Strengthening Pharmaceutical Innovation in Africa Designing strategies for national pharmaceutical innovation: choices for decision makers and countries
Final Study Report: revised after review by the Extended Technical Committee on the Pharmaceutical Manufacturing Plan for Africa
Supporting - The African Union’s Pharmaceutical Manufacturing Plan for Africa - Global Strategy and Plan of Action on Public Health, Innovation and Intellectual Property
African Union Council on Health Research for Development (COHRED) The NEPAD Agency of the African Union (New Partnership for Africa's Development) with contributions from The George Institute for International Health
COHRED Council on Health Research for Development
AFRICAN UNION Acknowledgments This report presents the results of a study done between 2007 and 2009 in a collaboration between the Council on Health Research for Development (COHRED) and the New Partnership for Africa’s Development (NEPAD), as part of the project “The Yaoundé Process - Strengthening health innovation in Africa – From Agendas to Action”, funded by the Netherlands Ministry of Foreign Affairs (DGIS). The George Institute for International Health contributed the Pharmaceutical Innovation Grid and its related tools in Chapter 5. The report was reviewed by: Prof. Abdallah Daar, McLaughlin-Rotman Centre for Global Health, University of Toronto Dr. Precious Matsoso, Director Secretariat for Public Health, Innovation and Intellectual Property (PHI), WHO Dr. Charles Mgone, Director European Union and Developing Countries Clinical Trials Partnership (EDCTP).
The authors acknowledge the following people who provided valuable comment, reflection and advice that enhanced this report: Alain Aumonier, Vice President, Relations with International Institutions, Sanofi-Aventis; Director of Public Health Partnerships, IFPMA; Willbert Bannenberg, Technical Director, International Secretariat for the Medicines Transparency Alliance (MeTA); Robert Buizert, Senior Consultant, IDA Solutions; Nicoletta Dentico, Advisor on Public Health, Innovation and Intellectual Property, IQsensato; Chris Edlin, Director of Chemistry, iThemba Pharmaceuticals; Simon Efange, Professor, University of Buea, Cameroon; Charles Gardner, Global Forum for Health Research; Emily Harwit, Monitoring and Priority Sector Coordinator, eeagrants, Brussels, Belgium; Richard Laing, Policy, Access and Rational Use, Medicine Policy and Standards, WHO; Rose Leke, Professor, Head of Department of Microbiology, Immunology and Haematology, University of Yaoundé, Cameroon; Tom Mboya Okeyo, Ambassador to United Nations, Deputy Permanent Representative, Permanent Mission of Kenya, Geneva, Switzerland; Sisule Musungu, President, IQsensato; Vinand Nantulya, Senior Policy and Implementation Officer, FIND; Mariane Ngoulla, Health and HIV Advisor, ECOWAS, Abuja, Nigeria; Solomon Nwaka, Business line Leader, TDR; Geneva, Switzerland; Barthelemy Nyasse, Professor, University of Yaoundé, Cameroon; Echeazor Ogu, Bon Science Pharma and Biotech consulting and training, Newark, USA; Eva Ombaka, Ecumenical Pharmaceutical Network, Nairobi, Kenya; Clive Ondari, coordinator, Policy, Access and Rational use, Medicines Policy and Standards, WHO; Bernard Pecoul, Executive Director, DNDi; Giorgio Roscigno, Chief Executive Officer, FIND; Harry Van Schooten, Euvadis; Tido Von Schoen-Angerer, Executive Director, Campaign for Access to Essential Medicines, MSF; Nadine Vohrer, Business Environment and Policy Support Unit, Private Sector Development Branch, United Nations Industrial Development Organisation (UNIDO); Charles Wambebe, President, International Biomedical Research in Africa.
Keywords Innovation for health/ Technology transfer/Pharmaceutical innovation/ Pharmaceutical research and Development/ Research for Health / National Health Research Systems / Africa /Noordwijk Medicines Agenda/ African Union Pharmaceutical Manufacturing Plan/Global Strategy and Plan of Action on Public Health, Innovation and Intellectual Property (GSPOA) / Council on Health Research for Development / COHRED / The New Partnership for Africa’s Development (NEPAD).
Citation Berger, M; Murugi, J; Buch, E; IJsselmuiden C; Moran, M; Guzman, J; Devlin, M; Kubata, B. Strengthening pharmaceutical innovation in Africa. Council on Health Research for Development (COHRED); New Partnership for Africa’s Development (NEPAD) 2010.
© 2010 Council on Health Research for Development (COHRED) New Partnership for Africa’s Development (NEPAD). ISBN 92-9226-038-3
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Printed on 100% recycled paper with environmentally friendly ink. Strengthening Pharmaceutical Innovation in Africa
Final report of the study and Pharmaceutical Innovation Tool. Revised after review by the Extended Technical Committee on the Pharmaceutical Manufacturing Plan for Africa.
The initiative: Strengthening Pharmaceutical Innovation Africa, is endorsed by the African Ministerial Conference on Science and Technology (AMCOST)*
* Political endorsement by Science and Technology Ministers for the NEPAD Agency/African Research for Health Initiative (NARHI) During its fourth ordinary session held from 7-10th March 2010 in Cairo, the African Ministerial Conference on Science and Technology (AMCOST IV) adopted the following: • It noted and appreciated the progress made by the AUC and the NEPAD Agency in the implementation of the CPA. • It commended the NEPAD Agency for its program on pharmaceutical innovation and harmonization of drugs registration in the AU Member States in line with (i) the Global Strategy and Plan of Action on Public Health, Innovation and Intellectual Property of the World Health Organization; (ii) the AU Health Strategy and Pharmaceutical Manufacturing Plan for Africa; and (iii) the Africa Science and Technology Consolidated Plan of Action of the African Union. Foreword
Practical approaches for countries: Africa’s perspective on medicines access and pharmaceutical innovation.
This study and the resulting initiative, Strengthening Pharmaceutical Innovation in Africa, come at an important moment in the development of pharmaceutical innovation strategies in Africa and in achieving access to essential medicines for all in Africa.
Two landmark agreements for research and medicines production in Africa have been reached. The Global Strategy on Public Health, Innovation and Intellectual Property is a mechanism signed by 192 countries that calls for increased investments for research and production of medicines that are needed by countries, to be coordinated by them. The Pharmaceutical Manufacturing Plan for Africa, adopted by the Summit of the African Union in 2007 is the basis for a more coordinated approach to local medicines production – based on countries’ needs.
These agreements and other developments set the foundation and a long-term political agreement for the planning and financing of medicines research and production on the African continent.
At the same time, much work remains to be done to make national and regional pharmaceutical and health innovation a reality for our countries. Countries need to better understand their current situation, their potential for engaging in local research and medicines production and they need to develop strategies to do this.
This report and tool mark the starting point of an initiative to strengthen pharmaceutical innovation in Africa. It started with a study and practical reflection between countries on what is needed to provide better access and encourage local production of medicines in Africa. It was reviewed and revised by the Extended Technical Committee on the Pharmaceutical Manufacturing Plan for Africa incorporating the core committee of member state representatives and other experts in health and health policy, science and technology, trade and industry and pharmaceuticals – in Pretoria in February 2010. The initiative, its study and pharmaceutical innovation tool, have been endorsed by the African Ministerial Conference on Science and Technology (AMCOST) at its meeting in Cairo in March 2010.
The regional dimension will have an important place in this process. As an African vision and agenda for pharmaceutical innovation emerge, the Regional Economic Communities will have an important role to play, both as catalysts and ‘multipliers’ to build consensus, and move the plan forward by coordinating member countries. The collaborative spirit in which this report was produced fits well with two of NEPAD’s core mandates: building capacity of Africa’s health research and science and technology sectors; and making knowledge management and sharing a way of working for science, across the continent. The process started by this study serves both of these goals.
These two mandates are also central to the Memorandum of Understanding between NEPAD and the Council on Health Research for Development (COHRED), which provides technical support to NEPAD and countries for this initiative. It was first signed in 2005 and renewed and updated this year for a further five years. Under this strategic partnership, NEPAD calls on COHRED to provide technical input, to conduct studies on questions of health research – especially for system building – and to support NEPAD’s long-term investment in creating African centers of excellence in various aspects of health research. In a linked initiative, ‘Research for Health Africa’, NEPAD and COHRED are working together to build and develop the capacity of managers and health research systems in a number of countries.
Based on the comments and review by the Extended Expert Committee, I encourage my African colleagues working in research for health, science and technology, and trade and industry to make use of the pharmaceutical innovation tool presented here and of the new knowledge generated by the study. In doing this we will start developing a broad- based perspective and consensus on Africa’s needs for access to medicines and pharmaceutical innovation for our future.
Dr Ibrahim Assane Mayaki Chief Executive Officer New Partnership for Africa’s Development - NEPAD NEPAD Planning and Coordination Agency Table of Contents
Executive Summary 7
1 Introduction 10 1.1 What is “pharmaceutical innovation”? 10 1.2 Issues for pharmaceutical innovation in Africa 10
2 Context analysis 15 2.1 Africa’s burden of disease 15 2.2 Africa in the global pharmaceutical picture 15 2.3 The poverty factor 16 2.4 Changing landscape, new actors, new funding sources 17 2.5 The Global Strategy and Plan of Action on Public Health, Innovation 18 and Intellectual Property in Africa 2.6 The Noordwijk Medicines Agenda and Yaoundé Process 18
3 A picture of pharmaceutical innovation in Africa 20 3.1 The African landscape is complex 20 3.2 Available evidence is not effectively disseminated 20 3.3 Better coherence and coordination are necessary 22 3.4 Countries need to be placed at the centre of decisions for pharmaceutical innovation 22
4 Essential building blocks for national pharmaceutical innovation 24 4.1 Prerequisites 24 4.1.1 Creating an investment-friendly environment 24 4.1.2 Enabling policies and supportive initiatives 24 4.1.3 Strengthening functional health research systems as essential foundations 26 4.2 Essential components 28 4.2.1 Intellectual Property: The Achilles’ heel? 28 4.2.2 Technology transfer: What needs to be shared and how? 32 4.2.3 Local pharmaceutical production: Is it the solution? 33 4.2.4 Pharmaceutical industry and health partnerships: what is their role? 34 4.2.5 Delivery and access: are they neglected? 34 4.3 Several cross cutting issues are critical factors of success 38 4.3.1 Governance 38 4.3.2 Financing 39 Current investment in African pharmaceutical innovation is low 4.3.3 Legal and regulatory framework 40 Drug regulation 4.3.4 Human resources and knowledge management 41 Human resources Open sources of information 4.3.5 Partnerships 43 5 Tools and approaches 44 5.1 General approaches to developing a pharmaceutical innovation system 44 5.2 Framework for developing a national pharmaceutical innovation system 45 5.3 Pharmaceutical Innovation Grid for assessment, priority setting and strategy design 49 5.4 Database of pharmaceutical innovation initiatives 55 List of pharmaceutical innovation initiatives Database of pharmaceutical innovation literature 5.5 Country case studies 56 Case study 1 – Approach for African Country 'A' Case study 2 – Approach for African Country 'B'
6 The way forward – Conclusions and recommendations 62 6.1 Where are we now? 62 6.2 Major findings and conclusions of the Yaoundé Process 63 6.2.1 A growing demand for pharmaceutical innovation in Africa – and globally 63 6.2.2 Complexity of the landscape of pharmaceutical innovation 65 6.2.3 Lack of approaches to help countries make decisions on engagement 65 6.3 Proposed next steps 66 6.3.1 Operationalising strategies and plans of action 66 6.3.2 Obtaining high-level political support for implementation 67 6.3.3 Starting implementation 67 6.3.4 Developing additional tools, frameworks and guidelines if and when needed 70 6.3.5 Monitoring and evaluating 70 6.4 Conclusion 71
Annexes Annex 1: Tools 72 - Innovation system framework 72 - Pharmaceutical Innovation Grid 73 - Article data base 76 Annex 2: Abbreviations and acronyms 83 Annex 3: Glossary 86 Annex 4: Capacity-strengthening matrix 88 Annex 5: Detailed table of initiatives 89 Annex 5-A: Global initiatives 89 Annex 5-B: Regional initiatives 91 Annex 5-C: Multi-country initiatives 93 Annex 5-D: National initiatives 95 Annex 5-E: Public Private Partnerships 98 Annex 5-F: International Organisations initiatives 99 Annex 5-G: Pharmaceutical partnerships in Africa initiatives 100 Annex 5-H: National Pharmaceutical initiatives 104 Annex 6: Visual mapping of initiatives 105 Annex 7: Visual mapping of building blocks 106 Annex 8: Noordwijk Medicines Agenda 107
Endnotes 110
Endorsed by Africa’s ministers Executive summary of Science and Technology
The Initiative for Strengthening Pharmaceutical The initiative: Strengthening Pharmaceutical Innovation Africa, Innovation in Africa was endorsed in March 2010 by the African Ministerial Conference on Science and Technology This publication provides the evidence base and direction for the initiative: (AMCOST) as the starting point for African countries to put into Strengthening Pharmaceutical Innovation in Africa. action the: The initiative is based on the study conducted by NEPAD and COHRED in • Global Strategy and Plan of 2008-2009 on the pharmaceutical innovation landscape and current approaches Action on Public Health, in Africa. From these findings, the first pharmaceutical innovation tool – the Innovation and Intellectual Pharmaceutical Innovation Framework and Grid – has been produced. Property of the World Health Organization • African Union Health Strategy Strengthening Pharmaceutical Innovation in Africa is a long-term and Pharmaceutical capacity building programme created by African research and political leaders Manufacturing Plan for Africa. who are active in health research and pharmaceutical innovation. The initiative supports African countries to craft strategies and build skills and to engage in Guided by NEPAD the initiative is pharmaceutical innovation and access to medicines for the benefit of the an effective coordinating mechanism for pharmaceutical continent’s population. innovation, medicines access and The initiative is a partnership between the African Union; the New research capacity strengthening Partnership for Africa’s Development (NEPAD) – ensuring implementation and activities in Africa. support to countries; and the Council on Health Research for Development (COHRED) – bringing technical support to NEPAD and countries for research capacity strengthening.
Study and analysis of innovation and medicines access in Africa Call for Partners The study presented here (Chapters 1-4) is the first of its kind to analyze The Initiative is seeking partners countries’ needs and the obstacles to putting pharmaceutical innovation into among pharmaceutical and action in a low/middle income country context. It presents a map of development organisations to innovation and access activities in Africa (Strengthening Pharmaceutical support developing of countries’ capacity for research and Innovation in Africa - NEPAD, COHRED 2009 www.nepad.org - innovation, in areas such as: www.cohred.org/African_Innovation). • Work with countries to develop national and regional strategies Tool for countries - pharmaceutical innovation framework and grid for pharmaceutical innovation Chapter 5 presents the tool for countries – the Pharmaceutical Innovation and access. Framework and Grid. Developed as part of the study, it is a unique planning • Targeted capacity building of tool, that has been reviewed and adapted to countries needs. The tool helps senior research managers, policy countries do self-assessments, develop strategies, build capacity and makers and researchers to better design and manage partnerships to engage in innovation and improve access to essential medicines. innovation and access activities. • Regional meetings and Validation and expert review exchanges to share experience This report reflects the views and needs of African countries. The study, and the and forge partnerships – Pharmaceutical Innovation Framework and Grid, have been critically reviewed between policy makers, by the Extended Technical Committee on the Pharmaceutical Manufacturing pharmaceutical producers, Plan for Africa it included experts from 11 African countries that are the core of research organizations and civil society. the Committee, national leaders in research and policy making, members of • Further development of useful the African pharmaceutical industry, representatives of civil society and tools and processes to help members of several international organisations, including the World Health implement the WHO ‘Global Organization (see Meeting Final Statement and participants list in Annexes). Strategy’, and the AU Health Their insights and comments are included in this updated final report. Strategy and the Pharmaceutical Manufacturing Plan for Africa.
7 Country needs and global Moving forward: Strengthening pharmaceutical innovation in Africa. health initiatives in Africa Chapter 6 details comments received from the group1, and presents their recommendations on how the initiative on Strengthening Pharmaceutical Today there are many initiatives and organisations that do research Innovation in Africa can be taken forward to support countries to provide and develop cures to neglected pharmaceutical access and innovation to their populations. diseases, that produce and deliver Strengthening Pharmaceutical Innovation in Africa has three broad areas: medicines, and improve access to • Preparing an action plan and proposal to secure funding to provide medical products in Africa. ongoing support to countries for strategy development and capacity More than 120 have been building. identified in this study and • Identifying a core of countries interested in becoming ‘first presented in a map (See page 21). adopters’ of the Pharmaceutical Innovation Framework and Grid, This diverse field of players is supported by NEPAD and COHRED. This will be the first practical generally shaped by the interests approach to putting the GSPOA and AU Pharmaceutical business plan of international programmes and into action at country and regional level. funders and often does not • Close monitoring of this work (for a proof of concept), and sharing this directly engage with countries and learning with other countries in Africa and beyond as a part of the process. their public health needs.
The goal of the initiative, Strengthening Pharmaceutical Summary of recommendations Innovation In Africa, its study and tools is to provide the perspective (Full recommendations are detailed in Chapter 6) and evidence that helps countries to manage their affairs for This Pharmaceutical Innovation Tool (Framework and Grid) was pharmaceutical innovation and reviewed by the AU Technical Committee on the Pharmaceutical access to medicines. Manufacturing Plan for Africa; extended to include a broad group of African leaders in research and policy, pharmaceutical development partners, and members of civil society held in the Pretoria meeting (February, 2010),
The Committee recommended the use of this tool by African countries to design strategies and build their capacity for national and regional innovation.
The study complements previous studies on innovation. The experts confirmed that this study and tool converge with the results of their analysis in 2007. They recommend to use the report findings and tool to support the African Union’s business plan for the Pharmaceutical Manufacturing Plan for Africa (PMPA).
Supporting harmonization and evaluation of the 'Global Strategy' and African Pharmaceutical Manufacturing Plan. The experts said that the tool is a useful mechanism for coordinating and harmonising between the various players involved in implementing the Pharmaceutical Manufacturing Plan for Africa (PMPA); and for monitoring and evaluation aspects of the PMPA and WHO Global Strategy and Plan of Action on Public Health, Innovation and Intellectual Property (GSPOA). The group recommended: • Establishing objectives and milestones for pharmaceutical innovation and manufacturing in Africa. • Creating mechanisms to stimulate research and development, technology transfer and other conditions needed to facilitate and strengthen manufacturing in Africa. • Creating a coordination mechanism to ensure better synergy and improved intra and inter-regional support.
8 Implementing innovation in countries “How can my country provide • Establish a mechanism to manage information on country better access to essential developments. medicines?” • Create a workshop series to ensure governments and regulatory The answer to this simple question authorities the best available information and share expertise and is a complex one that requires lessons learned – to include mentoring and partnerships (4.-6 sessions detailed reflection. per year over 5 years). To invest in national pharmaceutical innovation, countries can focus on long-term Ensuring Access: economic benefits by • Strengthen policies and enforce regulations on substandard drugs, strengthening science and dumping of medicines, and donated drugs resulting in mono-therapy technology and adjacent sectors, and increased resistance. such as drug delivery • Build capacity of agencies to ensure safe, high quality medicines. infrastructure. Or they can focus on improving universal access to • Strengthen drug regulatory capacity, especially for inspection, quality essential medicines. control and laboratory work. • Increase national capacities to address international intellectual property Both approaches are viable. And countries often mix the two laws, health insurance. objectives when considering • Explore regional partnerships to share expertise between countries. innovation strategies. In the end, • Build will contribute to sustainable financing and improve access. decision makers must be clear on the balance they want to achieve Manufacturing: and craft a strategy that meets their short and longer term goals • Universities to align curricula to produce the skills needed. — economic development, • African governments to establish fund to provide low interest loans. improved access, or both. • Country to forge partnerships with agencies (e.g. UNIDO) for WHO The expertise needed for local prequalification. medicines production extends well • Governments to assist local manufacturers to overcome challenges of beyond public health. It also prequalification, especially cost of bio-equivalence studies. covers research and development, • Build capacity in traditional and phyto-medicines, cultivating medicinal intellectual property, trade and plants. Including specific skills of national regulatory authorities in commerce, tax and tariff policies, drug regulatory and registration taxonomy, quality control and microbiology, among others. issues, finance, raw materials • Increase competitiveness of local manufacturers. procurement, medicines, • Do feasibility studies to provide evidence for financing local pharmaceutical manufacturing manufacturing. and marketing. The capacity to produce should Capacity building for R&D not be viewed independently • Establish an enabling research environment and build human and from the need for building national capacity for innovation. institutional resources for creating a critical mass of scientific leaders across research institutions in Africa, building up on specific competence already existing in various research institutions and looking for networking opportunities and collaborations, for instance by encouraging the development of regional centres of excellence. • Promote partnerships between research institutions and private sector to build up capacity in real novel drug discovery. • Build up specific capacities for dealing with traditional medicines, especially in the areas of developing remedies, pharmacology training, expertise in taxonomy, quality control of medicinal plants and microbiology, among others. • Encourage African states to allocate 2% of their national budget for research.
9 Chapter 1 Introduction
A ‘systems’ approach 1.1 About this report to innovation Across Africa today there are dozens of activities in the broad area of pharmaceutical This initiative advocates innovation – focusing on procurement, development and access to drugs. In contrast, that countries take a there are no comprehensive descriptions and little evidence on the current status of systems and evidence-based 2 approach to shaping their pharmaceutical innovation . pharmaceutical innovation This study aims to fill this information gap. And to equip decision makers to strategies and priorities. decide where they want to go with pharmaceutical innovation—and reflect on how It encourages them to set to get there. realistic targets for access Most current thinking on innovation is based on evidence from developed countries. and innovation and provides Apart from some surveys undertaken by the Technical Committee of the AU a tool to guide decision makers in the creation of a Pharmaceutical Manufacturing Plan to inform the implementation of the plan, this national innovation system study is perhaps the first of its kind to offer a critical analysis of the constraints, for health – the resources and challenges in the region— from the viewpoint of African decision Pharmaceutical Innovation makers. It focuses on how countries can put innovation into action to support their Framework and Grid. health needs – in terms of priorities, investment needs – and provides tools for decision Successful pharmaceutical innovation is the result of a makers to design national and regional innovation strategies. complex web of interactions This report also attempts to clarify issues of research and innovation for health and between many stakeholders, development. These are much-discussed in the ‘inner circle’ of global health debates including multiple and intergovernmental bodies, but less understood by national decision makers who government ministries, regulatory authorities, and define national policies and strategies in the health, science and technology. private and public research, development, teaching and 1.2 Background and context healthcare delivery With non-communicable disease on the rise and infectious disease continuing to take a institutions. Countries have diverse landscapes for heavy toll on people’s health, Africa is confronted with a very high disease burden. Yet, health research, innovation there are well known and sometimes simple solutions that can help African populations and pharmaceutical address their health problems, especially if they had regular access to safe and effective production. treatment and care. Access to medicines is a recognised and well-established universal Each will implement the human right; but one that is far from being guaranteed for a majority of Africans. Global Strategy and Plan of 3 Action (GSPOA) in a African governments have taken decisive steps in a series of ministerial declarations different way and needs to to address this problem. The African Union (AU) has adopted a clear policy position ‘to better understand where pursue, with the support of our partners, the local production of generic medicines on they are situated in terms the Continent and make full use of flexibilities within the Trade and Related Aspects of of health innovation and access to essential medical Intellectual Property Rights (TRIPS) and Doha Declaration on TRIPS and Public Health’. To products, to decide where this end, the AU adopted the Pharmaceutical Manufacturing Plan for Africa in 2007 they want to go and how to and gave mandate to a technical committee to coordinate the efforts. get there. The AU and the New Partnership for Africa’s Development (NEPAD) are spearheading a number of initiatives to promote knowledge-based economic growth in Africa and to strengthen countries’ capacity for policy formulation in the science, technology and innovation sector that includes pharmaceutical innovation. At the global level, awareness of the need for the international community to improve access to affordable, essential medical products for vulnerable populations has increased over the past decade. Challenged by the burden of HIV/AIDS and pressure from civil society for increased access to antiretroviral medicines, the international community started negotiating new rules and developed new mechanisms for improving access to affordable, good quality, essential drugs and medical products. While great efforts are being made to provide incentives and support to enhance the accessibility of low and middle countries to life saving drugs – particularly with
10 NEPAD-COHRED - Strengthening Pharmaceutical Innovation in Africa the emergence and multiplication of product development public private partnerships – certain diseases and conditions primarily affecting developing countries remain truly neglected4. The problem of access to essential medical products – diagnostics and vaccines as well as medicines – persists for reasons that are complex and often interlinked. They have to do with trade agreements, market size, drug pricing, intellectual property and competition within the pharmaceutical industry as well as with a progressively drying R&D pipeline, the financing of R&D and pharmaceutical production, procurement and supply issues, and the failures of health systems in many poor countries and regions. This complex situation calls for a comprehensive approach that will improve coherence among many players across different sectors. The Global Strategy and Plan of Action on Public Health, Innovation and Intellectual Property (GSPOA) is probably the most important initiative to date that enables developing countries to access the drugs they need and to support innovation in these regions. Adopted in 2008 by the World Health Assembly, the Global Strategy reached Access to medicines is a well-established universal an international consensus on the need to provide long-term support and financial human right; but one that mechanisms for needs-driven research and development on ‘diseases that is far from being disproportionately affect developing countries’. guaranteed for a majority The GSPOA and the African Union Pharmaceutical Manufacturing Plan (PMPA) of Africans. are mechanisms that aim to put countries in the driver’s seat for access, research and local medicines production. Together, they form the first comprehensive framework and promise of long-term funding to support countries’ strategies for pharmaceutical innovation. The GSPOA and the African Union’s PMPA are aspirational statements that need to be translated into practical work plans and action. With clear political support for the need for access to drugs for low- and middle- income countries, the big challenge now – for global health stakeholders and countries – is how to effectively implement the Plan of Action. Africa faces particularly challenging gaps in access to essential medical products. Countries have very different needs and resources and not all will be able to implement all aspects of the Global Strategy. This report proposes an overview of pharmaceutical innovation today, analyses its main gaps, challenges and resources and presents a framework for assessing, prioritising and planning pharmaceutical innovation strategies.
1.3 What is ‘pharmaceutical innovation’? Health innovation covers a wide range of scientific, medical, economic and social issues. This study focuses on the concept of pharmaceutical innovation— the discovery, development, production and delivery process that enhance the availability of medical products and people’s access to them. In this case, ‘medical products’ include diagnostics, drugs, vaccines and medical devices. The industry view of pharmaceutical innovation is largely linear, as illustrated in the drug pipeline that ranges from discovery to registration (Figure 1). In 2006, the WHO Commission on Intellectual Property Rights, Innovation and Health (CIPIH) described innovation in the developed world as a cycle from discovery of new lead products to development and delivery of new tools and back to discovery through effective demand based on health needs and post marketing research5. CIPIH noted that economic constraints in low income countries lead to significant gaps in this cycle. Despite pressing health needs, the demand for pharmaceutical innovation is weak. Figure 2 represents the ‘3D’ Innovation Cycle – of demand, discovery and development.
11 Research focuses on various problems and results in diverse discoveries: new drugs, new vaccines, and new diagnostics. Beyond all this, existing tools adapted for local application and relevance, new strategies to use these tools, new social or economic policies to reinforce their use or create a supportive environment for their application fall under the umbrella of ‘health innovation’. Just as there is no universally accepted definition of innovation, there is no single definition of what an innovation system is, or what constitutes such a system. Industrialised countries, and some innovative developing countries, may have a structured system to stimulate, support and create innovation, with well-defined actors, established institutions and clear coordinating mechanisms and policies. Many other countries do not have a structured system, only a loose network of players involved in research, industry, or the social aspects of innovation.
1.3.1 Issues for pharmaceutical innovation in Africa The African population has the world’s highest burden of infectious and neglected diseases, and faces a rapidly-rising burden of non-communicable diseases. The hardest hit groups are women and children – half the world’s deaths of under-five’s are on this continent. This situation is further compounded by a lack of access to essential medicines for many of the affected populations. These health needs have been largely overlooked by a predominant focus on drug development for lucrative ‘western’ markets. The World Health Organization estimates6 that at least one-third of the world’s population lacks access to essential medicines. In poorer areas of Asia and Africa this figure is as high as 50%. This gap in Africa’s access to essential medicines highlights an urgent need to prioritize the public health agenda, in areas such as improving weak health systems, increasing the health workforce in quality and numbers, and more directly addressing the needs of disenfranchised populations. The development of knowledge-based economies, including a thriving pharmaceutical sector, will support the continent’s economic development. Recent international trade rules – requiring that countries comply with World Trade Organization TRIPS regulations7 – risk jeopardizing access to essential medicines by driving up cost of generic pharmaceuticals, which are affordable today. To mitigate this risk, the Doha Ministerial Declaration on the TRIPS Agreement and Public Health confirmed in 2001 that TRIPS should not prevent Members from taking
Figure 1, Drug pipeline, from discovery to registration
The linear approach of the classic pharmaceutical product development pipeline
Drug Lead Lead Preclinical Phase I Phase II Phase III Registration discovery identification optimisation transition
Adapted from Solomon Nwaka and Robert G. Ridley. Virtual drug discovery and development for neglected diseases through public–private partnerships. Nature Reviews Drug Discovery (2003) 2: 919-928
The innovation process as a cycle which presents demand and the population's health needs.
Translational Research 12
Discovery • Lead identification/
‘
M NEPAD-COHRED - Strengthening Pharmaceutical Innovation in Africa measures to protect public health, and that countries can use public health safeguards in the TRIPS Agreement. This was a major achievement that allowed India – one of the major exporters of pharmaceuticals to Africa today – and China, to manufacture and export drugs, making affordable antiretroviral medicines (ARVs) available in developing countries and worldwide. While TRIPS flexibilities offer a window of opportunity (until 2016) for the least developed countries to locally manufacture pharmaceutical products needed for public health, the practical implementation of this policy could be hampered by countries’ lack of capacity to manage legal, scientific, technical and fiscal aspects of pharmaceutical innovation. Very few low and middle-income countries are likely to be in a position to take advantage of this opportunity. In addition, recently- negotiated bilateral trade agreements further limit the ability of some countries to produce generic drugs and may have adverse consequences on the affordability of essential drugs8. Nevertheless, developing countries are striving to find alternative solutions. Some seek South-South collaboration to develop production. For example, the Indian company CIPLA is establishing manufacturing plants in Africa. Brazil, too, is providing support to African countries to strengthen their pharmaceutical innovation. The complex and dynamic trends in the global pharmaceutical market and global trade rules highlight the need for African countries to strengthen their capacity on two fronts: for research, development and local pharmaceutical production; and the ability to engage constructively in debates and deliberations that affect the health of their populations. In this picture, high income countries are well placed to support Tthehe capacity linear adevelopmentpproach of ofthe their cla slowersic p harmincomeaceu counterpartical products. t development pipeline
1.4 Scope and method TheDrug geographical Lead scope of theLead study is Africa.P reclinIt focusesical onPha diseasesse I that Phase II Phase III Registration discovery identification optimisation transition disproportionately affect Africa, including neglected tropical diseases. The method used was keyword internet searches, key informant interviews and discussions review of literature and documentation9, participation and consultation in Adapted from Solomon Nwaka and Robert G. Ridley. Virtual drug discovery and development for neglected a number of international meetings and consultations on pharmaceutical in several diseases through public–private partnerships. Nature Reviews Drug Discovery (2003) 2: 919-928 low income countries. The data obtained was analyzed manually along main emerging themes. The draft report was externally peer reviewed.
Figure 2, ‘3D’ Innovation Cycle
The innovation process as a cycle which presents demand and the population's health needs.
Translational Research
Discovery • Lead identification/ optimization Development • Basic research ‘3D’ • New/improved tools • Preclinical and clinical INNOVATION development CYCLE
Demand for new / Market approval improved tools and and manufacture post-marketing research Delivery • Getting products to patients
13 Step 1: Identifying and categorising projects and programmes contributing to the improvement of access to medical products in Africa. Global, regional and national examples were considered.
Step 2: examination of a minimum set of conditions, policies; human, structural and financial resources to identify initiatives most likely to be successfully implemented in any African country.
To guide reflection and analysis, several visual tools were used throughout the study process (Annexes 6 and 7) resulting in the development of the framework and grid presented in Chapter 5.
1.4.1 Limitations Due to limited scope, budget and time, the pharmaceutical innovation initiatives mapped in this paper are not exhaustive. A few illustrative, thought-provoking examples have been chosen, based on their unique contributions to specific components of pharmaceutical innovation in Africa. The extent to which some of the initiatives listed in this report contribute to pharmaceutical innovation in Africa has yet to be clarified. Evaluating the effectiveness of these initiatives was beyond the scope of the study and will be an important next step. Finally, the report reflects the predominant situation in a majority of African countries; but it does not fully represent the continent’s heterogeneity. It is hoped that subsequent phases of the project – that aim at using the tools developed as a result of this work – will allow for more in depth study of the specifics of disease burden, R&D capacities, production potential and level of development of the countries selected for implementation.
14 NEPAD-COHRED - Strengthening Pharmaceutical Innovation in Africa
Context analysis Chapter 2
2.1. Africa’s burden of disease Africa is home to 11% of the world’s population. It consumes less than 1% of global health expenditure10. Yet it carries 25% of the world’s burden of disease.
Major contributors to this disease burden are: • diseases of poverty, such as malnutrition, • infectious diseases, such as HIV/AIDS, malaria, diarrhoeal diseases, pneumonia • neglected tropical diseases (NTDs) • diseases predominantly affecting African populations, such as sickle cell disease
• non-communicable diseases, which are on the rise. 2/3 of the global value of pharmaceutical These problems are further compounded by limited access to safe, effective, quality and products are produced in affordable medicines, vaccines and diagnostic tools. Africa’s disease burden raises 5 countries (USA, Japan, concern on many fronts. Unmet health needs result in high morbidity and mortality, France, Germany and UK). Japan and USA creating a vicious cycle of poverty, disease, disability and death. contributed to 47% of global production value in 1999. Malaria’s economic burden Africa bears 90% of global malaria deaths. In addition to this, the direct and indirect impact of malaria results in an estimated US $12 billion annual income loss in Africa, which translates to a 1.3 % annual loss in growth domestic product (GDP) in malaria-endemic countries11. These significant health and economic losses from malaria and other high-burden diseases are compounded in countries struggling under a heavy debt burden, faced with weak governance, prolonged war and civil conflict, famine and other environmental catastrophes.
2.2 Africa in the global pharmaceutical picture Two thirds of global value of pharmaceutical products are produced in 5 countries; USA, Japan, France, Germany and UK. Japan and USA jointly contributed to 47% of global production value in 199912.
Figure 3,13 Local pharmaceutical R&D and production (WHO 2004)
15 In 1998, more than 97 % of research and development activities occurred in developed countries14. Africa’s capacity for pharmaceutical R&D and local drug production is among the lowest globally. Overall, 37 countries have some pharmaceutical production, and only South Africa has limited primary production of active pharmaceutical ingredient (API) and intermediates15. Local production in Africa therefore relies on imported active ingredients. As a result, the sustainability of African pharmaceutical supply remains highly contingent on foreign funding and manufacturing. While national capacity for local production has increased – with, for example, Egypt and Tunisia producing between 60% and 95% of their national requirements for essential medicines16 – it is still dramatically low in many countries of the continent, and Africa will remain dependent on imports for at least the medium-term. These disparities are replicated in global R&D for health needs specific to Africa. Though much effort is needed to address the dismal and outdated pool of products available for use in Africa, stimulating interest for R&D is an onerous task in this Prevailing trends in predominantly market-driven industry. From 1975 to 2004, only 1.3% of the 1556 new the global pharmaceutical chemical entities registered were meant for use in tropical diseases and tuberculosis, sector bring additional 17 barriers to Africa’s even though these diseases account for 12% of the global disease burden . Despite access to essential bearing a disproportionately large share of the global disease burden, African markets pharmaceutical products. remain unattractive because most countries have poor public health financing mechanisms and their already disenfranchised populations largely resort to out-of- pocket payments to finance their health care18. Prevailing trends in the global pharmaceutical sector pose additional barriers to Africa’s access to essential pharmaceutical products. Pharmaceutical R&D pipelines are running dry as ‘low hanging fruit’ (chemical entities that are easy to develop) have already been picked. In addition to this, there is increased competition from emerging pharmaceutical markets such as Brazil, Russia, India and China (BRIC) which are broadening their drug portfolios beyond generic products to include innovator drugs for western markets. For Africa, this situation brings a comparative advantage in the area of pharmaceutical innovation, development and production using African Traditional Medicine and the continent’s rich biodiversity as raw materials of choice. This presents a unique opportunity for investment in pharmaceutical innovation in Africa. Over 80% of Africa’s natural raw materials have not been subjected to standard scientific evaluation. Furthermore, about 67% of new medicines introduced worldwide from 1981 to 2002 were derived from natural sources. These facts provide compelling justification for investing in biodiversity as basic raw materials for pharmaceutical innovation, development and production.
2.3 The poverty factor The disparities in global pharmaceutical research, development and production are a reflection of underlying global inequities in health and socioeconomic development. Poverty is a break on the potential of countries, regions and the continent to develop. A poor country has fewer resources to invest in pharmaceutical innovation, especially in the face of competing priorities and limited resources. This is illustrated by the low levels of government commitment to financing health research and development in science and technology in most African countries. With the exception of South Africa, which invests 0.9%.of its GDP in research and development, R&D intensity in the rest of Sub- Saharan Africa is generally less than 0.3% of GDP19. Further, the potential for private- sector contributions to bridging financing gaps is hampered by the high business risk posed by unstable political environments, poor governance, and weak or absent legal and regulatory frameworks.
16 NEPAD-COHRED - Strengthening Pharmaceutical Innovation in Africa
Better health creates more wealth. Health as a driver of economic development. Some decision makers recognise that the ultimate benefit of stronger pharmaceutical innovation in Africa goes beyond curing disease and delivering medicines; saying that a healthier workforce brings significant economic gains to a country, as people can better contribute to economic development. Evidence also shows that knowledge-based economies are a catalyst for helping countries break the poverty/disease/disability/death cycle. Driving this are interventions that focus on health, equity and development considerations.
Comments on Commission on Macroeconomics and Health 200120, WHO Commission on Social Determinants of Health 200521
2.4 Changing landscape, new actors, new funding sources In the past decade, changes in the environment, demography, patterns of diseases and the global economy have created new challenges for research. Low-income countries are facing an increase in non-communicable diseases, along with the ongoing threat of infectious conditions – some re-emerging as a consequence of HIV/AIDS or drug resistance. A host of Public Private Partnerships (PPPs) have emerged to address these challenges. Their approach is to stimulate R&D for neglected diseases while minimising business risk. This R&D is typically done as not-for-profit or no-profit-no-loss, by partnerships involving public, multilateral and bilateral agencies, pharmaceutical companies, NGOs and philanthropies. These partnerships, especially those developing new medical products based on the needs identified by the most disadvantaged countries – known as Product Development Public-Private Partnerships (PDPPPs) – are seen as a positive force. They have raised great expectations for expanding the pool of products available for improving the health status of the most deprived populations. However, some prevalent diseases and conditions— for example, trypanosomiasis, schistosomisasis or filariae — are still truly neglected, partly because of restricted potential markets.
New partners develop medicines for neglected diseases The Novartis Institute for Tropical Diseases in Singapore is one example of the institutions and projects created specifically by global pharmaceutical companies to address neglected diseases. Such initiatives are motivated by corporate social responsibility and ethical concerns, and a strategic eye on engaging emerging markets in developing countries. The Bill and Melinda Gates Foundation is another new and important player. It is trying to stimulate the emergence and application of innovative scientific techniques and approaches to neglected diseases and speed-up the development of new drugs, diagnostics and vaccines.
17 2.5 The Global Strategy and Plan of Action on Public Health, Innovation and Intellectual property Another new force in the medicines development landscape is the Global Strategy and Plan of Action (GSPOA) on Public Health, Innovation and Intellectual Property. The strategy and plan resulted from the work of the Intergovernmental Working Group on Public Health, Innovation and Intellectual Property22. The Strategy and Plan of Action were adopted in 2008 by the 193 WHO member countries after a six-year consultation and negotiation process. It is a mechanism to ensure long-term, needs-driven, research and development and a funding framework for medicines that affect developing countries. The strategy and plan propose clear objectives and priorities for promoting innovation, building capacity, improving access and mobilising resources. The funding levels called for are US$ 149 billion between 2009 and 2015 – an average of US$ 21 billion per year.
Implementation of the Global Strategy and Plan of Action – 8 core elements Global Strategy and Plan 1. Prioritizing research and development needs of Action at regional and country level is entrusted 2. Promoting research and development to the Secretariat for 3. Building and improving innovative capacity Public Health, Innovation 4. Transfer of technology and Intellectual Property 5. Application and management of intellectual property (PHI) of the WHO. 6. Improving delivery and access 7. Ensuring sustainable financing mechanisms 8. Establishing monitoring and reporting systems
An expert working group has been set up to examine current financing of product R&D and study proposals for innovative sources of funding. Its report is due in 2010. The implementation of the Strategy and Plan of Action at regional and country level has been entrusted to the Secretariat for Public Health, Innovation and Intellectual Property (PHI) of the WHO.
2.6 Noordwijk Medicines Agenda and Yaoundé Process In parallel with the IGWG and Global Strategy process, the Organisation for Economic Cooperation and Development (OECD) and the Netherlands together brought a group of countries to discuss stimulating innovation and accelerating development and delivery of medicines for neglected and emerging infectious diseases. The approach included medicines, vaccines and diagnostics needed by developing countries23. The resulting call for action was called the Noordwijk Medicines Agenda24, 25, a positive step by OECD countries to become more active in providing incentives for drugs research and production to deal with neglected diseases. The action plan recommended, among other things, increased networking and partnerships between research actors. The Yaoundé Process grew out of a need identified by the Cameroon’s Minister of Public Health, supported by some African participants at the Noordwijk meeting, to develop a ‘complementary African agenda’ to look at medicines access and long-term socioeconomic development from the perspective of the African countries. This ‘complementary agenda’ aimed to develop and strengthen an African vision on health innovation and medicines R&D and production, and build north-south partnerships. The Council on Health Research for Development (COHRED) was engaged to facilitate this work, named the ‘Yaoundé Process’.
18 NEPAD-COHRED - Strengthening Pharmaceutical Innovation in Africa
The primary goal of the Yaoundé Process was to strengthen health innovation in Africa and complement: • the GSPOA on Public Health, Innovation and Intellectual Property by putting its principles into action at regional and country level. • the work of NEPAD for harnessing political support of African leaders, harmonising regulations and processes in public health and health care systems, and for “shaping and driving a new research and innovation agenda”.26
A platform for African countries to assess needs and design innovation strategies The Noordwijk Medicines Agenda and the Yaoundé process, support African countries, global health players and the Global Strategy and Plan of Action, to: • Assess the situation of innovation activities, projects and programmes in Africa today. • Identify African countries’ specific needs for technologies and skills to strengthen pharmaceutical R&D, production and delivery to improve populations’ access to medical products. • Implement the Global Strategy and Plan of Action at region and country level. • Inform NEPAD’s efforts to harness political support of African leaders, harmonise regulations and processes in public health and health care systems, and shaping a new research and innovation agenda.
This will lead to the creation of new evidence and tools to put African countries in a stronger position to negotiate with partners and assist countries to design national health innovation strategies and action plans.
19 Chapter 3 A picture of pharmaceutical innovation in Africa
3.1 The African landscape is complex This chapter presents a map of innovation initiatives and activities in Africa. This information aims to improve understanding of the current landscape and major challenges for the continent. It offers a starting point for further discussion and reflection on the current state of play for pharmaceutical innovation in Africa and encourages others to contribute useful information and participate in a dialogue. This is the first attempt to provide a comprehensive view of all initiatives working to increase access to essential drugs in Africa. It is not complete. The study presents Despite the dozens of initiatives in Africa for examples of initiatives and activities contributing to the improvement of pharmaceutical pharmaceutical innovation innovation and access to medical products in Africa. It attempts to give a clear view of and access to medicines, a what is currently in progress, who are the players. It points to issues that countries face closer look points to the in developing national strategies for pharmaceutical innovation approaches. lack of a grand plan for The first step was to identify the many programmes and initiatives designed to the continent - defined by improve pharmaceutical innovation and access to essential drugs in Africa and group the needs of countries. them into broad categories. This information is presented in annex 5. Step-two displayed them in a logical way. The resulting map (Figure 4) shows the different initiatives according to their main level of interaction – national, regional, global – and grouped by the elements of the pharmaceutical innovation process their mostly contribute to. The map helps to identify gaps and potential synergies (see Annex 6).
3.2 African traditional medicine has an important role to play The World Health Organization (WHO) estimated that some 80% of people living in developing countries use traditional medicine to address their health care needs. In some rural areas (constituting about 70% of the continent’s population), traditional medicine may be the only health care system that is available, accessible and affordable for them. Even in urban areas, many people consult Traditional Medicine Practitioners (TMPs), before going to Conventional Medicine Practitioners (CMPs) if traditional approaches fail to respond. It has also been observed that some patients routinely combine herbal medicines obtained from TMPs or open markets with conventional medicines. Evidently, the public has confidence in TMPs and the products they dispense. Cost may be a factor in the widespread use of traditional medicines. And certainly, the long history of traditional medicine use has made it an important and inseparable part of African culture. The natural environment provides man with resources for his survival. Plants, animals and minerals constitute the major natural resources used by man for promotive, preventive, curative and rehabilitative health. In Africa, these resources have been used by traditional medicine practitioners who acquired their knowledge and skills through observation, spiritual revelation, experience, training and direct information from their predecessors over many centuries. In recognition of the crucial role that African traditional medicine plays in health care delivery in Africa, in 2001, the African Regional Committee of the World Health Organization adopted the Regional Strategy on Traditional Medicine which aims to promote the development and integration of traditional medicine into the public health care delivery system. In 2001, the Summit of African Heads of States declared 2001-2010 the Decade for African Traditional Medicine. In 2004, the African Union developed a Plan of Action and an Implementation Strategy for traditional medicines which were adopted by the Ministers
20 NEPAD-COHRED - Strengthening Pharmaceutical Innovation in Africa Figure 4 Examples of pharmaceutical innovation initiatives in Africa mapped along the drug development and access pipeline. (COHRED 2009)
AU/NEPAD Bio technology AU/NEPAD local production ARIPO BIO VENTURES OAPI Innovation Hub EPN BioPAD MSF GIBEX / Africa UNIDO/GTZ/BMZ/KFW iThemba
AtoZ Text mills AA4A MALI TRADITIONAL MEDICINES Regional pooled procure- HAI Africa KEMRI Kenya, LAGRAY Company Ghana ment initiatives INRUD National Institute for Pharmaceutical Research and Development (NIPRD)
GATES FOUNDATION IDA Solutions
EDCTP ATM Research ACTION MEDEOR Network NACCAP META
Basic Research Development Testing Production and Procurement Delivery and discovery (phase I, II,III) Marketing Supply Use Storage Implementation Distribution research
GSPOA on Public Health, Innovation and Intellectual Property WHO PSM, TCM
TDR
UNESCO - African Science, Technology and Innovation Policy Initiative
PATH
Multinational Pharmaceutical Companies, Eli Lilly MDRTB, GSK-ASPEN Partnership CFW SHOPS DUKA LA DAWA • PDPPPs (DNDI, FIND, MMV, IOWH) SADC, EAC, CEMAC, ECOWAS LIVING GOODS • PPPs (GATB, IVI, INTERNATIONAL PARTNERSHIP FOR Regulation and CARE SHOPS MICROBICIDES,...) harmonization initiatives • GLOBAL TB VACCINE FOUNDATION n Regional initiatives n UN Initiatives n Public-private partnerships n National initiatives n NGOs/networks n International initiatives n Pharmaceutical companies
The map of pharmaceutical innovation in Africa reveals a complex landscape with multiple actors – including governments, pharmaceutical companies, UN agencies and other international organisations, NGOs, Public Private Partnerships and civil society organisations. These players are engaging with countries at various levels and sectors, addressing different steps of the pharmaceutical innovation process. A large number of initiatives have been identified. The information emerging points to the lack of a ‘grand plan’ – or coordinated approach to pharmaceutical innovation on the continent. There are gaps in different parts of the innovation process and much potential for duplication. Perhaps most striking is the picture of international agencies, and other health programmes and initiatives active across Africa, effectively shaping the innovation and medicines access policies for the continent, without the transparent or explicit involvement of national governments.
21 of Health in Africa and endorsed by the Summit of African Heads of State. In addition, the WHO developed tools which Member States can use to integrate African Traditional Medicine into the public health care delivery system.
3.3 Available evidence is not effectively disseminated There is a reasonable amount of evidence on pharmaceutical innovation in Africa, but no centralized repository. Knowledge on the topic is shared within the circles of specialists involved in particular steps of pharmaceutical innovation but rarely outside each specific group. To complicate matters, much of this information is presented in a format that is not accessible to non-specialists, creating a barrier for its translation into actionable policies, strategies and action plans. One striking example is the current debate on intellectual property rights as incentives or barriers to innovation and improved access to drugs. Many government officials in Africa find it difficult to make meaningful contributions to the discussions Activities exist in Africa and to take appropriate decisions at national level as they lack expertise in intellectual that cover almost every property management. step of the pharmaceutical innovation process. In the first meeting of the African Network for Drugs and Diagnostics Innovation27, African researchers clearly identified the lack of bridges and information sharing between them and industry, investors and intellectual property managers as a key obstacle to developing their discoveries into usable, safe and affordable medical products. There are gaps in the conceptual thinking on pharmaceutical innovation as it applies to the African context. Most current thinking ‘for Africa’ is based on research from the developed world, on experiences in the rapidly developing new economies – Brazil, Russia, India, China – and on studies done in selected African countries. Furman and colleagues28 propose a framework for assessment of national innovative capacity, but their research included only two African countries - South Africa and Mauritius. Morel and colleagues29 highlight the ‘need for innovation system theorists and global health practitioners to develop a more sophisticated literature on health innovation in developing countries’. In addition, existing evidence is poorly disseminated. Some of those interviewed for this study highlighted communication barriers related to: • A lack of inter-sectoral mechanisms to enable communication at international, regional and country levels, and between policy and technical levels. • High turnover of policy makers, which makes it difficult to ensure a shared vision and a continuum of knowledge. • Low absorptive capacity of countries.
Activities can be found in Africa that address almost every step of the pharmaceutical innovation process, but little seems to be done in terms of monitoring and evaluating the various initiatives to improve pharmaceutical R&D, production and access in the region. Also, the local activities identified seem to focus mostly on discovery, especially for traditional medicines, and on facilitating supply and use of medical products. Global efforts, in turn, tend to concentrate on the first steps of the process, with only a few initiatives focussing on delivery and access. The study found little evidence of explicit attempts to build pharmaceutical innovation capacity in countries as a part of these many initiatives.
3.4 Better coherence and coordination are necessary Analysis of the current landscape suggests the need to improve coherence and to leverage the African strengths in pharmaceutical innovation – at continental, regional
22 NEPAD-COHRED - Strengthening Pharmaceutical Innovation in Africa and national levels. One such effort is the African Ministerial Council on Science and Technology (AMCOST) which adopted Africa’s science and technology plan of action30 in 2005. It focuses on improving the quality of science, technology and innovation policies in six areas: • Supporting the African Science, Technology and Innovation Indicators Initiative (ASTIII) • Improving regional cooperation in science and technology • Building public understanding of science and technology • Building a common African strategy for biotechnology • Building science and technology policy capacity • Promoting the creation of technology parks
The African Union’s’ Pharmaceutical Manufacturing Plan for Africa is another example. It charts the way for local production of medicines to treat HIV/AIDS, tuberculosis and malaria. Various public-private drug development partnerships (PPDPs) can also take a more coherent approach to local production, but some have questioned the extent to which these partnerships improve the capacity and promote the growth of the nascent African industry31. The current effort by AU/NEPAD to harmonise drug regulation around Regional Economic Communities (RECs) is another example. But much still needs to be done for harmonising expectations and efforts across levels, especially between globally and nationally (or regionally) driven programmes.
3.5 Countries need to be placed at the centre of decisions for pharmaceutical innovation While African governments show a growing interest in improving their populations’ access to affordable essential drugs, there are currently no tools, no methods that countries can use to take action to strengthen pharmaceutical innovation in a way that addresses national priorities. African interests and demands exist at all levels of pharmaceutical innovation but very few deliberate strategies are in place to operationalise it. The Global Strategy and Plan of Action process has demonstrated the eagerness of African countries’ involvement in the global debate on needs-driven R&D for access to essential drugs. As a result, there is an increasing demand for pharmaceutical innovation from African countries. However, this demand tends to focus on local production and demonstrates insufficient understanding of the implications of embarking on this complex process, its consequences and other possible options to ensure medicines access – following a national or regional strategy. Pharmaceutical innovation initiatives typically approach national partners in an uncoordinated manner, and are driven by their own objectives. International programmes will sometimes do national needs assessments and set objectives that should result from self-evaluation and priority-setting done by the country from a broader perspective of national health and development needs. To embark on improving access to medicines, research and development and local production – and more generally to participate in putting the Global Strategy and Plan of Action into practice at country and regional level – African countries need to be at the centre of the decision making processes for pharmaceutical innovation. It is their responsibility and prerogative to understand the system and critically assess where they want to go and how they want to get there. The role of the international community, then, is to inform and support national decision-making processes and make available the knowledge, technical tools, human and financial resources that countries require – not assuming control of country-level processes.
23 Chapter 4 Essential building blocks for national pharmaceutical innovation
This chapter discusses requirements and conditions for countries to consider when developing a pharmaceutical innovation strategy. After reflection on these points, decision makers and research managers can use the tools and guides in Chapter 5 to design their national strategies and put an innovation plan into action. A map of some of the main elements described below – elements that need to be put in place for a national innovation strategy to be effectively implemented – is located in Annex 7.
4.1 Prerequisites 4.1.1 Creating an investment-friendly environment A solid and stable political system is the number one requirement for attracting investment to a country. A recent survey of32 chief executive officers from East Africa noted political risk as the single most significant challenge for business in East Africa. These CEOs proposed that the private sector engage governments to deliver on good governance and management as a priority. Linked to this are a number of infrastructure and framework components that underpin a knowledge-based economy. Governments’ illustrate commitment to this through: • The presence of a national science and technology/innovation policy. • Effective government policies and laws on intellectual property and drug regulation, including effective structures for law enforcement. • Incentives to attract foreign direct investment, such as tax breaks, local indirect tax exemptions and lower custom tariffs. • Mechanisms to finance innovation through government funding or links with the private sector or external funders. • Research institutions with specific mandates in core relevant areas of science, technology and innovation where Africa has comparative advantage.
Credible national priorities contribute to create a favourable environment Evidence-based priority setting enables the focused targeting of resources, a process which facilitates innovation. With specific reference to the Southern African context, Du Toit33 proposes the following principles for prioritising, innovation and research that are: 1) absolutely necessary for national competitiveness (e.g. information technology andbiotechnology); 2) present some “geographic” advantage (e.g. astronomy and “human origins”); 3) present a “problem” advantage (e.g. HIV/AIDS vaccine for Africa); 4) present a “knowledge” advantage (e.g. traditional knowledge or deep-level mining).
4.1.2. Enabling policies and supportive initiatives A comprehensive policy framework is also required – for health and health research, science and technology, industry, trade, law and education. In emerging economies where proactive policies have been established to stimulate health innovation, a key early step has been to establish close collaboration between health and science and technology. Brazil offers a good example of close coordination
24 NEPAD-COHRED - Strengthening Pharmaceutical Innovation in Africa between the ministries of health and science and technology to spearhead national research and innovation for health. During the past decade, many African countries have shown interest in developing their national health research systems. Recent evidence suggest, however, that only a few African countries have a health research policy in place. A number of multilateral and bilateral initiatives exist in Africa to strengthen country capacity for policy formulation in the science, technology and innovation sector– many coordinated by the AU and NEPAD. Improvement of Africa’s policy environment is needed both nationally and at the regional level – as demonstrated by the present efforts of NEPAD and Africa’s Regional Economic Communities to harmonise drug regulations in Africa. Further efforts are also needed to better articulate national, regional and global policies.
Table 1: Examples of policy-level initiatives for science, technology and innovation in Africa
Focus Initiative Policy Development • AU/NEPAD Consolidated Science and Technology Plan at national and regional level of Action • African Science, Technology and Innovation Policy Initiative – UNESCO collaboration • Africa Technology Policy Studies Network (ATPS) • UN Science and Technology Cluster support to the AU Consolidated Plan of Action
Influencing Policy at global level • Global Strategy and Plan of Action on Public Health, Innovation and Intellectual Property GSPOA • IQSensato • Knowledge Ecology International • MSF Access Campaign • OXFAM • Third World Network
Advocacy for coherent global policy approaches A number of initiatives seek to influence global policy on issues related to public health, trade and intellectual property management in LMICs, including Africa. Sustained advocacy efforts from the Médecins Sans Frontières (MSF) access campaign achieved drastic price reductions in developing countries for antiretroviral medicines (ARVs) for the treatment of AIDS-related conditions. The generic antiretroviral fixed-dose combination Lamivudine/Stavudine/Nevirapine (3TC/d4T/NVP) now costs US $87 per patient per year. This is a price reduction of 99% compared to the cost of the 2001 originator product (US $10,000 per patient per year). The price difference before and after generic producers started making ARVs constitutes a more than a 99% price reduction34.
25 4.1.3 Strengthening functional health research systems as essential foundations Priority setting and research management That research is to be essentially needs-driven is a central message of the GSPOA. However, there is still a long way to go to make this a reality for many low and middle income countries. While there are well trained researchers in many African countries, the extent to which they work on national priorities is often not in their power to decide. In many cases, the key question is indeed “who sets the priorities?” Many low and middle income countries contribute more to their overall budget for research institutions and workforce than they receive from external sources. Yet, it is the external contributions that often decide what research questions are being addressed. Recent studies35 show that research projects in Africa tends to be mostly financed by external sources. Most countries rely on foreign partners for research funds and these partners usually commission research as disease or condition specific – or vertical – programmes. For example, between 1991 and 2000, 100% of research project funds in Tanzania came from foreign sources36. Uganda does not provide any project funding for health research37, while external research project income totals some $24 million38. This leads to a situation where national research production in many LMICs addresses only a few high profile health conditions – those for which funding is available – neglecting other major national priorities that can benefit from research. The recently published G-FINDER 2008 survey reveals that over $2.5 billion was spent on neglected disease R&D in 2007. Of this amount, almost 80% went to three diseases: HIV/AIDS, malaria and tuberculosis39. Other diseases responsible for high disease burden in Africa, for example helminth infections, childhood disability, hypertension or pneumonia, receive limited attention and financial support. Not all countries in Africa have a health research policy and well installed processes to prioritise, plan and implement research with all concerned stakeholders – including negotiating with external research funders for ensuring that the research they support addresses national needs. Country-level mechanisms are needed at to help set national research priorities and manage research in a way that addresses them.
From health research to ‘research for health’ Research can be a key driver of technical, social and economic development in low- and middle-income countries, but its full potential is rarely fully realised. Health research is essential for pharmaceutical and technical innovations, for improving health systems performance, to control epidemics of acute and chronic conditions, to measure impact of interventions and to give timely warning of potential environmental threats and risk factors. The new concept of ‘Research for Health’40 - emphasizes a multi-sectoral approach in the use of research to improve health, health equity and development of countries.
26 NEPAD-COHRED - Strengthening Pharmaceutical Innovation in Africa
Figure 5, ‘Research for Health’
Context of Health Research (COHRED 2007) Health System
Social and Political development Health
Economic Health Research development
Research for Health "It is critical for low and medium income countries (LMICs) to achieve and sustain the minimum Individual and institutional capacity building knowledge-based mass Development of the pharmaceutical innovation sector requires presence of a critical needed for creativity, mass of knowledgeable, skilled and motivated professionals, and an enabling credibility and innovation institutional environment. in health and development. There are a number of initiatives focused on building research capacity at The vigorous call to action for building and retaining institutional and individual level. At the most basic level are initiatives focusing on the health workforce in institutes of higher learning such as the Nelson Mandela Institute. At the more LMICs must also include technical level, efforts are directed at training scientists in particular techniques or for strategic action for researching on specific diseases of high prevalence in Africa– for example through the research capacity African Programme for Onchocerciasis Control, APOC, and the African Malaria strengthening.’’ Network, AMANET. While these and several others are reputed for building and (Lansang, GFHR Updates Vol. 4) strengthening disease specific research capacity – efforts for building up technical or managerial capacities that are applicable across national research systems have been much less deliberate and sustained. For many years, capacity strengthening efforts tended to concentrate on developing individual capacities in specific domains and scientific specialities that were felt to face the greatest needs. Many stakeholders increasingly recognise the value of a systems approach to research for health and the need to build enabling institutional and national environments.
Research capacity gaps In addition to the gaps mentioned above, Africa faces a lack of resources specific to the complex pharmaceutical research, production and delivery process. A 2008 health product survey identified the most significant human resource capacity gaps for pharmaceutical innovation as being in preclinical / safety pharmacology and raw material processing to GMP standards41. Experts consulted during our survey also highlighted gaps in capacity to conduct clinical trials quality assurance systems and drug regulation. The European and Developing Countries Clinical Trials Partnership (EDCTP) is an initiative that aims to strengthen capacity for clinical trials, especially the regulatory and ethical review components through partnerships with African institutions. To achieve this, EDCTP collaborates with other organizations such as WHO, UNESCO, AMANET, COHRED, among others. These and other examples of initiatives to build up research capacity in Africa are highlighted in the table below. A more detailed mapping can be found in Annex 5.
27 Table 2: Examples of initiatives to address research capacity gaps
Focus Examples of Initiatives Higher education • Nelson Mandela Institute
Drug discovery and • African Network for Drugs and Diagnostics Innovation (WHO/TDR/ANDI) development • AU/NEPAD panel on biotechnology • Global Institute for Bio-Exploration – Africa (GIBEX-Africa) • International Centre for Genetic Engineering and Biotechnology (ICGEB) • Natural Products Research Network of Eastern and Central Africa (NAPRECA) • Special program for research and training in tropical diseases (TDR)
Clinical trial capacity, • African Poverty Related Infection Oriented Research Initiative (APRIORI) including ethics • Council on Health Research for Development (COHRED) review committees • European Developing Countries Clinical Trial Platform (EDCTP) • Initiative to Strengthen Health Research Capacity in Africa (ISHRECA) • Malaria Clinical Trial Alliance (MCTA) • Special program for research and training in tropical diseases (TDR)
Knowledge • WHO Health Research Systems Analysis (HRSA) management • WHO International Clinical Trials Registry Platform (ICTRP)
Disease focused • African AIDS Vaccine Program (AAVP) • African Program for Onchocerciasis Control (APOC) • African Malaria Network Trust (AMANET) • South African Malaria Initiative (SAMI) • Special program for research and training in tropical diseases (TDR) • Mali malaria research centre
4.2 Essential components 4.2.1 Intellectual property: The Achilles’ heel? Intellectual property is another essential issue that African countries must address. The challenge for countries is to work within intellectual property rules to provide incentives for pharmaceutical R&D based on pro-public health and pro-access principles. Challenges abound. Not all African countries have adopted national intellectual property measures that protect their populations’ health interests. They often lack the skills in intellectual property management and face difficulties negotiating patent conditions and existing agreements to ensure procurement of the most cost-effective and high-quality drugs to meet their specific disease needs. A 2009 NEPAD paper42 highlights gaps for intellectual property management in science, technology and innovation in public health. These include knowledge gaps for: • implications of intellectual property rights on technology transfer • access to medicines and foreign direct investment • implications of the range of TRIPs flexibilities. Intellectual property and access There is an ongoing debate on intellectual property and its influence on access to medicines in developing countries. One side argues that the high price of innovator medicines poses a major barrier to poor countries’ access to essential and life-saving medicines. The other side feels that protection and reinforcement of intellectual property is a necessary incentive for innovation and for returns on the investments made to bring new products to market.
28 NEPAD-COHRED - Strengthening Pharmaceutical Innovation in Africa
High medicine prices are linked to the patent life of the medicine. The 1994 TRIPs Agreement reinforced patenting requirements by allowing exclusive rights for a company to determine the price of a new product for up to 20 years from the time it comes to market. This agreement broadened the scope of protection to include both product and process patents, as well as patent protection on medicines and food products. As a result, countries like India and China that were previously able to produce cheap generic medicines through reverse engineering can no longer do so. India and China have been the source of most of the generic medicines used in Africa, and the concern is that access to medicines could be severely hampered by this new regulation. In the PMPA, African ministers of health recognise that “the fact that India and China had to comply with both process and product patent laws by 2005 was seen as a potential threat to affordability and access to essential drugs in Africa43”.
Intellectual property protection: impact on public health The World Trade Organization (WTO) is an international organization of 148 Member Countries dealing with the rules of trade. In joining the WTO, Members adhere to specific agreements. Of these agreements, Trade-Related Aspects of Intellectual Property Rights (TRIPS) establishes minimumstandards for a set of intellectual property rights that WTO Members institute through national legislation. TRIPS also contains provisions that allow a degree of flexibility and sufficient room for countries to accommodate their own patent and intellectual property systems and developmental needs. Patents on medicines have been one of the most hotly- debated topics since the adoption of the TRIPS Agreement because patents grant exclusivity for the duration of the patent term and result in patent holders having control over the production, supply, distribution and, by virtue of exclusivity, price. It is argued that patents are crucial for pharmaceutical innovation and that, without them, there will be no financial incentive to fund the costs of discovery and development of new medicines. However,medicines prices in developing countries are often well above production costs. Developing countries account for a very small fraction of the global pharmaceutical market and the generation of income to fund more research and development is not dependent on profit from these markets. Indeed, until now, the patent protection system has provided very little incentive for research and development of new medicines needed for diseases afflicting developing countries, which highlights the ineffectiveness of relying solely on the private sector to develop essential medicines. In many countries where payment for pharmaceuticals is “out-of-pocket” and health insurance is rare, escalating and unrealistic prices play a central role in denying access to patients of life-saving medicines.
WHO Drug Information Vol 19, No. 3, 2005
29 While generic production is possible for many essential medicines because they are off-patent in most of the developing countries, this does not apply to new medicines, which are subject to 20-year protection. The TRIPS Agreement introduced global minimum standards for protecting intellectual property rights (IPR), including patents. The agreement now also requires all WTO Members, with few exceptions of the least-developed countries, to comply with the agreement by 2016, by adapting their laws to the minimum standards of IPR protection. In 2001, the Doha Declaration on public health (‘Doha Declaration’) authorised the use of flexibilities such as compulsory licensing and parallel importation as means to address problems of access to essential drugs. However, in most developing country contexts, the effective implementation of these flexibilities is hampered by a number of constraints, that Musungu44 and colleagues group into two levels: constraints associated with the incorporation and general implementation of the flexibilities, and constraints in the framing and implementation of supporting legal and policy measures. “The patent system (as In assisting Member States in their implementation of the TRIPS Agreement and currently implemented) is the Doha Declaration, the WHO also has found that developing countries have a very expensive way to stimulate R&D. difficulties obtaining access to accurate and up-to-date information on the patent Consumers pay eight or status of essential medicines. Such difficulties often stem from the lack of capacity in nine dollars in higher national patent offices to administer the patent system (including managing effective prices to stimulate one search mechanisms) and to respond to the public health needs. This has the potential dollar in R&D spending“ to compromise the procurement of the most cost-effective, quality medicines, and Love & Hubbard.46 thus hinders the improvement of access to essential medicines. It further highlights the difficulties that developing countries face in capturing the promised benefits of an intellectual property system. Since the DOHA Declaration, new mechanisms and policy measures have been put in force to maximize IP protection. The TRIPS-plus and related bilateral free trade agreements (FTAs) protect pharmaceutical markets by limiting / posing barriers to the exploitation of TRIPS flexibilities.45 This further increases the difficulties facing countries with limited expertise and resources in intellectual property management Regional initiatives by organizations such as ARIPO, OAPI, SARIMA and WARIMA in collaboration with WIPO offer potential avenues to address the intellectual property management gaps in Africa. Improving intellectual property management skills in African countries will be a key factor of success for enhancing the African people’s access to essential medical products.
Intellectual property and innovation Concerned about the adverse consequences of intellectual property on access, public health advocates are increasingly calling for mechanisms to de-link the cost of R&D from the cost of the product and for prioritisation of public health over profit goals. New incentives are needed to foster innovation, which do not rely on the promise of benefits derived from intellectual property rights and exclusivity. A number of mechanisms have been proposed as alternatives, including prize funds, R&D treaty, the health innovation facility, the UNITAID medicines patent pool, among others. Not all of them win unanimous support and more work needs to be done for analysing the advantages and disadvantage of the different proposals as objectively as possible.
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The Expert Working Group (EWG) was established in 2008 by the World Health Assembly to review current financing and coordination of R&D and discuss innovative frameworks for financing R& D and stimulating innovation, as well as to examine the coordination of R&D. There are currently about 90 proposals circulating for new mechanisms that the EWG may have to consider. The working group proposes to analyse the mechanisms in terms of their ability to achieve the desired R&D goals rather than focussing on their type and nature (push or pull)47. As noted by the Taskforce on International Innovative Financing for Health Systems, “Largely, funds have been raised and delivered in much the same fashion…regardless of the development problem being tackled.”48 With this in mind, the EWG has chosen a practical rather than a theoretical approach to help policy makers to decide which proposal to support or implement. “Mechanisms will be examined in relation to their stated R&D goal rather than their ‘type’, with key questions being: What disease area, product type, innovation type, R&D area and R&D actors does this mechanism seek to fund and/or incentivize? How well does it achieve this objective? The evaluations will have a strong technical element, assessing the likely performance of proposals in the R&D world, as well as the policy world.” Examples of practical implementation of some intellectual property mechanisms in Africa are summarized in the table below.
Table 3: Examples of practical implementation of intellectual property mechanisms in Africa
Year Policy regulations Summary of mechanism Examples of implementation in Africa 1994 WTO Agreement on Trade Related Mandates global minimum standards for Aspects of Intellectual Property Rights the protection of intellectual property (TRIPs)49
2001 Doha Declaration on TRIPs and Public Affirms that "the TRIPS Agreement 1. Compulsory licenses or government use Health50 does not and should not prevent authorizations for local production or Members from taking measures to importation of generic medicines: Gabon, protect public health". Ghana, Ivory Coast, Swaziland, Zimbabwe51, and Mozambique52 ‘TRIPs Flexibilities’ Measures include compulsory licensing 2. Import of generic products53: Angola, Benin, and parallel importation. Burkina Faso, Burundi, Central African Republic, Chad, Democratic Republic of Congo, Djibouti, Gambia, Guinea, Guinea- Allows members to determine grounds Bissau, Lesotho, Malawi, Mali, Mauritania, upon which such licences are granted. Mozambique, Niger, Senegal, Rwanda, Tanzania, Togo, Uganda, Zambia. Extends time by which LDCs are 3. Voluntary licensing agreements with required to implement TRIPS obligations pharmaceutical companies: Ethiopia, from 2006 to 2016. Kenya, South Africa, Tanzania, Zimbabwe.
2003 ‘August 30 Decision54’ Provides interim waiver on requirement Rwanda (Importer) and Canada that compulsory licensing be (producer and exporter).55 predominantly for the supply of the domestic market
31 4.2.2 Technology transfer: What needs to be shared and how? Technology transfer concerns many aspects of the pharmaceutical innovation system such as transfer of knowledge, experience and technical tools. It also covers processes that improve research, production, delivery and use of medical products. Any one of these factors may be appropriate for Africa, depending on countries’ context, priorities and resources. It is often said that technology transfer could play a crucial role in solving the problem of pharmaceutical production in Africa. But in reality, little is known about the extent, nature and impact of current technology transfer initiatives. Technology transfer is increasingly regarded as a more realistic and attractive option for partners on both sides. In this context, there is a need to better document existing technology transfer initiatives, their determinants (incentives and disincentives), successes and failures, and the lessons learned. This will allow testing of conventional wisdom on the difficulty of transferring technology to Africa, and finding new paths for putting in place the essential prerequisites on both industrial countries and African countries’ sides to make technology transfer possible, sustainable and successful. Current experiences suggest that important prerequisites are infrastructure and skills. Many believe that the willingness of the pharmaceutical industry to transfer its know-how and techniques is not sufficient for successful transfer of technology. Recipients of transferred technology must also have minimum absorptive capacity to receive and effectively appropriate the technology transferred – and work in a policy and political environment that is conducive to pharmaceutical innovation. Absorptive capacity is determined by the existence of a sustainable and efficient cadre of highly skilled scientists. Business intelligence is also crucial for dealing with trade, investment and industry challenges. A facilitative policy environment is essential to attract substantive investment.
Scarce information on technology transfer in Africa Efforts to collect and analyse information on relevant experiences and their impact have been very scarce. In 2004, the UK Department for International Development (DfID) commissioned a study to document technology transfer experiences between developed and developing country firms in the pharmaceutical sector, and examine the motivations behind these agreements. To date, the DFID study56 remains the only serious attempt to analyse technology transfer initiatives. Since 2004, the environment has changed, as have perspectives and opinions of major actors. More information on current technology transfers would be useful.
Information and perspectives gathered from those interviewed during this study – including representatives of the pharmaceutical industry – suggests that a better understanding of the expectations of the different partners and of the incentives will attract transfer of technology into low and middle income countries. It can facilitate more and better collaboration between industry in wealthy countries and emerging African players – to mutual benefit.
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Table 4: Examples of transfer of technology in African countries
Company / Organization Activity Comments Tanzania Production of Olyset, long-lasting Technology source: Sumitomo A to Z company insecticide-treated bed nets Chemicals, Japan
Kenya Growth and extraction of Artemisia is grown locally in Advanced Bio-extracts pharmaceutical grade Kenya and Tanzania. Extracts are artemesinin and artemesinin- supplied to Novartis for based derivatives production of artemesinin-based drugs such as Coartem.
South Africa Local production of Technology transfer with Aspen Pharmacare pharmaceutical products GlaxoSmithKline, Bristol-Myers Squibb, Gilead, Merck, for production of ARVs. Has received WHO pre-qualification status
Italy, South Africa, India Molecular biology and Offers training, funding and International Centre for biotechnology advisory services “‘The role of the South as a Genetic Engineering and ‘technology user’ is Biotechnology (ICGEB) becoming increasingly problematic and raises the Ethiopia, DRC Congo, Production of Plumpy’nut, a Technology source – Nutriset – spectre of a cumulative and Niger, Malawi, high-protein, high-energy France Mozambique peanut-based paste classified by path-dependent growth in Nutriset – plumpy’nut WHO as a ready-to-use equalities between North therapeutic food and South in the future, particularly in science-based industries such as biopharmaceuticals.” 4.2.3 Local pharmaceutical production: is it the solution? Mytelka 2006: (From Mytelka In recent years, African governments have taken significant steps toward addressing L K; Pathways and policies to their health challenges. These steps include improving access to medicines and (Bio) Pharmaceutical Innovation developing local production. The 2005 AU Conference of Health Ministers: Gaborone Systems in Developing Declaration and Roadmap Towards Universal Access To Prevention, Treatment and Countries, Innovation and Industry; Dec 2006) Care adopted a clear policy position: ‘to pursue, with the support of our partners, the local production of generic medicines on the continent and to making full use of flexibilities within the Trade and Related Aspects of Intellectual Property Rights (TRIPS) and Doha Declaration on TRIPS and Public Health’. The AU adopted the Pharmaceutical Manufacturing Plan for Africa (PMPA) in 2007 and established a Technical Committee to undertake technical development of these efforts. Benefits expected from local pharmaceutical production include: • foreign exchange savings • job creation (thus alleviating poverty and promoting social development) • facilitation of technology transfer • stimulation of export markets • availing of cheaper raw materials • improving/enhancing self-sufficiency in drug supply • National pride/self-esteem
African Union policy on universal access to medicines Based on the African Union (AU) assembly Decision by 55 African ministers of health during the Abuja Summit in January 2005 and on the 2005 Gaborone Declaration on a roadmap towards universal access to prevention, treatment and care, the AU policy position is ‘to pursue, with the support of our partners, the local production of generic medicines on the continent and to making full use of flexibilities within the Trade and Related Aspects of Intellectual Property Rights (TRIPS) and DOHA Declaration on TRIPS and Public Health’.
33 Current status In 2007 the AU published a report on barriers for local production of essential medicines, particularly those needed to treat HIV/AIDS, tuberculosis (TB) and malaria. A situation analysis was done by the technical committee of the pharmaceutical manufacturing plan for Africa. As of 2005, 37 of the 46 WHO/AFRO countries had drug production activity, though only one (South Africa) had limited primary production of active pharmaceutical ingredient (API) and intermediates57.
Technical barriers identified in this analysis included: weak national drug regulatory authorities, uneven distribution to the consumer market, human resource gaps (in training and retention), and legal barriers, especially with regard to the impact of the TRIPS agreement on the acquisition of API.
Table 5: Local production capacity, based on WHO/AFRO 2005 data58
Capacity for local production Number of Countries None; import all pharmaceutical products 9 Import API, product packaging and labelling; repackage bulk forms 34 Import API; produce finished dose forms; reformulate products 25 (e.g. FDC) Manufacture API and intermediates 1
All pharmaceutical industry activity 37
Snapshot of Pharma manufacturing in Africa The 2008 International Finance Corporation report59 confirms these findings and the fragmentation of pharmaceutical manufacturing capacities of African countries. - Outside South Africa, more than 70 percent of Sub-Saharan Africa’s estimated $1 billion in annual pharmaceutical production is concentrated in South Africa, where Aspen Pharmacare, the only vertically integrated manufacturer in the region, is the clear leader. - Nigeria, Ghana and Kenya together represent about 20 percent of Sub-Saharan Africa’s pharmaceutical production (see Figure A3.2). Of these three countries, only Kenya produces significant volumes for regional export—between 35 and 45 percent of Kenyan manufacturers’ revenues come from exports to other Eastern African Community (EAC) and Common Market for- Eastern and Southern Africa (COMESA) countries. - Overall, 37 Sub-Saharan African countries have some pharmaceutical production, with 34 having capacity for formulation and 25 limited to packaging or labelling. - Only South Africa has a limited degree of API production. Most production outside South Africa is of non-complex, high volume, essential products, such as basic analgesics, simple antibiotics, anti-malarial drugs, and vitamins.
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In May 2008, African Ministers of Health met to update the progress of the PMPA60. Six priority areas were identified and countries were tasked with coordinating activity in these in areas. (see Table 6).
Table 6: Country coordination of priority areas of the pharmaceutical manufacturing plan for Africa
Priority area Countries to coordinate Mapping of local production capacity Gabon Situation analysis and compilation of findings Cameroon Manufacturing agenda Kenya, Libya, Egypt Intellectual property issues South Africa, Angola Political, geographical and economic considerations South Africa Financing Nigeria
Local medicines production – UN programme A United Nations Industrial Development Organization (UNIDO) programme61 strengthens local production of essential generic drugs in developing countries. It works with small and medium-sized companies, business partnerships, investment promotion and through south-south cooperation. The project was initiated in 2005 and focuses on medicines for treatment of HIV/AIDS, malaria, tuberculosis and some neglected tropical diseases. The first phase of the project (2006 – 2008) centered on Africa and Asia with activity in eight African countries: Botswana, Lesotho, Mali, Nigeria, Senegal, Uganda, Zambia and Zimbabwe.
Appropriate decisions on local production need an in-depth analysis Despite these intense regional efforts, some experts argue that local pharmaceutical production in many developing countries may not be a feasible or cost-effective option, and could bring to market more expensive products with limited ability to penetrate developing world markets62. Given the low consumer and institutional purchasing power in most African countries, the market for finished product is almost entirely dependent on the ability to access international funds. Access to these funds requires WHO prequalification status, an expensive and lengthy qualification process, which local producers find challenging to attain and maintain. It has been argued that local pharmaceutical industries are subject to inefficiencies due to high start-up costs, the cost of subsidizing production, and higher prices of finished products. Because pharmaceutical production is capital-intensive and employs relatively few people, it cannot, as an isolated sector, lead to economic development. Some experts also feel that local production can promote development, but only when the market prescribes it, and that the survival or failure of these companies should be left to market forces63. Ultimately, the decision to manufacture pharmaceutical products locally lies with countries. Informed decisions on whether or not to embark on local production can be based on: • The cost for a local producer to meet international quality standards. This includes WHO prequalification and continuous quality standards from manufacture to point-of-sale and use - including capacity for bioequivalence testing. • Business performance: profitability and sustainability of local pharmaceutical production ventures, including ability to penetrate regional and international markets when local markets are not sufficient.
35 • Evidence on health impact: e.g. local production make pharmaceutical products more accessible? Are local products cheaper than imported equivalents? Is their quality comparable to that of originator products?
4.2.4 Pharmaceutical industry and health partnerships: what is their role? There are currently over 200 ongoing health partnerships with the pharmaceutical industry aimed at promoting health in the developing countries through a wide range of access, capacity building and R&D programs64 (details in Annex 5-G: Pharmaceutical partnerships in Africa). They are set in the context of the overall goal of achieving the health-related Millennium Development Goals and focus on a wide range of priority health issues, including HIV/AIDS, malaria, tuberculosis, tropical diseases, preventable diseases, child and maternal health, and chronic diseases. The nature of the health partnerships varies and may comprise of single or multiple pharmaceutical companies and a wide range of partners, such as: governments, generic pharmaceutical manufacturers, the UN and other international organizations, NGOs and academia. A number of these partnerships are components of larger global initiatives, such as the Accelerating Access Initiative, PEPFAR Partnership for Paediatric HIV care, Stop TB Partnership, Roll Back Malaria, International Trachoma Initiative and the Global Alliance to Eliminate Lymphatic Filariasis. The approaches used by partnerships to improve access are mostly commodity donation, preferential pricing, and technology transfer and licensing agreements with local pharmaceutical industries (see Annex 5-G). For example, technology transfer agreements with a number of multinational companies have facilitated the local production of generic antiretroviral medication for treatment of HIV/AIDS in Kenya, India and South Africa. Some examples of these are detailed in Table 7.
4.2.5 Delivery and access: are they neglected? One of the central messages of the first African Health Report, published in 200768, is that the essential problem to be resolved for improving the health of African populations is to strengthen the fragile health systems of many African countries. Strong and efficient systems are essential to ensure regular access to medical products. The challenges are many: Drugs, diagnostics and vaccines need to be properly transported, stored, prescribed and used, which requires adequate numbers of trained health personnel in strategic locations, as well as roads, stores and a reliable cold chain, to name a few. The Technical Committee of the PMPA notes, among other considerations, that “the transportation system should be functional so as to facilitate the distribution of medicines without much increase to the price of manufacturing69”. In addition, the problem of limited access to essential medicines should not be reduced to the issues of availability and affordability discussed in this report. Accessibility also involves physical access to health care facilities, gender issues and social acceptability. Much more needs to be done to improve procurement, delivery, prescription practice and rational use of medicines in many African countries. Also, while serious efforts need to be made to strengthen R&D activities that truly address the needs of low- and middle-income countries, increasing the availability of affordable drugs of good quality does not, on its own, guarantee universal access to life-saving drugs in Africa.
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Table 7: Technology transfer and ARV licensing in Africa65
Technology donor Technology recipient Comments Boehringer-Ingelheim Aspen Pharmacare A non-assert declaration for production of www.boehringer-ingelheim.com South Africa nevirapine.
Various Boehringer Ingelheim is willing to grant and has offered a royalty-free licence to the Canadian company Apotex for production of nevirapine in Canada (and export to Rwanda as part of the triple combination "Apo Triavir")66
Bristol-Myers Squibb Aspen Pharmacare Transfer of intellectual property and technical www.bms.com South Africa know-how related to manufacturing, testing, packing, storage and handling of API and finished dosage form of Atazanavir.
Various Since 2001, BMS has a policy of not enforcing its patents for HIV products in sub-Saharan Africa and has immunity from suit agreements for stavudine and didanosine with 5 African generic companies.
Gilead Sciences Aspen Pharmacare Manufacture and distribution of generic versions www.gilead.com South Africa of Viread® and Truvada®
Various Non-exclusive licensing agreements with 10 Indian generic companies allowing distribution of generic versions of tenofovir in 95 developing countries, including in Africa
GlaxoSmithKline South African generic companies: Manufacture and distribution of generic versions www.gsk.com Aspen Pharmacare, Thembalami Pharmaceuticals of lamivudine and zidovudine67. (Pty) Limited, Feza Pharmaceuticals, Biotech Pharmaceuticals, Cipla Medpro Kenyan generic companies: Cosmos Pharmaceuticals , Universal Corporation
Merck & Co. 5 South African generic manufacturers Manufacture and distribution of generic versions www.merck.com of efavirenz.
Roche AIDS Technology Aspen Pharmacare (South Africa), Cosmos Voluntary license for manufacture of generic Transfer Initiative Pharmaceuticals (Kenya), Universal Corporation versions of saquinavir. www.roche.com (Kenya), Addis Pharmaceutical Factory (Ethiopia) Since 2008, pan-African training seminars are Varichem Pharmaceuticals (Zimbabwe), Regal held for local manufacturers Pharmaceuticals (Kenya), CAPS Pharmaceuticals Ltd (Zimbabwe), Shelys Pharmaceuticals (Tanzania), Zenufa Laboratories (Tanzania)
The WHO Essential Medicines Department spearheads most of the initiatives to ensure global access to safe, effective and quality pharmaceutical products, including in Africa. In addition there are many other regional, sub-regional and country-level efforts to promote delivery and access. These efforts vary in scope, focus and approach. While conducting a detailed analysis of all delivery and access initiatives was beyond the scope of this study, several illustrative cases are outlined in Annex 5: Detailed Mapping of Initiatives. The Medicines Transparency Alliance (MeTA) is a joint initiative of the WHO, Health Action International (HAI) and the UK Department for International Development (DfID) that supports national efforts to enhance transparency and build capacity in medicines policy, procurement and supply-chain management. The ARV access for Africa (AA4A) aims to build capacity for supply chain management for ARV commodities. Other examples include the innovative Child and Family Wellness shops
37 (CFWshops) in Kenya, which adapt the traditional franchising model to distribute essential medicines in remote communities. Although there is presently a growing interest for local production in many African countries, many stakeholders admit that, even if high-quality, low-price drugs were locally produced, the problem of most disadvantaged people accessing the drugs they need and using them effectively would not necessarily be solved. Some strongly argue that the overall process of improving access to drugs is heavily skewed towards the production side, while much more could be achieved in terms of equitable access by reducing the inefficiencies of the procurement and delivery side70. In some cases, pooled procurement alone could have significant positive impact on access. For instance, Kenya, Tanzania and Uganda try to jointly develop pooled procurement and hope to be able to decrease drug prices by 25% compared to the normal price. While it is often argued that one problem faced in some African regions is the small size of the potential market for certain drugs, one study showed almost minimal influence of a medicine’s market size and retail price71; the price mostly depends on the reliability of payment and on the regularity of supply. The Expert Committee of the PMPA has undertaken an analysis of the respective size of potential markets for locally produced drugs and has come up with estimations of countries grouping to create potentially viable markets72. This should facilitate the development of pharmaceutical production at regional level, based on geographic, economic, linguistic, and other criteria. The Committee considers that the dimension of the consumer market is essential in the definition of the regions for ensuring that regional production increases African populations’ access to essential drugs through a real reduction of prices with the economy of scale. Other strategies used to bridge medicines’ access gaps include differential and tiered pricing, drug donation schemes and pooled procurement. To strike the right balance, it is important to take into account the diversity of needs and resources that guide Africa’s choice of approach for securing access to essential drugs. Some countries, such as Egypt and Tunisia, are in a position to produce essential medicines locally to meet most of their national needs. Others rely exclusively on imported medicines and will continue to do so for the short and medium-term. Improving access through appropriate tax measures or other incentives may be a crucial step for importing countries. However, measures facilitating access to imported drugs should not jeopardise efforts to produce drugs locally. Likewise, the goal of strengthening local manufacturing in Africa should not conflict with the need of many African countries to ensure to affordable medicines today.
4.3 Several cross-cutting issues are critical factors of success 4.3.1 Governance For African countries to effectively strengthen national research and innovation for health, a range of interventions are needed – at the national, regional and global levels. These activities can be done by different stakeholders, public or private, operating in sectors such as health, science or economy. Mechanisms are needed to coordinate these efforts to ensure they contribute to providing national public goods, ensuring health equity, and strengthening pharmaceutical innovation. The governance function is generally the government’s mandate. The governance and management of the national ‘innovation system for health’ provides leadership and strategic direction to ensure that it produces research and medical products of good quality that are relevant to the country’s needs. Governance functions include: strategic vision, system structure, policy formulation, priority setting, monitoring and evaluation, promotion and advocacy, and the setting of norms, standards and ethical frameworks73. Many African countries do not have a well-defined national health research
38 NEPAD-COHRED - Strengthening Pharmaceutical Innovation in Africa system, let alone a ‘health innovation system’. Governance structures are one of the first elements these countries need to put in place to guide the development of appropriate policies and mechanisms and to minimise the risk of the various players acting in an uncoordinated manner.
4.3.2 Financing Current investment in African pharmaceutical innovation is low. Given the lack of economic incentives for development of products to fight diseases that affect Africa, alternative financing mechanisms are needed to catalyze pharmaceutical innovation on the continent. Governments’ commitment to financing science and technology research and development are low worldwide, and in African countries, mostly absent (but this seems to be changing). South Africa is an exception. Data from UNESCO reveal that while investment for R&D in Sub-Saharan Africa is generally less than 0.3% of GDP, South Africa invests 0.9% of its GDP.74 Through its department of science and technology, the South African More innovative approaches for financing government funds the Council for Scientific and Industrial Research (CSIR) whose focus research and innovation for is on research, development and innovation in bioscience, nanotechnology and health are urgently needed. synthetic biology. As a part of its national biotechnology strategy, the South African Countries need tools Department of Science and Technology (DST) has set up three regional innovation to decide which of the centres that fund biotechnology: BioPAD, Cape Biotech and LIFElab. 90 + existing proposals best Venture philanthropy, such as funds from the Bill and Melinda Gates Foundation, fit their context. has in the last decade encouraged the creation of public-private partnerships that seek to develop much-needed innovator products, such as new antimalarial drugs or diagnostic tools easy to use in resource poor settings. Funding from the Gates Foundation has facilitated a number of regional and national initiatives including efforts to strengthen pharmaceutical innovation systems, such as the NEPAD research on innovation systems and the strengthening of regional drug registration. Other than philanthropic sources, the Global Fund to Fight Tuberculosis, AIDS TB and Malaria (GFATM) also provides funding to enable access to interventions needed for these diseases. The Global Fund has launched the affordable medicines facility for Malaria (AMFm) and a mechanism to expand access to artemesinin-based combination therapies (ACTs) for malaria. Cost reduction is achieved by negotiating a lower price for ACTs, then paying a large proportion of this directly to manufacturers on behalf of buyers (the practice of buyer ‘co-payment’). Other special funding mechanisms include UNITAID, which raises funds from a solidarity tax on airline tickets. UNITAID funds facilitate access to essential medicines and diagnostic tools for HIV/AIDS, malaria and tuberculosis. Some venture capital funding is also available for pharmaceutical innovation in Africa. Examples include Bio-ventures, a South African- based biotechnology and life sciences venture capital fund founded in 2001. While these efforts represent positive steps in the right direction, when considered in light of recent GSPOA estimates75, they are unlikely to cover the huge costs required to strengthen innovation for health in low- and middle-income countries. More innovative approaches for financing research and innovation for health are urgently needed – and countries will need tools to decide which of the more than 90 proposals currently circulating best fit their own context and requirements. The evaluation framework presently developed by the WHO Expert Working Group will be essential to guide countries in their assessment and decisions on the most appropriate mechanism to finance their national pharmaceutical innovation. Based on a practical rather than a theoretical approach, the EWG framework will help policy makers to decide which mechanism to support or implement – in relation to its stated R&D goal rather than its ‘type’. The key questions to consider will be:
39 what disease area, product type, innovation type, R&D area and R&D actors does this mechanism seek to fund and/or incentivize? How well does it achieve this objective? The evaluations will have a strong technical element, assessing the likely performance of proposals in the R&D world, as well as the policy world. Whatever the mechanism chosen for financing a particular R&D project, who makes the decisions/designs/sets up the characteristics and objectives of each mechanism is extremely important for ensuring that they are relevant to the needs of LMICs, realistic and sustainable to the extent needed. The evaluation and accountability of the different mechanisms are essential. African experts at the Pretoria meeting identified three sources of financing for pharmaceutical innovation: private funding, public funding and joint ventures. The experts noted that commercial organisations determine their entry points in the innovation chain and raise their own resources. They felt that public funding should be used primarily to create an enabling environment for local manufacturing and to invest in areas that do not attract immediate private sector interest – such as drug, vaccine or diagnostics discovery for neglected diseases. The group proposed the creation of an Innovation Fund supported by a business plan to put the it into action regionally or continent-wide. Possible financing options mentioned were: direct taxation (import levies); indirect taxation (consumption tax on luxury goods like tobacco); joint ventures, product development ‘public private partnerships’ (such as Drugs for Neglected Diseases Initiative – DNDi or Medicines for Malaria Venture - MMV); loans and loan guarantees; trading concessions at the World Trade Organization; and donor funding. The future solution will most probably rely on a combination of mechanisms. Whatever the incentives for strengthening the R&D, production and delivery of the affordable medicines, diagnostics and vaccines needed in low and middle income countries, they should end up ensuring a predictable and sustainable funding of innovation for health, an innovation which will be essentially targeted at country self- defined needs and will contribute to the creation of global public goods.
4.3.3 Legal and regulatory framework Whatever choices African governments make with regard to interventions designed to boost pharmaceutical innovation, their political commitment must translate into fostering and implementing the essential legal changes or improvements needed to attract the various stakeholders to engage into the national effort. The legal and regulatory framework needs to be developed or improved with regard to many sectors of the national activity, including health, education, trade and industry, science and technology, tax and finances, among others. Establishing a strong drug regulatory system is perhaps the most essential.
Drug regulation While putting in place the general legal and regulatory framework required for minimising risk factors and promoting social and economic development through strengthened health R&D, African countries must pay particular attention to developing the regulatory system which will ensure that medical products – be they imported or locally produced – will be safe and of good, sustained quality, and will be rationally used. To achieve this, all pharmaceutical products need to be subjected to pre-marketing evaluation, market authorization, and post-marketing review. These are complex procedures that need highly specialized legal, administrative and technical skills, and few African countries have the capacity to perform all functions.
40 NEPAD-COHRED - Strengthening Pharmaceutical Innovation in Africa
Drug regulation functions revolve around the concept of Quality Assurance, which defines the set of activities undertaken to ensure that the medicines are in compliance with the required quality for the intended purpose. This process includes Good Manufacturing Practices (GMP) that guarantee that the medical products are manufactured in a consistent manner – and are controlled in accordance with the specifications established at the time of the products registration, for their intended use. GMPs are essential to ensure the quality and traceability of the medicines. The role of National Regulatory Authorities (NRA) is fundamental to monitoring the compliance to GMP standards and to building trust in the process and, ultimately, in the quality and safety of the products. As African experts76 underline, the essential role of the NRA is indeed to protect the citizen’s health by ensuring the safety and efficiency of health products, establishing the necessary legal and regulatory frameworks to this end, and monitoring their application. Assessments conducted by WHO have highlighted significant challenges to In addition to training, mechanisms need to be put effective functioning of national drug regulatory authorities, the key ones being in place to ensure the human resource gaps and weak or absent legal and regulatory frameworks. The retention of trained current trend is towards harmonisation of regional drug regulation, based on the professionals to pass on obvious benefits that would accrue from pooling individual country capacities. their experience to others. In February 2009, NEPAD, in collaboration with partners, held a workshop on These mechanisms include harmonisation of drug registration in Africa. Their proposal is to situate regional drug- salaries commensurate with their responsibilities, career registration efforts at the regional economic communities (RECs) which are the: prospects, and minimum Community of Sahel-Saharan States (CEN-SAD), Common Market for Eastern and permanent contractual Southern Africa (COMESA), Economic Community of West African States (ECOWAS), engagement at the East African Community (EAC), Economic Community of Central African States enterprise after training. (CEEAC/ECCAS), Southern African Development Community (SADC), The ‘brain drain’ while Intergovernmental Authority of Development (IGAD) and Arab Maghreb Union undesired, is natural if the working conditions are not (AMU/UMA). adequate for workers. Proposed guiding principles77 are: Collaboration among Member States and with Source: Technical analysis of other RECs by establishing intra- and inter-REC collaborative forums; sharing expertise the local capacity of African and using risk-based approaches to minimise duplication of effort and allocate countries to produce essential resources efficiently; implementation of the "Regulatory Documentation Package" medicines including HIV/AIDS, developed by WHO; and sustaining project activities after initial (financial) support malaria and TB drugs. Technical Committee on the has been withdrawn. Political will and commitment was highlighted as the key to Pharmaceutical Manufacturing success of regional cooperation. Plan for Africa, October 2007, Addis Ababa. 4.3.4 Human resources and knowledge management Human resources Strengthening pharmaceutical R&D, production and delivery in any country requires wide-ranging expertise and skills in multiple sectors and at different levels of the system. For the health sector alone, pharmacists and health care providers are needed as much researchers, laboratory technicians and drug regulators and inspectors. But lawyers, intellectual property specialists, economists, investors, as well as teachers and skilled industry labour will be also needed to contribute to a functional health innovation system. If indigenous national capacities are not available, countries may compensate by calling upon their neighbours and pulling scarce resources together for collectively covering the range of interventions needed. This however requires a critical mass of appropriate human resources across the region and sufficient capacities in every networking country for managing national or sub-regional health innovation systems. The lack of human resources in the health sector is widely recognised as one of the most important problems to be solved in Africa today. The main message of the African Regional Health Report78, published for the first time in 2006, states that,
41 “firstly, Africa can build on its recent progress only by strengthening its fragile health systems; and secondly, that these systems remain weak today due to a lack of adequate human and financial resources.” Data is scarce on human resources for health research, but general data on human resources for health are quite telling. While Africa bears 25% of the world disease health burden, it has only 1.3% of the health workforce79. This is partly the result of migration of health workers out of their home countries, in search of better salaries and working conditions. For example, more than 23% of America's 771,491 physicians received their medical training outside the USA, the majority (64%) in low-income or lower middle-income countries. A total of 5,334 physicians from sub-Saharan Africa are in that group, a number that represents more than 6% of the physicians practicing in sub-Saharan Africa now. Nearly 86% of these Africans practicing in the USA originate from only three countries: Nigeria, South Africa and Ghana80. As a proxy for human resources available for pharmaceutical research, drug “In the longer term, the regulation and distribution, it is interesting to consider the data available on development of innovative pharmacists in a few countries81. While countries like Cameroon or Côte d’Ivoire have capacity for health research in developing countries will some 700 and 1300 pharmacists respectively, others like Benin or Niger have only be the most important 11 and 20. To put those numbers in perspective, it is interesting to compare to determinant of their ability countries like Iraq (with more than 7500 pharmacists) and Pakistan (more than 8000). to address their own need Looking at these figures, it would seem straightforward to argue that careful for appropriate health-care planning is needed – at least between the health and education sectors – to ensure technologies.’’ that appropriate human resources with the necessary skill sets will be available at “Public health, innovation and intellectual property country and/or regional level for the mid- to long-term. Such efforts for better rights” Report of the matching education content and scope with public health needs along the Commission on, Intellectual pharmaceutical production and access pipeline will need to be supported by proactive Property Rights, Innovation policies and strategies to retain human resources for health research and innovation. and Public Health (CIPIH) WHO, 2006. Open sources of information Access to knowledge is central to the process of innovation. Pharmaceutical companies have large amounts of data on early discoveries that have never been developed. This is a valuable source of new knowledge that developing countries’ research institutions and pharmaceutical companies can tap. In the past, agreements have been negotiated for creating open registries, but such negotiations need to be repeated for every company and are far from being common practice. Many pharmaceutical companies see sharing their databases as a threat to their competitivity. In recent years, new mechanisms have been created to facilitate access to and dissemination of information on different aspects of the pharmaceutical R&D process. The Special Programme on Research and Training for Tropical Diseases (TDR) supported the creation of networks to improve the access of researchers to scientific information on drug R&D and production. Examples include the Compound Screening Network, and the Drug Target Network – that have databases with potential drug targets. WHO has created the International Clinical Trials Registry Platform that offers this information to all those involved in health care decision-making. These and other publicly-accessible databases and compound libraries are vital tools to improve access to scientific information and support further research in low and middle income countries. These examples are a start, but much more remains to be done. Other initiatives to create open registries should be encouraged. The problem of limited access to information is compounded in Africa, where relevant information, especially related to traditional medicine, is kept in small circles of local experts, and seldom finds its way to a broader research community. Access to information is further hampered by poor Internet access in some African countries.
42 NEPAD-COHRED - Strengthening Pharmaceutical Innovation in Africa
4.3.5 Partnerships In her 2006 study, Mytelka82 describes how, despite capacity gaps and through effective linkages with regional and international networks, some countries have accelerated progress in pharmaceutical innovation. She highlights the importance of interaction between four types of policies – those that strengthen the knowledge base, stimulate capacity building, open spaces for local firms and create incentives for innovation. One example is the successful research, development and local production of Niprisan, a drug for management of sickle cell disease. This success was possible through collaboration between local traditional healers and researchers at the Nigeria Institute for Pharmaceutical Research and Development, guided by a policy that encouraged a focus on local health needs and provided space for the emergence of indigenous Nigerian firms. This approach is also supported by earlier work by Furman and colleagues83, who proposed that national innovative capacity depends upon the strength of a nation’s ‘A key factor in developing policies is to recognize the common innovation infrastructure (cross-cutting factors which contribute broadly to importance of innovation innovation throughout the economy), the environment for innovation in a nation’s systems, the 84 industrial clusters, and the strength of linkages between these two. More recently, interconnectedness of the Singer, Daar, and colleagues have proposed a ‘convergence innovation model’ to innovation process, and the catalyse life sciences innovation and commercialisation in Africa. This model would need to link together the help address linkage gaps between science, business and capital. activities of different players in the public and At the global level, partnership approaches facilitate research, development, private sectors.’ production and delivery of medicines in Africa. Many of these focus on research and “Public health, innovation and development for neglected diseases and diseases that contribute to Africa’s high intellectual property rights” burden of disease – mainly HIV, tuberculosis and malaria. These public-private- Report of the Commission on, product-development partnerships are responsible for some 75% of all neglected Intellectual Property Rights, disease drug development85. They include the TB Alliance (drugs for tuberculosis), Innovation and Public Health (CIPIH) WHO, 2006. Medicines for Malaria Venture (anti-malarials), Institute for One World Health (technologies and drugs for a range of diseases including diarrhea and malaria), and Drugs for Neglected Diseases Initiative (kinetoplastid parasitic diseases). The extent to which these partnerships practically promote the growth of the nascent African industry has been questioned, as most of these partnerships are based in developed countries, with sometimes insufficient representation of African researchers at senior staff or board level86.
43 Chapter 5 Tools and approaches
The Pharmaceutical Innovation tools presented in this chapter were jointly developed by The George Institute for International Health and COHRED.
5.1 General approaches to developing a pharmaceutical innovation system This chapter offers reflection, tools and guidelines that countries can use to design a national strategy for pharmaceutical innovation. The critical starting point for a strategy that supports pharmaceutical innovation is to clearly define the country’s ultimate goals. Does the strategy strike a balance between creating a commercial national pharmaceutical sector and improving the population’s access to medicines? For example, if the objective is mainly access – not production and sales – this public health goal may be better served by importing cheaper medicines, or Why pharmaceutical innovation: access or by employing other strategies such as tiered pricing. commerce? The tools presented in this chapter have been developed to assist decision makers and planners interested in strengthening their national pharmaceutical innovation Pharmaceutical innovation policies need to balance capacity to address this question. access and industrial goals The tools are: - a system development framework Country planners need to reflect on a number of -an innovation grid to guide policy makers on the steps needed to achieve questions: access, manufacturing and R&D capacity - a list of pharmaceutical innovation initiatives • Do we need to produce medicines locally or - a database of pharmaceutical innovation literature provide maximum access to our population Experiences to help developing countries move up the innovation ladder • Do we want to create a Successful pharmaceutical innovation is the result of a complex web of interactions pharmaceutical between many stakeholders, including multiple government ministries, regulatory technology sector to drive authorities, and private and public research, development, teaching and healthcare economic development. delivery institutions. Both paths are useful and African countries, such as South Africa or Kenya, with high pharmaceutical not mutually exclusive but innovation capacity have followed different development pathways to get there and different skills and their experiences offer alternative models for developing countries to move up the investment are needed for innovation ladder. each. Decision makers must be clear on the balance they The implementation phase of a national strategy brings a new set of tasks and want to achieve, and craft a questions. Decisions need to be made on what structures, policies and activities need to strategy that meets their be in place to ensure they can reach their chosen goal. These include health research goals — economic systems, regulatory and intellectual property systems; industry; tax and tariff policies; development, improved ethics boards; governance structures and policies; financing systems; human resources access, or both. strategies; or ways to engage community involvement. Designing an effective and realistic national innovation strategy Few African countries like South Africa, Kenya and Nigeria, have in place most of the essential steps of the pharmaceutical innovation process – or will be able to have them in the near future. Some countries have assessed their needs and potential to produce and deliver medicines and have made strategic choices on where they can excel in part of the pharmaceutical production chain. • Mauritius has opted to develop specific elements of the pharmaceutical R&D and production process. It is developing its capacity for clinical trials. • Guinea Bissau is poorly resourced and lacks most prerequisites for developing pharmaceutical innovation system. It has started developing a national health research policy and building up a functional system for health research.
44 NEPAD-COHRED - Strengthening Pharmaceutical Innovation in Africa
• Tunisia has defined excellence in specific aspects of the pharmaceutical innovation chain as a national science and technology priority. It recognises that, as a small country it cannot excel in all aspects of pharmaceutical innovation and has chosen to add value at specific areas of the chain
Developing country governments interested in building national pharmaceutical innovation capacity face the task of deciding how to move forward, how and where to get involved and which policies they need to have in place to move along the development pathway (e.g. regulatory and intellectual property systems; industry, tax and tariff policies; ethics review committees; governance structures and policies; financing; human resources strategies; and community involvement). Access to pharmaceutical innovation can be achieved in many ways, ranging from importing drugs and vaccines to building and relying upon a domestic pharmaceutical industry that develops its own medicines (see Figure 7: Innovation milestones). Deciding on the best path, the country needs to assess their current capacity, available options, and which of these options are likely to deliver the best results with regard to What can we realistically do? health and/or economic goals. Two new mechanisms have emerged that aim to put countries in the driver’s seat for The starting point for access and local medicines production – the Global Strategy and Plan of Action on developing a pharmaceutical innovation Public Health, Innovation and Intellectual Property and the African Union or access strategy is a well- Pharmaceutical Manufacturing Plan. Together, they form the first comprehensive policy structured reflection. It framework and promise of long-term funding to support countries’ strategies for should involve different pharmaceutical innovation. ministries and other To put these mechanisms into action at national level, country decision makers need players active in medicines to gain skills and perspectives to asses their needs and make the right choices to access – and will help decide what can be support their pharmaceutical development. The Pharmaceutical Innovation Framework realistically achieved. tool and case studies presented in this chapter were designed to support countries to move forward. Findings from this study point to a growing pharmaceutical-innovation sector in Key questions: Africa. Countries seem to have two contrasting motivations for pursuing Should we manufacture pharmaceutical innovation – improving public health needs and developing a local locally? pharmaceutical sector that can generate profits. The balance between the public health Do we have the skills, and and the economic agendas is a delicate one and may account for some of the tensions can we build and maintain at global level and the increased calls for prioritization of health over profits. infrastructure over a 15 year horizon?
What innovative capacities 5.2 Framework for developing a national pharmaceutical need to be developed? innovation system If our objective is better delivery of medicines to National pharmaceutical innovation system development these populations a The starting point for strengthening a country's pharmaceutical innovation system is to procurement and present a clear picture of the current state of affairs – and the areas where development distribution programme may be more effective should be targeted. Taking this view, countries can apply a number of approaches, tools than organizing local and methods to implement a strategy of system development or strengthening. production. Figure 6 provides a framework that decision makers can use to develop a national innovation system for health. It provides a roadmap for engaging all stakeholders – including all relevant governmental sectors, civil society and private sector – in a collaborative process of assessment, priority setting and design of a health and pharmaceutical innovation strategy. Such processes are generally led and managed by the government. But all other partners need to be involved to ensure the relevance and success of the effort.
45 Stage 0: Basic requirements Three components must be in place for a country to start building or strengthening pharmaceutical innovation: • Political stability and security • A minimum of infrastructure, such as roads, reliable power supply and water supply • A functioning banking and economic sector, with external partners that put reasonable business risk in perspective. A show of commitment from political leaders and decision makers is fundamental to creating a conducive environment for pharmaceutical innovation. The multi-sectorial nature of pharmaceutical R&D, production, access and use (including health, science and technology, trade, industry, education) calls for early commitment and coordination across these actors. Advocacy and awareness activities may be needed to get partners’ involvement across these sectors – both from government and non- governmental groups.
Stage 1: Prerequisites If the basic requirements for a stable environment have been satisfied, a number of crucial elements need to be in place to launch the effort with a reasonable chance for success. Two key prerequisites are: • Governance and management mechanism: The government must be willing to take action, catalyse changes and make solid initial decisions. Doing so should translate into first-level actions for securing a basic management system; bringing together representatives of the main sectors of activity for minimal oversight and decision-making on the innovation effort; setting up priorities; and developing strategies
How can countries use the Global Strategy and Plan of Action to meet their innovation needs The Global Strategy and Plan of Action on Public Health Innovation and Intellectual Property (GSPOA) is a landmark document – the result of a seven-year consultation and agreement between 193 member countries of the World Health Assembly. This is the first global policy of its kind that links the world of global health research with countries’ needs. For low-income countries, the GSPOA is an important tool to guide negotiations with potential partners for pharmaceutical innovation. To move into action, countries need tools and resources to help analyse their specific national context and decide how to apply pharmaceutical innovation, and with which partners they can achieve this. The first step for countries is to assess their situation and develop a clear vision of how the GSPOA, the African Union Pharmaceutical Manufacturing Plan and other international initiatives can help address specific national needs. Approaches to health research and pharmaceutical production in Africa take many forms. In this light, there is no single solution for implementing the Global Strategy and other mechanisms. Countries need to set priorities and develop implementation plans and timelines for strengthening their pharmaceutical innovation. The choice of strategic approach centers on two questions: 1) What is the preferred path to improving access to medicines in the country; 2) If the choice is local production of medicines and other health products – how will a country balance this with its objectives for local production as a path toward public health or economic-development?
46 NEPAD-COHRED - Strengthening Pharmaceutical Innovation in Africa
• Public health priorities: To make well-informed decisions for improving access to affordable, high- quality and safe drugs, decision makers need to be aware of the national health status and disease burden, as well as of the medical products that have been identified as essential. This can be accomplished by developing a national list of health priorities and corresponding essential medicines. Public health priorities will be better defined by involving all stakeholders, including civil society and the private sector from the start.
Stage 2: Assessment and decision-making In the context of health and pharmaceutical innovation, countries should first prioritise major objectives in terms of public health and economic development. To this end, the George Institute for International Health, in partnership with the Council on Health Research for Development (COHRED) have developed a grid to guide countries to make decisions on pharmaceutical innovation. Using the grid, national decision makers and managers of pharmaceutical innovation will be guided to consider existing information on their public health needs and resources. Using the Framework, policy makers will: • Assess where the country is in terms of R&D, production, delivery and use of medical products • Identify gaps and overlaps in their pharmaceutical innovation systems • Make decisions on where to focus in order to achieve innovation milestones, improve access, and support R&D or manufacturing.
Excerpts of the proposed grid are presented in Figures 7 and 8.
Stage 3: Essential building blocks Once the priority area and innovation milestones are selected, some additional research may be needed for a more detailed assessment of the current national resources and needs in that particular field for deciding on priorities and taking the first concrete steps toward putting in place supportive policies, a basic skill set in health and science and technology, as well as necessary mechanisms for management and evaluation. • Policy framework: Several policies, laws and regulations may be required to ensure the success and sustainability of a national pharmaceutical innovation system. These include, for example: health research policy, trade and investment policy, intellectual property policy, drug regulations, industrial policy and good manufacturing practices. • Human resources: Even if no particular system exists to stimulate R&D, production and delivery of medical products, at least a few knowledgeable and committed individuals must be available for planning, implementing and supervising the interventions in the different sectors concerned, such as scientists, regulators, managers, among others. • Financial resources: Basic financial support needs to be available for enabling the first assessment and decision-making process and for designing strategies for first implementation. This seed funding usually comes mostly from public sources, national or external (bilateral or multilateral) donors.
The choice of essential components to put in place first and the sequence of steps to achieve objectives will vary, depending on the country’s priority focus. For instance, a focus on access will require countries to establish or strengthen the relevant legislation
47 Figure 6: Framework for developing a national pharmaceutical innovation system (COHRED 2009) Using health innovation to improve population health, health equity and development
Stage of development Actions needed Basic requirements - supportive environment Political commitment to pharmaceutical innovation Advocacy, awareness, data and discussion. and improved access to medical products Identify key individuals/groups that can initiate and catalyse the process. Political support across government sectors: health, Develop a common understanding of pharmaceutical innovation. Mobilisation across science and technology, trade, industry, education, legal sectors for a multisectorial approach to innovation Business environment and basic infrastructure Increase reliability of essential infrastructure, e.g. banking system, power supply, transport, Level 1 needs – pre-requisites Management mechanism for pharmaceutical Establish mechanisms and structures appropriate to the country’s existing structures innovation and access to medical products and aspirations. These need to be multisectorial. Particular attention should be given to collaboration between health and S&T sectors. Public health priorities Credible and regularly updated public health priorities Complementary priorities for health research and pharmaceutical innovation - essential drugs, diagnostics and vaccines Level 2 needs – assessment and decision-making Assessment of current national situation of Identifying where the country sits in terms of innovation milestones; where are the pharmaceutical innovation major gaps; who are the major stakeholders. The COHRED/GI Pharmaceutical Innovation Assessment framework provides a guide to these activities Decision on pharmaceutical innovation goals Informed by the assessment and public health and development strategies, focus on one of the 3 milestones, access, manufacturing or R&D and /or set national goals for the component chosen or for each component
Level 3 needs –essential building blocks Policy framework for pharmaceutical access, A number of policies need to be in place for each component, for example: manufacturing and R&D Access: drug regulations, trade policy, tax policy Manufacturing: industrial policy, good manufacturing practices Human Resources R&D: research policy, intellectual property management Develop a human resources strategy and plan aligned with priorities Address all relevant sectors: public health, science and technology, industry, judiciary, economy, trade, education Stable, predictable financing Develop a pharmaceutical innovation financing strategy, Ensure it addresses national and foreign funding from the public and private sectors
Level 4 needs – Collaboration Partnerships Regional, inter-country collaborations for product development, clinical trials, cross- registration, quality control. National PDPPPs; North-South and South-South transfers of knowledge, processes and technologies
Level 5 needs – optimising the pharmaceutical innovation system Improving pharmaceutical innovation system For example: components Access - Pooled procurement - Community based delivery Manufacturing - Technology transfer arrangements; - Good manufacturing practices - Post market quality control R&D - Good research contracting; - Intellectual property management; - Clinical trials ethics; - Merit-based promotion system of scientists All levels - Community demands for medical products - Monitoring & evaluation - Institution building.
48 NEPAD-COHRED - Strengthening Pharmaceutical Innovation in Africa and regulation on drug regulatory authorities, intellectual property and trade agreements. A focus on R&D may require building up or reinforcing the national health research system. And a focus on manufacturing will require the country to address major issues related to transfer of knowledge, processes and technologies, trade agreements and intellectual property, good manufacturing practices and quality control.
Stage 4: Complementing resources and capacities Depending on priorities established and the decisions made, additional policies and regulations will need to be developed and implemented, specialised capacities may need to be built up, reinforced and maintained, and predictable and reliable financing secured, in order to ensure sustainability. At this stage, strengthening collaborations with key national and external partners will be crucial for mid- and long-term success. One issue to consider is that many African countries will – in the short term – not soon be in a position to undertake some of the interventions needed for good performance of the pharmaceutical innovation and access system. In such cases, it may be more feasible for several countries within an African region to develop complementary capacities and to “outsource” some steps to be more cost-effectively performed in a neighbouring country. For example, a country with well-developed and reliable laboratory facilities could perform quality control for neighbours’ medical products. Similarly, education and training of groups of professionals with very specific skills (for example, drug regulators and controllers or intellectual property managers) could take place in one country within each region. Stage 5: Optimising the pharmaceutical innovation system Once the country has the essential building blocks in place to achieve the top-priority innovation milestones, it can develop or strengthen other elements of its pharmaceutical system and move to the next milestone. As the country moves forward, many additional elements will likely need to be developed in different sectors. For countries, the first step in designing a pharmaceutical National pharmaceutical innovation system development innovation strategy is to assess the current situation The starting point for strengthening a country's pharmaceutical innovation system is to and decide at which level to present a clear picture of the current state of affairs – and the areas where development enter the innovation process, should be targeted. Taking this view, countries can apply a number of approaches, tools focusing on: and methods to implement a strategy of system development or strengthening. - Improved access to imported medicines - Manufacturing - Research & development 5.3 Pharmaceutical Innovation Grid for assessment, priority setting and strategy design These choices are not necessarily mutually exclusive Innovation Grid and countries may determine Because the innovation grid has been developed from the perspective of a government realistic objectives for each decision maker, practical steps and technical capabilities are the focus, rather than milestone, depending on current level of development theoretical considerations. In particular, the grid is designed to help countries: and available resources. - Assess where they are in terms of the innovation milestones outlined in Figure 7. - Identify gaps in progress against each innovation milestone - Identify practical steps needed to achieve the next innovation milestone
More generally, this grid can help to identify bottlenecks and opportunities for strengthening pharmaceutical innovation, and determine how to transition from one level of innovation to the next. This grid can also guide formulation of other frameworks and guidelines, for example those that explore how to phase growth initiatives, step by step, in a sustainable manner.
49 The grid allows policy makers to assess their current capacity with respect to innovation milestones at national level: - Ability to access low-cost, safe efficacious and quality imported medicines - Ability to manufacture medicines (generics) - Ability to research and develop innovative medicines
The grid also identifies the capabilities and policies required to achieve each milestone, as well as which actors will be responsible for taking action. Activities are allocated as follows: - Department of Health (including hospitals and public research centres) - Department of Education (including universities) - Department of Science and Technology - Department of Trade - Department of Taxation and Finance - Regulatory authorities (including medicines and IP regulators) - Industry - Other (civil society groups, regional organisations).
The grid and its three innovation milestones are a practical tool to help countries address a complex area with inter-linked interventions by multiple partners. The grid provides a simple tool to help understand and navigate this complex landscape. In particular, the classification into three over-arching areas and seven milestones should help countries to phase in their approach to strengthening innovation based on a detailed and fair assessment of resources. However, access is applicable to the entire spectrum of innovation and should be considered as a cross-cutting issue. To better understand how the grid can be applied, see Figure 8, an excerpt that focuses on the “access” milestone. (More detailed demonstrations of the grid are provided in case studies outlined in Section 3.1.)
Figure 7, Innovation milestones: 7 critical complexity levels
Innovation milestone Research and Novel vaccine innovation
, Development
e Novel drug innovation y v t i i t s Early pharmaceutical innovation (fixed dose x c e e e combinations, diagnostics, reformulations) l n f i f p c i e
m d
, Manufacturing Manufacturing vaccines o e e c f
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g s y manufacturing APIs n t i o i s l t
Formulating and packaging imported API a a s e u s
r (active pharmaceutical ingredients) into drugs q e c c n c I
A Imported medicines Minimum baseline: Access to affordable, qulity imported medicines
50 NEPAD-COHRED - Strengthening Pharmaceutical Innovation in Africa
Checklist for designing a pharmaceutical innovation strategy In this example, a policy maker assessing where their country is situated in terms of access to affordable, quality, imported medicines can read from left to right across the table.
Figure 8, Summary of Grid
Innovation Legislative Dept. of Dept. of Dept of Dept. of Dept. of Tax Regulatory Industry Examples: milestones framework Health / Education / Science and Trade authorities initiatives to public public Technology engage with hospitals / universities public research centres
Access Imported medicines
Manufacturing - Formulating, packaging imported Active Pharmaceutical Ingredients (APIs) to finished products - Producing drugs, including APIs - Producing vaccines
Research and Development - Early pharmaceutical innovation (Fixed dose, diagnostics, reformulations) - Novel drug innovation (small molecules) - Novel vaccine + other biologics innovation (large molecules)
Questions that may arise: - Is there relevant and necessary legislation and regulation in place (e.g. an intellectual property policy that includes the TRIPS flexibilities, a national medicines policy; a legislative mandate for regulatory authority activities, such as clinical trial review, product recall, pharmaceutical factory inspections)? - Has the country signed up for all procurement mechanisms that give access to low- cost, quality imported products (e.g. the Global Fund, UNICEF, GDF, GAVI, AMFm)?xx - Are the necessary customs controls in place to monitor the quality of products coming into the country? - Has a review been done of taxes, tariffs and duties on pharmaceuticals along the supply chain, and where possible, have these been minimised? - Has the national patent office (or regional patent group) optimised implementation of the TRIPS flexibilities? - Is there a Medicines Regulatory Authority (MRA) able to conduct the regulatory tasks outlined in the grid, either alone or in conjunction with regional regulatory groupings?
A country that can answer ‘yes’ to all or most of these questions is very well placed to start building towards the next chosen innovation milestone, be this in manufacturing or product development.
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54 NEPAD-COHRED - Strengthening Pharmaceutical Innovation in Africa
A country that cannot answer “yes” on most points might instead choose to maximise their ability to access existing medicines before the move toward local manufacturing or R&D. While such a decision would be driven partly by a desire to secure the health of their population, it also would reflect the reality that before more advanced innovation milestones can be reached, earlier and more fundamental elements must be in place. A domestic pharmaceutical industry will require that many of the capacities outlined at the ‘access’ level be in place, including a functioning Patent Office, a National Medicines Policy, an MRA with the ability to review clinical trials and inspect factories, and tax policies that do not impact on the affordability of medicines in circulation.
5.4 Database of Pharmaceutical innovation initiatives Three additional resources have been developed to assist policy makers interested in strengthening domestic pharmaceutical innovation capacity: • A list of pharmaceutical innovation initiatives • A database of pharmaceutical innovation literature • Case studies using the capacity-building tools
List of pharmaceutical innovation initiatives The last column of the grid gives examples of current initiatives that can help governments achieve an innovation milestone, for instance, information on where they can seek help or partnerships and opportunities for shared or subsidised resources. For instance, a developing country might find, after assessing their situation against the grid, that they have gaps in their ability to fully access low-cost, quality imported medicines. By referring to the ‘initiatives’ column, they can identify groups or programmes to assist in filling these gaps. For example: • WHO drug and vaccine pre-qualification, which verifies the safety, quality and efficacy of medicines to support national Medicines Regulatory Authorities, whose resources are stretched • Regional networks of regulatory authorities (e.g. West African Drugs Regulatory Authority Network (WADRAN) and harmonisation activities led by Regional Economic Communities such as the Southern African Development Community (SADC), the East African Community (EAC) and the Common Market of Eastern and Southern Africa (COMESA) that can provide shared product testing and factory inspections or work on harmonising medicines regulation • Regional intellectual property organisations (e.g. ARIPO, OAPI) • Centralised procurement agencies that can secure quality medicines for developing countries at very favourable prices (e.g. UNICEF for EPI vaccines; GDF for TB drugs; GAVI for a range of newer vaccines; Clinton Foundation for ARVs; Global Fund)
Many countries will already be aware of or signed up to many of these initiatives, however the checklist allows any gaps to be quickly identified. Please note that because the framework is a work in progress – and because new initiatives are continually developed – not all initiatives are yet logged. This also applies for the list of initiatives presented in Annex 5.
Database of pharmaceutical innovation literature One other resource to assist pharmaceutical innovation decision makers is presented in this report: a database of literature (Annex 1: Tools - Article Database) relevant to each
55 innovation milestone outlined in Figure 7 and 8. Here’s how this will work: Policy makers assessing a country’s situation in terms of access to imported medicines can search the database for articles relevant to ‘access’. Using key words, policy makers can narrow the search to articles on ‘intellectual property’ or ‘pricing’. Although key articles have been included in the database, it does not include all materials on each topic. The database will expand, however, as new key articles are published.
Using the grid: three important points 1. The innovation milestones and the grid are a simplification of a very complex arena. These tools are designed to give policy makers an overview and to provide an entry point for more detailed work. Capturing the level of detail involved in every activity is beyond the scope of these tools. 2. Although the skills needed to achieve each milestone are substantially more complex than those associated with the preceding milestone, this does not mean that milestones must be followed in a linear fashion. For example, although “R&D” are often mentioned together, the research and the development of pharmaceuticals are, in fact, two very different tasks. ‘Development’ is an industrial activity and is within reach of countries with existing industrial capacity. ‘Research’ is the invention and development of new medicines. This is a scientific activity requiring skills in sophisticated science, pharmacology and medicine, and a comprehensive clinical trial network. 3. Innovation milestones included in the grid are designed to guide national policy makers. However, some activities might be approached at the regional level should objectives be shared by neighbouring countries and if harmonization initiatives are pursued.
For example, a country with limited manufacturing capacity but a robust science and biotechnology research sector – that can conduct licensure-standard clinical trials – can potentially enter the innovation pathway at the early drug innovation stage, and from there explore ‘upward’ and ‘downward’ strategies. The country may decide to build its drug discovery capacity, relying on joint ventures for clinical development or out-licensing to Indian or South African groups for manufacture of finished products. Alternatively, it may decide to develop its capacity for domestic pharmaceutical manufacturing, with a primary focus on simple re-formulations and combinations as a prelude to moving to full pharmaceutical innovation. The move to develop manufacturing or research capacity requires that most of the prerequisites outlined in the first ‘access’ level of the grid be in place (access, manufacturing and research and development). This must be done before addressing legislative, regulatory, tax, customs and patent policies covering pharmaceutical use. Countries embarking on this growth curve will need to establish or strengthen governance and management mechanisms around research and innovation for health. Inter-sectoral cooperation is needed between stakeholders from the relevant government players (such as health, science and technology, legal, trade, finance and education), civil society, intergovernmental other international organisations, and the private sector. This includes training efforts to address identified capacity gaps.
5.5 Country case studies The following case studies illustrate how capacity-building efforts might play out in “the real world.” Please refer to the grid detailed in Figure 8, as you consider how a country can assess its position in terms of pharmaceutical innovation milestones, determine gaps and assess opportunities for expanding its innovation capacity.
56 NEPAD-COHRED - Strengthening Pharmaceutical Innovation in Africa
Case study 1 - Approach for African country A
Country A is a mid-size African country with a population of under 50 million and an average life expectancy of around 50 years.
Legislative, policy and institutional framework in Country A • For pharmaceutical management: - Pharmaceuticals Act from the 1950s - National Pharmaceutical Policy (which ensures the safety, efficacy, quality and best use of medicines). The policy is comprehensive and was updated and strengthened in the past 5 years - Up-to-date legislation dealing with importation of counterfeit pharmaceuticals - Pharmacy Board to regulate implementation of the Pharmaceutical Act and Policy - National formulary of pharmaceutical products • For science and technology: - Science and Technology Act from the 1970s - Science and Technology Policy - National Council for Science and Technology, which heads the public research system • For management of intellectual property issues: - An up-to-date Intellectual Property Act that complies with the Trade Related Aspects of Intellectual Property Rights (TRIPS) agreement - A National Patent Office, however this reviews only around 5 patents per year, most pertaining to agricultural products, not pharmaceuticals - The government is currently building IP capacity at the main national university and through foundation of a specific IP research institute.
Level of access to safe, effective, quality medicines in Country A • Country A has a healthy domestic pharmaceutical market consisting mostly of imported Indian generic medicines • The Ministry of Health procures medicines on behalf of public hospitals through an international bidding process, and increases access to quality affordable medicines by using international initiatives such as the Global Fund, the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR), UNICEF, the Clinton Foundation and GAVI. • Country A’s regulatory authority has capacity to review less complex regulatory dossiers (e.g. generic drugs), taking an average 6-12 months to review and register a generic product. However, it has limited experience in assessing more complex dossiers, e.g. for novel drugs or vaccines • Country A has a WHO-accredited National Quality Control Laboratory that can accurately and reliably test and verify the quality of generic drugs, and of simple toxoid vaccines • Medicine prices are not regulated in Country A and there are significant price variations across regions and sectors. Public and Mission procurement attain competitive prices below international reference prices, but patient prices are relatively high compared with neighbouring countries. • Country A’s intellectual property laws include TRIPS flexibilities, such as compulsory licensing and parallel importation. Compulsory licensing has yet to be used, however parallel importation of ARVs has been used.
57 Manufacturing capacity in Country A • Country A’s pharmaceutical manufacturing base has grown dramatically over the last decade, with over 30 registered pharmaceutical manufacturers collectively supplying 50% of the regional market. However, the scope of manufacturing is limited, with companies predominantly repackaging formulated drugs and processing bulk components (imported APIs and excipients) into drugs. The bulk of locally manufactured preparations are non-sterile, over-the-counter (OTC) products. • Country A hosts branches of several multinational pharmaceutical companies, including GlaxoSmithKline, Astra Zeneca, Pfizer, Sanofi Pasteur, Eli Lilly and Novartis. These have regional sales, marketing and sometimes manufacturing functions in Country A, but no local R&D programmes. • Most local pharmaceutical manufacturers have made an effort to adopt good manufacturing practices (GMP) but compliance is far from ideal, and inadequate GMP enforcement has been identified as the main reason for poor quality products. • Country A encourages domestic manufacturers by providing low import duties on active pharmaceutical ingredients (APIs) and other tax benefits. Country A is also a signatory to various African regional treaties that exempt many regional goods from import duty (including possibly pharmaceuticals?).
Pharmaceutical research capacity in Country A • Country A has a strong research and tertiary education base in both the private and public sectors, with a number of universities conducting biotechnology and information technology (IT) programmes. • The National Medical Research Institute has a long history of sophisticated health and clinical research • Country A has an impressive clinical trials network and extensive experience in clinical research. Several centres have the capacity to conduct large-scale drug and vaccine trials to international licensure standards, and have trialled drugs, diagnostics or vaccines for hepatitis, HIV/AIDS and its opportunistic infections, malaria, tuberculosis, schistosomiasis and filariasis, among others. • Ethics review committees are in place to approve clinical trials, and all trials are approved by the pharmaceutical regulatory authority. However, there is no national clinical trial register. • An IP audit showed that IP management by researchers was improving with two R&D institutions and three universities having technology transfer offices, although not all were fully functional. • However, early stage pharmaceutical innovation is very limited (i.e. discovery of potential new medicines). • Human resource shortages are a brake on Country A’s pharmaceutical innovation capacity. • National funding for research is limited, and this is a significant constraint on research. Recognizing the problem, the government recently set up a US$3m innovation fund to facilitate research in science, technology and innovation.
58 NEPAD-COHRED - Strengthening Pharmaceutical Innovation in Africa
Opportunities This assessment shows that Country A has established a solid legislative, regulatory, research and education base to support pharmaceutical innovation, and identifies two key areas of opportunity for Country A to expand its pharmaceutical innovation capacity: 1. Given its large domestic and regional market, strong science base, and existing pharmaceutical tabletting and packaging industry, this analysis suggests Country A is in a good position to expand its pharmaceutical manufacturing capacity, including future production of active pharmaceutical ingredients. Areas to target to move to this next level are domestic GMP qualification, and upgrading of manufacturing facilities and skills for API manufacturing. 2. Country A’s strong clinical trial network and sophisticated research capacity lend themselves to a move into early pharmaceutical innovation, for instance product reformulations or development of novel fixed-dose combinations of existing products. Key challenges will be to address human resource shortages (including pharmacology and pharmaceutical skills), increase funding streams to domestic applied research, and increasing regulatory capacity to overview dossiers and clinical trials of new product formulations and combinations.
Case study 2 - Approach for African country B
Country B is a small African country with a population of under 5 million. Courtesy of economic growth, it has a relatively high GDP in African terms and, as a result, is now seeing the ‘double burden of disease’ typical of countries in epidemiological transition. That is, infectious diseases commonly seen in developing countries, but also an increasing burden of non-communicable diseases more common to high-income countries. As a result, Country B is increasingly being targeted by pharmaceutical companies as a potential site for clinical trials of products for non-communicable diseases such as diabetes, cancer and cardiovascular disease.
Legislative, policy and institutional framework in Country B • For pharmaceutical management: - Pharmacy Act (early 1980s) mandating registration of pharmaceutical products and regulation of pharmacies, but now considered out of date - A Pharmacy Board whose main function is to regulate pharmacies and pharmacists. The Board also registers medicines for domestic use, but has limited capacity to review and assess new medicines - National formulary of pharmaceutical products - No dedicated Medicines Regulatory Authority, and no nationwide pharmacovigilance or counterfeit control systems, although plans are underway (see Clinical Trial Bill) - A new Clinical Trial Bill, due to be passed in 2009, will include provisions for a new medicines regulatory authority and pharmacovigilance committee - Country B is a member of several regional economic communities working to harmonise medicines regulatory standards and quality Assurance • For science and technology - A Science and Technology Policy is in place • For management of intellectual property issues: - A Copyrights Act and Patents and an Industrial Designs and Trademarks Act are in place, both of which comply with the Trade Related Aspects of Intellectual Property Rights (TRIPS) agreement
59 - Country B recently ratified the TRIPS protocol allowing it to produce drugs under compulsory licensing for export to regional economic communities. However, its small manufacturing base (see below) will restrict its ability to do so • Country B has built a good health care system
Level of access to safe, effective, quality medicines in Country B • Almost all of Country B’s pharmaceuticals are imported, mainly from Indian manufacturers. • Country B has some of the highest pharmaceutical tariffs in Africa, with 2001 data ranking it in the top 15 African countries for tariffs on active pharmaceutical ingredients and finished products, including a 10% mark-up on the CIF (cost, insurance and freight) price • Country B is involved in initiatives by several Regional Economic Communities to secure pooled procurement of medicines in order to lower costs
Manufacturing capacity in Country B • Manufacturing capacity is very modest. There are two domestic generic manufacturers and no multinational pharmaceutical companies (MNCs).
Pharmaceutical research capacity in Country B • Country B has limited technical expertise in research, and the health research agenda focuses on non-communicable diseases such as cardiovascular disease, asthma and cancer • Country B has a Central Health Laboratory with biochemistry, microbiology, virology and pathology divisions. It conducts research in the areas of diabetes, hepatitis B and HIV/AIDS • A national university conducts research and has a medical studies centre • Research volume is modest. The Research Council, the country’s main research centre, has funded only 33 biomedical research projects in the last 15 years • Five state hospitals have the capacity to conduct trials, but there is no trial network • Country B has a Research Ethics Committee, but no regulatory review of clinical trials • Country B is currently undertaking a major reform of its legislation to ensure it can maximise the opportunity to host clinical trials of industry products
Opportunities for Country B This assessment shows that Country B is at the earliest Innovation Milestone. Some fundamentals are in place, or will be in place shortly, including a good health care system, and legislation and regulation for medicines and intellectual property. The manufacturing base is limited, however, and there is limited technical expertise in pharmaceutical research. This suggests Country B is not well-positioned to embark on pharmaceutical manufacturing or innovation research at this point in its development. This assessment suggests priorities for Country B would be to: • Put in place the fundamental elements of innovation, including: - Developing a National Pharmaceutical Policy covering safety, efficacy, quality, best use of medicines, prescribing practices, generic use. - Institute a National Council for Science and Technology to head and coordinate the public research system
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• Focus on improving access to affordable, quality, imported medicines for the population - Review membership of global procurement mechanisms for affordable quality products (e.g. GDF, UNICEF, AMFm.) - Review pharmaceutical tax and tariff policies - Implement legislation dealing with importation of counterfeit pharmaceuticals - Support the new MRA to review dossiers of imported generic products (either nationally or in conjunction with regional regulators)
If Country B wishes to attract clinical trials from industry, the following areas would be priorities: • Support the new Medicines Regulatory Authority to register, evaluate and approve clinical trial protocols and plans to inspect clinical trial sites • These MRA activities could be developed domestically but a quicker, more cost- efficient approach could be to liaise with regional or other external regulators to conduct joint trial approvals and inspections while the MRA is in the early stages • Develop a mechanism to coordinate clinical trial reviews and inspections by the current Research Ethics Committee and the proposed new MRA • Create clinical trial hubs in the existing hospitals, and use these to build trial networks in the surrounding areas • Upgrade the proposed trial hubs, field sites and laboratories to international standards (GCP and GLP) • Conduct training in data management and in meeting international standards including ICH, GCP, GLP • Consider membership of the African Vaccine Regulatory Forum (AVAREF), set up in 2006 to support MRAs and Ethics Committees in African countries that were targeted for clinical trials of new vaccines • Encourage the proposed National Council for Science and Technology to work with the National University to develop a curriculum relevant to pharmaceutical trials and research (e.g. applied pharmacology, immunology, epidemiology).
61 Chapter 6 The way forward – Conclusions and recommendations
6.1 Where are we now? This report provides the evidence base and direction for the initiative Strengthening Pharmaceutical Innovation in Africa. Its purpose is to contribute to the improvement of health, equity and development in Africa, through better access to essential drugs by supporting health knowledge and technology transfer and a public goods approach to pharmaceutical R&D and production. The initiative provides a road map for African countries and their supporters to engage productively in pharmaceutical innovation – primarily, but not exclusively, driven by improving access to essential drugs. Economic development on its own remains a second important driver for pharmaceutical innovation, as highlighted in the Pharmaceutical Manufacturing Plan for Africa. The work leading to this report resulted in two major outputs: • A map of the many pharmaceutical innovation efforts in progress in Africa linked to improving access to drugs. This map is a first effort to show the complexity of the field. It is an essential tool to help countries understand the nature of the international efforts that apply regionally and possibly in their own countries. This understanding is the basis for rational decision making and for developing the capacity to exercise appropriate governance of pharmaceutical innovation within their borders – or across borders with neighbouring countries. • a “pharmaceutical innovation framework and grid” which guides decision makers through the options for countries interested in starting pharmaceutical innovation to improve drug access or develop their economy. This tool encourages countries to ask themselves serious questions about their level of engagement and provides options for immediate and longer term action. It serves as a road map for countries to make a difference through pharmaceutical innovation – not just in terms of drug production but also by creating an environment that favours efficiency in procurement, regulation and logistics management, for example.
As this work unfolded, two important developments occurred that have or may have a direct impact on pharmaceutical innovation in low and middle income countries in general, and in Africa in particular. These include; • the adoption of the Global Strategy and Plan of Action for Public Health, Innovation and Intellectual Property (GSPOA) by the World Health Assembly in 2008 • the Bamako 2008 Ministerial Forum on Research for Health in Mali, which brought together, for the first time, ministers of health and ministers of science and technology to discuss “research for health” – including pharmaceutical innovation.
The emphasis given to pharmaceutical innovation by these two global activities and the availability of practical tools that countries can use to start operationalising pharmaceutical innovation create momentum for full implementation of the Declaration of the Algiers Ministerial Conference on Health Research, the Bamako Call for Action, the WHO GSPOA on Public Health, Innovation and Intellectual Property and the African Union Pharmaceutical Manufacturing Plan, among others.
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The partners believe that the approach we have developed and the tools we propose can help the various stakeholders in Africa to take such concrete steps and put in place coherent strategies to implement the measures recommended by these important events and documents. Under NEPAD’s guidance, this African initiative for improved access to medicines and local production will contribute to the expansion of a well functioning innovation system for health in Africa that makes the best use of African human capacity and natural resources to improve health on the continent – and contribute to its economic development. Soon after the Pretoria meeting where African experts reviewed the report – improved and approved the approach and tools – the initiative Strengthening Pharmaceutical Innovation in Africa was endorsed by the African Ministerial Conference on Science and Technology as a starting point for African countries to put into action the Global Strategy and African Pharmaceutical Manufacturing Plan. This provides impetus for the first steps of implementing the initiative and will help identify countries where the approach can be applied and tested.
6.2 Major findings and conclusions of the analytical process 6.2.1 A growing demand for pharmaceutical innovation in Africa – and globally
“The leadership of the African Union is committed to ensuring access to essential medicines for countries in need, irrespective of their level of Pharmaceutical technological development and manufacturing capacity.” Manufacturing Plan for Pharmaceutical Manufacturing Plan for Africa, Ministers’ meeting, 10-13 April 2007 Africa – 6 priority areas In 2007 the African Union There is a tremendous interest in pharmaceutical innovation as a way to improve health adopted the Pharmaceutical and access to drugs for the poorest people and countries. As a result, there is also a Manufacturing Plan for Africa to focus on: growing demand from low and middle income countries and regions to become more • Mapping active partners in finding lasting solutions in that area. This is demonstrated, among • Situation Analysis and others, by the time and resources devoted by the Member States of WHO – for almost Compilation of Findings two and a half years – to the complex negotiations of the Intergovernmental Working • Manufacturing Agenda Group (IGWG) that developed the GSPOA. • Intellectual Property Issues National interest: • Political, Geographical and Economic Considerations While most African countries got increasingly involved in reflections shaping the • Financing international debate on access to essential medical products, Kenya – together with Brazil – was instrumental in the World Assembly’s discussions of 2008 and 2009 as well as in the IGWG, thus taking an active role in the development of the GSPOA. Nigeria played an essential facilitating role in the creation of the African Network for Drug Discovery and Innovation (ANDI) supported by WHO/TDR. South Africa is home to some of the most successful ventures of the continent in the pharmaceutical production, like ASPEN Pharmacare, and is the only African country producing Active Pharmaceutical Ingredients; small biotech companies emerge regularly; and the country has one of the most efficient drug regulation systems of Africa. Smaller countries like Ghana – with the creation of the La Gray pharmaceutical company – also develop their private pharmaceutical industry, and others, like Rwanda, make deliberate and sustained efforts to build – almost from scratch – a comprehensive system to ensure their people’s regular access to safe and good quality medicines. These are only a few examples of an increasingly dynamic pharmaceutical sector in Africa. Regional interest: In October 2008, African researchers, pharmacists, academics, representatives of the African Manufacturing Association and African expatriates gathered in Abuja, Nigeria
63 to create ANDI (WHO/TDR), which aims to facilitate the development of African discoveries and research results – including traditional medicine – into usable medical products of good quality, by pooling regional resources and promoting better interaction between researchers and drug developers and producers. In February 2009, NEPAD, with funding from the Gates Foundation and the technical support of WHO, brought together all Regional Economic Communities and most of the National Regulatory Authorities of Africa to spearhead regional and national efforts for strengthening and harmonising drug regulation across the continent. In February 2010, the African Union Commission, together with NEPAD and COHRED organised a special meeting of an Extended Technical Committee of the Pharmaceutical Manufacturing Plan for Africa, with support from the Netherlands’ Ministry of Foreign Affairs and the Swiss Agency for Development and Cooperation to review the initial version of the report, its study and tools – Strengthening Pharmaceutical Innovation in Africa – prepared by NEPAD, COHRED and contributions from the George Institute for International Health. The meeting brought together a unique cross-sectoral gathering of experts and stakeholders active in all aspects of pharmaceutical innovation on the continent. Global interest: The debates in WHO for developing the Global Strategy and Plan of Action mobilised a lot of interest, including experts in the pharmaceutical industry and non-governmental organisations who informed the debates of the Intergovernmental Working Group. The discussions around the financing of the Strategy and Plan of Action are mobilising all stakeholders in innovation and research for health in active debates – through open electronic consultations – on how to provide incentives for innovation without undermining access to medicines. Many NGOs like MSF, Save the Children, HAI, or more recently IQSensato, participate actively to the debates on access to medicines and play an essential role in questioning the decisions of the international health research community and holding the public stakeholders accountable for their decisions on pharmaceutical innovation and access. The private sector too is developing new approaches to keep up to speed and respond to the growing demand for more equity in drug production and access. More than 200 public private partnerships have emerged during the past decade to build up capacity, to transfer technology and knowledge, and to support research and facilitate access to medical products in developing countries. New research centres have been created or supported by the pharmaceutical industry in the South to better cater for the needs of low and middle income countries, like the Novartis Centre in Singapore or the International Vaccines Research Centre in Korea Global and national interests are not necessarily convergent. There is a difference in the nature of the interest demonstrated towards pharmaceutical innovation at the different levels. African countries seem in general more interested in the trio of discovery, traditional medicine and biotechnology, in addition to better understanding and improving procurement and delivery, while at global level the interest is more on discovery, development and testing. Delivery and procurement generate less interest at global level in general. For this reason alone, countries need to be partners in the global drive towards more equitable access to drugs. It is only when adequately addressing all facets of the R&D, production and delivery of medical products that effective solutions will be possible. Coherence and complementarity of the efforts at all levels is certainly one of the keys to long term success in that domain.
64 NEPAD-COHRED - Strengthening Pharmaceutical Innovation in Africa
6.2.2 Complexity of the landscape of pharmaceutical innovation This study identified more than 120 different initiatives or programmes active in access to medical products in Africa. A number of these are global initiatives with an exclusive or partial focus on Africa. These partnerships bring together small groups of players (2- 3) and extend to groupings of 20-30 different entities. They are from the public and private sectors – some groupings are all public, others all private, and some public- private. There are gaps at all levels, as most initiatives work in specific parts of the innovation spectrum. Donor countries and international organisations are also members of several partnerships, and these activities are not necessarily coordinated – despite membership overlap, creating a lack of coherence, even within institutions. Almost no country in Africa, and very few in other low and middle income countries – with the notable exception of Brazil – have a ’grand plan’ for pharmaceutical innovation. There are lots of actors and initiatives but paucity on long term vision, comprehensive approaches, coherence and coordination. There is lots of information, although not widely disseminated and seldom analysed within a more general context, but much less evidence on what works. There is even less evidence of whether national policies on pharmaceutical innovation are evidence-informed or, simply, work. To make sense of this and to determine where appropriate action can be taken by countries and in countries, we need tools and approaches that simplify, that encourage understanding and synergy, and that can lead to the identification of practical steps forward. The ‘Pharmaceutical Innovation Grid’ is intended to provide this guidance.
6.2.3 Lack of approaches to help countries make decisions on engagement The intersection between public health, pharmaceutical production and intellectual property rights remains a complex and disputed domain. Countries need tools and support to make rational decision about their engagement into pharmaceutical innovation in ways that fit their heterogeneous needs and resources. They must undertake an in-depth analysis of public health and innovation issues at regional and national level, develop strategies to address the gaps identified and put in place the essential building blocks of a pharmaceutical innovation system – all of which are core to ensuring that their people have access to essential medical products . Low and middle income countries – already faced with overwhelming disease burden, fragile health and science and technology systems, and limited human resources in the pharmaceutical innovation domain – are now also faced with a veritable tsunami of efforts to improve access to drugs. Early reactions to the pharmaceutical innovation map show that many - even well- resourced initiatives and actors – are unaware of the complexity of the landscape, let alone the governments in low and middle income countries that are to benefit from these efforts. Before they can have an overview, based on evidence and reliable analysis, they cannot even hope to exercise minimal governance in this area. The ‘grid’ is a world first – there have been no previous attempts to create such an enabling tool. It encourages system thinking and will promote coordination, coherence, overview and oversight, and a focus on national priorities in health and science and technology. Our hope and assumption is that the map and the ‘pharmaceutical innovation grid’ developed as part of the Yaoundé process will enable African countries to refine their analysis of pharmaceutical innovation, and that African decision makers can use these two tools for catalyzing progress in areas identified by the PMPA Technical Committee or others, as may be relevant in individual counties and regions. However, the Grid also has generic appeal and may well be applicable in countries beyond Africa.
65 6.3 Proposed next steps 6.3.1 Operationalising strategies and plans of action. The GSPOA and the African Union’s PMPA are aspirational statements that need to be translated into work plans and approaches to implementation. The development of the ‘Pharmaceutical Innovation Grid’ aims to support countries to translate these global plans into action at national, regional and continental level. This report, its pharmaceutical innovation tool – the Framework and Grid – were considered to be extremely useful by he African Union’s Extended Technical Committee on the Pharmaceutical Manufacturing Plan for Africa. The review confirmed convergence of the findings of this study with an analysis done by the Expert Committee in 2007. They recommended using the report and the tools it proposes to inform and support the African Union in developing a business plan for the PMPA. They also recommended using them to contribute to achieving the goals of the PMPA. The experts of the Extended Technical Committee said that the tool provides a mechanism for coordinating and harmonising among different stakeholders involved in implementing the PMPA. This, they said, creates the basis for monitoring and evaluation of some aspects of the GSPOA and the PMPA, and provides evidence to support the implementation of specific aspects of these two strategies. The study findings and tool also support priority setting for implementing these mechanisms – nationally, regionally and for the African continent. It assists countries and regions to identify gaps and use these as evidence to gain donor and partner support. Participants in the Pretoria meeting recommended: · Establishing short and long-term objectives and milestones for pharmaceutical innovation and manufacturing in Africa. · Prioritising the creation of mechanisms to stimulate research and development, technology transfer and other conditions needed to facilitate and strengthen manufacturing in Africa. · Creating a coordination mechanism to ensure better synergy and improved intra and inter-regional support. · Establishing a mechanism to capture and keep up-to-date information about country developments. · Making the tool and related documents available in all official African Union languages and adapting its formulation to a language that is understandable across sectors, professional cultures and backgrounds.
Participants recognised that establishing strong communication mechanisms is essential to the effective use of the tool, and that to achieve their goals; the different stakeholders will need to meet, share information and resources and generally improve their collaboration.
AMCOST commends the NEPAD Agency for its programmes on pharmaceutical innovation and harmonization of medicines registration in the AU member states in line with the Global Strategy and Plan of Action on Public Health, Innovation and Intellectual Property (GSPA), AU Health Strategy, AU Pharmaceutical Manufacturing Plan for Africa and CPA AMCOST Resolution, March 2010
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6.3.2 Obtaining high-level political support for implementation In additional to having appropriate technical tools and approaches, political support is essential to the long term success of pharmaceutical innovation playing a proper role in improving health, equity and development. The Pretoria meeting was a first important step toward getting broad African review and support for the pharmaceutical innovation strengthening process initiated by NEPAD, COHRED and their partners. The participants to the meeting recognised that successful national pharmaceutical innovation requires a combined effort of political support, technical expertise and financial commitment between several sectors (such as education, finance, law and trade), particularly between health and science and technology. As a first step toward securing political support for the initiative on ‘Strengthening Pharmaceutical innovation in Africa’ the report, tool and Pretoria Meeting Statement of partners were presented in Mach 2010 to the meeting of the African Ministerial Conference on Science and Technology (AMCOST), which commended the work accomplished by NEPAD and its partners. Several of its member countries expressed an interest in implementing the Framework and Grid.
6.3.3 Starting implementation Capacity building is recognised as vital to strengthening pharmaceutical innovation in Africa. To define the focus and content of the workshop series, essential capacities and skills will need to be prioritised according to countries’ and regions’ specific gaps and needs. Key areas to be strengthened have already been identified for each milestone. Access: - Health care policy making must be strengthened and regulations enforced to address the challenges of substandard drugs, dumping of drugs close to expiry, and donated drugs that may result in mono-therapy and increase the risk of resistance - The capacity of governments to handle well-meaning donations must be improved to make sure that they do not undermine access or the capacity of local manufacturers. - The capacities of medicines regulatory authorities must be strengthened to ensure access to safe, efficacious, high quality medicines - Capacity should be developed in inspection, quality control, laboratories’ work and management. Quality assurance systems are critical; this responsibility should be located at different levels of pharmaceutical innovation. - There is a need to build capacity in international intellectual property laws and regulations - Regional collaborations should be explored to address capacity constraints in laboratory technologies, and in other areas, such as policy making or enforcement mechanisms. Countries would benefit from the lessons of other countries. - Participants recognised that enforcement depends largely on national mechanisms like training and strengthening judiciary institutions. - Strengthening capacity in health insurance will contribute to sustainable financing and improve access.
67 Manufacturing: - Achieving WHO prequalification for African products is a very significant hurdle, but is important as it is considered the hallmark of certification. It calls for specific capacities, facilities, and for personnel skilled in prequalification standards. The high capital investment needed to meet the minimum standards and the prohibitive costs of borrowing capital are a major hindrance. - Universities should realign their training curricula to produce the right calibre of personnel - African governments should establish a fund that lends at low interest since commercial rates are prohibitive - Partnerships should be harnessed and fostered with agencies like UNIDO to assist African companies working towards WHO prequalification - Governments must assist local manufacturers to overcome the challenges of WHO prequalification, especially given the cost of bio-equivalence studies. Local companies could benefit from ‘preliminary prequalification’ if they reach certain milestones. Companies could be prequalified rather than qualifying particular products - Strengthening regional capacity offers good alternatives. Some countries are looking to establish common facilities like bio-equivalence centres, common review and inspection of facilities, harmonised review process of dossiers – that account for certification by another agency within the region6 - Capacity building is needed for handling of traditional medicines and phyto- medicines and cultivation of medicinal plants. This also implies the capacity development of national regulatory authorities, including expertise in taxonomy, quality control of medicinal plants, microbiology. - Local manufacturers’ competitiveness must be increased, of example through an increased marginal preference for locally manufactured medicines. - Feasibility studies are needed to strengthen the case for financing of local manufacturing capacity. - Improvements in Africa’s manufacturing capacity will create an enabling environment and address critical criteria for improved competitiveness, such as the cost of power.
Research and development - R&D is expensive and calls for collaboration. - An enabling research environment should be created, for example through supporting research ethics - Institutions in Africa need to build up the necessary capacity – human resources and institutional strengthening – to draw and attract funding for R&D. This could be done among others through funding Masters, PhDs and other degrees for creating scientific leaders in Africa - Infrastructure development and networking opportunities should be supported to create a critical mass across research institutions in Africa - Regional centres of excellence should be encouraged through collaborations that foster regional partnerships, promote local ownership and are able to attract independent funding that allows the development of research - Recognising that specific institutions have competence in certain areas of research, support should be provided to them to move into other areas beyond their current areas of research, for example moving from malaria to tuberculosis research - There is a need to develop capacity for testing of products from the very outset rather than at later stages
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- Partnerships between private sector and research institutions should be promoted to build capacity in real novel drug discovery. Governments and institutions like AU/NEPAD should lobby and encourage the creation of a mechanism that supports funding of competitive proposals that lead to the commercialisation of products - Capacity building needs of traditional medicine require particular attention as the AU decade for traditional medicine will end this year. Capacity is needed in the area of developing remedies, training people in pharmacology, in mixture of active components from many plants (as distinct from pure substances) - States should be encouraged to allocate 2% of their national budget for research 7
The African experts at the Pretoria meeting of the Extended Technical Committee of the Pharmaceutical Manufacturing Plan for Africa (February 2010) concluded that human resources development is crucial in all areas of R&D, and monitoring and evaluation are critical to the success of pharmaceutical access, manufacturing and research and development.
Workshop series - Increasing technical understanding of pharmaceutical innovation Governments and regulatory authorities in low and middle income countries need to have the best available information to make informed decisions on where to engage with the pharmaceutical innovation process. Given the complexity of the domain, it is essential to provide a multi-year, on-going workshop series open to all interested countries in Africa. All players in the pharmaceutical innovation field will be able to contribute, both financially and technically. It is foreseen as a 4-6 workshop series per years over 3-5 years, covering different regions and languages. Workshop follow-up may include mentorship, partnerships and other mechanisms of increasing national capacities. The challenges and possible solutions highlighted in the Pretoria meeting confirm that capacity building and training needs are diverse, specific to the African countries and regions concerned and cover a broad range of issues. Countries need to carefully evaluate their most pressing needs and design their capacity building strategies accordingly. However, some of the gaps to be addressed are quite similar from one country to the next and it has been repeatedly stressed that regional strategies and collaborations could efficiently help developing the skills and capacities needed across Africa. A good example of regional efforts now in progress is the harmonisation of drug regulation, supported by NEPAD and the Regional Economic Communities (RECs), for which regional capacity building strategies are being developed. In a similar way, it is envisaged that the initiative Strengthening Pharmaceutical Innovation in Africa will collaborate with African RECs and other partners to establish a series of workshops to increase African countries’ capacities in areas identified as critical for implementing pharmaceutical innovation, for example – drug regulation, intellectual property management, laboratory techniques, research management and leadership.
Implementation – pilot countries One of the major inputs of the Pretoria meeting, enhanced by the technical workshops series, will be a concerted effort by NEPAD, COHRED and the other partners of the project – donors, technical experts and other stakeholders – to work with interested countries for the first phase of implementation. As resources will be limited, strong emphasis will be put on a “pilot country” approach – in which countries are included on the basis of interest expressed, feasibility and level of commitment.
69 One critical step in the implementation will be the dissemination of the report Strengthening Pharmaceutical Innovation in Africa, its approach and tools. Implementation should start with further assessment of the situation by the technical partners, including NEPAD and COHRED, in countries and regions – to encourage ownership of the approach. The tool will be adapted and translated into the African Union official languages and people will be supported to use it. Existing knowledge on the status of each country should be included in the assessment. Another essential step is to establish or reinforce local production facilities that address priority needs defined by African countries and comply with quality and safety standards. Key elements for developing local manufacture will be: - Developing a framework for facilitating technology transfers and joint ventures with access to venture capital facilities. This can be facilitated by the AU, following the examples from malaria nets and tuberculosis. - Mobilising resources: this is a role for the African Union, that can get support in their negotiations from many partners, like UNECA. - Mobilising private sector partners to start manufacturing, for example through Chambers of Commerce and local associations.
It will also be essential to have in place fully functional regulatory authorities for quality assurance, with the help of WHO and relevant authorities, and make sure that local manufacturers comply with Good Manufacturing Practices, obtain pre-qualification and can register their products through a reliable and appropriate process. At the same time, the African Union could facilitate the creation of incentives for African manufacturers, for example through public tenders. Good distribution practices should also be established; WHO and other experts can assist African countries to develop relevant policies. Implementation in pilot countries should be driven by national governments. Specific national approaches will depend on each country’s specific situation, its objectives, most crucial gaps and key resources. Facilitation provided by technical experts should allow for a flexible use of the Framework and Grid. This will ensure a thorough assessment of the country’s current innovation status, the adaptation of the tool and approach to the country’s situation, and encourage development of a partnership between the main national players in pharmaceutical innovation.
6.3.4 Developing of additional tools, frameworks and guidelines if and when needed It is very clear that the map and grid developed as part of this project are just the beginning of what is needed to support countries in operationalising pharmaceutical innovation. During the implementing phase, other frameworks may be developed as complements to the first pharmaceutical innovation grid proposed and to facilitate the implementation of some of its components. More information is needed to better understand some of the essential elements for building up innovation systems, how to prioritise them within a particular African national context, and in which sequence to put them in place. Another adaptation needed of this Version 1.0 of the Grid is one that offers a phased approach.
6.3.5 Monitoring and evaluating COHRED and NEPAD have already decided on an extensive collaboration on an innovative web-based framework for the management of research systems. For the health field it is the Health Research Web (www.healthresearchweb.org) and for the African Science and Technology Innovation Indicators project it is the African Science & Technology Web (www.africanscienceweb.org).
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The advantages of this system are that it offers the first Pan-African research management information system, suitable for national, regional and institutional use, and the fact that it is controlled by the countries. NEPAD and COHRED will collaborate in adapting this web-based platform to measure and communicate progress in implementing the GSPOA in Africa and the African Union’s PMPA.
6.4 Conclusion This paper highlights the tremendous momentum currently focused on pharmaceutical innovation in Africa. Collective and concerted efforts to help countries harness these energies for the advancement of public health and socio-economic development are both timely and useful. While political awareness has increased with the recent endorsement of essential policy directions and plans –especially of the GSPOA at global level, and of the African Union at regional level –African countries will need support to translate these into national policies and strategies and, above all, concrete actions. The present report is the first result of a process aiming to bring along the practical changes needed to move towards more innovation for health in Africa by Africa.
71 Annex 1 Tools - Innovation System Framework
Stage of development Actions needed Basic requirements - supportive environment Political commitment to pharmaceutical innovation Advocacy, awareness, data and discussion. and improved access to medical products Identify key individuals/groups that can initiate and catalyse the process. Political support across government sectors: health, Develop a common understanding of pharmaceutical innovation. Mobilisation across science and technology, trade, industry, education, legal sectors for a multisectorial approach to innovation Business environment and basic infrastructure Increase reliability of essential infrastructure, e.g. banking system, power supply, transport, Level 1 needs – pre-requisites Management mechanism for pharmaceutical Establish mechanisms and structures appropriate to the country’s existing structures innovation and access to medical products and aspirations. These need to be multisectorial. Particular attention should be given to collaboration between health and S&T sectors. Public health priorities Credible and regularly updated public health priorities Complementary priorities for health research and pharmaceutical innovation - essential drugs, diagnostics and vaccines Level 2 needs – assessment and decision-making Assessment of current national situation of Identifying where the country sits in terms of innovation milestones; where are the pharmaceutical innovation major gaps; who are the major stakeholders. The COHRED/GI Pharmaceutical Innovation Assessment framework provides a guide to these activities Decision on pharmaceutical innovation goals Informed by the assessment and public health and development strategies, focus on one of the 3 milestones, access, manufacturing or R&D and /or set national goals for the component chosen or for each component
Level 3 needs –essential building blocks Policy framework for pharmaceutical access, A number of policies need to be in place for each component, for example: manufacturing and R&D Access: drug regulations, trade policy, tax policy Manufacturing: industrial policy, good manufacturing practices Human Resources R&D: research policy, intellectual property management Develop a human resources strategy and plan aligned with priorities Address all relevant sectors: public health, science and technology, industry, judiciary, economy, trade, education Stable, predictable financing Develop a pharmaceutical innovation financing strategy, Ensure it addresses national and foreign funding from the public and private sectors
Level 4 needs – Collaboration Partnerships Regional, inter-country collaborations for product development, clinical trials, cross- registration, quality control. National PDPPPs; North-South and South-South transfers of knowledge, processes and technologies
Level 5 needs – optimising the pharmaceutical innovation system Improving pharmaceutical innovation system For example: components Access - Pooled procurement - Community based delivery Manufacturing - Technology transfer arrangements; - Good manufacturing practices - Post market quality control R&D - Good research contracting; - Intellectual property management; - Clinical trials ethics; - Merit-based promotion system of scientists All levels - Community demands for medical products - Monitoring & evaluation - Institution building.
72 NEPAD-COHRED - Strengthening Pharmaceutical Innovation in Africa
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82 NEPAD-COHRED - Strengthening Pharmaceutical Innovation in Africa
Annex 2 Abbreviations and acronyms
AA4A ARV Access for Africa ARV Anti Retro Viral AAVP African AIDS Vaccine Program AAHA Aid Alignment and Harmonisation ACTs artemesinin-based combination therapies AFRO WHO Regional Office for Africa AMANET African Malaria Network AMCs advance market commitments AMCOST African Ministerial Council on Science and Technology AMFM Affordable Medicines Facility for Malaria AMU/UMA Arab Maghreb Union ANDI African Network for Drugs and Diagnostics Innovation (WHO/TDR) API active pharmaceutical ingredient APOC African Programme for Onchoceriasis Control APRIORI African Poverty Related Infection Oriented Research Initiative ARIPO Africa Regional Intellectual Property Organization ARV antiretroviral ASTII African Science, Technology and Innovation Indicators Initiative AtM AtM Index. Access to Medicines Index AU African Union AVAREF African Vaccine Regulatory Forum BMGF Bill and Melinda Gates Foundation BMZ Bundesministerium Für Wirtschaftliche Zusammenarbeit (German Federal Ministry for Economic Development Cooperation) BRICs Brazil, Russia, India, China CEEAC/ECCAS Economic Community of Central African States CEN-SAD Community of Sahel-Saharan States CFWshops Child and Family Wellness shops CIPIH Commission on Intellectual Property Rights, Innovation and Public Health CMH Commission on Macroeconomics and Health COHRED Council on Health Research for Development COMESA Common Market for Eastern and Southern Africa (COMESA) CSF cost, insurance and freight CSDH Commission on Social Determinants of Health CSIR Council for Scientific and Industrial Research DfID Department for International Development DNDi Drugs for Neglected Diseases Initiative DST Department of Science and Technology (South Africa) EAC Eastern African Community ECCAS Economic Community of Central African States ECOWAS Economic Community of West African States EDCTP European Developing Countries Clinical Trial Platform EDR Extreme Drug Resistance EPI Expanded Programme on Immunisation EWG Expert Working Group FDA Federal Drug Administration FIND Foundation for Innovative New Diagnostics
83 FTA Free Trade Agreement GAVI Global Alliance for Vaccines And Immunisation GDP gross domestic product GDF Global Drug Facility GFATM Global Fund for, HIV/AIDS, Tuberculosis and Malaria GIBX Global Institute for Bio-Exploration-Africa GMP Good Manufacturing Practices GSK GlaxoSmithKline GSPOA Global Plan and Strategy of Action on Public Health, Innovation and Intellectual Property HAI Health Action International HRSA Health Research Systems Analysis (WHO) HIV/AIDS Human immunodeficiency virus/acquired immunodeficiency syndrome ICEGB International Centre for Genetic Engineering and Biotechnology IFC International Finance Corporation IGWG Intergovernmental Working Group on Public Health, Innovation and Intellectual Property ICTRP WHO International Clinical Trials Registry Platform IDA International Development Association IGAD Intergovernmental Authority of Development INRUD International Network for Rational Use of Drugs ISHRECA Initiative to Strengthen Health Research Capacity in Africa IPR intellectual property rights KEI Knowledge Ecology International LDCs least-developed countries LMICs low- and middle-income countries MCTA Malaria Clinical Trial Alliance MDGs Millennium Development Goals MeTA Medicines Transparency Alliance MMV Medicines for Malaria Venture MNCs Multinational pharmaceutical companies MSF Médecins Sans Frontières NACCAP the Netherlands-African partnership for capacity development and clinical interventions against poverty-related diseases NAPRECA Natural Products Research Network of Eastern and Central Africa NEPAD New Partnership for Africa’s Development NIPRID Nigeria Institute for Pharmaceutical Research and Development NGO non-governmental organization NMA Noordwijk Medicines Agenda NRA National Regulatory Authorities OECD Organization for Economic Co-operation and Development OAPI Organisation Africaine de la Propriété intellectuelle OTC over-the-counter (medicines) PDPPP Product Development Public Private Partnerships PEPFAR President’s Emergency Plan for AIDS Relief PIC-S Pharmaceutical Inspection Cooperation Scheme PMPA Pharmaceutical Manufacturing Plan for Africa PPP public-private partnership PPDDP1 public-private drug development partnerships PSMIP Public Service Management Insurance Plan R&D research and development RECs regional economic communities
84 NEPAD-COHRED - Strengthening Pharmaceutical Innovation in Africa
SADC Southern African Development Community SAMI South African Malaria Initiative SARIMA South African Research and Innovation Management Association SME subject-matter expert STI Science, Technology and Innovation (Rwanda) TDR Special Programme on Research and Training in Tropical Diseases TRIPs Trade-related aspects of intellectual property rights TWN Third World Network UNITAID international facility for scaling up access to treatment for HIV/AIDS, malaria and tuberculosis UNCTAD United Nations Conference on Trade and Development UNESCO United Nations Educational, Scientific and Cultural Organization UNIDO United Nations Industrial Development Organisation WADRAN West African Drugs Regulatory Authority Network WARIMA West African Research and Innovation Management Association WHA World Health Assembly WHO World Health Organization WIPO World Intellectual Property Organization WTO World Trade Organization
85 Annex 3 Glossary
Innovation: As defined by the Commission on Intellectual Property Rights, Public Health and Innovation (CIPIH): ‘3 D’- ‘Discovery, Development, and Delivery’
Neglected diseases: As defined as type II and III diseases by the Commission on Macroeconomics and Health (CMH): • Type II: incident in both rich and poor countries, but with a substantial proportion of the cases in poor countries (e.g. HIV/AIDS, tuberculosis) • Type III: overwhelmingly or exclusively incident in developing countries (e.g. African sleeping sickness (trypanosomiasis), African river blindness (onchocerciasis)
Health products tools: Terms used to refer to medicines, vaccines and diagnostic devices.
Technology transfer /transfer of technology As defined by the United Nations (accessed from DFID 2004), as the ‘Process of sharing knowledge, skills, expertise and know-how’, divided into four categories: • Technoware, including physical objects and equipment • Humanware, including skills and human aspects of technology management and learning • Infoware, including designs, blueprints, and document-embodied knowledge on information and technology • Orgaware, including organisational knowledge needed to operate a given technology
Research for health In the most traditional and narrow sense of health research, ‘medical research’ deals with the medical conditions of individuals and aims to solve the core health problems of individuals, families and countries. Based on the recognition that the health of populations can be greatly improved by better understanding population characteristics and behaviour, ‘population health’ or ‘public health’ research focuses on epidemiology, social and development sciences, including economics. It is supplementary to ‘medical research’, which describes great benefit of health and health equity worldwide. The ministerial summit on ‘knowledge for better health’, held in Mexico in 2004, defined commitments to ‘health systems research’ – that is, the type of operational research that helps improve performance and coverage of health systems. This followed evidence that in low-income countries, simple improvements in health care provision could result in major health improvements. These types of research (‘medical’, ‘population’ and ‘health systems’ research) are aimed at conditions that affect health directly – for example, through better medicines, behaviour change or improved health care provision. Important as these are, this view of ‘health research’ does not address the multi-sectoral nature of health nor does it address the potential for social and economic benefits and development. The concept of ‘research for health’ attempts to address all these issues. Health research does not only solve direct health problems, it can also provide employment, lead to innovation, support institutional development, enhance a culture of evidence-informed policy throughout government, and even contribute to employment and economic growth.
86 NEPAD-COHRED - Strengthening Pharmaceutical Innovation in Africa
WHO prequalification project The WHO Prequalification project ensured unified standards of quality, safety and efficacy for medicines needed to treat HIV/AIDS, malaria and tuberculosis. Any manufacturer wishing their medicines be included in the pre-qualified products list must present extensive information on the product (or products) to allow qualified assessment teams to evaluate quality, safety and efficacy. The inspection teams also assesses the manufacturer’s working procedures for compliance with WHO Good Manufacturing Practices (GMP). The standards against which the assessment teams evaluate both the quality specifications of medicines and the manufacturing sites are based on the principles and practices agreed upon by the world’s leading regulatory agencies and adopted by the WHO Expert Committee on Specification for Pharmaceutical Preparations.
Drug regulation Medicine (drug) regulation is the totality of all measures – legal, administrative and technical – needed to promote and protect public health by ensuring that: medicines meet required quality, safety and efficacy standards; health professionals and patients have the necessary information to enable rational use of medicines; medicines are appropriately manufactured, stored, distributed and dispensed; illegal manufacturing and trade are detected and adequately sanctioned; promotion and adverting is fair, balanced and aimed at rational drug use; and access to medicines is not hindered by unjustified regulatory work
Intellectual Property (IP) Creative ideas and expressions of the human mind that have commercial value and are entitled to the legal protection of a property right. The major legal mechanisms for protecting intellectual property are copyrights, patents, and trademarks. IP rights enable owners to select who may access and use their intellectual property and to protect it from unauthorized use.
Business risk Refers to the ‘probability of loss inherent in a firm's operations and environment (such as competition and adverse economic conditions) that may impair its ability to provide returns on investment
87 Annex 4 Research Capacity Strengthening matrix
COHRED has developed a research capacity strengthening matrix (RCS Matrix) to illustrate that capacity strengthening needs to be considered from different levels to become comprehensive. The RCS Matrix guides managers to improve national capacities to focus their interventions on improving research capacity where they are most needed and most likely to contribute to the sustainability of the health research system.
Countries that are willing to further engage into pharmaceutical innovation and local production of medicines may find this matrix useful when guiding assessment of the status of their health research and innovation systems and when identifying priority needs for capacity strengthening. Ultimately, only countries with functional health research systems are best placed to take up the challenge of pharmaceutical R&D and production.
Level of Locus of Individual Institution Research system Socio-economic International development intervention and political collaboration and linkage Nature of intervention
1 ‘capacity master level grants basis of NHRS Increase demand good parnership building’ training management for research
2 ‘capacity doctoral level merit-based research ethics civil society fair research strenghtening’ training promotion review capacity engagement contracting system
3 ‘performance networking research monitoring and focus on health, focus on research enhancement’ researchers, peer communication evaluation of equity and competitiveness equity-focus reviews output and soc-economic impact development
88 NEPAD-COHRED - Strengthening Pharmaceutical Innovation in Africa
Annex 5 Detailed mapping of initiatives
Annex 5-A: Global Initiatives
Global Initiatives
Initiative Aim / Mission/ Objectives Focus Comments Partners
Commission on Mandated by WHA resolution 56.27 to Intellectual Property A time-limited body to WHO Intellectual Property ‘…collect data and proposals from the Rights, Innovation, Public consider the relationship Commission members Rights, Innovation and different actors involved and produce an Health between intellectual property Public Health (CIPIH) analysis of intellectual property rights, rights, innovation and public innovation, and public health, including health. Created by WHA in 2004 the question of appropriate funding and incentive mechanisms for the creation of A report of commission’s new medicines and other products against findings was published in 2006 diseases that disproportionately affect developing countries…’
Intergovernmental Mandated by WHA resolution 59.24 “to Public health, innovation, First session: December 2006 WHO secretariat Working group (IGWG) draw up a global strategy and plan of intellectual property Second session WHO member states on Public Health, action in order to provide a medium-term 1st part: November 2007 Experts Innovation and framework based on the recommendations 2nd part: April – May 2008 Intellectual Property of the Commission; such strategy and plan of action would aim, inter alia, at securing www.who.int/gb/phi/ Created by WHA in 2006 an enhanced and sustainable basis for needs-driven, essential health research and development relevant to diseases that disproportionately affect developing countries, proposing clear objectives and priorities for research and development, and estimating funding needs in this area.”
TDR Aim: To help coordinate, support and Research and training Facilitates global research and Co-sponsored by: UNICEF, Special program for influence global efforts to combat a on neglected infectious training through partnerships UNDP, World Bank, WHO research and training in portfolio of major diseases of the poor diseases with research institutions, tropical diseases and disadvantaged. ministries of health, disease WHO is the executing Focus on neglected infectious diseases control programmes, industry, agency An independent global that disproportionately affect poor and academia and non- programme of scientific marginalized populations. governmental organisations. collaboration. Is developing a strategy to Established in 1975. help implement the WHO Global Strategy and Plan of Action, particularly regarding elements 1, 2 and 3
http://www.who.int/tdr/
WHO Technical TCM’s priority is to assist countries in Priority areas: Medicines www.who.int/medicines/areas/ WHO secretariat Cooperation on Essential their efforts to increase the availability, Policy and Supply technical_cooperation/en/ WHO member states Medicines (TCM) affordability and rational use of high- Management; quality medicines. It achieves this by Regulation and Based in WHO Geneva supporting country and regional Registration; structures and by building medicines Intellectual Property expertise. Rights; Traditional Medicines
UNESCO – African Union Contribute to AU consolidated plan Research and Inaugural meeting of the S&T African Union (AU) / NEPAD Science through Development cluster took place in July 2004 United Nations science and and Technology (S&T) - Assessment of the status of science Statistics technology cluster in initiative and technology policy formulation Policy development www.unesco.org support of AU/NEPAD : - Facilitation of initiatives for Science, UNESCO (convener) Based in Paris Technology and Innovation (STI) policy UNECA, UNIDO, WIPO, development in countries where these UNEP, UNDP, IAEA, ILO, are absent UNCTAD, OSAA, UNU - Development of common African STI MERIT, FAO, WHO indicators - Creation of an African STI observatory - Creation of a science park
89 Initiative Aim / Mission/ Objectives Focus Comments Partners
UNIDO UNIDO supports the establishment, Local production of Implemented by UNIDO GTZ expansion and upgrading of essential medicines for BMZ pharmaceutical subject-matter experts HIV/AIDS, tuberculosis, KFW (SMEs) in selected least-developed malaria. countries (LDCs) through promotion of business partnerships, investment promotion and South–South cooperation.
Activities include: Workshops on utilization of TRIPS flexibilities: Ethiopia (2005), Tanzania (2006), Thailand (2007) Regional workshop on pharmaceutical production in West & Central Africa, Dakar 2007
(http://pharma-dakar.wikispaces.com/)
Research on pharmaceutical sector profiles of Lesotho, Uganda, Zambia, Zimbabwe, Nigeria, Senegal, Laos, and Cambodia.
Health Research Systems To produce, share and utilize research for National Health Research www.who.int/rpc/health_ • WHO Analysis (HRSA) Initiative better health and health equity, and Systems research/background/en/ • WHO member states integrate knowledge gained within all index.html • Alliance for Health Policy levels of health systems and Systems Research (AHPSR) • Council on Health Research for Development (COHRED) • Global Development Network (GDN) • Global Forum for Health Research • Johns Hopkins Bloomberg School of Public Health (JHSPH) • Rockefeller Foundation (RF) • Swedish International Development Agency (SIDA/Sarec) • Wellcome Trust (WT)
IQSensato Mission: To shape international policy- Research and Policy September 2008: Multi making on development by harnessing Think Tank stakeholder consultation on Established 2007 the multidisciplinary research and implementation of the strategy analytical capacities in, and from www.iqsensato.org Based in Geneva developing countries. Current projects include implementation of the WHO Global Strategy on Public Health, Innovation and Intellectual Property
Grand Challenges in Goal: To fund research that promises to Funding Grand challenges explorations Gates foundation Global Health Initiative greatly advance work against diseases is a new initiative launched in Canadian Institutes of that disproportionately affect people in October 2007 to spur Health Research Founded in 2003 the developing world. innovations in global health Foundation for the National research. Institutes of Health Focus on 14 grand challenges http://www.gcgh.org/ Wellcome Trust
NACCAP Aims at long-term investment in R&D R&D www.nwo.nl/naccap Netherlands Netherlands – African activities in Africa thereby strengthening African governments Partnership for Capacity the capacity of African R&D centres. Sub - Saharan Africa Development and Clinical Interventions Against Poverty-related Diseases
Launched in 2002
EDCTP – European and Aims to accelerate development of new Clinical Trials, Capacity Over 80 million Euros 16 participating European Developing Countries or improved tools (drugs, vaccines, and Development approved for research into member states, sub- Clinical Trials Partnership microbicides) against HIV/AIDS, malaria Strengthening prevention of HIV/AIDS, Saharan countries, relevant and tuberculosis Regulatory and Ethics tuberculosis and malaria in public private partnerships, Founded in 2003 Review Mechanisms Africa (in June 2008) philanthropic organisations Funds mainly phase II and III clinical trials and private sector for HIV/AIDS, TB, Malaria in Sub-Saharan www.edctp.org Africa
90 NEPAD-COHRED - Strengthening Pharmaceutical Innovation in Africa
Initiative Aim / Mission/ Objectives Focus Comments Partners
International Centre for ICGEB provides a scientific and Biotechnology Transfer Components in Trieste, New Interactive network Genetic Engineering and educational environment of the highest Training Delhi and Cape Town. with 38 affiliated Biotechnology (ICGEB) standard and conducts innovative Funding centres in 59 ICGEB research in life sciences for the benefit of www.icgeb.trieste.it member states. Advisory services developing countries ICGEB is part of the UN The centre is dedicated to advanced system. research and training in molecular biology and biotechnology.
Annex 5-B: Regional Initiatives
Regional Initiatives
AU/NEPAD To facilitate open and informed regional Biotechnology ‘1Freedom to innovate’ (2007) AU member states High-level African panel on multi-stakeholder dialogue on, inter alia, is a report by a panel of Regional Economic modern biotechnology scientific, technical, economic, health, experts, suggesting specific Communities social, ethical, environmental, trade and and practical measures to intellectual property protection issues advance development, quality associated with or raised by rapid of life and environmental developments in modern biotechnology. sustainability through biotechnology.
www.nepadst.org/biopanel/ index.shtml
AU AU ministers of health at the AU Local Production 1st meeting of technical AU member states Pharmaceutical assembly held in 2005 in Abuja committee held in 2007 Manufacturing Plan undertook to pursue, with the support (Addis Ababa). (PMPA) for Africa of partners, the local production of Phase I generic medicines on the continent, and www.africa-union.org/../DOCS/ to make full use of the flexibilities Annex%204%20-%20Search Adopted in 2005 by AU within the DOHA declaration on TRIPS %20tool%20local%20manufa conference of ministers and Public Health. cturing%20Oct%202007.doc
AU PMPA phase II 6 priority areas: Local Production www.africa- AU member states 1. Mapping of local production union.org/root/ua/conferences/ Meeting held in capacity (coordinator – Gabon) 2008/mai/sa/17mai/2%20PHA May 2008 2. Situation analysis and compilation of SE%20II%20PLAN%20FOR%2 findings (coordinator – Cameroon) 0IMPLEMENTATI. 3. Manufacturing agenda (coordinator – Kenya, Libya, Egypt) 4. Intellectual property issues (coordinator Angola, South Africa) 5. Political, geographic, economic considerations (coordinator - South Africa, AU commission) 6. Develop sustainable financing systems (coordinator – Nigeria)
African Science, To develop national science, technology Policy Development http://www.unesco.org/ AU member states Technology and and innovation (STI) policies for African science/psd/thm_innov/africa_ UNESCO Innovation Policy countries without one. innov.shtml Initiative Project duration 2008 – 2010 STI policy review and Launched October 2007 formulation began in Part of UNESCO's contribution to AU 2008: Benin, Burundi, Central consolidated plan of action for science African Republic, Madagascar and technology & Tanzania.
African Network for ANDI aims to promote and sustain Research and www.who.int/tdr/svc/news- WHO TDR Drugs and Diagnostics African-led R&D innovation through the Development events/events/tdr/andi African scientists based in Innovation discovery, development and delivery of Africa and in the diaspora (ANDI) affordable new tools, including those Not operational yet. Business based on natural products and plan presented in October 2009 Launched 2008 traditional medicines. ANDI plans to also support capacity and infrastructure Secretariat in TDR development in Africa.
91 Initiative Aim / Mission/ Objectives Focus Comments Partners
Africa Technology Policy Its mission is to improve the quality of Policy Making www.atpsnet.org 16 member states Studies Network (ATPS) science, technology and innovation Research Generation and 14 potential member systems research and policy making in Dissemination states (currently have Africa by strengthening capacity for Capacity Building observer status) science and technology knowledge generation, communication and dissemination, use and mastery for sustainable development in Africa.
Ongoing studies: to map health innovation systems, identifying key actors, their interactions and boundaries; to explain performance of interventions; to identify system failures that constrain innovation capacity; to develop practical options to strengthen the innovation system in which the initiatives are situated. Participating countries: Tanzania, Uganda, Kenya, Benin, Cote d’Iviore, Nigeria, Lesotho, Swaziland, South Africa
ARIPO Established to pool resources of its Intellectual Property www.aripo.org 16 member states Africa Regional Intellectual member countries in industrial property 14 potential member Property Organization matters. states (currently have observer status)
OAPI Central registration system for 16 French Intellectual Property Headquarters in Yaoundé, 16 member states Organisation Africaine de la speaking African States Cameroun Propriété Intellectuelle (African Intellectual Property http://www.oapi.int Organization)
South African Research 1. Professional development and capacity Capacity building http://www.sarima.co.za/ South Africa and Innovation building Innovation and Department of Science Management Association 2. Promotion of best practice in the Technology Transfer and Technology (DST) management and administration of Operations DFID (SARIMA) research and innovation. Carnegie Cooperation Research 3. Creation of awareness in academic and of New York public forums of the value of a stronger research and innovation SARIMA operates at system and the contribution it can institutional, national make to economic and social and international level, development. and across the research 4. Advocacy of appropriate national and value chain, from institutional policy in support of research management research and innovation and to commercialization of participation in the development and research. testing of policy.
Advancement of science, technology and innovation, including addressing the asymmetries in access to, and diffusion of, knowledge between North and South.
West African Research 1. Professional development and capacity Capacity building http://www.warima.org and Innovation building Advocacy Management Association 2. Promotion of best practices Technology Transfer 3. Increasing awareness of research and Innovation (WARIMA) innovation issues in academic and public fora 4. Advocacy of appropriate national and institutional policy in support of research and innovation and participation in the development and testing of policy 5. Advancement of science, technology and innovation, including addressing the asymmetries in access to, and diffusion of, knowledge between North and 'South' 6. Advancement of a code of professional standards through a framework of values and principles which members are expected to follow 7. Enhancement of the profile of the profession
92 NEPAD-COHRED - Strengthening Pharmaceutical Innovation in Africa
Initiative Aim / Mission/ Objectives Focus Comments Partners
Initiative to Strengthen To promote the creation of self-sustaining Research capacity http://www.mrc.ac.za/ Major sponsors: Health Research Capacity pools of excellence capable of initiating researchdevelopment/ Wellcome Trust (UK) in Africa and carrying out high-quality health ISHReCAbrochure.pdf SIDA-SAREC (ISHReCA) research in Africa as well as translating WHO/TDR research products into policy and practice Launched 2007 through better integrated approaches of capacity building at individual, institutional and system levels.
International Network To design, test, and disseminate effective Access and Use www.inrud.org 20 African, Asian, Latin for the Rational Use of strategies to improve the way drugs are American, and Eastern Drugs (INRUD). prescribed, dispensed, and used, with a European countries Established in 1989 particular emphasis on resource poor WHO department of Secretariat based in countries Medicines Policy and Management Sciences for Standards Health / USA Harvard Medical Karolinska Institute
Annex 5-C: Multi-country initiatives
Multi-country initiatives
APRIORI APRIORI aims at establishing a state-of- Capacity building for Based at Kilimanjaro Medical A NACCAP project with African Poverty Related the art clinical research centre, and by Clinical Research Centre, Moshi, Tanzania African (Ethiopia, Mali, Infection Oriented Research involving African centres of excellence, Tanzania) and European Initiative strengthening www.priornetwork.org/db/ (Denmark, Netherlands, South-South collaboration. overzichten/index.php U.K) partners Duration of project 2006 – 2010
African AIDS vaccine Mission: to advocate and support a Biomedical sciences; www.who.int/vaccine_research/ WHO Programme (AAVP) coordinated effort to contribute to the Population-based studies; diseases/hiv/aavp/en/ UNAIDS global HIV vaccine development goals, Ethics, Law and Human African Countries A WHO – UNAIDS ensuring that appropriate and affordable Rights; National Strategic supported programme vaccines are developed for Africa in the Planning; Advocacy and shortest possible time. Resource Mobilization
Malaria Clinical Trials Aim: to strengthen clinical trial capacity, Capacity Building: An INDEPTH project, funded MMV Alliance (MCTA) share results of real, on-the-ground trial Human Resources and by Gates Foundation MVI activities and to codify best practices. Physical Infrastructure AMANET www.indepth- African countries: Gabon, network.org/mcta Gambia, Ghana, Kenya, Malawi, Mozambique, Nigeria, Senegal and Tanzania
Global Institute for An R&D network that promotes ethical, Bioexploration www.gibex.org University of Yaoundé-1, BioExploration-Africa natural product-based pharmacological Cameroon (GIBEX- Africa) bio-exploration to benefit human health University of Nairobi, Kenya in Africa. GIBEX-Africa is guided by the University of Dar-es-Salaam, pioneering “Reversing the Flow” Tanzania Makerere University, paradigm intended to bring Uganda pharmacological screens to Africa University of Botswana, (Screens-to-Nature technology) and Botswana University of Cape reverse the human brain drain. Town, South Africa Kwame Nkrumah University of Science and Technology, Ghana Olabisi Onabanjo University, Nigeria University of Lagos, Nigeria Federal University of Technology, Minna, Nigeria University Cheikh Anta Diop, Senegal University of Zambia, Lusaka,Zambia Rutgers, the State University, New Jersey USA University of Illinois at Urbana- Champaign, USA
93 Initiative Aim / Mission/ Objectives Focus Comments Partners
Africa Institute of Focus is on drug discovery, development Research www.aibst.com University of Zimbabwe Biomedical Science and and optimum clinical use of medicines in Education & Training University of Nairobi Technology Africa in areas of malaria, tuberculosis, Commercial Activities (Kenya), HIV/AIDS and other tropical diseases. Obafemi Awolowo (AiBST) University (Nigeria), Karolinska Institute (Sweden), Antwerp University (Belgium), Gothenburg University (Sweden) Astra Zeneca (Sweden) Southern African Regional Co-operation in Biochemistry, Molecular Biology and Biotechnology (SARBIO) International Society for the Study of Xenobiotics International Union of Pharmacology
African Malaria Network Mission: To promote capacity Has a 4-year project www.aibst.com African sites: Burkina Trust (AMANET) strengthening and networking of malaria aimed at building Faso, Ghana, Kenya, vaccine research and development in institutional health Mali, Sudan, Founded in 1995 Africa. research ethics in Africa Tanzania, Uganda, Zambia www.amanet-trust.org European partners: Denmark, Netherlands EDCTP
ARV Access for Africa Mission: To provide pharmaceutical Access, Pharmaceutical www.aa4a.co.za African countries (AA4A) management skills and increase local Supply Chain Netherlands capacity for public health care initiatives Management Based in South Africa to ensure access to quality health care An IDA solutions project services in low and middle income countries.
Access to Medicines Index AtM index’s main purpose is to raise Access www.atmindex.org Many stakeholders (AtM Index) awareness on access to drugs and to drawn from: improve collaboration between Non governmental stakeholders. The ATM index aims at organizations and offering objective and comparative academia, Governments information regarding the approaches of (WHO; DFID ; pharmaceutical companies to ATM issues. Netherlands), Pharmaceutical Industry, Investor Community, Donors
MeTA – To support national efforts to enhance Access, research Global Alliance launched in DFID The Medicines transparency and build capacity in 2007 WHO Transparency Alliance medicines policy, procurement and supply Initial country focus in http://www.dfidhealthrc.org/ Health Action chain management. Africa: Ghana, Uganda, MeTA/index.html International (HAI) Zambia
Health Action Goal: access, by all consumers, to good Access www.haiafrica.org An informal network of International – Africa quality, affordable medicines that are consumers, NGOs, health (HAI –Africa) rationally prescribed and used. care providers, academicians and HAI Africa works to achieve a more individuals in more than balanced structure of power within the 20 countries in Sub- medicines sector, as a consequence of Saharan Africa stronger medicine-related civil society promoting increased organizations (CSOs) and activists that access to essential empower consumers and promote medicines competent providers, well informed donors and governments.
94 NEPAD-COHRED - Strengthening Pharmaceutical Innovation in Africa
Initiative Aim / Mission/ Objectives Focus Comments Partners
Ecumenical EPN aims to facilitate the development of Access www.epnetwork.org African member Pharmaceutical Network compassionate, just and sustainable countries (EPN) quality pharmaceutical care in and through the church health care system.
SECOVIPI 3-year project set up to help address the Intellectual Property http://www.ruiggian.org/ Cameroon,Gabon, (Service commun virtuel many IP-related infrastructural and research/projects/projectlg. Republic of Congo, en propriété resource challenges faced by health php?ID=24 Central African Republic intellectuelle - Virtual research institutes in developing Chad, Equitorial Guinea Shared IP Service) countries. Colombia OAPI Launched 2004 Over 130 scientists, lawyers and research CEMAC commission institution managers have been trained in WIPO (coordinator) key practical skills to enable them to Geneva International protect, manage and exploit their Academic Network research results. (RUIG-GIAN) (Funder) University of Geneva Graduate Institute of International Studies (HEI), Geneva Swiss Tropical Institute, Basel; International Institute for Management Development (IMD), Lausanne Council on Health Research for Development (COHRED).
NAPRECA: Natural Expand existing research programs and Research Capacity http://sites.ias.edu/sig/rise/ Makerere University, Products Research Network formalize educational activities in such napreca Uganda of Eastern and Central natural products (NP) fields as University of Nairobi, Africa engineering, biochemistry, environmental Kenya science, pharmacology, economic Sokoine University, development, and nutrition. Tanzania An active research network of 10 member countries
Annex 5-D: National initiatives
National initiatives (selected examples):
Bioventures - Bioventures is a biotechnology and life Venture Capital Fund http://www.bioventures.co.za/ South Africa sciences venture capital fund that invests in South African start-up companies.
Council for Scientific CSIR’s mandate is to contribute to Bioscience www.csir.co.za The CSIR’s shareholder is and Industrial Research improved quality of life and industrial Nanotechnology the South African (CSIR) biosciences competitiveness through research, Synthetic Biology Parliament, held in proxy by development and innovation and in the Minister of Science and Initiated in 1945 response to the National Research and Technology. Development Strategy and National South Africa Biotechnology Strategy. Receives an annual grant (close to 40% of its total income) from Parliament, through the Department of Science and Technology (DST).
BioPAD Mission: To broker partnerships between Venture Capital Firm www.biopad.org.za One of the three researchers, entrepreneurs, business, Biotechnology Regional (Biotechnology Partners government and other stakeholders to Innovation Centre (BRIC) and Development) promote innovation and create established by the sustainable biotechnology businesses in Department of Science and Initiated in 2002 support of South Africa's needs. Technology (DST). Initiated by a group of interested South Africa At least 10 completed projects awaiting biotechnology stakeholders commercialization, commercialized, or with the aim of boosting licensed to other companies. biotechnology development Commercialized projects include in the region. molecular diagnostic kits for tick borne The centre is governed as a pathogens (RLB kit / RT-PCR assay). Trust.
95 Initiative Aim / Mission/ Objectives Focus Comments Partners
LIFElab Provides funding to biotechnology Funding www.lifelab.co.za LIFElab is the trade name projects on human health and Biotechnology Capacity of the East Coast South Africa bioprocessing. Human health portfolio Building Biotechnology (ECoBio) focus is infectious diseases (e.g. Regional Innovation HIV/AIDS, TB and malaria). Centre.
One of three Biotechnology Regional Innovation Centres (BRICs) set up by the Department of Science and Technology (DST) under the auspices of its National Biotechnology Strategy.
Cape Biotech An umbrella forum aimed at creating a Biotechnology Industry www.capebiotech.co.za biotechnology industry hub in the Hub South Africa Western Cape. The CBI represents the interests of industry, academia, government, finance, the public and all other role players in the field of biotechnology.
The Innovation Hub Africa's first internationally accredited Science Park www.theinnovationhub.com A subsidiary of Blue IQ science park and a full member of the Investments Holdings. South Africa International Association of Science Parks. More than 65 resident companies within its five Its purpose is to develop a science park core focus areas: ICT, environment where high-tech biotechnology, entrepreneurs, small and medium size engineering, smart enterprises, world-class businesses, manufacturing and academic and research organisations and electronics. Has formal venture capitalists can meet, network and and operational links to prosper. academic and research institutions, government agencies and departments, and local and international business enterprises.
South African Malaria Mission: To facilitate an integrated R&D www.acgt.co.za/sami/index. Consortium membership, Initiative programme of malaria research and html includes academic (SAMI) capacity development in South Africa and institutes, specialized eventually in the rest of Africa to improve research and disease malaria prevention and control. control institutes, and South Africa the Medical Research Planned outputs include: identification Council and validation of drug and insecticidal targets; development of drug and insecticidal candidates; improved diagnostics; and new tools for gathering epidemiological information.
Bridgeworks Kenya A venture capital company incubating Venture Capital Firm www.bridgeworks.ch/bilder and commercializing technologies _inhalt/glance.pdf addressing key global concerns associated with soil, health and education
National Institute for Mission: To apply appropriate modern Drug Development Development of Niprisan NIH Pharmaceutical Research science and technology resources to Traditional Medicine (for treatment of sickle cell Howard University, and Development stimulate local raw material production Drug Policy disease) is one of NIPRID’s U.S.A. (NIPRD) through effective collaboration with the milestones Xechem Pharmaceutical industry and other experts within and Co. Ltd Nigeria outside Nigeria; develop herbal medicines www.niprd.org/ Nigerian Universities to pilot stage for local entrepreneurs/ Pharmaceutical manufacturers; develop quality standards Manufacturers Group of for herbal and orthodox drugs for the the Manufacturers purpose of control and regulation; provide Association of Nigeria quality assurance service on all drugs used (PMG-MAN) for healthcare delivery in Nigeria; provide Traditional Medicine safety data and essential information on Practitioners herbal and other drugs that are used in UNIDO Nigeria, and make Nigeria self – sufficient in the production of its essential drugs in such a way that would guarantee the overall health of Nigerians.
96 NEPAD-COHRED - Strengthening Pharmaceutical Innovation in Africa
Initiative Aim / Mission/ Objectives Focus Comments Partners
Kenya Medical Research Public health research institute whose Basic Research, Research institute with a Kenyan Ministries: Foundation (KEMRI ) aim is to improve the quality of health Development production facility for products Health; science and and human life through research. Testing innovated at the research technology Established in 1979 Innovation Hub, institute. Some achievements: Kenyatta National Training Site Discovery, development and Hospital Kenya production of diagnostic kits Kenyan Universities for hepatitis B (Hepcell kit) and Regional Partners HIV (Kemcom kit) International Partners
http://www.kemri.org/
Navrongo Health Mission: to conduct research into major Clinical Trials www.navrongo.org www.navrongo.org Research Centre national and international health Capacity Building • WHO/TDR problems with the aim of informing • Meningitis Research Ghana policy for the improvement of health. Foundation • IDRC • Bill and Melinda Gates Foundation Rockefeller Foundation • USAID
NIH
Ifakara Health Institute Mission: To develop and sustain a rural Research www.ihi.or.tz Many national, regional district based health research and Training and international Founded in 1956 development resource centre capable of Research includes clinical collaborators that include generating new knowledge and relevant trials, implementation research and training Tanzania information regarding priority problems research, health systems institutes and funding in health systems at district, national and research, demographic partners. international level, through research, sentinel surveillance and training and services aimed at achieving disease prevention better health and community development.
Mali Malaria Research Viewed by many as model as a model Malaria research http://obtoure.africa- Government of Mali Centre for research centres in developing including; vaccines, web.org/MRTC.htm Others include; USAID, countries, as its research is planned, diagnostics, immunology NIH, Rockefeller Initiated in 1989 directed, and executed by African and genetics, and foundation, WHO, IAEA scientists. Also has a robust training prevention program for new generation of Malian scientists critical to the success and sustainability of the program. Current training programs in biology, tropical medicine, medical entomology, and epidemiology.
Mali Traditional The official institute connected to the Traditional medicines WHO collaborating Medicines National Institute of Research in Public centre Health (INRSP: Institut National de Established in 1973 Recherché en Santé Publique).
Main activities include: registration of traditional practitioners, medicinal plants, research and development of Improved Traditional Medicines (ITMs).
CFWshops Mission: To improve access to essential Access Innovative solutions for access, Project of the (Child and Family drugs, basic health care and prevention adapt traditional franchising HealthStore Foundation Wellness Shops) services for children and their families model distribute essential MSH provides technical Kenya through business models that maintain medicines in remote advisory services business and clinical standards, are communities. Founded in 2000 geometrically scalable, and achieve economics of scale. http://www.cfwshops.org/
97 Annex 5-E: Public-private product development initiatives
Public Private Product Development Partnerships (PPDPs) for neglected diseases: (Activity in Africa)
Initiative Aim / Mission/ Objectives Focus Comments Partners
Drugs for Neglected Research and development of new and Research and In March 2007, DNDi launched Oswaldo Cruz Foundation Diseases Initiative (DNDi) improved treatments for neglected Development (in collaboration with Sanofi- (Brazil) diseases. Research activities are at all Aventis) ASAQ, a fixed dose Indian Council for Medical Founded in 2003. stages of drug development; discovery, combination of artesunate and Research Disease focus: preclinical, clinical and post-clinical. amodiaquine Kenya Medical Research Leishmaniasis, Human Institute African Trypanosomiasis, www.dndi.org/ Ministry of Health of Chaga’s disease and Malaysia, Pasteur Institute Malaria. Médecins sans Frontières (MSF) TDR
Foundation for Mission: to develop rapid, accurate and Research and /www.finddiagnostics.org/ TDR Innovative New affordable diagnostic tests for poverty- Development Diagnostics’ industry Diagnostics (FIND) related diseases, through public-private Testing Other organizations partnerships
Launched 2003 Diagnostic tools
Disease focus: Tuberculosis, Human African Trypanosomiasis, and Malaria
Medicines for Malaria Mission: to bring public, private and Research and Over 30 projects Venture (MMV) philanthropic sector partners together to Development 19 new classes of anti-malarial fund and manage the discovery, Testing drugs in discovery. Established in 2000 development and registration of new medicines for the treatment and www.mmv.org prevention of malaria in disease-endemic countries.
TB Alliance Mission: to ensure the widespread Research and www.tballiance.org A range of institutions (Global Alliance for TB availability of affordable, faster and Development worldwide that share a Drug Development) better tuberculosis drug regimens that Testing clear interest, and a will advance global health and prosperity. significant stake, in Launched in 2000 ensuring the development of a faster, better cure for tuberculosis.
Aeras Global TB Vaccine Aim: to help develop new concepts and Research and www.aeras.org Partners include Foundation tools to control the global TB epidemic. Development universities, biotechnology Testing and pharmaceutical Founded in 1997 Aeras goal: to develop, test, characterize, companies, vaccine license, manufacture and distribute at manufacturers, least one new TB vaccine by 2015 foundations, advocates, and governments.
Research partners in South Africa – (for phase I clinical trials), and in Kenya, Uganda (to develop field sites with EDCTP for phase II, IIb and III studies)
International Partnership Aim: To prevent HIV transmission by Research and www.ipm-microbicides.org Academic institutions, for Microbicides accelerating the development and Development pharmaceutical and availability of a safe and effective Testing biotechnology companies, Founded in 2002 microbicide for use by women in non-governmental and developing countries. international organizations.
International AIDS Mission: to ensure the development of Research and IAVI is sponsoring HIV vaccine Global scientific and policy Vaccine Initiative safe, effective, accessible, preventive HIV Development trials in Kenya, Rwanda, South advocacy partners vaccines for use throughout the world Capacity Building Africa, Uganda, and Zambia, Founded in 1996 Policy analysis Advocacy and is collaborating with local partners to collect epidemiological data and to build capacity for future large- scale trials. www.iavi.org
98 NEPAD-COHRED - Strengthening Pharmaceutical Innovation in Africa
Initiative Aim / Mission/ Objectives Focus Comments Partners
South African AIDS Established to co-ordinate the research, Research and www.saavi.org.za Collaborators: Vaccine Initiative development and testing of AIDS Development African AIDS Vaccine vaccines in South Africa Testing Programme (AAVP) Formed in 1999 Botswana Harvard AIDS Institute Ethiopian AIDS Vaccine Initiative (EAVI) European Developing Country Clinical Trials Partnership (EDCTP) European Union (EU) HIV Vaccine Trials Network (HVTN) International AIDS Vaccine Initiative (IAVI) National Institutes of Health (NIH) Nigerian AIDS Vaccine Programme (NAVP)
Annex 5-F: International organization initiatives
International Organizations
Initiative Aim / Mission/ Objectives Focus Comments Partners
PATH PATH’s mission is to improve the health of Research and Health technology focus on Local communities, people around the world by advancing Development innovation for diagnostics, governments, NGOs, UN, Founded in 1997 technologies, strengthening systems, and newborn health, nutrition, safe Private sector (business) encouraging healthy behaviours. injection, safe water, vaccine delivery and woman initiated protection.
Currently involved in meningitis and pneumococcal vaccine development
www.path.org
Action Medeor To provide basic drugs and medical Local Production Current projects, manufacture German Medical Aid equipment to developing countries Technology Transfer of ARVs and ACTs in Tanzania Organization Established in 1964 and DR Congo. One of the goals; support local development and production of drugs in collaboration with local manufacturers. http://gb.medeor.org
Médecins Sans Frontières Advocate for greater access and Advocacy www.accessmed-msf.org exemptions to licensing. Monitor “MSF access campaign” drug prices.
99 Annex 5-G: Pharmaceutical partnerships in Africa initiatives
Pharmaceutical Partnerships in Africaci: Access (examples)
Disease Focus Program Program Scope and Industry Partners Other Partners Country Focus (Africa)
HIV/AIDS Accelerating Access Initiative Access – Pricing Abbott UNAIDS Boehringer-Ingelheim WHO www.who.int/hiv/AAI_fs_4Q2005.pdf Developing countries, Bristol-Myers Squibb World Bank including in Africa Gilead Sciences UNICEF GlaxoSmithKline UNFPA Merck & Co. Inc. Roche Technology Transfer & ARV Licensing in Developing Access - Licensing Boehringer-Ingelheim Various generic Countries Bristol-Myers Squibb pharmaceutical Kenya, South Africa Gilead Sciences manufacturers www.boehringer-ingelheim.com, www.bms.com, GlaxoSmithKline www.gilead.com, www.gsk.com, www.merck.com, Merck & Co. Inc. www.roche.com Roche
lisabeth Glazer Paediatric AIDS Foundation Access - Donation Abbott EGPAF Boehringer-Ingelheim www.pedaids.org Developing countries, Johnson and Johnson including in Africa
PMTCT Abbott Rapid HIV Test Donation Program Access – Donation Abbott Various partners
www.abbottglobalcare.org Sub-Saharan Africa
PMTCT: Viramune® Donation Program Access - Donation Boehringer-Ingelheim EGPAF Governments www.boehringer-ingelheim.com Developing countries, Rotary International including in Africa UNICEF
HIV South Africa Access – Donation Johnson & Johnson HIV South Africa www.hivsa.com/hivsa/index.stm South Africa
J&J Health Care Training Fund Capacity building – Johnson & Johnson AMREF Training in health care IDA Solutions www.jnj.com, supply chain management www.idasolutionsdplatform.org
Pfizer Diflucan ® Partnership Access - Donation Pfizer Various partners
www.diflucanpartnership.org www.pfizerglobalhealth.com PEPFAR Partnership for Paediatric AIDS Treatment Access - Pricing Abbott PEPFAR Bristol-Myers Squibb UNAIDS www.pepfar.gov Developing countries, Gilead UNICEF including in Africa GlaxoSmithKline WHO Merck & Co. Inc.
Sikiliza Leo Project Access – Donation Johnson & Johnson Sikiliza Leo
www.tibotec.com Uganda
Tuberculosis Lilly MDR-TB Partnership Access – Pricing and Lilly WHO licensing Other partners
www.lillymdr-tb.com Worldwide, including in Africa WHO
Novartis TB DOTS Donation Access – Donation Novartis
www.novartisfoundation.org Tanzania Stop TB Partnership Access – Donation, pricing AstraZeneca Stop TB GlaxoSmithKline MSF www.stoptb.org Endemic countries & IFPMA Red Cross vulnerable populations, Lilly Other partners including in Africa Novartis
100 NEPAD-COHRED - Strengthening Pharmaceutical Innovation in Africa
Disease Focus Program Program Scope and Industry Partners Other Partners Country Focus (Africa)
Malaria ACCESS II – Improving Access to Effective Malaria Access – Pricing Novartis Swiss Tropical Institute Treatment Other partners Tanzania www.novartisfoundation.org
GSK and Access to Malaria Care Access – Pricing GlaxoSmithKline Various partners
www.gsk.com/malaria Developing countries including in Africa
Novartis Coartem® Access – Pricing Novartis WHO MMV www.novartis.com Developing countries, including in Africa
Millenium Villages Project Access – Donation Novartis Ilolangulu Village
www.novartisfoundation.org Tanzania
Roll Back Malaria Partnership Access – Pricing GlaxoSmithKline Roll Back Malaria Novartis Other partners www.rollbackmalaria.org Developing countries Sanofi-aventis including in Africa
Sanofi-aventis: Impact Malaria Access-Pricing Sanofi-aventis Various national and international partners, www.impact-malaria.com Benin, Madagascar, including universities Republic of Congo, Tanzania
Tropical Diseases Global Alliance to Eliminate Lymphatic Filariasis Access – Donation GlaxoSmithKline GAELF (GAELF) Merck & Co. Inc. WHO Endemic countries, Other partners www.filariasis.org including in Africa Johnson & Johnson Carter Centre Guinea Worm Eradication Program (GWEP) Access – Donation WHO Other partners www.cartercenter.org/health/guinea_worm/ 9 African countries index.html
International Trachoma Initiative (ITI) Access – Donation Pfizer Edna McConnell Clark Novartis Foundation www.trachoma.org Developing countries, Other partners including in Africa Merck & Co. Inc. WHO Leprosy Elimination Access – Donation WHO Merck KGaA World Bank www.novartisfoundation.org Developing countries Sanofi-aventis Other partners including in Africa WHO Merck Mectizan® Donation Program Access – Donation Sanofi-aventis WHO Johnson & Johnson Other partners www.mectizan.com Lymphatic filariasis, WHO onchocerciasis Other partners Merck Praziquantel Donation Program Task Force for Child Endemic countries, Survival and Development www.merck.de including in Africa Access – Donation Sanofi-aventis ‘Most Neglected Disease’ Program Schistosomiasis www.sanofi-aventis.com 8 priority control countries Sanofi-aventis Sleeping Sickness Program Access – Pricing
www.sanofi-aventis.com Chad, Ethiopia, Sudan, Soil-Transmitted Helminthiasis Togo
www.jnj.com Access – Donation
R&D Access – Donation
101 Pharmaceutical Partnerships in Africa: Research and Development (R&D) (examples)
Disease Focus Program Program Scope and Industry Partners Other Partners Country Focus (Africa)
HIV/AIDS Gilead Clinical Development Partnerships Clinical research to Gilead US CDC develop new medical GlaxoSmithKline US NIH www.gilead.com interventions WHO GSK’s HIV-Collaborative Research Programme for Bristol-Myers Squibb Other partners Resource-Poor Settings Uganda, Zimbabwe Crucell IAVI Support for clinical trials GlaxoSmithKline Becton, Dickinson & www.gsk.com Merck & Co. Inc. Company International HIV/AIDS Vaccine Initiative (IAVI) Developing countries Pfizer Gates Foundation including in Africa Rockefeller Foundation www.iavi.org Vaccine R&D USAID Access World Bank
Worldwide including in Africa
International Partnership for Microbicides Development, Bristol-Myers Squibb International Partnership manufacture and Gilead for Microbicides www.ipm-microbicide.org distribution of Johnson & Johnson microbicides Merck & Co. Inc. HIV Vaccines Trials Merck & Co. Inc. HIV Vaccine R&D Pfizer Network IPM has been granted Merck & Co. Inc. Other partners www.merck.com royalty-free license and Paediatric Formulations for ARVs technology transfer by Abbott pharmaceutical company Bristol-Myers Squibb www.abbott.com, www.bms.com, partners Gilead www.gilead.com, www.gsk.com GlaxoSmithKline Rwanda, South Africa, Tanzania Vaccine R&D
South Africa Clinical studies
Developing countries
Tuberculosis Stop TB Partnership R&D AstraZeneca Stop TB GlaxoSmithKline MSF www.stoptb.org Endemic countries & IFPMA Red Cross vulnerable populations, Lilly Other partners including in Africa Novartis
Aeras Global TB Vaccine Foundation R&D Crucell Aeras Global TB Vaccine GlaxoSmithKline Foundation www.aeras.org Kenya, South Africa Other partners www.crucell.com www.gsk.com
Global Alliance for TB Drug Development (TB R&D Bayer HealthCare DFID Alliance) Cumbre NIAID South Africa, Zambia GlaxoSmithKline USAID www.tballiance.org KRICTciii Other Partners Novartis
GSK-TB Alliance Drug Discovery Program R&D GlaxoSmithKline GSK-TB Alliance Drug Discovery Program www.gsk.com South Africa Stellenbosch University
Moxifloxacin TB Clinical Trials (Bayer HealthCare) R&D Bayer HealthCare TB Alliance www.bayerscheringpharma.de South Africa, Zambia
Sanofi-aventis R&D for TB R&D Sanofi-aventis TB Alliance Other partners www.sanofi-aventis.com International, including in Africa
102 NEPAD-COHRED - Strengthening Pharmaceutical Innovation in Africa
Disease Focus Program Program Scope and Industry Partners Other Partners Country Focus (Africa)
Malaria EurartesimTM International Development Program R&D Sigma-Tau MMV
www.mmv.org, www.sigma-tau.org Burkina Faso, India, Kenya, Mozambique, Uganda, Zambia Medicines for Malaria Venture (MMV) R&D Bayer HealthCare MMV Chong Qing Holley Other partners www.mmv.org Benin, Kenya, Mali, Genzyme Mozambique, GlaxoSmithKline Tanzania, Zambia Merck & Co. Inc. Novartis Pfizer Sanofi-aventis Shin Poong Sigma-Tau Novartis R&D for Malaria R&D Novartis TDR Other partners www.novartis.com Benin, Kenya, Mali, Mozambique, Tanzania, Zambia
Pfizer - Zithromax®/chloroquine for Malaria R&D Pfizer Various partners
www.pfizer.com/responsibility Burkina Faso, Côte d'Ivoire, Ghana, Kenya, Mali Sanofi-aventis – DNDI Malaria Medicines R&D Sanofi-aventis DNDI Other partners www.sanofi-aventis.com Cameroon, Côte www.dndi.org d'Ivoire, Gabon, Liberia, Madagascar, Mali, Senegal, Uganda
Sanofi-aventis: Impact Malaria R&D Sanofi-aventis Various national and international partners, www.impact-malaria.com Benin, Madagascar, including universities Republic of Congo, Tanzania
Gilead – AmBisome for Leishmaniasis R&D Gilead WHO
www.gilead.com/access_developing_world
Tropical Diseases GSK’s Sitamaquine for Leishmaniasis R&D GlaxoSmithKline Various partners
www.gsk.org Kenya
Merck Serono Collaboration with TDR R&D Merck KGaA TDR Other partners www.merck.de Developing countries including in Africa
Next-Generation Onchocerciasis Treatment R&D R&D Wyeth TDR
www.wyeth.com Democratic Republic of Congo Ghana, Liberia Nifurtimox-Eflornithine for Sleeping Sickness R&D Bayer HealthCare TDR Sanofi-aventis Other partners www.bayerscheringpharma.de, Democratic Republic www.sanofi-aventis.com of Congo Uganda
103 Annex 5-H: National pharmaceutical industry initiatives
National pharmaceutical industries (selected)
Initiative Aim / Mission/ Objectives Focus Comments Partners
ASPEN Holdings Research and www.aspenpharma.com ASPEN Holdings /Aspen Pharmacare Development Licensing agreements with Local Production Eli Lilly, GlaxoSmithKline, South Africa (including API and Gilead, Bristol-Myers- generic drugs Squib, Merck and Co.
Pharmaceutical manufacturing facilities in South Africa, East Africa, Latin America and India
Advanced Bio-Extracts Production of low cost, pharmaceutical Local Production Main plant in Athi River, Action Medeor Limited grade artemisinin, and artemisinin-based Kenya. Extracts and purifies Acumen Fund Kenya derivatives. Artemesinin from its supply Centre pour le chain of locally grown plant in dévelopment de A private holding Kenya and Tanzania, and l’entreprise company purifies crude artemesinin from Cordaid sister company in Uganda. DFID EVD international http://www.abextracts.com ondernemen en samenwerken GTZ IFCcvii Mediplan Novartis Technoserve USAID A to Z Text Mills Production of long Bed nets impregnated with a • Sumitomo Chemicals, lasting insecticide treated long-lasting insecticide, Japan Tanzania bed nets (Olyset) effective for up to five years • Government of instead of the usual six Tanzania months, with no need for re- treatment
www.olyset.net/resourcecenter /events/ iThemba Pharmaceuticals iThemba Pharmaceuticals (Pty) Ltd. is an Drug Discovery www.ithembapharma.com Founded by (global) emerging drug discovery company to researchers and eminent South Africa research and develop new and Small Molecule Therapies academicians with affordable medicines for infectious investments from LIFElab diseases of the poor. and BioPAD.
LaGray chemical Goal: to make drugs available and Research Capacity for manufacture: company affordable in Sub – Saharan Africa, Development from API to finished dosage sustainably. Testing forms. Plans to collaborate Ghana with Howard University (USA) Local Production on drug discovery and development research.
http://www.lagraychem.com/
Xechem Nigeria Limited Xechem seeks to explore Nigeria’s and Basic research, Production of NICOSAN, a • National Institute for other African countries’ extraordinary development, Production plant derived breakthrough Pharmaceutical Founded in 2002 biodiversity to develop drugs from natural drug for treatment of sickle Research and sources for the treatment of life cell disease, discovered by Development (NIPRD) threatening illnesses and other diseases. Nigerian scientists. • Xechem International
Xechem research park has state of the art cGLP/cGMP facilities in Abuja, Nigeria
http://www.xechemnigeria.co m/aboutus.htm
104 NEPAD-COHRED - Strengthening Pharmaceutical Innovation in Africa
Annex 6 Visual mapping of initiatives (COHRED)
AU/NEPAD Bio technology AU/NEPAD local production ARIPO BIO VENTURES OAPI Innovation Hub EPN BioPAD MSF GIBEX / Africa UNIDO/GTZ/BMZ/KFW iThemba
AtoZ Text mills AA4A MALI TRADITIONAL MEDICINES Regional pooled procure- HAI Africa KEMRI Kenya, LAGRAY Company Ghana ment initiatives INRUD National Institute for Pharmaceutical Research and Development (NIPRD)
GATES FOUNDATION IDA Solutions
EDCTP ATM Research ACTION MEDEOR Network NACCAP META
Basic Research Development Testing Production and Procurement Delivery and discovery (phase I, II,III) Marketing Supply Use Storage Implementation Distribution research
GSPOA on Public Health, Innovation and Intellectual Property WHO PSM, TCM
TDR
UNESCO - African Science, Technology and Innovation Policy Initiative
PATH
Multinational Pharmaceutical Companies, Eli Lilly MDRTB, GSK-ASPEN Partnership CFW SHOPS DUKA LA DAWA • PDPPPs (DNDI, FIND, MMV, IOWH) SADC, EAC, CEMAC, ECOWAS LIVING GOODS • PPPs (GATB, IVI, INTERNATIONAL PARTNERSHIP FOR Regulation and CARE SHOPS MICROBICIDES,...) harmonization initiatives • GLOBAL TB VACCINE FOUNDATION
n Regional initiatives n UN Initiatives n Public-private partnerships n National initiatives n NGOs/networks n International initiatives n Pharmaceutical companies
105 Annex 7 Visual mapping of building blocks (COHRED)
Research Managers Social Researchers Regulators
Technicians Pharmacists
High Skills IP Managers Health Care Workers Creative Researchers Raw materials Energy Production Transport Decentralised Plants Cold Chain Health Centres Well equipped and financed research Institutions Packaging
Intellectual Property Policy
Trade and Investment Policy Industrial Policy
Health Research Policy Health Sector Policy
Basic Research / Development Testing Production Procurement Delivery Discovery Supply Use Implementation Storage Research Distribution
Ethical Review GMP Drug Regulation
R&D System Quality Control Community
Health Research System Health Care System
Knowledge and Information Management System
Training/Capacity building
Financing
Governance / Coordination / Harmonisation
Monitoring and Evaluation
n Human Resources n Systems n Operational inputs n Cross cutting issues n Policies
106 NEPAD-COHRED - Strengthening Pharmaceutical Innovation in Africa
Annex 8 Noordwijk Medicines Agenda
Noordwijk Medicines Agenda Noordwijk-aan-Zee, Netherlands, 21 June 2007 The OECD High Level Forum on Medicines for Neglected and Emerging Infectious Disease: Policy Coherence to Enhance their Availability (HLF) was organised in collaboration with the government of the Netherlands. Improving global health is a shared responsibility. The HLF was attended by high level officials of developed and developing countries, and senior representatives from industry, the scientific community, international and non- governmental organisations who met to contribute a coherent, open agenda for action. The HLF sought to build on and complement international momentum to stimulate innovation and radically accelerate the development and delivery of medicines, vaccines and diagnostics for neglected and emerging infectious diseases that disproportionately affect developing countries. Participants made it clear that many health issues in developing countries cannot and will not be solved by developments in health technologies alone. Nevertheless, such technologies are important and efforts to accelerate innovation and to reduce poverty and its consequences must go hand and hand. The High Level Forum Recognises that: - Infectious diseases have a serious socio-economic impact in addition to the burden placed on health systems, particularly in developing countries. - It is in the economic interest of all countries to mobilise resources for the control of neglected and emerging infectious diseases, bearing in mind that incentives to address neglected and emerging diseases may differ and that both sets of diseases require international and national attention. - Research and development (R&D) is essential to make available innovative, safe and effective medicines, vaccines, and diagnostics for neglected and emerging infectious diseases and thus to achieve, in the long term, a sustainable response to major global health challenges. Continued investment in basic science is essential to feed innovation in health. - Access to affordable essential drugs and availability of the benefits of new technologies is a core element of development as identified in the Millennium Development Goals (Goal 8), which calls for a global partnership in this area. - Work to improve the availability and accessibility of medicines, vaccines and diagnostics for neglected and emerging infectious diseases that primarily affect developing countries is ongoing in international organisations such as the World Health Organisation (WHO) and in other international partnerships and bodies. - A number of recently created public and private initiatives, (e.g. public-private product development partnerships (PDPs) and industry philanthropic programmes) have increased research and development on some neglected infectious diseases and raised international awareness of the extent of the problem. - Many developing countries do not have the research infrastructure to address R&D for neglected diseases. - Functioning health systems in developing countries are necessary to ensure access to care and basic medicines. - Innovation includes both the development of new healthcare products and the delivery and diffusion of those products, and any efforts to improve the availability of medicines, vaccines, and 2 diagnostics must be accompanied by efforts to improve access to health care and to strengthen health systems.
107 Acknowledges that: - In both developed and developing countries, there is an urgent need for greater policy coherence in health, science, development, trade, finance and industry policies in order to tackle neglected and emerging infectious diseases, as well as a need to increase policy makers’ understanding of the interdependencies of these policy areas. - The WHO Intergovernmental Working Group on Public Health, Innovation and Intellectual Property (IGWG) presents a unique opportunity to reach international agreement on an integrated framework for accelerating innovation and improving access to medicines in the developing world. As well as mobilizing more concerted efforts of governments, industry, research institutes and non-governmental organizations, such a framework would help to strengthen coherence among international organizations and initiatives. - OECD governments have taken promising initial steps to establish long-term predictable financing to meet the Millennium Development Goals, but more effort is required. - The protection and use of intellectual property rights (IPRs) are important in encouraging investments in research and development of medicines, vaccines, and diagnostics but are not sufficient to stimulate innovation for neglected and emerging infectious diseases. Complementary reward systems may also play an important role. - Product development partnerships (PDPs) are an innovative and potentially successful model of collaborative R&D that leverage industry investments and foster innovation to increase the availability and accessibility of health technologies. They, as well as some other recent initiatives, lack long term sustainable financing and alone are not sufficient to foster innovation throughout the entire innovation cycle, from the test tube to the patient. - Long-term development aims for medicines for neglected diseases should include not only incentives for R&D in OECD countries, but incentives to increase R&D and technology capacity in developing countries. - New approaches to more open innovation and collaborative research, as well as access to knowledge, can further increase the efficiency and lower the costs of developing new, safe and effective medicines, vaccines and diagnostics for neglected and emerging infectious diseases as well as broaden the involvement of researchers, academic institutions, laboratories and companies globally. - Activities in pharmaceutical innovation, manufacturing and trade are increasingly crossing national borders, which necessitate enhanced collaboration among, and strengthening of, regulatory agencies to ensure safety, quality and efficacy of healthcare products as well as to maintain public trust. - The capacity of developing countries and their institutions must be strengthened and utilised in order to foster their contribution to global R&D efforts, and to ensure that innovation reaches the patients most in need. - Continued efforts must be made to engage a broad range of stakeholders to ensure policy coherence and take forward the elements of this agenda.
The High Level Forum calls upon: governments both of OECD and developing countries to demonstrate political leadership and to join with industry, product development partnerships, investors, shareholders, intergovernmental organisations and non- governmental organisations to further intensify collaborative efforts and promote coherent policies to improve the availability of and access to medicines, vaccines and diagnostics for neglected and emerging infectious diseases.
Actions should focus on the following areas: Exploring in conjunction with the WHO/IGWG process how greater efforts to collaborate in prioritising, developing and delivering innovative medicines, vaccines and diagnostics could increase investments and
108 NEPAD-COHRED - Strengthening Pharmaceutical Innovation in Africa the number of researchers involved in R&D for neglected and emerging infectious diseases that primarily affect developing countries. Specifically: - Pursuing the viability of a global, virtual collaborative drug development network drawing on existing initiatives, including those of the WHO/TDR, PDPs, and regional (e.g. south-south and north-south) technology networks. - Facilitating the development and operation of a sustainable architecture for the sharing and exchange of knowledge, data and research tools necessary for the discovery of medicines, vaccines and diagnostics for neglected and emerging infectious diseases. - Identifying the infrastructure needs to underpin such efforts to accelerate the discovery of medicines, vaccines and diagnostics for neglected and emerging infectious diseases. - Forecasting effective demand for essential medical technologies. - Ensuring that there is sustained high level political support and adequate funding for the WHO/IGWG activities including implementation of the Global Strategy and Plan of Action. - Considering the African Health Strategy and the Pharmaceutical Manufacturing Plan for Africa adopted by the African Union Health Ministers in April 2007.
Exploring and evaluating for-profit and not-for-profit models to promote innovation and stimulate the development of new medicines, vaccines and diagnostics for neglected and emerging infectious diseases primarily affecting developing countries. In particular explore: - The potential value of sustainable collaborative mechanisms for IPRs (such as patent pools or other IP and data management entities). This work could be carried out by the OECD as part of its ongoing work on collaborative mechanisms for IPRs in co- operation with other relevant international organisations. - Alternative policy mechanisms to reward innovation (e.g. advanced market commitments, prize fund models, valorisation of intellectual assets) to better understand how these could contribute to the development of medicines, vaccines and diagnostics for neglected and emerging infectious diseases. The strengths and limitations of alternative mechanisms could be considered, as well as monitoring pilot phases of existing mechanisms. This should involve empirical testing. - Comprehensive and inclusive approaches to innovation that place delivery of new health technologies to patients at its core. - Mechanisms to promote the transfer of technology, knowledge and technical skills to strengthen developing country innovation systems. - Supporting and providing incentives to new models of partnerships between developing and developed countries to accelerate R&D for neglected diseases. - Synergies and complementarities between research and development financing to support R&D in developing countries by harmonising OECD Official Development Assistance (ODA) mechanisms. - The use of existing flexibilities of multilateral agreements to foster innovation and access.
Supporting developing countries-led efforts in strengthening their own health, local production and research systems, including prevention, to ensure availability and accessibility of medicines, vaccines, diagnostics and other preventative technologies for neglected and emerging infectious diseases in accordance with the principles of the Paris Declaration on Aid Effectiveness (March 2005). In particular: • Improving predictability and transparency of funding including official development assistance. • Taking steps to strengthen the capability of developing countries to manage issues of intellectual property, including using available flexibilities to the fullest extent, and to build sustainable networks and capacity for global research.
109 Endnotes
1 See footnote on title page. 2 NEPAD has since published a report on science, technology and innovation for Public Health in Africa (February 2009). http://www.nepadst.org/doclibrary/pdfs/stipha_mar2009.pdf\ 3 Based on the African Union (AU) assembly decision taken by 55 African ministers of health during the Abuja Summit in January 2005 and on the 2005 Gaborone Declaration, which established a roadmap towards universal access to prevention, treatment and care. 4 G-Finder 2008, Neglected Disease Research and Development: How much are we really spending? http://www.thegeorgeinstitute.org/research/health-policy/current-projects/g-find-global-funding-of-innovation-for- neglecteddiseases.cfm 5 Report of Commission on Intellectual Property Rights and, Innovation and Public Health. Geneva 2006: WHO, 204 p. 6 WHO. WHO medicines strategy. Framework for action in essential drugs and medicines policy 2002 -2003. Geneva: World Health Organization; 2000. WHO/EDM/2000.1. 7 Trade-related aspects of intellectual property rights 8 Ellen R. Shaffer & Joseph E. Brenner: A Trade Agreement’s impact on Access to Generic Drugs. Health Affairs 28, number 5 (2009) 9 Method: • Information was gathered from February 2008 to May 2009. • Keywords used for the Internet-based literature review were: ‘Africa’, ‘developing countries’, ‘health innovation systems’, ‘pharmaceutical research and development’, ‘local pharmaceutical production’, ‘technology transfer’, ‘neglected tropical diseases’ . • Discussions were held with key informants in various sectors of pharmaceutical innovation in developing countries, especially in Africa. The aim was to get input from a cross-section of informants across the pharmaceutical innovation spectrum; from discovery to delivery and access. • Documentation referred to or obtained from key informants was reviewed. • Participating in global and regional meetings on specific aspects of pharmaceutical innovation in developing countries, including Africa, was key. 10 WHO fact sheets. http://www.who.int/mediacentre/factsheets/fs302/en/index.html 11 WHO Roll Back Malaria; http://www.rbm.who.int/cmc_upload/0/000/015/370/RBMInfosheet_3.htm 12 World Medicines Situation, WHO 2004. http://apps.who.int/medicinedocs/en/d/Js6160e/3.html 13 World Medicines Situation, WHO 2004 14 Trouiller P, Olliaro P, Torreele E, Orbinski J, Laing R, Ford N. Drug development for neglected diseases: a deficient market and a public-health policy failure. Lancet, 22 June 2002, 359:2188-94 15 First Meeting of the Technical Committee on the Pharmaceutical Manufacturing Plan for Africa October 2007; Report. www.africa-union.org 16 Idem 17 Chirac P, Torreele E. Global framework on essential health R&D. Lancet, 12 May 2006, 1560 - 61 18 World Health Statistics 2007, WHO. http://www.who.int/whosis/whostat2007_6healthsystems_nha.pdf 19 UNESCO Institute for Statistics Fact sheet: A global Perspective on Research and Development, October 2007, No. 05 ((Less than one-half of the countries in Africa can provide data) 20 Macroeconomics and health: Investing in health for economic development. Report of the WHO Commission on Macroeconomics and Health. WHO 2001 21 Source: WHO commission on Social Determinants of Health; http://www.who.int/social_determinants/en/index.html 22 Resolution WHA59.24 23 Noordwijk Medicines Agenda, 21 June 2007 24 See www.oecd.org/sti/biotechnology/nma 25 See annex 8 26 Kalua F.A., Awokedu A., Kamwanja L.A. and J.D.K. Saka (eds). 2009. Science, Technology and Innovation for Public Health in Africa. Monograph, NEPAD Office of Science and Technology, Pretoria, Republic of South Africa 27 October 2008, Abuja, Nigeria. See http://apps.who.int/tdr/svc/news-events/news/andi-endorsement 28 Furman J.L., Porter M E, Stern S, Determinants of National Innovation Policy; Research Policy 31 (2002) 899–933 29 Morel C, D Broun, A Dangi, C Elias, C Gardner, RK Gupta, J Haycock, T Heher, P Hotez, H Kettler, G Keusch, A Krattiger, F Kreutz, K Lee, R Mahoney, RA Mashelkar, Hong-ki Min, S Matlin, M Mzimba, J Oehler, R Ridley, P Senanayake, H Thorsteinsdóttir, PA Singer and Mikyung Yun. 2005. Health Innovation in Developing Countries to Address Diseases of the Poor. Innovation Strategy Today 1(1):1-15. www.biodevelopments.org/innovation/index.htm 30 http://www.africa- union.org/root/UA/Annonces/HRST/Africa%20s%20Consolidated%20Plan%20of%20Action.pdf 31 Tucker T.J, Makgoba M.W, Public-Private Partnerships and Scientific Imperialism, in SCIENCE, 23 MAY 2008 VOL 320 32 Growth in a Changing Market report, a CEO outlook for 2009, Daily Nation (Kenya), 16April 2009. 33 Daan du Toit. Bridging the innovation chasms: Innovation Policy Challenges in Africa and Opportunities for Partnership with Europe. Accessed: http://www.africanaxis.org/Presentations/innovation%20seminar/daan%20du%20toit.pdf
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34 MSF campaign for essential medicines website: http://www.msfaccess.org/main/hiv-aids/utw-interview-with- campaign-pharmacist/ 35 See COHRED statement 2007: Are international health research programmes doing enough to develop research systems and skills in low and middle income countries? 36 Kitua AY, Swai GBR, Urrio T. Fund flows to health research institutions in Tanzania. Daar es Salaam: Tanzania Health Research Forum, 2002 37 COHRED. Donor alignment and harmonization in relation to national health research priorities project: Uganda country report. Geneva: COHRED, 2008 38 Uganda National Council for Science and Technology. Research registration status report for 2005. Kampala: UNCST, 2006 39 Moran M, Guzman J, Ropars AL et al. Neglected disease research & development: how much are we really spending? The George Institute for International Health, February 2009 40 Adopted by Ministers of Health at the Bamako 2008 Ministerial Forum 41 Presented during the launch of the African Network for Drugs and Diagnostics Innovation (ANDI), Abuja, October 2008. 42 Science, technology and innovation for public health in Africa: http://www.nepadst.org/doclibrary/pdfs/stipha_mar2009.pdf\ 43 Pharmaceutical Manufacturing Plan for Africa. Third Session of the African Union Conference of Ministers of Health. 9-13 April 2007, Johannesburg, South Africa. 44 Musungu S, Villanueva S, Blasetti R. Utilizing TRIPS Flexibilities for Public Health Protection through South- South Regional Frameworks. South Centre April 2004 45 Stiglitz, J. E. (2009). Trade agreements and health in developing countries. The Lancet, 373/9661, 363-365. 46 Love J, Hubbard T. The big idea: prizes to stimulate r&d for new medicines. Chicago-Kent Law Review Volume 82, Number 3 ?2007 47 EWG working document “introduction to inventory framework and criteria” http://www.who.int/phi/ewg/en/index.html 48 Background paper from the Taskforce on International Innovative Financing for Health Systems, co-chaired by the UK Prime Minister and the President of the World Bank, 2009 49 http://www.wto.org/english/tratop_e/trips_e/t_agm2_e.htm 50 http://www.who.int/medicines/areas/policy/tripshealth.pdf 51 Ellen F.M. t’Hoen. The Global Politics of Pharmaceutical Monopoly Power. AMB Publishers. 2009 52 Martin Kohr. Patents, Compulsory Licenses and Access to Medicines: Some Recent Experiences. Intellectual Property Series. Third World Network. 2007 53 Ellen F.M. t’Hoen. The Global Politics of Pharmaceutical Monopoly Power. AMB Publishers. 2009 54 http://www.wto.org/english/tratop_E/TRIPS_e/implem_para6_e.htm 55 Ellen F.M. t’Hoen. The Global Politics of Pharmaceutical Monopoly Power. AMB Publishers. 2009 56 Cheri Grace Leveraging the Private Sector for Public Health Objectives: A Briefing Paper for DFID on Technology Transfer in the Pharmaceuticals Sector. DFID 2004 57 First Meeting of the Technical Committee on the Pharmaceutical Manufacturing Plan for Africa October 2007; Report. www.africa-union.org 58 Report on the Third Session of the African Union Conference of Ministers of Health 9– 13 April 2007, Johannesburg, South Africa. http://www.africa-union.org/root/UA/Conferences/2007/avril/SA/9- 13%20avr/doc/en/Overview_of_the_theme_MIN.pdf 59 “The Business of Health in Africa. Partnering with the private sector to improve people’s lives” International Finance Corporation 60 Source: Proceedings from meeting of African Ministers of Health to report progress on the PMPA, held in May 2008, in Geneva, May 2008 61 https://www.unido.org/fileadmin/media/documents/pdf/Procurement/Notices/0910/16001981/ Appendix%201%20%202%20TOR%20and%20Qualification%20Requirements.PDF 62 Kaplan W., Laing R, Local production of pharmaceuticals: industrial policy and access to medicines. World Bank HNP discussion paper. 2005 63 Bate R., Local production in developing countries: How economic protectionism undermines access to quality medicines. International Policy Network, January 2008. 64 Partnerships to build healthier societies in the developing world. © IFPMA 2009 - www.ifpma.org/healthpartnerships 65 Partnerships to build healthier societies in the developing world. © IFPMA 2009 - www.ifpma.org/healthpartnerships 66 http://www.boehringer-ingelheim.com/corporate/news/information_material/hiv_policy_paper.pdf 67 GlaxoSmithKiline: Our contribution to the fight against HIV/AIDS in developing countries www.gsk.com/media/aids_contribution_dev.pdf 68 The Health of the People: the African Regional Health Report http://whqlibdoc.who.int/afro/2006/9290231033_eng.pdf 69 First Meeting of the Technical Committee on the Pharmaceutical Manufacturing Plan for Africa October 2007; Report. www.africa-union.org 70 Kaplan W., Laing R, Local production of pharmaceuticals: industrial policy and access to medicines. World Bank HNP discussion paper. 2005 71 PAN AFRICAN EXPERTS MEETING ON ACCESS TO AND RATIONAL USE OF MEDICINES organized by Health Action International, HAI-Africa in collaboration with the Ecumenical Pharmaceutical Network. 14, 15 November 2007, Nairobi, Kenya
111 72 First Meeting of the Technical Committee on the Pharmaceutical Manufacturing Plan for Africa October 2007; Report. www.africa-union.org 73 Adapted from COHRED work on development of National Health Research Systems 74 UNESCO Institute for Statistics Fact sheet: A global Perspective on Research and Development, October 2007, No. 05. (Less than one-half of the countries in Africa can provide data) 75 See 2.5 above 76 First Meeting of the Technical Committee on the Pharmaceutical Manufacturing Plan for Africa October 2007; Report. www.africa-union.org 77 Presentation made by Dr. H. Hogerzeil, Director Essential Medicines and Pharmaceutical Policies, WHO, Geneva during the 2009 workshop on harmonization of drug registration 78 The Health of the People: the African Regional Health Report http://whqlibdoc.who.int/afro/2006/9290231033_eng.pdf 79 Crisis in human resources for health in the African region. Africa Health Monitor. January-June 2007. Vol.7, No.1 80 Hagopian et al.The migration of physicians from sub-Saharan Africa to the United States of America: measures of the African brain drain. Human Resources for Health 2004. http://creativecommons.org/licenses/by/2.0 81 Global Atlas of the Health Workforce. WHO, Geneva, 2006 82 Mytelka L K; Pathways and policies to (Bio) Pharmaceutical Innovation Systems in Developing Countries, Innovation and Industry; December 2006. 83 Furman J.L., Porter M E, Stern S, Determinants of National Innovation Policy; Research Policy 31 (2002) 899–933 84 Singer P, Daar A et al; Commercializing African health research: building life science convergence platforms. Global Forum Update on Research for Health Volume 5. 2008. 85 Moran M: Partnership Dynamics, Issues and Challenges. Global Forum Update on Research for Health Volume 4 86 Tucker T.J, Makgoba M.W, Public-Private Partnerships and Scientific Imperialism, in SCIENCE, 23 MAY 2008 VOL 320
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