Biomanufacturing Strategies: Market drivers, build-vs-buy decisions and opportunities in contract relationship management

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