Foreword |
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xv | |
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Preface |
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xix | |
Acknowledgements |
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xxii | |
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1 The biomedical drug, diagnostic, and devices industries and their markets |
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1 | (35) |
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1.1 The healthcare industry |
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1 | (1) |
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1.2 Biomedical technology - definition and scope; applications |
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2 | (2) |
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1.3 Drugs and biotechnology - definition and scope |
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4 | (4) |
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1.4 Devices and diagnostics - definition and scope |
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8 | (2) |
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1.4.1 Medical devices industry |
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8 | (1) |
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1.4.2 Diagnostics - IVD industry |
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9 | (1) |
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10 | (1) |
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1.6 Biomedical industry clusters |
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11 | (2) |
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1.6.1 Biopharmaceutical and biotechnology concentration in clusters |
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11 | (2) |
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1.6.2 Biomedical device clusters |
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13 | (1) |
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1.7 Competitive analysis of an industry or sector with Porter's five forces model |
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13 | (4) |
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1.7.1 Competitiveness summary for the pharmaceutical industry |
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14 | (1) |
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1.7.2 Competitiveness summary for the biomedical devices industry |
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15 | (1) |
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1.7.3 Competitiveness summary for the diagnostics market |
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15 | (2) |
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1.8 Industrial value chains |
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17 | (7) |
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1.8.1 Drug development process |
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20 | (3) |
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1.8.2 Biomedical device and diagnostic development process |
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23 | (1) |
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1.9 Technology trends in biomedical device and drug development |
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24 | (5) |
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1.9.1 Drug development technology trends |
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24 | (3) |
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1.9.2 Medical device and diagnostics technology trends |
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27 | (1) |
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1.9.3 Emerging technologies and materials in the nucleic acid diagnostics field |
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27 | (2) |
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1.10 Convergence of technologies in biotechnology |
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29 | (2) |
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31 | (5) |
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Appendix 1.1 Industry classification system for government and other databases |
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33 | (3) |
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2 Markets of interest and market research steps |
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36 | (27) |
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36 | (1) |
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2.2 General market research methodology |
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37 | (3) |
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2.2.1 Reports, projections, and historical data |
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37 | (1) |
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37 | (1) |
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38 | (1) |
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39 | (1) |
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2.2.5 Primary sources of information in biomedical market research |
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39 | (1) |
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2.2.6 Secondary sources of information |
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40 | (1) |
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2.3 Sizing and segmenting the markets (a stepwise approach) |
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40 | (4) |
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2.3.1 Market size segmented by application |
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40 | (1) |
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2.3.2 Market size segmented by geography for drugs, devices, and IVD |
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41 | (1) |
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2.3.3 How big is the market for my technology or innovation? |
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42 | (2) |
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44 | (3) |
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45 | (1) |
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46 | (1) |
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2.5 The referral chain - developing market context and understanding customer needs |
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47 | (13) |
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2.5.1 Market context - insight into biology or disease pathology |
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47 | (1) |
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2.5.2 Market context - the referral chain |
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48 | (2) |
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2.5.3 What competitive or alternate products exist? |
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50 | (1) |
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2.5.4 Defining the end user |
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50 | (3) |
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2.5.5 Defining the indication |
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53 | (7) |
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2.6 Market research in the context of medical device design and development |
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60 | (3) |
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3 Intellectual property, licensing, and business models |
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63 | (41) |
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3.1 Types of intellectual property |
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63 | (1) |
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3.2 Patents and patent rights |
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64 | (1) |
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64 | (1) |
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65 | (1) |
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65 | (1) |
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66 | (1) |
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66 | (1) |
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3.4 What can and cannot be patented? |
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66 | (2) |
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3.4.1 What cannot be patented (from the US PTO website) |
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66 | (1) |
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3.4.2 Can living things be patented? |
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66 | (2) |
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3.4.3 What type of invention or discovery is patentable? |
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68 | (1) |
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3.5 Protecting intellectual property by filing a patent |
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68 | (10) |
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3.5.1 How long do issued patents last in the USA? |
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68 | (1) |
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3.5.2 How much does it cost to get a patent? |
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68 | (1) |
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3.5.3 Considerations before filing a patent |
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69 | (1) |
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3.5.4 Steps to prepare a patent filing |
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70 | (1) |
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3.5.5 What is in a patent? How to read an issued patent |
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70 | (3) |
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3.5.6 Provisional patent application |
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73 | (1) |
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3.5.7 Priority date and publicizing inventions |
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73 | (3) |
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3.5.8 International patent filings and the Patent Cooperation Treaty (PCT) process |
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76 | (1) |
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3.5.9 Patent prosecution process |
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76 | (2) |
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3.5.10 Rough estimate of patent costs for project budgets |
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78 | (1) |
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3.6 Patent infringement and freedom to operate |
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78 | (4) |
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3.6.1 Patent infringement and protecting your rights |
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78 | (2) |
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3.6.2 "Freedom to practice" or "freedom to operate" |
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80 | (2) |
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82 | (2) |
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3.7.1 Why register your trademark? |
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83 | (1) |
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3.7.2 Filing a trademark with the US PTO |
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83 | (1) |
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3.7.3 International filing of trademarks |
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84 | (1) |
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84 | (1) |
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84 | (1) |
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3.10 Intellectual property commercialization and technology transfer |
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85 | (3) |
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3.10.1 Commercial use of intellectual property |
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85 | (1) |
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3.10.2 Technology transfer in academic research institutions |
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86 | (1) |
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86 | (2) |
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88 | (7) |
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3.11.1 Key non-financial terms of license agreements |
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88 | (2) |
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3.11.2 Financial terms in a license |
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90 | (5) |
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3.11.3 "Boilerplate" clauses in the license agreement |
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95 | (1) |
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3.12 Biotech business models and IP management strategies |
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95 | (6) |
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3.12.1 What is a business model? |
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97 | (1) |
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3.12.2 Practical note on business models for drug, device, and diagnostic innovator companies |
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98 | (1) |
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3.12.3 Emergent dominant business models among biotechnology (drug) companies |
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99 | (2) |
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101 | (3) |
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4 New product development (NPD) |
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104 | (68) |
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4.1 Why have a new product development (NPD) process just get it done! |
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105 | (1) |
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4.2 Planning and preparing an NPD process for biomedical technologies (drugs, devices, and diagnostics) |
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106 | (4) |
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4.2.1 The project proposal document |
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106 | (1) |
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4.2.2 Strategy and competency of the company and goal of the project |
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107 | (1) |
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4.2.3 Product life cycle planning |
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108 | (1) |
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108 | (1) |
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4.2.5 Identify key unknowns and risks |
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109 | (1) |
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4.2.6 Build a milestone-based plan for product development |
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109 | (1) |
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4.2.7 Specific risks known to occur frequently during the development of biomedical products |
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109 | (1) |
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4.3 Kill the project early or try some more? |
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110 | (5) |
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4.3.1 Early failure is better than late failure in biomedical product development |
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110 | (3) |
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4.3.2 When to kill a project |
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113 | (2) |
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4.4 Uncertainty-based view of product development processes |
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115 | (3) |
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118 | (2) |
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118 | (1) |
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4.5.2 How to configure a stage-gate process plan for my biomedical product |
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119 | (1) |
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4.5.3 Unique features of biomedical development |
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119 | (1) |
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4.6 Ethical requirements in biomedical product development |
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120 | (1) |
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4.6.1 Institutional Animal Care and Use Committee (IACUC) |
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121 | (1) |
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4.6.2 Institutional Review Board (IRB) |
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121 | (1) |
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4.7 Define the product and process - indications and endpoints |
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121 | (3) |
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4.8 Typical drug development process |
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124 | (14) |
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4.8.1 Discovery and pre-clinical testing |
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124 | (8) |
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4.8.2 Distinctions in pre-clinical development of biotechnology drugs (large molecule biologics) |
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132 | (1) |
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4.8.3 Drug candidate clinical testing to market approval |
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132 | (5) |
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4.8.4 Manufacturing, marketing, sales, and reimbursement |
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137 | (1) |
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4.8.5 Keeping a record for the FDA |
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138 | (1) |
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4.8.6 General stage-gate process for new drug development |
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138 | (1) |
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4.9 Typical diagnostics development process |
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138 | (6) |
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4.10 Typical device development process |
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144 | (10) |
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4.10.1 Discovery, feasibility, and optimization - design and pre-clinical testing |
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145 | (5) |
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4.10.2 Special considerations for device clinical trial design |
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150 | (3) |
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4.10.3 Device manufacturing |
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153 | (1) |
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4.10.4 Keeping records for the FDA |
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154 | (1) |
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4.10.5 Device development stage-gate process |
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154 | (1) |
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4.11 A few general notes on biomedical product development |
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154 | (2) |
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156 | (4) |
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4.12.1 Project management tools - Gantt charts and critical path |
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156 | (2) |
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158 | (1) |
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4.12.3 Team management in a matrix environment |
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159 | (1) |
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160 | (2) |
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4.14 How to get your project funded in a larger organization |
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162 | (4) |
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4.14.1 The art of persuasion |
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162 | (1) |
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162 | (1) |
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4.14.3 Valuation decision - net present value (NPV) |
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162 | (2) |
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164 | (2) |
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4.15 Outsourcing product development |
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166 | (2) |
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4.16 Summary of pre-clinical certifications and laboratory regulations |
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168 | (2) |
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170 | (2) |
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5 The regulated market: gateway through the FDA |
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172 | (54) |
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5.1 The FDA: its role and significance for biomedical product development |
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172 | (2) |
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5.1.1 Introduction and history |
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172 | (2) |
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5.1.2 Role of the FDA and significance for product development |
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174 | (1) |
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5.2 Organization and scope of the FDA |
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174 | (5) |
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5.2.1 Divisions of the FDA |
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174 | (1) |
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5.2.2 What the FDA does not regulate |
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175 | (1) |
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5.2.3 What does the FDA regulate? |
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176 | (1) |
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176 | (2) |
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5.2.5 Science rules - most of the time |
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178 | (1) |
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5.2.6 International harmonization |
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179 | (1) |
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5.3 Regulatory pathways for drugs (biologicals or synthetic chemicals) |
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179 | (17) |
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5.3.1 Pre-clinical studies regulated by the FDA |
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181 | (2) |
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5.3.2 Filing an investigational new drug application (IND; or form FDA 1571) |
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183 | (2) |
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5.3.3 Working with the FDA in formally arranged meetings |
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185 | (1) |
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5.3.4 New drug application submission |
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185 | (2) |
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5.3.5 Clinical trials done in foreign countries |
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187 | (1) |
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187 | (1) |
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5.3.7 Regulatory pathway for copies of already approved drugs (generic or biosimilar drugs) |
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188 | (1) |
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5.3.8 Regulatory pathway for OTC (over-the-counter) drugs |
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188 | (1) |
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5.3.9 Post-market clinical studies (Phase IV) and safety surveillance by FDA |
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189 | (1) |
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5.3.10 Schematics of IND, NDA, and ANDA review processes |
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190 | (2) |
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5.3.11 Speeding up access to drugs |
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192 | (3) |
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5.3.12 Market exclusivity for new drugs and the Hatch Waxman Act 1984 |
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195 | (1) |
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5.3.13 Drugs: helpful FDA websites and the Electronic Orange Book |
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195 | (1) |
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196 | (1) |
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5.5 Devices: regulatory pathways and NPD considerations |
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196 | (11) |
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5.5.1 Step 1 Determine the jurisdiction of the FDA center - is it a device? |
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197 | (1) |
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5.5.2 Step 2 classify the medical device - what controls and regulations apply? |
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198 | (1) |
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5.5.3 Step 3 determine marketing application required to be submitted |
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199 | (1) |
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5.5.4 Working with the FDA in formal meetings |
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200 | (1) |
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5.5.5 General controls and exempt devices |
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201 | (1) |
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5.5.6 Pre-clinical considerations - special controls and QSR for Class II and III devices |
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201 | (3) |
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5.5.7 The use of master files (MAF) |
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204 | (1) |
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5.5.8 510(k) submission type and content |
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204 | (2) |
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5.5.9 PMA submission content |
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206 | (1) |
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5.5.10 Types of PMA submission |
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206 | (1) |
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5.5.11 Humanitarian use devices (HUDs) |
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207 | (1) |
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5.6 Diagnostics: regulatory pathways and NPD considerations |
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207 | (8) |
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5.6.1 In vitro devices - regulatory clearance or approval steps to market |
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209 | (1) |
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5.6.2 Pre-clinical and clinical considerations for in vitro devices |
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210 | (2) |
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5.6.3 Clinical Laboratory Improvement Amendments program |
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212 | (1) |
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5.6.4 Analyte-specific reagents or "home-brew" tests |
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212 | (3) |
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5.7 Emerging regulatory guidelines for co-development of pharmacogenomic diagnostic tests and drugs |
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215 | (2) |
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5.8 Combination products, genetic material, and tissues |
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217 | (7) |
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5.8.1 Cellular, tissue, and gene therapies |
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219 | (5) |
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224 | (2) |
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226 | (38) |
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226 | (1) |
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6.2 Technology transfer to manufacturing operations (drugs, devices, and diagnostics) |
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227 | (1) |
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6.3 Regulatory compliance in manufacturing |
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228 | (5) |
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6.3.1 Current good manufacturing practices |
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228 | (2) |
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230 | (1) |
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6.3.3 Drug manufacture regulations - control systems reviewed for compliance |
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230 | (1) |
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6.3.4 Device and diagnostic manufacture regulations - control systems reviewed for compliance |
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231 | (2) |
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6.4 Manufacturing standards |
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233 | (4) |
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6.4.1 What are standards and what is their purpose? |
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233 | (2) |
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6.4.2 Who sets standards? |
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235 | (1) |
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6.4.3 Which of the thousands of standards apply to my product? |
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236 | (1) |
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6.4.4 What are "clean room" standards? |
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236 | (1) |
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6.5 Manufacturing in drug development |
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237 | (8) |
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6.5.1 Process validation before approval |
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240 | (2) |
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6.5.2 Bulk drug scale-up and production stages |
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242 | (1) |
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6.5.3 Commercial manufacturing planning |
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243 | (2) |
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6.6 Manufacturing in devices and diagnostics |
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245 | (2) |
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6.6.1 Design for manufacturability |
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247 | (1) |
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6.6.2 Design for assembly |
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247 | (1) |
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6.7 Manufacturing in diagnostics |
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247 | (3) |
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6.7.1 Labeling requirements for in vitro devices |
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250 | (1) |
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250 | (2) |
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252 | (12) |
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Appendix 6.1 Compliance to pharmaceutical GMP |
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254 | (4) |
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Appendix 6.2 Compliance to device and diagnostic GMP |
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258 | (6) |
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7 Reimbursement, marketing, sales, and product liability |
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264 | (53) |
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264 | (1) |
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7.2 Healthcare system in the USA |
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265 | (4) |
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7.2.1 Economic impact of the healthcare system |
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265 | (1) |
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7.2.2 Insurance coverage of the US population |
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265 | (1) |
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7.2.3 Who pays for the national healthcare costs? |
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266 | (3) |
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7.3 Flow of payments and distribution models for products and services |
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269 | (2) |
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7.4 Distribution and payment flow for biomedical product types |
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271 | (3) |
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7.4.1 Drugs and biologics: product payment and distribution model |
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271 | (2) |
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7.4.2 Devices and diagnostics: product payment and distribution model |
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273 | (1) |
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7.5 Components of the reimbursement process |
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274 | (17) |
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276 | (6) |
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282 | (2) |
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284 | (7) |
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7.6 Reimbursement planning activities |
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291 | (1) |
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7.7 Reimbursement path for self-administered drugs (mostly pills) |
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292 | (1) |
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7.8 Reimbursement path for devices and infused drugs |
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293 | (9) |
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7.8.1 Reimbursement path for physician-administered drugs (continued) |
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294 | (2) |
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7.8.2 Reimbursement path for devices (continued) |
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296 | (6) |
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7.9 Reimbursement pathway for in vitro diagnostics (IVDs) |
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302 | (2) |
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7.10 Major differences among selected national healthcare and reimbursement systems |
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304 | (1) |
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305 | (2) |
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307 | (2) |
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309 | (8) |
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Appendix 7.1 Technology assessment center for coverage determination |
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313 | (4) |
Glossary and acronyms |
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317 | (13) |
Index |
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330 | |