Manufacturing of Biologics - Increasing Demand for Monoclonal Antibodies and Recombinant Proteins Drives Increases in Capacities and Innovative Production Technologies

1 Table of Contents 3
1.1 List of Tables 7
1.2 List of Figures 8
2 Introduction 10
2.1 GBI Research Report Guidance 10
3 Biologics Manufacturing – Overview 11
3.1 Overview of Biologics 11
3.1.1 Therapeutic Functions of Biologics 11
3.2 Overview of Manufacturing 12
3.3 Overview of the Biologics Manufacturing Process 12
3.3.1 Evolution of Biologics Manufacturing 13
3.3.2 Overview of Microbial Fermentation 14
3.3.3 Overview of Mammalian Cell Culture Systems 14
3.3.4 Overview of Upstream Bioprocessing 14
3.3.5 Overview of Downstream Bioprocessing 15
3.4 Overview of the Biologics Manufacturing Industry 15
4 Role of Manufacturing in the Biologics Industry 16
4.1 Comparison of Manufacturing in Pharmaceutical and Biotechnology Industries with Manufacturing in Other Industries 16
4.2 Comparison of the Manufacture of Biologics with the Manufacture of Small Molecules 18
4.3 Manufacturing Models 19
4.3.1 Transgenic model 20
4.3.2 Advantages 22
4.3.3 Disadvantages 22
4.4 Mammalian Model 23
4.5 Microbial Model 25
4.5.1 Major Challenges during Microbial Manufacturing Process 26
4.6 Stakeholders for Biologics Manufacturing 27
4.6.1 R&D Division 27
4.6.2 Marketing Division 28
4.6.3 Sales Division 28
4.6.4 Manufacturing Division 30
4.7 Stakeholders for Manufacturing within the Industry 31
4.7.1 Raw Material Suppliers 31
4.7.2 Packaging Suppliers 32
4.7.3 Distributors 33
5 Biologics Manufacturing Processes 35
5.1 Raw Materials 35
5.2 Upstream Bioprocessing 37
5.2.1 Key Considerations While Initiating Upstream Processes 37
5.2.2 Emerging Production Systems in Upstream Bioprocess 38
5.3 Downstream Bioprocess 39
5.3.1 Major Check Point during Down Stream Processing 41
5.3.2 Emerging Technologies in Downstream Processing 42
5.4 Packaging 44
5.4.1 Various Packaging Strategies for Biologics According to Different Time Periods 44
5.5 Storage and Security 45
5.6 Disposal of Wastes 46
5.7 Supporting Technology 47
5.7.1 Process Analytical Technology 47
5.8 Key Positions in Biologics Manufacturing and their Roles 48
5.9 Challenges and Unmet Needs in Biologics Manufacturing 49
5.9.1 Challenges 49
5.9.2 Technological challenges 50
5.9.3 Capital Challenges 51
5.9.4 Regulatory Challenges 51
5.10 Unmet Needs in Biologics Manufacturing 52
5.10.1 High Yield Maintenance 53
5.10.2 Cost 53
5.10.3 Time 55
5.10.4 Regulatory Ease 56
6 Biologics Manufacturing Industry 57
6.1 Market Characterization of Biologics Manufacturing Industry 57
6.1.1 Historical Scenario 57
6.1.2 Present Scenario 57
6.1.3 Probable Future Scenario 58
6.2 Market Forecast 59
6.3 Industry Analysis 61
6.3.1 Barriers to Entry 61
6.3.2 Determinant of Buyers' Power 62
6.3.3 Determinant of suppliers' power 62
6.3.4 Threat of substitute Products 62
6.3.5 Rivalry among Existing Firms 63
6.4 Drivers and Restraints for Growth of Biologics Manufacturing 63
6.4.1 Drivers 64
6.4.2 Restraints 66
6.5 Biologics Manufacturing Capacity 68
6.6 Contract Biologics Manufacturing Market 71
6.6.1 Major Reasons for CMOs Growth 73
6.6.2 Need of CMO's 73
6.6.3 The Fragmentation of the Biologics Industry 74
6.6.4 Required Features of an Effective CMO 76
6.7 US Biologics Manufacturing Market 76
6.7.1 Key Drivers for US Biologic Market 77
6.7.2 Key Restraints 78
6.8 European Biologics Manufacturing Market 79
6.8.1 Key Drivers and for European Biologics Manufacturing Market 80
6.8.2 Key Constraints 81
6.9 Japanese Biologics Manufacturing Market 82
6.9.1 Key Drivers for Japanese Biologics Market 83
6.9.2 Key Constraints 85
6.10 Profiles of Key Players across the World in Biologics Manufacturing 86
6.10.1 Lonza Group Ltd 86
6.10.2 Boehringer Ingelheim 88
6.10.3 Sandoz 90
6.10.4 Avecia 92
6.10.5 Diosynth Biotechnology 94
6.10.6 DSM Biologics 96
6.10.7 SAFC Pharma 97
6.10.8 Amgen Inc. 98
6.10.9 Genentech 100
6.10.10 Genzyme Corporation 102
6.10.11 Biogen Idec Inc 104
6.11 Other Prominent Players within Europe and Japan 106
6.12 Future Players in Biologics Manufacturing 107
6.12.1 Teva 107
6.12.2 Biocon Ltd 108
6.12.3 Biopartners 109
6.12.4 Cangene 110
6.12.5 Phage Biotechnology 111
6.12.6 Reliance GeneMedix plc. 112
6.12.7 STADA Arzneimittel AG 113
6.12.8 Dr. Reddy's 114
6.13 Strategies in Biologics Manufacturing 115
6.13.1 Strategic alliances for Biologics Manufacturing 115
6.13.2 M&A for Biologics Manufacturing 116
6.13.3 In-House manufacturing 118
6.13.4 Outsourcing or Contract Manufacturing 119
7 Regulatory Landscape 123
7.1 Unifying Approach towards Regulatory Procedures among Major Nations (USA Japan and Europe) 123
7.1.1 Similarity Requirement 124
7.2 The US Regulatory Landscape 124
7.2.1 Regulatory Framework of the US for Biopharmaceutical Industry 124
7.2.2 Process for Getting the Approval 125
7.3 Europe Regulatory Landscape 127
7.3.1 Regulatory Framework for Biologics 127
7.3.2 The Committee for Medicinal Products for Human Use (CHMP) 128
7.3.3 Biologics Working Party 129
7.3.4 EMEA Guidelines 130
7.3.5 Key Changes in EMEA Guidelines 131
7.3.6 Types of Guidelines within the Biologics Legislative 131
7.3.7 Conclusion 132
7.4 Japan 133
7.4.1 Japanese Regulatory Framework 134
7.4.2 Health Policy Bureau 134
7.4.3 Office of Biologics 1 135
7.4.4 Office of Biologics 2 135
7.4.5 Review and guidelines 136
8 Manufacturing of Biologics- Emerging Countries 137
8.1 China 137
8.1.1 Foreign Manufacturing Setup Process 139
8.1.2 Key Growth Factors 139
8.1.3 Key Restraints 141
8.1.4 Key Biologics Manufacturers in China 141
8.2 India 143
8.2.1 Indian Regulatory System 144
8.2.2 Key Drivers 145
8.2.3 Key Constraints 147
8.2.4 Key Biologics Manufacturers in India: 148
8.2.5 Conclusion 149
8.3 Singapore 150
8.3.1 Regulations 150
8.3.2 Key Drivers 150
8.3.3 Key Biologics Manufacturers in Singapore 152
9 Manufacturing of Biologics– Appendix 154
9.1 Market Definitions 154
9.2 Abbreviations 154
9.3 Research Methodology 154
9.3.1 Coverage 155
9.3.2 Secondary Research 155
9.3.3 Primary Research 155
9.3.4 Expert Panel Validation 156
9.4 Contact Us 156
9.5 Disclaimer 156
9.6 Sources 156

1.1 List of Tables
Table 1: Biologics Manufacturing, Comparison of Biologics Manufacturing and FMCG Manufacturing, 2009 16
Table 2: Biologics Manufacturing, Comparison of Biologics Manufacturing and Small Molecules Manufacturing, 2009 18
Table 3: Biologics Manufacturing, Comparison of Models of Biologics Manufacturing, 2009 19
Table 4: Biologics Manufacturing, Economic Consideration of Mammalian v/s Transgenic, 2009 22
Table 5: Biologics Manufacturing, Differences between Microbial and Mammalian, 2009 24
Table 6: Biologics Manufacturing, Comparison among Various Hosts, 2009 26
Table 7: Biologics Manufacturing, Raw Material Suppliers, 2009 31
Table 8: Biologics Manufacturing, Packaging Suppliers, 2009 32
Table 9: Biologics Manufacturing, Key Distributors, 2009 33
Table 10: Biologics Manufacturing, Product Wise Suppliers for Raw Materials, 2009 36
Table 11: Biologics Manufacturing, Chromatography Types, 2009 40
Table 12: Biologics Manufacturing, Packaging Strategies For Biologics, 2009 44
Table 13: Biologics Manufacturing, Types of Wastes And Disposal Techniques, 2009 46
Table 14: Biologics Manufacturing, Key Roles in Production, 2009 48
Table 15: Biologics Manufacturing,( Logistics & Purchasing) Key Roles in Production, 2009 49
Table 16: Biologics Manufacturing, Unmet needs, Cost of Biologics, 2009 53
Table 17: Biologics Manufacturing, The US, Recent Biologics Product Expiry, 2009 76
Table 18: Biologics Manufacturing, Regulatory Landscape, Comparison, 2009 123

1.2 List of Figures
Figure 1: Biologics Manufacturing, Biologics Classification, 2009 11
Figure 2: Biologics Manufacturing, Biologics Manufacturing Steps, 2009 13
Figure 3: Biologics Manufacturing, Evolution of Biologics, 1999–2009 13
Figure 4: Biologics Manufacturing, Transgenic Model, Process Steps, 2009 20
Figure 5: Biologics Manufacturing, Mammalian Model, Process Steps, 2009 23
Figure 6: Biologics Manufacturing, Microbial Model, Process Steps, 2009 25
Figure 7: Biologics Manufacturing, Stakeholders, 2009 27
Figure 8: Biologics Manufacturing, Success Rate for Biologics by Phases, 2009 28
Figure 9: Biologics Manufacturing, Sales Models, 2009 29
Figure 10: Biologics Manufacturing, Experimental Strategies, Upstream Processing, 2009 37
Figure 11: Biologics Manufacturing, Features And Benefits Of Filtration Technology,2009 43
Figure 12: Biologics Manufacturing, Benefits of PAT, 2009 47
Figure 13: Biologics Manufacturing, Challenges, 2009 49
Figure 14: Biologics Manufacturing, Unmet Needs, 2009 52
Figure 15:Biologics Manufacturing, Major Components of Cost of Sales for Biologics, 2009 54
Figure 16: Biologics Manufacturing, Industry, Time Line for A New Biologics Drug, 2009 55
Figure 17: Biologics Manufacturing, Industry, Influenza Vaccine Time Line, 2009 56
Figure 18: Biologics Manufacturing, Global Biologics Revenue, 2007-2016 59
Figure 19: Biologics Manufacturing, Geographical Split, Biologics Revenue, 2009-2016 60
Figure 20: Biologics Manufacturing, Industry Analysis, 2009 61
Figure 21: Biologics Manufacturing, Industry, Key Drivers and Restraints, 2009 63
Figure 22: Biologics Manufacturing, Increasing Uptake of Biologics, 2006-2015 64
Figure 23: Biologics Manufacturing, Industry, Biocluster Benefits, 2009 65
Figure 24: Biologics Manufacturing, Manufacturing Capacity, 2007-2016 68
Figure 25: Biologics Manufacturing, Mammalian Manufacturing Capacity, 2007-2016 69
Figure 26: Biologics Manufacturing, Microbial Manufacturing Capacity, 2007-2016 70
Figure 27: Biologics Manufacturing, CMO Biologics Market, 2007-2016 71
Figure 28: Biologics Manufacturing, CMO Biologics Market, Geographical Split, 2009-2016 72
Figure 29: Biologics Manufacturing, CMO Fragmentation, 2009 75
Figure 30: Biologics Manufacturing, Key Drivers and Restraints, The US, 2009 77
Figure 31: Biologics Manufacturing, The US ,Biocluster, 2009 78
Figure 32: Biologics Manufacturing, Key Drivers and Restraints, Europe, 2009 80
Figure 33: Biologics Manufacturing, Key Drivers and Restrains, Japan, 2009 83
Figure 34: Biologics Manufacturing, Japan, Biologics Clusters, 2009 84
Figure 35: Biologics Manufacturing, Profiles of Key Players, Lonza, 2009 86
Figure 36: Biologics Manufacturing, Profiles of Key Players, Lonza, SWOT, 2009 87
Figure 37: Biologics manufacturing, Profiles of Key Players, BI, 2009 88
Figure 38: Biologics Manufacturing, Profiles of Key Players, BI, SWOT, 2009 89
Figure 39: Biologics Manufacturing, Profiles of Key Players, Sandoz, 2009 90
Figure 40: Biologics Manufacturing, Profiles of Key Players, Sandoz, SWOT, 2009 91
Figure 41: Biologics Manufacturing, Profiles of Key Players, Avecia, 2009 92
Figure 42: Biologics Manufacturing, Profiles Of Key Players, Avecia, SWOT, 2009 93
Figure 43: Biologics Manufacturing, Profiles Of Key Players, Diosynth, 2009 94
Figure 44: Biologics Manufacturing, Profiles of Key Players, Diosynth, SWOT, 2009 95
Figure 45: Biologics Manufacturing, Profiles of Key Players, DSM Biologics, 2009 96
Figure 46: Biologics Manufacturing, Profiles of Key Players, DSM Biologics, SWOT, 2009 96
Figure 47: Biologics Manufacturing, Profiles of Key Players, SAFC Pharma, 2009 97
Figure 48: Biologics Manufacturing, Profiles of Key Players, SAFC Pharma, SWOT, 2009 97
Figure 49: Biologics Manufacturing, Profiles of Key Players, Amgen, 2009 98
Figure 50: Biologics Manufacturing, Profiles of key Players, Amgen, SWOT, 2009 99
Figure 51: Biologics Manufacturing, Profiles of Key Players, Genentech, 2009 100
Figure 52: Biologics Manufacturing, Profiles of Key Players, Genentech, SWOT, 2009 101
Figure 53: Biologics Manufacturing, Profiles of Key Players, Genzyme, 2009 102
Figure 54: Biologics Manufacturing, Profiles of Key Players, Genzyme, SWOT, 2009 103
Figure 55: Biologics Manufacturing, Profiles of Key Players, Biogen, 2009 104
Figure 56: Biologics Manufacturing, Profiles of Key Players, Biogen, SWOT, 2009 105
Figure 57: Biologics Manufacturing, Future Emerging Players, Teva, 2009 107
Figure 58: Biologics Manufacturing, Future Emerging Players, Biocon, 2009 108
Figure 59: Biologics Manufacturing, Future Emerging Players, Biopartners, 2009 109
Figure 60: Biologics Manufacturing, Future Emerging Players, Cangene, 2009 110
Figure 61: Biologics Manufacturing, Future Emerging Players, Phage Biotechnology, 2009 111
Figure 62: Biologics Manufacturing, Future Emerging Players, Reliance GeneMedix, 2009 112
Figure 63: Biologics Manufacturing, Future Emerging Players, STADA, 2009 113
Figure 64: Biologics Manufacturing, Future Emerging Players, Dr. Reddy, 2009 114
Figure 65: Biologics Manufacturing, Strategies, 2009 115
Figure 66: Biologics Manufacturing, Strategies, Comparison, 2009 118
Figure 67: Biologics Manufacturing, Strategies, Mixed Sourcing Model, 2009 119
Figure 68: Biologics Manufacturing, Strategies, Key Check Points, CMOs, 2009 121
Figure 69: Biologics Manufacturing, Regulatory Landscape, The US, Process, 2009 125
Figure 70: Biologics Manufacturing, Regulatory Landscape, The US, FDA Process, 2009 126
Figure 71: Biologics Manufacturing, Regulatory Landscape, Europe, Process, 2009 128
Figure 72: Biologics Manufacturing, Regulatory Landscape, Japan, Framework, 2009 134
Figure 73: Biologics Manufacturing, Regulatory Landscape, Japan, Process , 2009 135
Figure 74: Biologics Manufacturing, Emerging markets, China, Regulation Process , 2009 138
Figure 75:Biologics Manufacturing, Emerging Markets, China, Drivers and Restraints, 2009 140
Figure 76: Biologics Manufacturing, Emerging Markets , India, Biologic Clusters, 2009 143
Figure 77:Biologics Manufacturing, Emerging Markets ,India, Key Drivers and restraints , 2009 146
Figure 78: Biologics Manufacturing, Emerging Markets ,Singapore, Key Drivers & Restraints , 2009 151