Table of Contents
Chapter 1 Introduction
1.1 Bioprocessing in the 21st Century
A word of caution
State of the Art
What is bioprocessing?
An industry committed to Mammalian cell expression systems
A changing landscape
Antibodies Rule the Roost
Pressures and Opportunities
1.2 Bioprocessing advances are incremental in scope
1.3 Range of the industry challenge
Chapter 2 Upstream Processing
2.1 Mammalian Cell Culture Expression Systems
Media development and the evolution of therapeutic antibodies
Cell Line Development: Engineering for Better Performance
Developing overproducing cell lines
Medarex selection procedure to avoid royalties.
Conventional cell lines: CHO, NSO, PER.6, other types
Chinese Hamster Ovary (CHO) Cells
Human cell lines
Selection for overproducers
2.2 Mammalian Cell Culture Media
Introduction to mammalian cell culture media strategies.
Elimination of serum from mammalian cell culture media.
Online sources of information
Many options for Cell Culture media optimization
2.3 Post translational modifications
2.4 Other Production Alternatives
Green Leafy Plants
Chesapeake PERL, Inc.
Alternatives to baculovirus for insect cell protein synthesis.
Protozoan Expression Hosts
2.5 Bioreactors: design and function
Computer modeling of bioreactor performance
Disposable bioreactor components
Disposables and Rapid response The rise and fall of large antibody production facilities.
Chapter 3 Downstream Processing
3.1 Disposables, reusables
Disposable Technology Comes of Age.
Disposable Storage Options
The Disposable Conundrum
The future of Disposables
3.2 Purification strategies
Fine-tuning contaminant removal through filtration technology
Current Polishing Strategies
Single Pass Tangential Flow Filtration
Recombinant Polyclonal Purification Challenges
Filter reconfiguration for Better Antibody Purification
Affinity tag purification.
Self Cleaving Affinity tag purification
Other Protein A Alternatives
Trends in Bioprocessing from the EU
3.3 Monitoring tools: HPLC-MS
Chapter 4 Optimizing Bioprocess Development
4.1 Time is Money
Avoiding revenue loss
The next challenge
The Example of Insulin
Develop processes that will survive upscaling
Economic savings from disposables
Flexibility Generates Cost Savings
Effective project management tools
Lean, Not Necessarily Mean
Chapter 5 Current Regulatory Status of Biologics
The Biologics Problem
European Guidelines on Biologics
Canadian regulatory policy for biologics
Status of US biosimilar regulation
Chapter 6 Conclusions Drawn While on the Road Ahead; Thoughts on the future of bioprocessing
6.1 Predicting the Future
Small, incremental steps will guide progress in bioprocessing.
6.2 The Rise of Foreign Competition
Drawbacks to China’s advance
Chinese Regulatory Policy
US and China: Price Competition
Will the US thrown away its advantages in bioprocessing?
The European threat
CMOs: Upsides and Downsides
6.3 Marketing Issues; Costs
Are Revolutionary Developments Possible in Bioprocessing?
Disposables in the Ascendant.
6.4 Options and Caveats
Good News and Challenges Ahead.
Short Term Trends in Bioprocessing
R&D is a major cost driver
Chapter 7 References