Biopharmaceutical Manufacturing: Principles, Processes, and Practices

✍ Scribed by Gilleskie G., Rutter C., McCuen B.

• Publisher: Walter de Gruyter
• Year: 2021
• Tongue: English
• Leaves: 348
• Series: De Gruyter STEM
• Category: Library

✦ Synopsis

Biopharmaceuticals, medicines made by or from living organisms (including cells from living organisms), are extremely effective in treating a broad range of diseases. Their importance to human health has grown significantly over the years as more biopharmaceutical products have entered the market, and now the biggest selling drugs in the world are biopharmaceuticals. Biopharmaceutical Manufacturing: Principles, Processes and Practices provides concise, comprehensive, and up-to-date coverage of biopharmaceutical manufacturing. Written in a clear and informal style, the content has been influenced by the authors’ substantial industry experience and teaching expertise. That expertise enables the authors to address the many questions posed over the years both by university students and professionals with experience in the field. Consequently, the book will appeal both to undergraduate or graduate students using it as a textbook and specialized industry practitioners seeking to understand the big picture of biopharmaceutical manufacturing. This book:
Introduces biopharmaceutical products and discusses Good Manufacturing Practice (GMP) standards
Describes concepts used in the design of manufacturing facilities
Incorporates examples based on real-life scenarios

✦ Table of Contents

Cover
Half Title
Also of Interest
Biopharmaceutical Manufacturing: Principles, Processes, and Practices
Copyright
Preface
Acknowledgements
Contents
1. An introduction to biopharmaceutical products
1.1 Definitions and background
1.1.1 Biopharmaceuticals
1.1.2 Recombinant medicines explained
1.1.3 Proteins: key ingredients in most biopharmaceutical products
1.1.4 A few final comments regarding terminology
1.2 Biopharmaceuticals vs. conventional small-molecule pharmaceuticals
1.3 Biopharmaceutical product classes and examples
1.3.1 Protein therapeutics
1.3.2 Vaccines
1.3.3 Gene therapies
1.3.4 Cell therapies
1.3.5 Biopharmaceutical impact
1.4 Biopharmaceutical drug product: formulation and containers
1.5 Biopharmaceutical drug product: quality
1.6 Summary
2. An overview of processes and facilities for biopharmaceutical production
2.1 Biopharmaceutical manufacturing processes – an overview
2.1.1 The main process
2.1.2 Supporting activities
2.1.3 Equipment for the main process and support activities
2.1.4 Amount of product to be produced
2.2 Process design
2.3 Manufacturing facilities
2.4 Summary
2.5 Review questions
3. Good Manufacturing Practice (GMP) for biopharmaceutical production
3.1 GMP regulations – an overview
3.2 cGMP regulations/guidelines and guidance documents
3.3 Notable cGMP requirements for biopharmaceutical manufacture
3.3.1 Personnel
3.3.2 Personnel gowning
3.3.3 Cleanroom behaviors
3.3.4 Equipment
3.3.5 Documentation system: procedures, records/reports and specifications
3.3.6 Testing: raw materials, in-process, drug substance, and drug product
3.3.7 Qualification and validation
3.3.8 Deviations and corrective and preventive actions (CAPA)
3.3.9 Batch disposition
3.3.10 Post-marketing surveillance
3.4 Summary
4. Upstream operations
4.1 Describing cell growth
4.2 Upstream processing and production modes: batch vs. fed batch vs. continuous
4.3 Bioreactor equipment design
4.4 cGMP considerations for upstream processing
4.5 Upstream process parameters and input material attributes
4.6 Upstream performance parameters
4.7 Upstream process development
4.8 Scaling up fermentation and cell culture
4.9 Summary
4.10 Review questions
5. Harvest operations, Part 1: cell lysis
5.1 Structure of cells commonly used in biopharmaceutical production
5.2 The need for cell lysis: intracellular vs. extracellular products
5.3 Cell lysis methods
5.4 High-pressure homogenizers
5.5 Homogenizer process and performance parameters
5.6 Procedure for a high-pressure homogenization step
5.7 Summary
5.8 Review questions
6. Harvest operations, Part 2: solid-liquid separations by centrifugation
6.1 Solid-liquid separations in biopharmaceutical processes
6.2 Centrifugation principles
6.3 Solid-liquid separation by gravity
6.4 Production centrifuges
6.4.1 Disc-stack centrifugation: an introduction
6.4.2 Disc-stack centrifuges: equipment details
6.4.3 Other types of production centrifuges
6.5 Disc-stack centrifuge cGMP operating procedure
6.6 Disc-stack centrifuge process and performance parameters
6.7 Sigma factor, centrifugation step design and scale-up
6.8 Summary
6.9 Review questions
7. Harvest operations, Part 3: solid-liquid separations by filtration
7.1 Filtration definition
7.2 Filtration applications in biopharmaceutical processing
7.3 Normal-flow vs. tangential-flow filtration
7.4 Solids retention by filters
7.5 Depth filtration
7.5.1 Depth filters and filter modules
7.5.2 Depth filtration equipment and procedures for production
7.5.3 Depth filtration parameters, performance and design
7.6 Tangential-flow MF overview
7.7 Unit operations for solid-liquid separation methods: a comparison
7.8 Other operations for solid-liquid separation
7.8.1 Acoustic wave separation
7.8.2 Flocculation
7.8.3 Magnetic cake filtration
7.9 Summary
7.10 Review questions
8. Purification operations: chromatography
8.1 Soluble impurities
8.2 Chromatographic principles
8.3 Creating separation: stationary phases, mobile phases, and properties of the solutes to be separated
8.3.1 Protein properties
8.3.2 The most common stationary phase: resins used in packed beds
8.3.3 Other stationary phase formats: membrane adsorbers and monoliths
8.3.4 Mobile phase properties and their impact on separation
8.4 Chromatography performance
8.5 Operational modes
8.6 Typical chromatography procedures for cGMP manufacturing
8.7 Chromatography equipment for biopharmaceutical production
8.8 Process and performance parameters for chromatography
8.9 Chromatography process design
8.10 Validation considerations for chromatography steps
8.11 Summary
9. Formulation operations: ultrafiltration
9.1 Basis of separation in UF and applications
9.2 UF equipment and process configurations for production
9.3 TFF membranes and modules
9.4 Typical TFF procedures for cGMP manufacturing
9.5 Process and performance parameters for tangential-flow UF and MF
9.6 TFF development and scale-up
9.7 Validation considerations
9.8 Single-pass TFF
9.9 Summary
9.10 Review questions
10. Summary and trends in biopharmaceutical processing
Glossary
References
Index