バイオマニュファクチャリング戦略

The contract biomanufacturing market achieved a value of $2.5bn in 2006, with growth expected to continue at an annual rate of 0- 5% until at least 20. The proportion of biologics in new drug approvals has risen by over 30% during the last decade, and with the current pipeline containing more than 500 protein and 50 peptide developmental drugs, this trend is set to continue. The commercial success of over 350 approved biologics has prompted the biotechnology industry to accelerate discoveries in further protein-based therapeutics, placing greater emphasis upon the importance of biomanufacturing. Many biotechnology companies are faced with limited resources, and as large-scale manufacturing continues to intensify, deciding whether it should be internalised or outsourced to partners or CMO' s is increasingly crucial in the development of a biotech firm. Biomanufacturing Strategies is a new report published by Business Insights that examines the future direction of biomanufacturing through a detailed analysis of market drivers, restraints and trends.

The production strategies and capacities of leading biopharma companies are assessed, and growth forecasts for microbial fermentations and mammalian cell culture are provided. This report will also detail the tactical balance required between a firm' s potential manufacturing capability and overall corporate strategy, in addition to profiling other key factors that bear crucial importance to the ‘build vs buy' decision. Use this report to identify the key criteria involved in CMO selection, compare the expansion strategies and capacity shares of leading players and analyse the growth drivers shaping the future of biomanufacturing.

Table of Contents

• Introduction
• Manufacturing of biologics
• The contract biomanufacturing market
• Outsourcing biomanufacturing
• Contract Manufacturing Organizations
• Trends in biomanufacturing

• Summary
• Introduction
• The state of the biomanufacturing industry
• Biotech drugs as blockbusters
• The contract biomanufacturing sector

• Overview of the biomanufacturing process
• Microbial Fermentation
• Mammalian cell culture
• Transgenics/plant systems

• Conclusions and key findings

• Summary
• Introduction
• The biopharmaceutical process
• The Upstream Process
  • Cell banking and seed culture
  • Production
  • Harvest and concentration
• The Downstream process
  • Purification of biopharmaceuticals
  • Formulation
• The importance of process integration

• Expression systems for therapeutic protein production
• Therapeutic protein production in microbes
• Mammalian cell culture
• Emerging production systems
  • Pichia and filamentous fungi
  • Transgenic protein production systems
  • Transgenic animals

• Summary
• Introduction
• Overview of the global contract biomanufacturing market
• The contract biomanufacturing market as part of the global pharmaceutical market
• Total market size forecasts
• Global biomanufacturing capacity forecasts

• Current market drivers
• Expansion of the market for biopharmaceutical products
• Facility cost
• Manufacturing expertise and innovation
• Risk reduction and time to market
• Growing regulatory burden and shortage of personnel
• The emergence of biosimilars

• Current market restraints
• In-house production and overcapacity
• Loss of manufacturing control
• Technology transfer and intellectual property (IP) concerns
• Increased competition among CMOs
• Longer clinical and approval times for biopharmaceuticals

• Summary
• Introduction
• The build vs. buy decision
• What is the strategy for the future of the biotech company?
• The outsourcing option and availability of external manufacturing capacity
• Capital requirements and operating cost structure
• Risk management

• Managing contract biomanufacturing
• Key selection criteria
• The CMO Selection Process
• The sponsor - CMO relationship
  • Starting the relationship
  • Technology transfer
  • Weekly and daily interaction
  • The reality of costs
  • When things go wrong
• Conclusions

• Summary
• Introduction
• Major players
• Lonza Group
  • Mammalian cell culture
  • Microbial fermentation
  • Biopharma services
• Boehringer Ingelheim
  • Boehringer Ingelheim' s expansion strategy
  • Boehringer Ingelheim' s contract services and proprietary technology platforms
• DSM Pharmaceutical Products
  • DSM Pharmaceuticals' contract services
• Celltrion
  • Bioreactor facilities
  • Celltrion expansion
• Diosynth
  • Diosynth' s contract manufacturing deals

• Medium-sized and small players
• Baxter BioPharma Solutions
  • Baxter' s contract services
• Cobra Biomanufacturing plc
  • Cobra' s contract services and proprietary technology platforms
• Xcellerex
  • PDMax™ Process Development Platform
  • FlexFactory™ Manufacturing
  • XDR™ - Xcellerex Disposable Reactor
  • Xcellerex' s funding and manufacturing deals
• Avecia
  • The pAVEway™ production platform

• Summary
• Introduction

• Bioprocess development strategies
• Production line selection and engineering
• Cell culture media
• Disposable technology
• Drivers for disposable technologies
• Single use and disposable bioreactor systems
• Disposable systems in downstream processes
• Improving productivity in downstream processing
• Harmonizing upstream and downstream capacities
• Transgenic production systems
  • Cost considerations
  • The perception of transgenics
• Process analytical technology (PAT)
  • Regulation shifts from product to process
  • Defining PAT and its meaning to a biomanufacturing company
  • PAT in biomanufacturing
  • Process control tools used for PAT
• Globalization / Offshoring to Asia
• Shared capacity - the future of biomanufacturing?
• Conclusions - The future of contract biomanufacturing

• Bibliography
• Index

• Figure 2.1: Schematic flow diagram of a typical biopharmaceutical process
• Figure 2.2: Expression system decision framework
• Figure 3.3: CMO market growth as part of the global pharmaceutical market, 2001 and 2007
• Figure 3.4: Size of the contract biomanufacturing market, 2000-2008e
• Figure 3.5: Ratio of biopharma companies producing 100% in-house (mammalian cell culture), 2003-2011e
• Figure 3.6: Biopharma companies planning to outsource at least part of their production, 2006 and 2011e
• Figure 3.7: Mammalian Cell Culture Bioreactor Capacity, 2003 -2009e
• Figure 3.8: Microbial Fermenter Volume Capacity, 2003 -2009e
• Figure 3.9: Number of biotech drugs and global biotech industry revenues, 1990-2005
• Figure 3.10: Antibody-derived therapies in biotechnology pipeline, 2007
• Figure 3.11: Cash reserves of biotech companies, 2005
• Figure 3.12: Sensitivity of fermentation volume required depending on yield and market demand74
• Figure 3.13: Factors creating capacity constraints by 2008
• Figure 3.14: CMO Mammalian Cell Culture Production Capacity Increase 2003 -2006
• Figure 3.15: Mean clinical and approval time-frames for biopharmaceuticals approved, 1996-2000 vs. 2001-2005
• Figure 4.16: Framework for the build vs. buy decision
• Figure 4.17: Mammalian Cell Culture Capacity Distribution for CMOs, 2004 and 2008(estimate)
• Figure 4.18: Distribution of biomanufacturing capacity
• Figure 4.19: Proposed timeline for commercial contract biomanufacturing
• Figure 4.20: Financial ‘Build or Buy' decision tree
• Figure 4.21: Transition (success) probabilities for biopharmaceuticals in different clinical phases, 2007
• Figure 4.22: Key criteria for selecting a CMO, 2006
• Figure 4.23: Critical issues when selecting a CMO, BioPlan Associates Survey, 2006
• Figure 5.24: Celltrion' s bioreactor capacity in Incheon, South Korea, 2007
• Figure 5.25: Revenue by lines of business in 2006 and 2007
• Figure 5.26: Revenue by geographical origin in 2006 and 2007
• Figure 6.27: Timelines for constructing and selecting high quality clonal cells
• Figure 6.28: Different types of culture media
• Figure 6.29: A 20L Wave bioreactor (Wave Biotech)

• Table 1.1: Top 10 biotech drugs by US sales ($bn), 2005 and 2006
• Table 2.2: Examples of production methods for recombinant therapeutic products
• Table 2.3: Marketed biopharmaceuticals and their expression platforms
• Table 2.4: Plant-based transgenic companies and their pipeline of recombinant proteins
• Table 2.5: Therapeutic proteins produced in transgenic animals
• Table 3.6: Number of operating facilities per segment 2004 and 2008(estimated)
• Table 3.7: New Technology - Modified Production Plant: Kogenate Bayer/FSR
• Table 4.8: Capital investment costs for antibody facilities using mammalian cell culture, 2000- 2009e
• Table 4.9: Cost of inaccurate capacity planning
• Table 4.10: Example of a request for proposal (RFP) content
• Table 4.11: Typical areas of responsibility as reported by sponsors
• Table 5.12: Capacity expansions in mammalian cell culture fermentation
• Table 5.13: Capacity expansions in microbial fermentation
• Table 5.14: Diosynth Biotechnology, US facilities, Research Triangle Park, NC
• Table 5.15: Diosynth Biotechnologies, microbial fermentation and mammalian cell culture volumes, 2007
• Table 5.16: Process development and cGMP manufacturing at Avecia, 2007
• Table 6.17: Capital investment estimates for antibody production for two different expression technologies
• Table 6.18: Comparison of cost per gram estimates at specified production rate