Center for Technological Development in Health Oswaldo Cruz Foundation, Ministry of Health of Brazil The Center for Technological Development in Health (CDTS)

Presentation to the Commission on Intellectual Property Rights, Innovation and Public Health (CIPIH) Oswaldo Cruz Foundation (FIOCRUZ) Rio de Janeiro, 02 February 2005

CDTS/FIOCRUZ œ Presentation to CIPIH, Rio de Janeiro, Brazil 2 February 2005 The Center for Technological Development in Health (CDTS)

Carlos M. Morel Scientific Coordinator CDTS/FIOCRUZ

CDTS/FIOCRUZ œ Presentation to CIPIH, Rio de Janeiro, Brazil 2 February 2005 Purpose of thispresentation

¢ To discuss the role and needs of disease-endemic countries in research, development and innovation ¢ To position Brazil and FIOCRUZ in the international context ¢ To present the CDTS project to members of CIPIH Background to this presentation

¢ Health is not only a consequence of development ô A central input into poverty reduction and long-term economic growth and social development ¢ The new production of knowledge ô Gibbons et al, 1994: Mode 1 and Mode 2 ô Pasteur‘s Quadrant, 1997: —Use-inspired basic research“ ¢ Innovative Developing Countries (IDCs) ô More active role in health product innovation, research & development, manufacturing and access ¢ FIOCRUZ ô Prominent role in Brazil‘s S&T and public health policies Health and developing countries

Health challenges and failures Innovation in developing countries

CDTS/FIOCRUZ œ Presentation to CIPIH, Rio de Janeiro, Brazil 2 February 2005 Health challenges for developing countries

¢ Provide access to existing health interventions (vaccines, drugs, etc) ô Cope with a —market failure“ and a —public health failure“ ¢ Deal with diseases that lack cost-effective tools for their control ô Diseases of poverty ¢ ”Neglected‘ and ”most-neglected‘ diseases ¢ Cope with a —science failure“ e.g. no vaccines available for use against parasite pathogens ô Emerging and re-emerging diseases Cost of providing 1% 0.1% 0.01% 0.001% 1002 ARVsto TB patients Sou

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V 2 Ukr I USA Vie H Dji Som Spa Eri Niger 1 0 -01 .1 0 1 1 10 1 02 0 103 00 10,4000 Gross national income ($billions) Economic Strength & Innovation Capability* Low High Innovation Capability Natural Resource Rich High Countries and small G8 Economic OECD countries Strength Least Developed Innovative Countries and other non- Developing Countries Low IDC Developing Countries (IDCs)**

(*) Report from Bellagio meeting May 2004, in preparation. Table modified from R.A. Mashelkar (2003) 10th Zuckerman Lecture: Nation Building through Science & Technology–A Developing World Perspective. Royal Society, London. (**) India, China, Brazil, South Africa, Thailand, Malaysia, Indonesia, Argentina Country GDP per US patents per Country US Patents classification(*) capita GDP per capita

1 United States G8, OECD 50000 36,006 1.389 2 Japan G8, OECD 36889 31,407 1.175 3 India IDC 444 487 0.913 4 China IDC 724 989 0.732 5 Germany G8, OECD 12960 24,051 0.539 6 Korea, Rep. OECD 4246 10,006 0.424 7 France G8, OECD 4906 24,061 0.204 8 Canada G8, OECD 4368 22,777 0.192 9 United Kingdom G8, OECD 4920 26,445 0.186 10 Italy G8, OECD 2147 20,528 0.105 11 Brazil IDC 209 2,593 0.081 12 Israel HIE 1231 15,792 0.078 13 Sweden OECD 1958 26,929 0.073 14 South Africa IDC 142 2,299 0.062 15 Australia OECD 1105 20,822 0.053 16 Switzerland OECD 1917 36,687 0.052 17 Belgium OECD 1055 23,749 0.044 18 Finland OECD 945 25,295 0.037 19 Austria OECD 657 19,749 0.033 20 Thailand IDC 64 2,060 0.031 21 Singapore HIE 564 20,886 0.027 22 Malaysia IDC 95 3,905 0.024 23 Indonesia IDC 19 817 0.023 24 Argentina IDC 64 2,797 0.023 25 Mexico OECD 129 6,320 0.020

(*) Report from Bellagio meeting May 2004, submitted for publication US Patents x GDP per capita

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81 83 85 87 89 91 93 95 97 99 01 19 19 19 19 19 19 19 19 19 19 20 Source: W eb ofScience: (ISI) YSecaiernce Indicators(ISI) - CD-Room Author: Prof. J. Guim arães (CNPq & CAPES) Productivesector investment(billionUS$) andnumberofpatents registeredin theUnitedStates byBrazilandSouthKorea Productive sector investment (US$ billion)

Productive sector Number of investment (US$ billion) US patents

Number of US patents

Cruz, C.H.B. (2003) A universidade, a empresa e a pesquisa que o país precisa. Cadernos de Estudos Avançados. Rio de Janeiro: Instituto Oswaldo Cruz. (1):5-22 Top 10 Biotechnologies for Improving Health in Developing Countries

1. Modified molecular technologies for affordable, simple diagnosis of infectious disease 2. Recombinant technologies to develop vaccines against infectious diseases 3. Technologies for more efficient drug and vaccine delivery systems 4. Technologies for environmental improvement (sanitation, clean water, bioremediation) 5. Sequencing pathogen genomes to understand their biology and to identify new antimicrobials 6. Female-controlled protection against sexually transmitted disease, both with and without contraceptive effect 7. Bioinformatics to identify drug targets and to examine pathogen-host interactions 8. Genetically modified crops with increased nutrients to counter specific deficiencies 9. Recombinant technology to make therapeutic products (e.g. insulin, interferons) more affordable 10. Combinatorial chemistry for drug discovery

Daaretal (2002) Nature Genetics32:229-232 FIOCRUZ

Research, Technological Development, Production, Services, Teaching, Training… and Innovation

CDTS/FIOCRUZ œ Presentation to CIPIH, Rio de Janeiro, Brazil 2 February 2005 FIOCRUZ and innovation in health

¢ 1900s‘: The creation of a new institution for the production of sera and vaccines represents a major step for Brazilian science and a landmark in health policy ¢ 2000s‘: New challenges, new and old public health threats, but also new opportunities are pushing FIOCRUZ to a new phase of growth and to a leading role in S&T&I for health

Stepan, N (1976) Beginnings of Brazilian Science, Oswaldo Cruz Medical Research and Policy. Science History Publications, New York Paradigm shift

¢ Failure of the linear model ¢ A new model

ô The two dimensional conceptual plane (Stokes, 1997)

ô Rescuing the importance of —use-inspired basic research“, or strategic research Considerations of use? No Yes ? g n i d n a s Pure basic Use-inspired s t e e s Y Y r research basic research e d n u Niels Louis l

a Bohr Pasteur t n e m a Research d n that u f o Pure applied o r systematizes N N o f particular research t s phenoRmogeenraTory e Peterson u ThomasAlvaEdison Q No Yes Considerations of use? No Yes ? g n i d n a s Pure basic Use-inspired s t e e s Y Y r research basic research e d n u Niels

l Oswaldo a Bohr Cruz t n e m a Research d n that u f o Pure applied o r systematizes N N o f particular research t s phenoRmogeenraTory e Peterson u ThomasAlvaEdison Q No Yes Considerations of use? No Yes ? g n i d n a s Pure basic Use-inspired s t e e s Y Y r research basic research e d n u Niels Carlos l a Bohr Chagas t n e m a Research d n that u f o Pure applied o r systematizes N N o f particular research t s phenoRmogeenraTory e Peterson u ThomasAlvaEdison Q No Yes Mode 1 and 2 of knowledge production

¢ Mode 1 ô Problems are set and solved in a context governed by the, largely academic, interests of a specific community ¢ Mode 2 ô Knowledge is carried out in a context of application Mode 1 and 2 of knowledge production

¢ Mode 1 ô Disciplinary ô Homogeneity ô Hierarchical ô Quality control by peer review judgements about contributions made by individuals ¢ NIH, CNPq, HHMI Mode 1 and 2 of knowledge production

¢ Mode 2 ô Transdisciplinary ô Heterogeneity ô Heterarchicaland transient ô Quality control uses additional criteria e.g. social, political, economic ¢ —Is the solution cost- effective? Competitive in the market? Socially acceptable? “ ¢ TDR, Grand Challenges Global Health, industry Scientific productivity of FIOCRUZ according to ISI‘s W eb of Science ISI‘s W eb of Science:In the period 1999- 2004 FIOCRUZ published 1.872 papers Evolutionofthescientificproductivity ofFIOCRUZ, 1999-2004 Journals used by FIOCRUZ authors Areas of FIOCRUZ research FIOCRUZ publications, 1999- 2004: Languages used Brazil: Key organizations in biotechnology

Brazil: Key organizations in biotechnology (Silveira et al, 2004)

Fundação Oswaldo Cruz (FIOCRUZ) Public, Federal

Instituto Butantan Public, São Paulo State

Instituto de Tecnologia do Paraná (TECPAR) Public, Paraná State

Instituto Ludwig Private

Empresa Brasileira de Pesquisas Agro-pecuárias (EMBRAPA) Public, Federal

Instituto Agronômico de Campinas (IAC) Public, Federal

Fundação Biominas Private, not for profit

Silveiraet al (2004) Recent evolution of biotechnology in Brazil. IE/UNICAMP #114:1-38 http://www.eco.unicamp.br/publicacoes/textos/download/texto114.pdf Key role of the public sector in the evolution of Brazil`s biotech Keyrole ofthepublicsector in the evolutionofBrazil`s biotech Partnerships between key public institutions and the private sector

Public Private Objective

FIOCRUZ (Bio-Manguinhos) GlaxoSmithKline Hib vaccine production

FIOCRUZ (Far-Manguinhos) GlaxoSmithKline Abacavir, Amprenavir, Fosamprenavir

FIOCRUZ (Far-Manguinhos) Roche Benznidazol

Instituto Butantan Aventis R&D on influenza vaccine

Instituto Butantan & Univ. São Paulo Sadia Erithropoietin; surfactants

Ritonavir, Saquinavir, Ritonavir+Saquinavir, FIOCRUZ (Far-Manguinhos) Cristália new protease inhibitors Control of Clostridium; swine somatotrophin EMBRAPA Vallée R&D New varieties of plants for the sugar-alcohol Instituto Agronomico de Campinas Copersucar industry

Silveira etal (2004) Recentevolutionofbiotechnologyin Brazil. IE/UNICAMP #114:1-38 http://www.eco.unicamp.br/publicacoes/textos/download/texto114.pdf FIOCRUZ: Inventions and patents

Patents Num ber of Areas inventions Requested Granted Brazil Abroad Total Brazil Abroad Total Drugs, m edicines 13 12 14 26 1 11 12 Equipm ents and devices 10 7 7 3 3 Diagnostics 8 5 7 12 2 2 4 Vaccines 7 5 28 33 1 18 19 Identification/detection of organism s 4 3 1 4 1 1 2 Other (insect repellents, culture m edia, 4 2 3 5 4 4 effluent treatm ent, educacional gam es)

Bioinsecticides 3 2 8 10 1 3 4

Total 49 36 61 97 13 35 48 Recent initiatives of FIOCRUZ on innovation in health

¢ Program on Technological Development of Health Products (PDTIS) ¢ Program on Innovation and Technological Development in Public Health (PDTSP) ¢ Program on Innovation ô Innovaccine: Draft resolution on new vaccines ¢ Center for Technological Development in Health (CDTS) CDTS: A bridge between R&D and production

Attrition rate R$ per project

Individual Industrial research PDTIS production by PAPES CDTS projects of PDTSP Bio-, Far-, FIOCRUZ PPPsor other partners

New strategic and managerial approaches to innovation The CDTS project CDTS: Basic components

¢ Technological platforms

ô Information

ô Products ¢ Animal experimentation ¢ Support laboratories ¢ Flexible laboratories ¢ Technological management and administration CDTS Platforms: Information

¢ Genomics ¢ Proteomics ¢ Microarrays and nanotechnology ¢ Lipid and polissacharideanalysis ¢ Bioinformatics CDTS Platforms: Products

¢ Recombinant proteins ¢ Protein crystalization ¢ Monoclonal & recombinant antibodies ¢ Oligonucleotidesynthesis CDTS: Animal experimentation

¢ Toxicity & immunogenicitytests ¢ Transgenesis ¢ NB III+ ¢ Best practices in animal experimentation ¢ Shared facilities with research groups at the Manguinhos campus CDTS: Support laboratories

¢ Flow citometry ¢ Microscopy ¢ Biological samples repository (biological, biotechnological, clinical) ¢ Toxicology ¢ Physico-chemical analysis CDTS: Flexible laboratories

¢ Laboratory areas allocated to the development of specific products

ô Product development partner(s)

ô Industrial/commercial partner(s) ¢ Provision of infrastructure support, best practices for product development and confidentiality of information CDTS: Technological management & administration

¢ Project and product management

ô Meeting rooms for the Product Research & Development committee (PRD) and the Product Development Teams (PDTs)

ô Infrastructure for the management and documentation storage related to clinical trials and ethical committees

ô Infrastructure for IPR and contract negotiations Science16.04.2004 Claire M. Fraser*

¢ Pharmaceutical companies are driving away from R&D of antimicrobials and vaccines ¢ Antibiotic resistance is growing ever larger ¢ W e are vulnerable not only to deliberate attacks but to natural outbreaks of emerging and reemerging diseases ¢ Academia, industry and government must work together to support R&D to create new drugs and vaccines against the world`s most deadly diseases

(*) President and Director, TIGR Thank you

morel@ fiocruz.br

CDTS/FIOCRUZ œ Presentation to CIPIH, Rio de Janeiro, Brazil 2 February 2005