Continuous biomanufacturing : innovative technologies and methods / edited by Ganapathy Subramanian.

Format:

Book

Contributor:

Subramanian, Ganapathy, editor.

Language:

English

Subjects (All):

Pharmaceutical industry.

Drugs--Research.

Drugs.

Drugs--Prices.

Physical Description:

1 online resource (631 pages) : color illustrations

Edition:

1st ed.

Place of Publication:

Weinheim, Germany : Wiley-VCH, [2018]

Summary:

This is the most comprehensive treatise of this topic available, providing invaluable information on the technological and economic benefits to be gained from implementing continuous processes in the biopharmaceutical industry. Top experts from industry and academia cover the latest technical developments in the field, describing the use of single-use technologies alongside perfusion production platforms and downstream operations. Special emphasis is given to process control and monitoring, including such topics as 'quality by design' and automation. The book is supplemented by case studies that highlight the enormous potential of continuous manufacturing for biopharmaceutical production facilities.

Contents:

Continuous Biomanufacturing: Innovative Technologies and Methods

Contents

List of Contributors

Part One: Overview of State-of-the-Art Technologies and Challenges

Chapter 1: Continuous Bioprocess Development: Methods for Control and Characterization of the Biological System

1.1 Proposed Advantages of Continuous Bioprocessing

1.1.1 Introduction

1.2 Special Challenges for Continuous Bioprocesses

1.2.1 The Biological System in Continuous Biomanufacturing

1.2.2 Inherent Changes in the Microbial System - Problem of Evolution

1.2.3 Lack of Process Information

1.2.3.1 Models-Based Process Development and Control for Continuous Processes

1.2.3.2 Engineering Approach to Complex Systems

1.2.4 Limited Control Strategies

1.2.4.1 Traditional Control Strategies for Continuous Cultures

1.3 Changes Required to Integrate Continuous Processes in Biotech

1.3.1 A Better Physiological Understanding of the Organisms and Their Responses on the Reactor Environment

1.3.1.1 Model Complexity

1.3.1.2 Models

1.3.2 Model-Based Process Monitoring

1.3.3 Implementation of Model Predictive Control

1.3.3.1 Model-Based Control

1.4 Role of Iterative Process Development to Push Continuous Processes in Biotech

1.4.1 Methods for Development of Continuous Processes

1.4.1.1 Alternative: Fed-Batch as a System to Simulate Quasi Steady-State Conditions

1.4.2 Mimicking Industrial Scale Conditions in the Lab: Continuous-Like Experiments

1.4.2.1 A Simple Model for Continuous Processes

1.4.2.2 Continuous-Like Fed-Batch Cultivations

1.4.3 Fast and Parallel Experimental Approaches with High Information Content

1.4.3.1 Computer-Aided Operation of Robotic Facilities

1.4.3.2 Model Building and Experimental Validation

1.5 Conclusions

References.

Chapter 2: Tools Enabling Continuous and Integrated Upstream and Downstream Processes in the Manufacturing of Biologicals

2.1 Introduction

2.2 Continuous Upstream Processes

2.2.1 Continuous Bioprocesses: With or Without Cell Recycle?

2.2.2 Early/Scale-Down Perfusion Development

2.2.3 Feeding and Operational Strategies in Perfusion Processes

2.2.4 Cell Retention Devices

2.3 Continuous Downstream Processes

2.3.1 Continuous Liquid Chromatography (CLC)

2.3.1.1 Continuous Annular Chromatography (CAC)

2.3.1.2 True and Simulated Moving Bed Chromatography (TMB/SMB)

2.3.1.3 Multicolumn Countercurrent Solvent Gradient Purification (MCSGP)

2.3.1.4 Periodic Countercurrent Chromatography (PCC)

2.3.1.5 Continuous Countercurrent Tangential Chromatography (CCTC)

2.3.2 Nonchromatographic Continuous Processes

2.3.2.1 Continuous Aqueous Two-Phase Systems

2.3.2.2 Continuous Protein Precipitation

2.3.3 Straight-Through Processes

2.3.4 Continuous Virus Clearance Processes

2.4 Integrated Continuous Processes

2.5 Concluding Remarks

References

Chapter 3: Engineering Challenges of Continuous Biomanufacturing Processes (CBP)

3.1 Introduction

3.1.1 Continuous Manufacturing

3.1.2 Continuous Manufacturing of Synthetic Molecules

3.1.3 Continuous Manufacturing of Biologics

3.2 Analysis of CBP Status

3.3 Case Studies

3.4 Status and Needs for Research and Development

3.5 Engineering Challenges

3.5.1 Platform Method of QbD-Driven Process Modeling Instead of Unit Operation Oriented Platform Approaches

3.5.2 Data Driven Decisions

3.5.3 Analytics

3.5.4 QbD Methods

3.5.5 Upstream and Downstream Integration

3.5.6 Buffer Handling/Recycling

3.5.7 Process Integration of Innovative Unit Operations.

3.5.8 ABC (Anything But or Beyond Chromatography) and AAC (Anything and Chromatography)

3.5.8.1 Liquid-Liquid Extraction Based on ATPE

3.5.8.2 Precipitation

3.5.8.3 Membrane Adsorbers

3.5.8.4 Innovative Materials Like Fibers or Matrices

3.5.9 Process Concepts for mAbs and Fragments

3.5.10 Single-Use Technology

3.5.11 Guided Decision for CBP

3.6 Conclusion and Outlook

Acknowledgments

Part Two: Automation and Monitoring (PAT)

Chapter 4: Progress Toward Automated Single-Use Continuous Monoclonal Antibody Manufacturing via the Protein Refinery Operations Lab

4.1 Introduction

4.2 Protein Refinery Operations Lab

4.2.1 Introduction

4.2.2 Protein Refinery Operations Lab: Design and Implementation

4.2.3 Protein Refinery Operations Lab: Process Analytical Technology (PAT) and Product Attribute Control (PAC) for the Transition to Real-Time Release (RTR)

4.2.3.1 Protein Refinery Operations Lab: Current State of PAT Technologies

4.3 Protein Refinery Operations Lab: Case Studies

4.3.1 Case Study: Perfusion

4.3.2 Case Study: Continuous Purification

4.3.3 Case Study: Proof of Concept Automated Handling of Deliberate Process Deviations

4.3.3.1 Perfusion Process Deviation Analysis (Bioreactor Temperature Shift)

4.3.3.2 Downstream Process Deviation Analysis (Viral Inactivation pH)

4.4 Summary

Part Three: Single Use Technologies and Perfusion Technologies

Chapter 5: Single-Use Bioreactors for Continuous Bioprocessing: Challenges and Outlook

5.1 Introduction

5.2 Single-Use Reactor Types

5.3 Material Aspects

5.4 Sensors

5.5 Reactor Design

5.5.1 Mass Transfer and Mixing Requirements for Continuous Processing

5.6 Scale-Up Aspects

5.7 Continuous Seed Train

5.8 New Mixer Designs

5.9 Future Outlook

Chapter 6: Two Mutually Enabling Trends: Continuous Bioprocessing and Single-Use Technologies

6.1 Introduction

6.2 Single-Use Technologies

6.2.1 History of Single-Use Technologies

6.2.2 Single-Use Upstream Processing

6.2.3 Single-Use Downstream Processing

6.2.3.1 Tangential Flow Filtration

6.2.3.2 Chromatography Steps

6.2.4 Early Skepticism

6.2.5 Current Trends and Future Predictions

6.3 Continuous Bioprocessing

6.3.1 Continuous Upstream Processing

6.3.2 Continuous Downstream Processing

6.3.2.1 Tangential Flow Filtration

6.3.2.2 Continuous Chromatography

6.3.3 Concerns for Continuous Bioprocessing

6.4 Integrated Single-Use Continuous Bioprocessing: Case Studies

6.4.1 Case 1: Genzyme

6.4.2 Case 2: Merck

6.4.3 Case 3: Bayer Technology Services

6.4.4 Comparison

6.4.5 Challenges and Solutions

6.4.6 Alternative Scenarios

6.5 Regulatory Aspects

6.6 Adoption Rate of Single-Use and Continuous Bioprocessing

6.7 Conclusions

Chapter 7: Perfusion Formats and Their Specific Medium Requirements

7.1 Introduction

7.1.1 History of Perfusion

7.1.2 Comeback of Perfusion

7.2 Characterization of Perfusion Processes

7.2.1 Productivity of Perfusion Processes

7.2.2 Cell Retention Devices

7.2.3 Steady-State Definition

7.3 Perfusion Formats

7.3.1 Innovative Perfusion Formats

7.4 Development Strategies for Perfusion Media

7.4.1 Cell Line-Specific Requirements

7.4.2 Scale-Down Models for Perfusion Processes

7.4.3 Scale-Down Cultivation Methods

7.4.4 Examples for Perfusion Scale-Down Applications

7.5 Process Development for Perfusion Processes

7.6 Case Study

7.6.1 Material and Methods

7.6.1.1 Semicontinuous Chemostat (SCC)

7.6.1.2 Repeated Batch (RB)

7.6.1.3 Semicontinuous Perfusion (SCP)

7.6.2 Results.

7.6.2.1 Determination of the Starting Cell Density

7.6.3 Scale-Down Model Comparison

7.6.4 Media Screening

7.6.5 Bioreactor Confirmation

7.7 Conclusion

Abbreviations

Part Four: Continuous Upstream Bioprocessing

Chapter 8: Upstream Continuous Process Development

8.1 Introduction

8.2 Upstream Processes in Biomanufacturing

8.2.1 Upstream Operating Modes

8.2.1.1 Fed-Batch Process

8.2.1.2 Continuous/Perfusion Process

8.3 The Upstream Continuous/Perfusion Process

8.3.1 Upstream Process-Type Selection

8.3.2 Component of Continuous Upstream and Downstream Processes

8.3.2.1 Upstream Components: Stainless Steel and Single-Use (Su)

8.3.2.2 Downstream Components: Stainless Steel and Single-Use (Su)

8.3.3 Cell Retention Devices Used in Perfusion Process

8.3.3.1 Spin Filters

8.3.3.2 The ATF System

8.3.3.3 Biosep Acoustic Perfusion System

8.3.3.4 TFF Cell Retention Device

8.4 Manufacturing Scale-Up Challenges

8.4.1 Process Complexity and Control

8.4.2 Cell Line Stability

8.4.3 Validation

8.5 Single-Use Technologies: A Paradigm Change

8.5.1 Application of SUBs in Continuous Processing

8.5.2 Single-Use Continuous Bioproduction

8.5.3 Single-Use Perfusion Bioreactors

8.5.3.1 Type of Single-Use Bioreactors for Perfusion Culture

8.5.4 Single-Use Accessories Supporting Perfusion Culture

8.5.4.1 Hollow Fiber Media Exchange

8.5.4.2 Continuous Flow Centrifugation

8.5.4.3 Acoustic Wave Separation

8.5.4.4 Spin filters

8.6 FDA Supports Continuous Processing

8.7 Making the Switch from Batch/Fed-Batch to Continuous Processing

8.8 Costs and Benefits of Continuous Manufacturing

8.9 Costs of Adoption

8.10 Continuous Downstream Processing

8.11 Integrated Continuous Manufacturing

8.12 Concluding Remark

Acknowledgment

Chapter 9: Study of Cells in the Steady-State Growth Space.

Notes:

Includes bibliographical references and index.

Description based on online resource; title from PDF title page (ebrary, viewed September 25, 2017).

ISBN:

9783527699919

3527699910

9783527699896

3527699899

9783527699902

3527699902

OCLC:

1004271395