Therapeutic Protein Production: A Changing Landscape Report

Therapeutic Protein Production: A Changing Landscape Report published by Insight Pharma Reports in July, 2010. This report price starts from US $ 3195.

Introduction

Abstract

Therapeutic Protein Production: A Changing Landscape examines the implications of and advances in upstream and downstream operations used in the production of therapeutic proteins. Improvements in protein yields per unit volume, the significance of introducing disposables throughout the process and the shift to animal extracts-free culture media are three of the major themes covered by this report. The impact of global competition, lower barriers to entry and the shift in the production bottleneck from upstream to downstream unit operations are presented together with likely shifts impacting the production outlook over the next five years. More than a dozen tables and figures in this report summarize the report' s findings.

• Pros and cons of animal cell culture
• Development of alternative production cell lines
• Improving protein production per volume of culture media
• Impact of disposables on cost and availability of proteins
• Bottlenecks appear on the downstream side of production
• Shift away from capital spending on fixed, reusable infrastructure
• Tackling biosimilar regulatory questions
• Dimensions of Asian and EU competition

Bioprocessing is the branch of biotechnology dealing with the production and purification of biological materials of commercial interest. This report focuses on the wide range of disciplines applied to the rapid and economical production of protein molecules. While most antibody biologics are anti-cancer agents, there are a number of other disease indications, including immune dysfunction, infectious disease and mental illness management, fueling the growth of this therapeutic area.

Trends in the upstream and downstream areas of monoclonal antibody production are encouraging and should help control the manufacturing costs of monoclonal antibodies. As indicated in this report, an increase in the use of disposables in upstream and downstream unit operations is underway. This shift away from fixed, reusable equipment is driving change in the industry, making available to cash-strapped small companies workable product quantities at affordable costs and allowing companies to enter clinical trials with promising but higher-risk, second-tier candidates. The availability of disposables has caused major biotech companies to question their strategy of large capital investments in reusable equipment.

This report identifies the continuing upstream versus downstream gap problem for the industry. Progress toward producing more protein per unit volume of culture medium has moved more rapidly and is placing pressure on the rates at which these proteins can be purified at the downstream end. This overall expansion has motivated regulatory agencies in Europe to redefine intellectual property guidelines and rules governing biosimilars. Legislation governing biosimilars has been passed in the US as part of the recent 2010 health care legislation.

This report also evaluates rising concern over the threat of Asian and European competition to the American biotech industry

About the author:

K. John Morrow, Jr., PhD, is a writer and consultant for the biotechnology industry. He obtained his PhD in genetics from the University of Washington in Seattle, and completed his training with post-doctoral studies in Italy at the Universita di Pavia and Philadelphia at the Fox Chase Cancer Institute. He has held faculty positions at the University of Kansas and at Texas Tech University Health Sciences Center. His writings include over 200 peer-reviewed journal papers, non-peer - reviewed coverage of the biotechnology industry, books, and marketing reports. A number of companies, including Meridian Bioscience, Affitech, Henderson-Morley Biotechnology, Brandwidth Communications, and Emergent Technologies have taken advantage of his consultancy services, provided through Newport Biotechnology Consultants.

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 (Golden 2009, See Appendix)
• A Changing Landscape
• The Pipeline
• Antibodies Rule the Roost
• Corporate Strategies
• 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
• Historical Background
• 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.C6, Other Types
• Chinese Hamster Ovary (CHO) Cells
• NSO Cells (Nonsecreting Mouse Myeloma)
• Per.C6 Cells (Golden 2009, See Appendix) (Primary Human Retinal 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
• Protein Hydrolysates
• Online Sources of Information
• Many Options for Cell Culture Media Optimization
• 2.3. Post-Translational Modifications
• Glycosylation
• S-Glutathionylation
• Other Modifications
• 2.4. Other Production Alternatives
• Bacteria
• Yeast
• Green Leafy Plants
• Chlamydomonas reinhardtii
• Microalgae
• Insect Cells
• 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: The Toolbox
• Single-Pass Tangential Flow Filtration (TFF)
• Recombinant Polyclonal Purification Challenges
• Filter Reconfiguration for Better Antibody Purification
• Affinity Tag Purification (Culp 2009 and Tomaselli 2009, See Appendix)
• Self-Cleaving Affinity Tag Purification
• Protein A
• Other Protein A Alternatives
• Trends in Downstream Bioprocessing from the European Union
• 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
• Lean, Not Necessarily Mean

CHAPTER - 5

CURRENT REGULATORY STATUS OF BIOLOGICS

• 5.1. 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
• China' s Advance
• Drawbacks to China' s Advance
• Chinese Regulatory Policy
• United States and China: Price Competition
• Will the United States Throw Away Its Advantages in Bioprocessing?
• India
• The European Threat
• CMOs: Upsides and Downsides
• 6.3. Marketing Issues; Costs
• Are Revolutionary Developments Possible in Bioprocessing?
• Disposables in the Ascendant
• Cell-Free Protein Production
• 6.4. Options and Caveats
• Good News and Challenges Ahead
• Short-Term Trends in Bioprocessing
• R&D Is a Major Cost Driver

REFERENCES

APPENDIX

COMPANY INDEX WITH WEB ADDRESSES

Press Release

The Changing Landscape of Therapeutic Protein Production

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