Title page
Contents
Acknowledgements 8
Foreword by the Directors-General 9
An integrated health, trade and IP approach to respond to the COVID-19 pandemic 10
Executive Summary 19
I. Medical technologies: the fundamentals 27
A. Public health and medical technologies: the imperative for international cooperation 29
1. Policy coherence 29
2. Scope of the study 30
3. The need for this study 30
4. Who should read this study? 31
B. The cooperating agencies: the WHO, WIPO and the WTO 32
1. World Health Organization 32
2. World Intellectual Property Organization 33
3. World Trade Organization 34
4. Trilateral cooperation 34
5. Other international key stakeholders 35
C. The global burden of disease and global health risks 36
1. Current estimates of global and regional burden of disease 36
2. Trends: major cause groups contributing to the total disease burden 36
3. Trends in global health risks 38
D. Factors shaping public health policy 39
1. Seeking effective outcomes within a complex policy environment 39
2. Transforming policy intersections 39
3. Building stronger links between local, national and global levels 40
4. The empirical challenge: an accessible base for policy 42
II. The policy context for action on innovation and access 45
A. Public health policy 47
1. Health and human rights 47
2. Access to essential medicines: an indicator for the fulfilment of the right to health 49
3. Universal access and the UN Sustainable Development Goals 49
4. Public health, innovation and access in the WHO 51
5. Cross-cutting efforts to tackle antimicrobial resistance 54
6. Regulation of health technologies 55
B. Intellectual property, trade and other policy dimensions 66
1. Intellectual property systems 66
2. Competition law and policy 98
3. Trade policy settings 101
4. Government procurement 106
5. Free trade agreements 108
6. Resolving trade disputes at the WTO 110
C. Economics of innovation and access to medical technologies 111
D. Genetic resources, traditional knowledge and traditional medicine 115
1. Traditional medicine knowledge systems 115
2. Traditional medical knowledge in health and IP policy 116
3. Traditional medicines regulation 116
4. Concerns about misappropriation of traditional knowledge and genetic resources 117
5. New approaches to IP protection of traditional medical knowledge 118
III. Medical technologies: the innovation dimension 133
A. Historical pattern of medical R&D 135
1. Innovation for medical technologies in context 135
2. From early discoveries to "wonder drugs" 135
3. Growth and evolution of the pharmaceutical industry 136
4. From non-exclusive licensing to restricted production 136
5. Trends in R&D 137
B. The current R&D landscape 141
1. A time of challenges and opportunities for pharmaceutical R&D 141
2. The key role of public-sector research in medical R&D 144
3. Medical R&D costs 145
4. Incentive models in the innovation cycle 146
5. Challenges in cancer medicines R&D 150
6. Orphan drugs and orphan indications 151
7. Registration of clinical trials in pharmaceutical product development 151
C. Overcoming market failures in medical product R&D 154
1. Diseases disproportionately affecting people in developing countries 154
2. Antimicrobials and antimicrobial resistance 155
3. The WHO R&D Blueprint for Action to Prevent Epidemics 157
4. WHO Expert Working Groups on R&D financing 158
5. Novel approaches to biomedical R&D 158
6. Product development partnerships 164
7. Research for neglected diseases: the role of pharmaceutical companies 166
8. WIPO Re:Search - Mobilizing intellectual property for global health 166
D. Intellectual property rights in the innovation cycle 169
1. IP management within the broader legal and policy framework at national and international levels 169
2. Intellectual property and the product development process 171
3. Patent filing strategies in the public and private sectors and the exercise of patent rights 171
4. Pre-grant issues: questions of patentability 172
5. Post-grant issues: questions related to the use of patents 179
E. Sharing of influenza viruses and access to vaccines and other benefits 183
1. WHO Global Influenza Surveillance and Response System 183
2. Intellectual property rights in the context of PIP negotiations 183
3. The PIP Framework 184
4. The PIP Framework and genetic sequence data 185
IV. Medical technologies: the access dimension 193
A. The context: health-systems-related determinants of access 195
1. Universal health coverage 196
2. International access frameworks: the value chain of medicines and health products 197
3. The meaning and measurement of "access" 198
4. Generic medicines policies, price controls and reference pricing 199
5. Taxes 206
6. Mark-ups 207
7. Rational selection and use of medicines 207
8. Effective and efficient procurement mechanisms 209
9. Sustainable financing 212
10. Manufacturing and technology transfer 212
11. Regulatory mechanisms and access to medical technologies 213
12. Substandard and falsified (SF) medical products 217
B. Access to health products in specific areas 220
1. HIV/AIDS 220
2. Antimicrobial resistance 222
3. Tuberculosis 223
4. Non-communicable diseases 224
5. Hepatitis C virus 227
6. Paediatric medicines 228
7. Vaccines 229
8. Medical devices 230
C. Intellectual-property-related determinants of access 232
1. Determinants of access prior to patent grant 233
2. Pre-grant and post-grant review procedures 235
3. Post-grant determinants of access 236
4. Patent information and its relationship with public health policy 255
5. Review of relevant provisions in free trade agreements 255
D. Other trade-related determinants of access 265
1. International trade and tariff data of health products 265
2. Competition law and policy 273
Annex I. Resolutions of the UN General Assembly and UN Human Rights Council Key Reports of the UN Special Rapporteur on the Right to Health 295
A. Selected Resolutions of the United Nations General Assembly 297
B. Selected Resolutions of the United Nations Human Rights Council 298
C. Key Reports of the United Nations Special Rapporteur on the Right to Health 299
Annex II. Selected Resolutions and Decisions of the World Health Assembly 300
Annex III. Special Compulsory Licences for Export of Medicines 304
A. Operation of the System: context and scope 306
B. Legal basis 306
C. Use of the System 306
D. Domestic implementation 309
Bibliography 312
Abbreviations 331
Table 2.1. Information available in MedsPaL and Pat-INFORMED 78
Table 2.2. Examples of search parameters for pharmaceutical substances 80
Table 2.3. Number of GATS commitments (as of 2020) 104
Table 2.4. Coverage in the health sector by parties to the WTO GPA 107
Table 3.1. PRVs issued, 2009-2019 162
Table 3.2. Pharmaceutical industry centres dedicated to NTDs R&D 167
Table 3.3. IP issues that may arise at each stage of the product development pipeline 170
Table 3.4. The different roles of patents in the medical devices industry and the pharmaceutical industry 172
Table 3.5. Summary of benefit-sharing options under SMTA 2 185
Table 4.1. Selected country experiences with compulsory licences and government-use licences 242
Table 4.2. Comparison of expected patent expiry dates and dates of SPC expiry in France, for selected medicines on the WHO EML 252
Table 4.3. Provisions in selected FTAs with a bearing on access and innovation in the pharmaceutical sector 256
Table 4.4. Public-health-related products 266
Table 4.5. International trade in health-related products: share of main importers, 2018 267
Table 4.6. International trade in health-related products: share of main exporters, 2018 268
Table 4.7. Net exporters of pharmaceutical products (categories A1, A2, A3), average 2016-2018 269
Table 4.8. Net importers of pharmaceutical products (categories A1, A2, A3), average 2016-2018 269
Table 4.9. Share of health product imports in total national imports, 2018 270
Figure 1.1. Leading causes of disease burden in DALYs in 2000 and 2016 globally 37
Figure 1.2. Leading causes of death in 2000 and 2016 globally 37
Figure 1.3. Global burden of disease ranking, 1990 and 2017 38
Figure 1.4. The distinct policy domains of public health 40
Figure 1.5. Policy intersections between distinct levels 41
Figure 2.1. Key challenges in implementing national action plans 55
Figure 2.2. Stewardship, innovation and access: a delicate balance of conflicting goals 55
Figure 2.3. Illustration of terms of patent protection and regulatory exclusivities 64
Figure 2.4. Growth of the top four technology fields, 2000-2019 82
Figure 2.5. PCT applications in the field of medical technology, including pharmaceuticals, 2000-2019 82
Figure 2.6. Main countries of origin of PCT publications in the field of medical technology, including pharmaceuticals, 2000-2019 83
Figure 3.1. Approvals of medicines by the US Food & Drug Administration, 1944-2019 138
Figure 3.2. Global R&D expenditures, PCT international application publications on pharmaceuticals and novel drug approvals in the United States, 2004-2019 138
Figure 3.3. Novel drug approvals, percentage with orphan designation and R&D expenditure as percentage of sales, 1999-2019 139
Figure 3.4. Patent publications by technology: performance by sector, income group and world, 1980-2017 140
Figure 3.5. Top countries of origin of PCT publications in the field of pharmaceuticals, 1996-2019 142
Figure 3.6. The innovation cycle 147
Figure 3.7. Timeline of the discovery of different antibiotic classes in clinical use 156
Figure 3.8. Number and sales values of PRVs 163
Figure 4.1. The WHO Health System Framework 196
Figure 4.2. The three dimensions of universal health coverage 197
Figure 4.3. Ensuring access along the value chain of medicines and health products 198
Figure 4.4. Local production and access to essential medical products: a framework for improving public health 214
Figure 4.5. Sales revenue per year of generic and originator ARVs in LMICs 221
Figure 4.6. Sales quantities per year of generic and originator ARVs in LMICs 222
Figure 4.7. Challenges in access to AMR-related technologies in LMICs 223
Figure 4.8. Detention of generic medicines in transit by EU Customs 254
Figure 4.9. Evolution of IP chapters in FTAs: developments from 2000 to 2019 260
Figure 4.10. Imports of health-related products 1995-2018, by value (in US$ million) and compound growth rates, 2018 267
Figure 4.11. Per capita imports of pharmaceutical formulations 1995-2018 270
Figure 4.12. Tariffs on health-related products: simple applied average versus WTO simple bound average rates, by product category, 2018 271
Boxes
Box 1.1. WHO-WIPO-WTO technical symposia 35
Box 1.2. The disability-adjusted life year (DALY) 36
Box 1.3. Health and medical technologies: fundamental concepts 42
Box 2.1. Selected reports on access to medicines and R&D 50
Box 2.2. The Global Strategy and Plan of Action on Public Health, Innovation and Intellectual Property 53
Box 2.3. CRISPR-Cas9 gene-editing technology 61
Box 2.4. CAR T-cell therapy 61
Box 2.5. Selected types of US regulatory exclusivity 63
Box 2.6. The Paris Convention 67
Box 2.7. TRIPS and public health: key milestones 68
Box 2.8. The Patent Cooperation Treaty 70
Box 2.9. Societal and moral values in the patent system 72
Box 2.10. WIPO Standing Committee on the Law of Patents 76
Box 2.11. Selected databases 78
Box 2.12. The example of colchicine 86
Box 2.13. The Madrid System for the International Registration of Marks 87
Box 2.14. Artificial intelligence and health 92
Box 2.15. Definition of flexibilities according to WIPO 95
Box 2.16. TRIPS flexibilities highlighted in the GSPA-PHI and Road Map for Access to Medicines, Vaccines and Other Health Products, 2019-2023 95
Box 2.17. The example of Cambodia: an LDC's terms of accession to the WTO 98
Box 2.18. Merger control in the European Union 100
Box 2.19. Antimicrobial resistance in the SPS Committee 103
Box 2.20. Product patents and access to innovative medicines in a post-TRIPS era 113
Box 2.21. The Nagoya Protocol on Access to Genetic Resources and the Fair and Equitable Sharing of Benefits Arising from their Utilization to the Convention on Biological Diversity (Nagoya Protocol) 118
Box 3.1. IP and licensing in the discovery of insulin 137
Box 3.2. Adaptation of medical devices to developing-country needs - the example of portableelectrocardiographs 144
Box 3.3. Monoclonal antibodies 145
Box 3.4. New innovation models in practice: tailoring a meningitis vaccine for Africa 149
Box 3.5. Advance market commitments in vaccines 150
Box 3.6. European Medicines Agency makes available clinical trials data 153
Box 3.7. Initiatives to revitalize the antimicrobial pipeline 157
Box 3.8. WHO R&D Blueprint for Action to Prevent Epidemics: priority list as at February 2018 158
Box 3.9. 2012 CEWG report: key recommendations 158
Box 3.10. Unitaid 160
Box 3.11. Examples of prize schemes 160
Box 3.12. Examples of successful product development partnerships 165
Box 3.13. Patenting products of nature - the Myriad case 173
Box 3.14. Examples of drug-device combinations 175
Box 3.15. How India defines and applies patentability criteria 177
Box 3.16. Second use patents: the case of fluoxetine 178
Box 3.17. WIPO Patent Search Report on PIP-Related Patents and Patent Applications 184
Box 4.1. The US Hatch-Waxman Act as a supply-side measure to encourage generic competition 200
Box 4.2. Price control and reference prices to reduce prices of medicines in Colombia 202
Box 4.3. Examples of databases of medicines prices 205
Box 4.4. Differential packaging 206
Box 4.5. Authorized generics 206
Box 4.6. The WHO Model List of Essential Medicines 208
Box 4.7. Cost reduction/improvements in value for money in the health-care sector through centralized procurement: the example of Ecuador 210
Box 4.8. Examples of European pooled procurement initiatives: the Beneluxa Initiative and the Joint Procurement Mechanisms 211
Box 4.9. Developing local production capacities in Ghana: support measures and challenges 213
Box 4.10. Europe: tightening controls to guarantee the safety of medical devices 215
Box 4.11. WHO Global Surveillance and Monitoring System for Substandard and Falsified Medical Products 219
Box 4.12. Innovative Medicines for Tuberculosis (iM4TB) Foundation 224
Box 4.13. WHO, Pricing of Cancer Medicines and its Impacts (2019) 225
Box 4.14. Access to insulin 226
Box 4.15. Buyers' clubs 228
Box 4.16. Gavi, the Vaccine Alliance 229
Box 4.17. Precision medicine and the patentability of diagnostic and treatment methods 234
Box 4.18. Guidelines for the examination of pharmaceutical patents: developing a public health perspective 235
Box 4.19. The US Patent Trial and Appeal Board 237
Box 4.20. Government-use licences: efavirenz and lopinavir/ritonavir in Thailand 239
Box 4.21. Government-use licences: hepatitis C treatment in Malaysia 240
Box 4.22. Compulsory licences as a litigation tool 242
Box 4.23. Case study on supply of ARVs to Rwanda 246
Box 4.24. The Medicines Patent Pool 248
Box 4.25. Access to Medicine Index 249
Box 4.26. Cases under IIAs and FTAs 263
Box 4.27. The emergence of global value chains 268
Box 4.28. How tariff reductions can save human lives: the example of mosquito nets 271
Box 4.29. Sectoral tariff negotiations in the GATT and the WTO 272
Box 4.30. The WTO Trade Facilitation Agreement 273
Box 4.31. Competition investigation into strategic patenting - cases from South Africa 274
Box 4.32. Action against sham litigation in the pharmaceutical sector in Brazil 275
Box 4.33. Reverse patent settlement ruling by the Supreme Court of the United States and subsequent developments 275
Box 4.34. The European Union's Guidelines on Technology Transfer Agreements, monitoring and enforcement against reverse patent settlements in the pharmaceutical sector 276
Box 4.35. Competition law enforcement against a reverse patent settlement in the Republic of Korea 276
Box 4.36. Abuse of dominance in South Africa 276
Box 4.37. Applying competition law to generic manufacturers 278
Box 4.38. General approaches to "excessive pricing" in domestic laws 278
Box 4.39. Examples of "excessive pricing" cases concerning pharmaceuticals 278
Box 4.40. Jurisprudence on competition authority scrutiny to enable competition through off-label use 279
Box 4.41. Hospital merger in Brazil 279
Box 4.42. The 2019 Health Market Inquiry of the Competition Commission of South Africa 280