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.
Some of the topics highlighted in the report:
- 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
治療用蛋白質製造環境的變化
2010年08月20日
Global Information, Inc.已開始銷售美國市場調查公司Insight Pharma Reports所發行的報告書「Therapeutic Protein Production: A Changing Landscape Report (治療用蛋白質之製造:競合環境)」
生物製程，是處理帶來商業利益的生物物質精製及製造、生物工藝學產業的1個部門。本書特別廣泛聚焦於有關迅速且便宜製造蛋白質分子的領域。
Insight Pharma在本報告中指出有關治療用蛋白質製造產業的上游部門•下游部門間有持續性差距的問題。本書處理的主題有改善蛋白質單位體積的產額、轉移到不包含動物原有成分的培養基、蛋白質生產過程引進一次性產品的重要性等。
本書亦分析擔憂歐洲及亞洲挑戰美國生物工藝學產業之競爭上威脅的問題。
本報告的主要話題：
- 贊成•反對培養動物細胞的意見
- 亞洲及歐洲的競爭
- 開發代替製造細胞株
- 蛋白質的可用性與成本對一次性產品之影響
- 資本轉投資到可固定再利用的基礎設施
- 改善每個培養基量的蛋白質製造量
- 理解生技仿製藥(Biosimilar)相關法規的疑點
