systems

9.6 Hybrid Systems

9.7 Perfusion Culture

9.8 Single-Use in Continuous Biomanufacturing

9.9 Roller Bottles

9.10 Mechanically Agitated Suspension Reactors

9.11 Hollow Fiber Media Exchange

9.12 Packed Bed Bioreactors

9.13 Hollow Fiber Perfusion Bioreactors

9.14 Continuous Flow Centrifugation

9.15 Acoustic Wave Separation

9.16 Conclusion

References

Chapter 10: Multicolumn Countercurrent Gradient Chromatography for the Purification of Biopharmaceuticals

10.1 Introduction to Multicolumn Countercurrent Chromatography

10.2 Introduction to Multicolumn Simulated Moving Bed (SMB) Chromatography

10.3 Capture Applications

10.4 Polishing Applications

10.5 Discovery and Development Applications

10.6 Scale-Up of Multicolumn Countercurrent Chromatography

10.7 Multicolumn Countercurrent Chromatography as Replacement for Batch Chromatography Unit Operations

10.8 Multicolumn Countercurrent Chromatography in Continuous Manufacturing

10.9 Process Analytical Tools for Multicolumn Countercurrent Processes

References

Chapter 11: Monoclonal Antibody Continuous Processing Enabled by Single Use

11.1 Introduction

11.2 Continuous Downstream Processing for Monoclonal Antibodies Unit Operation Development

11.3 Pilot-Scale Demonstration of the Integrated Continuous Process

11.4 Summary

References

Chapter 12: Continuous Production of Bacteriophages

12.1 Bacteriophages

12.2 Bacteriophage Cultivation

12.3 Continuous Purification of Bacteriophages

12.4 Conclusions

References

Chapter 13: Very High Cell Density in Perfusion of CHO Cells by ATF, TFF, Wave Bioreactor, and/or CellTank Technologies – Impact of Cell Density and Applications

13.1 Introduction

13.2 Equipment

13.3 Results and Discussion

13.4 Conclusions

Acknowledgments

References

Chapter 14: Implementation of CQA (Critical Quality Attribute) Based Approach for Development of Biosimilars

14.1 Background

14.2 Biosimilar Product Development

14.3 Attributes/Parameters in Biopharmaceuticals

14.4 Quality Attributes and Biosimilars Development

14.5 Quality, Safety, and Efficacy of Biosimilars

14.6 Implementing CQA Approach for Biosimilar Development

14.7 Summary

References

Chapter 15: Automated Single-Use Centrifugation Solution for Diverse Biomanufacturing Process

15.1 Introduction

15.2 Separation by Centrifugation

15.3 Separation by Filtration

15.4 Downstream Process Challenges of High Cell Density Cultures

15.5 Single-Use Centrifugation

15.6 kSep Technology

15.7 kSep System Configuration

15.8 Low-Shear Process

15.9 Perfusion

15.10 Concentration, Media Replacement, and Harvest of Cells

15.11 Continuous Harvest Clarification

15.12 Separation of Cells from Microcarriers

15.13 Summary

References

Chapter 16: The Review of Flexible Production Platforms for the Future

16.1 Introduction

16.2 Today's Processing Technology Advances

16.3 Todays Facility Designs

16.4 Future Processing and Facility Requirements

References

Chapter 17: Evaluating the Economic and Operational Feasibility of Continuous Processes for Monoclonal Antibodies

17.1 Introduction

17.2 Background on Continuous Processing

17.3 Tool Description

17.4 Case Study 1: Fed-batch Versus Perfusion Culture for Commercial mAb Production

17.5 Case Study 2: Semicontinuous Affinity Chromatography for Clinical and Commercial Manufacture

17.6 Case Study 3: Integrated Continuous Processing Flowsheets

17.7 Conclusions

Acknowledgments

References

Chapter 18: Opportunities and Challenges for the Implementation of Continuous Processing in Biomanufacturing

18.1 Introduction

18.2 A Brief History of Continuous Processing in Biomanufacturing

18.3 Opportunities for Continuous Processing in Biomanufacturing

18.4 Challenges for Implementing Continuous Processing in Biomanufacturing

18.5 Conclusions

Acknowledgment

Abbreviations

Note

References

Chapter 19: The Potential Impact of Continuous Processing on the Practice and Economics of Biopharmaceutical Manufacturing

19.1 Introduction

19.2 Background (Review of Status Quo – How We Make Biopharmaceutical Products Today)

19.3 The Rationale for Continuous Processing

19.4 The Obstacles for Implementation of Continuous Processing for Biopharmaceuticals

19.5 The Potential Impact of Continuous Manufacturing on Process Economics

19.6 The Potential Impact of Continuous Processing on Biopharmaceutical Manufacturing Practices

19.7 Summary

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 2.1

Table 2.2

Table 2.3

Table 2.4

Table 2.5

Table 2.6

Table 3.1

Table 3.2

Table 3.3

Table 3.A

Table 4.1

Table 4.2

Table 4.3

Table 4.4

Table 4.5

Table 4.6

Table 4.7

Table 4.8

Table 4.9

Table 5.1

Table 5.2

Table 6.1

Table 7.1

Table 7.2

Table 7.3

Table 8.1

Table 8.2

Table 8.3

Table 8.4

Table 9.1

Table 9.2

Table 9.3

Table 9.4

Table 9.5

Table 9.6

Table 9.7

Table 9.8

Table 9.9

Table 11.1

Table 11.2

Table 11.3

Table 11.4

Table 11.5

Table 11.6

Table 11.7

Table 12.1

Table 14.1

Table 14.2

Table 14.3

Table 14.4

Table 14.5

Table 16.1

Table 16.2

Table 17.1

Table 17.2

Table 17.3

Table 17.4

Table 17.5

Table 17.6

Table 18.1

Table 18.2

Table 18.3

Table 18.4

Table 18.5

Table 18.6

Table 18.7

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 2.1

Figure 2.2

Figure 2.3

Figure 2.4

Figure 2.5

Figure 2.6

Figure 2.7

Figure 3.1

Figure 3.2

Figure 3.3

Figure 3.4

Figure 3.5

Figure 3.6

Figure A.1

Figure 4.1

Figure 4.2

Figure 4.3

Figure 4.4

Figure 4.5

Figure 4.6

Figure 5.1

Figure 5.2

Figure 5.3

Figure 5.4

Figure 5.5

Figure 5.6

Figure 5.7

Figure 5.8

Figure 5.9

Figure 5.10

Figure 6.1

Figure 6.2

Figure 6.3

Figure 6.4

Figure 6.5

Figure 6.6

Figure 6.7

Figure 6.8

Figure 6.9

Figure 6.10

Figure 6.11

Figure 7.1

Figure 7.2

Figure 7.3

Figure 7.4

Figure 7.5

Figure 7.6

Figure 7.7

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 10.1

Figure 10.2

Figure 10.3

Figure 10.4

Figure 10.5

Figure 10.6

Figure 10.7

Figure 10.8

Figure 10.9

Figure 10.10

Figure 10.11

Figure 10.12

Figure 10.13

Figure 10.14

Figure 10.15

Figure 11.1

Figure 11.2

Figure 11.3

Figure 11.4

Figure 11.5

Figure 11.6

Figure 11.7

Figure 11.8

Figure 11.9

Figure 11.10

Figure 11.11

Figure 11.12

Figure 11.13

Figure 11.14

Figure 11.15

Figure 11.16

Figure 11.17

Figure 11.18

Figure 11.19

Figure 11.20

Figure 11.21

Figure 11.22

Figure 11.23

Figure 11.24

Figure 11.25

Figure 11.26

Figure 11.27

Figure 11.28

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 12.9

Figure 12.10

Figure 12.11

Figure 12.12

Figure 12.13

Figure 12.14

Figure 13.1

Figure 13.2

Figure 13.3

Figure 13.4

Figure 13.5

Figure 13.6

Figure 13.7

Figure 13.8

Figure 13.9

Figure 13.10

Figure 14.1

Figure 14.2

Figure 14.3

Figure 14.4

Figure 14.5

Figure 14.6

Figure 14.7

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

Figure 15.11

Figure 15.12

Figure 15.13

Figure 15.14

Figure 15.15

Figure 15.16

Figure 15.17

Figure 16.1

Figure 16.2

Figure 16.3

Figure 16.4

Figure 16.5

Figure 16.6

Figure 16.7

Figure 16.8

Figure 17.1

Figure 17.2

Figure 17.3

Figure 17.4

Figure 17.5

Figure 17.6

Figure 17.7

Figure 17.8

Figure 18.1

Figure 18.2

Figure 18.3

Figure 18.4

Figure 19.1

Figure 19.2

Figure 19.3

Figure 19.4

Figure 19.5

Guide

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Continuous Processing in Pharmaceutical Manufacturing

Edited by

Ganapathy Subramanian

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Library of Congress Card No.: applied for

British Library Cataloguing-in-Publication Data

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List of Contributors

Marc Bisschops

Tarpon Biosystems, Inc.

Worcester, MA

USA

and

Tarpon Biosystems Europe B.V.

BioScience Park

Archimedesweg 17

2333 CM Leiden

The Netherlands

Mark Brower

Merck & Co., Inc.

Merck Research Labs

BioProcess Development

2000 Galloping Hill Road

Kenilworth, NJ 07033

USA

Leda R. Castilho

Federal University of Rio de Janeiro (UFRJ)

Cell Culture Engineering Laboratory

COPPE, Chemical Engineering Program

21941-972 Rio de Janeiro

Brazil

William Cataldo

EMD Millipore

80 Ashby Rd.

Bedford, MA 01730

USA

Véronique Chotteau

KTH (Royal Institute of Technology)

School of Biotechnology

Cell Technology Group

Roslagstullsbacken 21

106 91 Stockholm

Sweden

Marie-Francoise Clincke

KTH (Royal Institute of Technology)

School of Biotechnology

Cell Technology Group

Roslagstullsbacken 21

106 91 Stockholm

Sweden

and

UCB Pharma S.A.

Allée de la Recherche, 60

1070 Brussels

Belgium

Aloke Das

Supply chain Management

Senior Analyst at Dell Inc.

Ireland

Willem A. de Jongh

ExpreS2ion Biotechnologies

DTU Science Park

Agern Allé 1

2970 Horsholm

Denmark

Alison Dupont

EMD Millipore

80 Ashby Rd.

Bedford, MA 01730

USA

Suzanne S. Farid

University College London

Department of Biochemical Engineering

The Advanced Centre for Biochemical Engineering

Torrington Place

London WC1E 7JE

UK

Pedro Ferreira Gomes

University of Porto

Faculty of Engineering

Laboratory of Separation and Reaction Engineering (LSRE)

Associate Laboratory LSRE/LCM

Department of Chemical Engineering

Rua Dr. Roberto Frias, s/n

4200-465 Porto

Portugal

Christopher Gillespie

EMD Millipore

80 Ashby Rd.

Bedford, MA 01730

USA

Sanjeev K. Gupta

Ipca Laboratories Ltd.

Department of Biotechnology (R&D)

Plot #125, Kandivali Industrial Estate, Kandivali (W)

Mumbai 460007

Maharashtra

India

Sa V. Ho

Pfizer

Biotherapeutics Pharmaceutical Sciences

1 Burtt Road

Andover, MA 01810

USA

Ying Hou

Merck & Co., Inc.

Merck Research Labs

BioProcess Development

2000 Galloping Hill Road

Kenilworth, NJ 07033

USA

Jad Jaber

EMD Millipore

80 Ashby Rd.

Bedford, MA 01730

USA

Nika Janež

The Centre of Excellence for Biosensors, Instrumentation and Process Control – COBIK

Center for Biotechnology

Tovarniška 26

5270 Ajdovšina

Slovenia

Maik W. Jornitz

G-CON Manufacturing Inc.

6161 Imperial Loop

College Station, TX 77845

USA

Mark-Henry Kamga

University of Massachusetts Lowell

Department of Chemical Engineering

1 University Avenue

Lowell, MA 01854

USA

Namjoon Kim

University of Massachusetts Lowell

Department of Chemical Engineering

1 University Avenue

Lowell, MA 01854

USA

Mikhail Kozlov

EMD Millipore

80 Ashby Rd.

Bedford, MA 01730

USA

Hae Woo Lee

Clinical Manufacturing Center

Daegu-Gyeongbuk Medical Innovation Foundation

Cheombok-ro 80

Dong-gu, Daegu

South Korea

Ping Li

East China University of Science and Technology

State Key Laboratory of Chemical Engineering

College of Chemical Engineering

130 Meilong Road, Xuhui

Shanghai 200237

China

José M. Loureiro

University of Porto

Faculty of Engineering

Laboratory of Separation and Reaction Engineering (LSRE)

Associate Laboratory LSRE/LCM

Department of Chemical Engineering

Rua Dr. Roberto Frias, s/n

4200-465 Porto

Portugal

Sunil Mehta

kSep Systems

1101 Hamlin Road

Durham, NC 27704

USA

Massimo Morbidelli

ETH Zurich

Institute for Chemical and Bioengineering

Vladimir-Prelog-Weg 1

HCI F 129

8093 Zurich

Switzerland

and

Chairman Dept. of Chemistry & Applied Biosciences

Institute for Chemical and Bioengineering

ETH Zurich

Vladimir-Prelog-Weg 1/HCI F129

CH-8093 Zurich-Hoenggerberg

Thomas Müller-Späth

ETH Zurich

Institute for Chemical and Bioengineering

Vladimir-Prelog-Weg 1

HCI F 137

8093 Zurich

Switzerland

Nico M.G. Oosterhuis

Easthouse Biotech Solutions BV

Landschrijverlaan 35

9451KT Rolde

The Netherlands

Sadettin S. Ozturk

MassBiologics of the University of Massachusetts Medical School

Process and Analytical Development

460 Walk Hill Street

Mattapan, MA 02126

USA

Matjaž Peterka

The Centre of Excellence for Biosensors, Instrumentation and Process Control – COBIK

Center for Biotechnology

Tovarniška 26

5270 Ajdovšina

Slovenia

Michael Phillips

EMD Millipore

80 Ashby Rd.

Bedford, MA 01730

USA

Aleš Podgornik

The Centre of Excellence for Biosensors, Instrumentation and Process Control – COBIK

Center for Biotechnology

Tovarniška 26

5270 Ajdovšina

Slovenia

and

Faculty of Chemistry and Chemical Technology

Ljubljana University

Vena pot 113

1000 Ljubljana

Slovenia

David Pollard

Merck & Co., Inc.

Merck Research Labs

BioProcess Development

2000 Galloping Hill Road

Kenilworth, NJ 07033

USA

James Pollock

University College London

Department of Biochemical Engineering

The Advanced Centre for Biochemical Engineering

Torrington Place

London WC1E 7JE

UK

Ajish Potty

EMD Millipore

80 Ashby Rd.

Bedford, MA 01730

USA

Lars Poulsen

ExpreS2ion Biotechnologies

DTU Science Park

Agern Allé 1

2970 Horsholm

Denmark

Thomas C. Ransohoff

BioProcess Technology Consultants, Inc.

12 Gill Street

Woburn, MA 01801-1728

USA

Alirio E. Rodrigues

University of Porto

Faculty of Engineering

Laboratory of Separation and Reaction Engineering (LSRE)

Associate Laboratory LSRE/LCM

Department of Chemical Engineering

Rua Dr. Roberto Frias, s/n

4200-465 Porto

Portugal

Romas Skudas

Merck Millipore

Frankfurter Str. 250

64293 Darmstadt

Germany

Franc Smrekar

Jafral d.o.o.

Koprska ulica 94

1000 Ljubljana

Slovenia

L. Richard Stock

BioProcess Technology Consultants, Inc.

12 Gill Street

Woburn, MA 01801-1728

USA

Matthew Stone

EMD Millipore

80 Ashby Rd.

Bedford, MA 01730

USA

William G. Whitford

GE Healthcare

HyClone Cell Culture

925 West 1800 South

Logan, UT 84321

USA

Alex Xenopoulos

EMD Millipore

80 Ashby Rd.

Bedford, MA 01730

USA

Seongkyu Yoon

University of Massachusetts Lowell

Department of Chemical Engineering

1 University Avenue

Lowell, MA 01854

USA

Ye Zhang

KTH (Royal Institute of Technology)

School of Biotechnology

Cell Technology Group

Roslagstullsbacken 21

106 91 Stockholm

Sweden

Preface

A continuous process requires the ability to think laterally and have a proactive mindset across the entire team from lab development through to production. Continuous manufacturing process is not new. It has been in use by the chemical, food, and beverage industries successfully. The biopharmaceutical industries are reluctant to engage in applying advanced technology on continuous processes, and are still using the batch process, which has been is use since the nineteenth century. The batch process is an archaic process that progresses sequentially step by step, creating a specified and fixed amount of therapeutic product, which in modern times is not state-of-the art. Several reviews and articles have shown that considerable advances have been made by technologist in offering systems for continuous processes. It has been established that continuous processing promises efficiency because it is a well controlled and flexible process, and there is less waste and produces higher quality products. There is considerable economic benefit in applying the continuous process in manufacturing.

Momentum is gathering pace behind the implementation of continuous manufacturing in the pharmaceutical industry. The regulatory bodies are now encouraging companies to move toward continuous manufacturing. Consequently, leading biopharma industries seem to be in the mend of thinking that the time is right for a major effort in the development of continuous processes in their organizations. As more companies look at the practical evidence from pilot and demonstration units, the adoption and commercialization of the new technology is picking up speed and currently several leading global biopharmaceutical industries are moving to implement continuous manufacturing processes in collaboration with technologist and suppliers. It will not be far away that industries will apply the continuous manufacturing process and thus we are setting up a Gold standard for the future, maybe in 10 years or more.

This book presents the most recent scientific and technological advances of continuous processing, as well as methods and applications in the field of biomanufacturing. Each chapter provides introductory material with an overview of the topic of interest; a description of the technology and methods, protocols, instrumentation, and application, and a collection of published data with an extensive list of references for further details.

It is our hope that this book will stimulate a greater appreciation of the usefulness, efficiency, and the potential of single-use systems in continuous processing of biopharmaceuticals, and that it will stimulate further progress and advances in the field of continuous processing to meet the ever-increasing demands and challenges in the manufacturing of therapeutic products.

The completion of this book has been made possible with the help and encouragements of many friends and colleagues. It is a great pleasure for me to acknowledge, with deep gratitude, the contribution of 19 authors of the chapters in this book. Their outstanding work and thoughtful advice throughout the project have been important in achieving the breadth and depth of this book.

I would be most grateful for any suggestions that could serve to improve future editions of this volume.

Finally, my deep appreciation to Dr Frank Weinreich of Wiley-VCH for inviting me to edit the volume and also to Lesley Fenske and her colleagues for their sustained encouragement and help.

Maidenhead, UK

June 2014

G. Subramanian