Can Brazil play a more important role in global tuberculosis drug production? An assessment of current capacity and challenges

BMC Public Health

Anete Trajman⁴  Alexandre Menezes²  Joel Keravec³  Andre Gemal¹ 

[1] Federal University of Rio de Janeiro and National Institute of Health Quality Control/Fiocruz, Rio de Janeiro, Brazil;Global Health Strategies, Rio de Janeiro, Brazil;Management Sciences for Health, Projeto MSH, Rio de Janeiro, Brazil;Universidade Gama Filho, Mestrado Profissional em Ensino na Saúde, Rua Manoel Vitorino 553, Prédio AG, 5o andar, Rio de Janeiro, Piedade, 20748-900, Brazil

关键词: Tuberculosis;    Quality control;    Pharmaceuticals;    Fixed dose combination;    Certification;    Antitubercular agents;   

Others  :  1162401
DOI  :  10.1186/1471-2458-13-279

 received in 2012-11-03, accepted in 2013-01-14,  发布年份 2013

【 摘 要 】

Background

Despite the existence of effective treatment, tuberculosis is still a global public health issue. The World Health Organization recommends a six-month four-drug regimen in fixed-dose combination formulation to treat drug sensitive tuberculosis, and long course regimens with several second-line drugs to treat multi-drug resistant tuberculosis. To achieve the projected tuberculosis elimination goal by 2050, it will be essential to ensure a non-interrupted supply of quality-assured tuberculosis drugs. However, quality and affordable tuberculosis drug supply is still a significant challenge for National Tuberculosis Programs.

Discussion

Quality drug production requires a combination of complex steps. The first challenge is to guarantee the quality of tuberculosis active pharmaceutical ingredients, then ensure an adequate manufacturing process, according to international standards, to guarantee final product´s safety, efficacy and quality. Good practices for storage, transport, distribution and quality control procedures must follow. In contrast to other high-burden countries, Brazil produces tuberculosis drugs through a strong network of public sector drug manufacturers regulated by a World Health Organization-certified national sanitary authority. The installed capacity for production surpasses the 71,000 needed treatments in the country. However, in order to be prepared to act as a global supplier, important bottlenecks are to be overcome. This article presents an in-depth analysis of the current status of production of tuberculosis drugs in Brazil and the bottlenecks and opportunities for the country to sustain national demand and play a role as a potential global supplier. Raw material and drug production, quality control, international certification and pre-qualification, political commitment and regulatory aspects are discussed, as well recommendations for tackling these bottlenecks. This discussion becomes more important as new drugs and regimens to treat tuberculosis are expected in a close future.

Summary

International manufacturers of raw material for tuberculosis treatment should undergo certification and pre-qualify their active pharmaceutical ingredients as a first step to ensure quality of tuberculosis drugs. At the country level, Brazilian public manufacturers should apply for international certification and tuberculosis drugs should be pre-qualified by international organisms. Finally, only with political commitment and large-scale production will Brazilian public sector manufacturers be able to partially supply the global market.

【 授权许可】

   
2013 Gemal et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]World Health Organization: WHO Global tuberculosis report 2012. Geneva, Switzerland: WHO; 2012:100.
• [2]HIV and TB Factsheets CDC HIV/AIDS [http://www.cdc.gov/hiv/resources/factsheets/hivtb.htm webcite]
• [3]United Nations Millennium Development Goals [http://www.un.org/millenniumgoals/aids.shtml webcite]
• [4]WHO, Stop TB Partnership: The Global Plan to Stop TB 2011–2015. Geneva, Switzerland: WHO; 2011:101.
• [5]World Health Organization: WHO Towards universal access to diagnosis and treatment of multidrug-resistant and extensively drug-resistant tuberculosis by 2015. Geneva, Switzerland: WHO; 2011:119.
• [6]Prasad R: Multidrug and extensively drug-resistant TB (M/XDR-TB): problems and solutions. Indian J Tuberc 2010, 57:180-191.
• [7]Furin J, Bayona J, Becerra M, Farmer P, Golubkov A, Hurtado R, Joseph JK, Keshavjee S, Ponomarenko O, Rich M, Shin S: Programmatic management of multidrug-resistant tuberculosis: models from three countries. Int J Tuberc Lung Dis 2011, 15:1294-1300.
• [8]Lienhardt C, Cobelens FGJ: Operational research for improved tuberculosis control: the scope, the needs and the way forward. Int J Tuberc Lung Dis 2011, 15:6-13.
• [9]Cobelens F, van den Hof S, Pai M, Squire SB, Ramsay A, Kimerling ME: Which new diagnostics for tuberculosis, and when? J Infect Dis 2012, 205(Suppl 2):S191-198.
• [10]de Oliveira EA, Labra ME, Bermudez J: [Public production of medicines in Brazil: an overview]. Cad Saude Publica 2006, 22:2379-2389.
• [11]Brasil. Ministério da Saúde: Manual de Recomendações para o Controle da Tuberculose no Brasil. 2011., 186http://portal.saude.gov.br/portal/arquivos/pdf/manual_de_recomendacoes_tb.pdf webcite
• [12]Kritski AL, Ruffino-Netto A: Health sector reform in Brazil: impact on tuberculosis control. Int J Tuberc Lung Dis 2000, 4:622-626.
• [13]Paim J, Travassos C, Almeida C, Bahia L, Macinko J: The Brazilian health system: history, advances, and challenges. Lancet 2011, 377:1778-1797.
• [14]Conde MB, Marques AMC, Cardoso NC, Pinheiro VGF, de TR DP, Machado Junior A, Lemos ACM, Netto AR, Durovni B, Sant’Anna CC, Lima D, Capone D, Barreira D, Matos ED, David FC, Marsico G, Afiune JB, Jamal LF, Hirata MH, Rabahi MF, Cailleaux-Cesar M, Palaci M, Morrone N, Guerra RL, Dietze R: III Brazilian Thoracic Association Guidelines on Tuberculosis. Jornal Brasileiro de Pneumologia 2009, 35:1018-1048.
• [15]Agência Nacional de Vigilância Sanitária [http://portal.anvisa.gov.br/wps/portal/anvisa/home webcite]
• [16]Galvao J: Brazilian policy for the distribution and production of antiretroviral drugs: a privilege or a right? Cad Saude Publica 2002, 18:213-219.
• [17]Fiocruz / Farmanguinhos Lista de produtos [http://www2.far.fiocruz.br/farmanguinhos/ webcite]
• [18]Fiocruz / Farmanguinhos Farmanguinhos combate a tuberculose [http://www2.far.fiocruz.br/farmanguinhos/ webcite]
• [19]WHO Prequalification of medicines by WHO [http://apps.who.int/prequal/query/ProductRegistry.aspx?list=tb webcite]
• [20]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 2002, 359:2188-2194.
• [21]Vieira FS: Ministry of Health’s spending on drugs: program trends from 2002 to 2007. Revista de Saúde Pública 2009, 43:674-681.
• [22]Vieira FS: Pharmaceutical assistance in the Brazilian public health care system. Revista Panamericana de Salud Pública 2010, 27:149-156.
• [23]Médecins Sans Frontières Access to Essential Medicines Campaign, The Drugs for Neglected Diseases Working Group: Fatal Imbalance The Crisis in Research and Development for Drugs for Neglected Diseases. Brussels, Belgium: Médecins Sans Frontières Access to Essential Medicines Campaign and the Drugs for Neglected Diseases Working Group; 2011.
• [24]Spilker B: Multinational Drug Companies: Issues in Drug Discovery and Development. 1989th edition. New York: Raven Pr; 1989.
• [25]Stop TB Partnership: Report of TB Drug Manufacturers Meeting Aug 29–30 2011, New Dehli. New Dehli, India; 2011:14.
• [26]World Health Organization: Prequalification of medicines by WHO. Fact sheet # 278. Available at http://www.who.int/mediacentre/factsheets/fs278/en/ webcite
• [27]Presidência da República do Brasil: Legislação Federal do Brasil. Lei 12.349/2010. 2010.
• [28]World Health Organization: WHO Global tuberculosis control 2011. Geneva, Switzerland: World Health Organization; 2011:258. www.who.int/tb/publications/global_report/ webcite
• [29]Inmetro - Instituto Nacional de Metrologia, Qualidade e Tecnologia [http://www.inmetro.gov.br/ webcite]
• [30]Ministério da Saúde. Agência Nacional de Vigilância em Saúde: Farmacopéia Brasileira 5a Edição - 2010 - Anvisa. 5th edition. Brasilia, DF: Editora Fiocruz; 2010.
• [31]Pan American Health Organization: Regional Plan for Tuberculosis Control, 2006–2015. Washington DC: Pan American Health Organization; 2006:80.
• [32]Sennes RU, Brito Filho A: Technological Innovations in Brazil. Performance, Policies and potential. Cultura Acadêmica: São Paulo; 2012.
• [33]Kritski AL, Villa TS, Trajman A, Lapa E, Silva JR, Medronho RA, Ruffino-Netto A: [Two decades of research on tuberculosis in Brazil: state of the art of scientific publications]. Rev Saude Publica 2007, 41(Suppl 1):9-14.
• [34]FEBRAFARMA: Origens e Trajetórias da Indústria Farmacêutica no Brasil. 1st edition. São Paulo: Narrativa 1; 2007:1.
• [35]DNDi: Drugs for Neglected Diseases Innitiatives Annual Report 2011. 2011, 34.
• [36]European Comission: Aid Effectiveness Agenda: Benefits of a European Approach. Available at http://www.fride.org/event/246/the-aid-effectiveness-agenda-in-european-and-south-south-cooperation webcite
• [37]Rede - TB [http://www.redetb.org/ webcite]
• [38]Grosset JH, Singer TG, Bishai WR: New drugs for the treatment of tuberculosis: hope and reality [State of the Art Series. New tools. Number 2 in the series]. Int J Tuberc Lung D 2012, 16:1005-1014.