[Estimating demand for anti-Chagas drugs: a contribution for access in Latin America]. / Estimación de la demanda de medicamentos antichagásicos: una contribución para el acceso en América Latina.

OBJECTIVE: Describe a tool to estimate demand for benznidazole and nifurtimox to treat Chagas disease, and report on its implementation in a group of Latin American countries. METHODS: The project was carried out in the following stages: 1) development of a tool to estimate demand, and definition of the evaluation and decision variables to estimate demand 2) data collection via a questionnaire completed by representatives of control programs, complemented with data from the literature; 3) presentation of the tool, followed by validation, and adaptation by representatives of the control programs in order to plan drug procurement for 2012 and 2013; and 4) further analysis of the obtained data, especially regarding benznidazole, and comparison of country estimates. RESULTS: Fourteen endemic countries of Latin America took part in the third stage, and a consolidated estimate was made. The number of estimated treatments, based on the number of tablets per treatment established in the regimen of reference was: 867 in the group under 1 year of age; 2 042 835 in the group from 1 to 15 years old; 2 028 in the group from 15 to 20 years old; and 10 248 in adults over 20. This means that it is possible to provide benznidazole to less than 1% of people for whom treatment is indicated. CONCLUSIONS: The development and systematic use of demand management tools can play a key role in helping to provide access to the anti-Chagas drugs. There is a significant gap between the projected demand for drugs and current estimates of prevalence rates.

Unveiling patenting strategies of therapeutics and vaccines: evergreening in the context of COVID-19 pandemic.

In the pharmaceutical sector, evergreening is considered a range of practices applied to extend monopoly protection on existing products. Filing several patent applications related to the same active pharmaceutical ingredient (API) is one of the most common manifestations of evergreening. During the COVID-19 pandemic, several health technologies were developed. This study aimed to analyze the extension of evergreening for selected health technologies for SARS-CoV-2 through patent filing strategies. Starting with the selection of three antivirals, one biological and two vaccines, a patent landscape was built based on public and private databases. Regarding these selected technologies, we analyzed some of the evergreening strategies used by different applicants, academic institutions or pharmaceutical companies and found a total of 29 applications (10 after the pandemic) for antivirals, 3 applications for a biological drug (1 after the pandemic), and 41 applications for vaccines (23 after the pandemic). Despite differences among the technologies, a common aspect found in all analyzed cases is the intense patent filing after the pandemic, aligned to the fact that those technologies were moving through the R&D process up to regulatory approval. The evergreening approach pursued has already been found in other diseases, with the risk of monopoly extension and also bringing legal uncertainty due to the lack of transparency of newer patent applications covering specific medical indications. Therefore, efforts to address evergreening should be pursued by countries, including the adoption of a public health approach to the patent examination of those technologies to prevent the granting of undeserved patents.

Pharmaceutical Services and comprehensiveness 30 years after the advent of Brazil's Unified Health System. / Assistência Farmacêutica nos 30 anos do SUS na perspectiva da integralidade.

This article examines pharmaceutical services and access to essential medicines in Brazil during the 30 years since the advent of Brazil's Unified Health System from a comprehensiveness perspective. The following topics are addressed: the "realignment" of pharmaceutical services; human resources in pharmaceutical services; the essential medicines concept; the rational use of medicines; technological advances and drug manufacturing; and ethical regulation. With a strong regulatory focus and a structural framework centered on the National Medicines Policy, the past three decades represent a mixture of progress and setbacks, considering the national complexities of the healthcare system and the political, economic and social changes that have influenced policy and access to medicines, which is a key concern even in the world's richest countries, as the forums of discussion on global health have demonstrated. We show that major steps forward have been taken, highlighting that the recent fiscal austerity measures imposed by the government threaten to seriously undermine social progress.

Os autores analisam a Assistência Farmacêutica (AF) e o acesso a medicamentos no Brasil na perspectiva do princípio da integralidade nos 30 anos do SUS. A partir da sua inclusão no movimento de reforma sanitária, foram selecionados temas relevantes, incluindo a reorientação da AF, a questão de recursos humanos, o conceito de medicamentos essenciais, o uso apropriado de medicamentos, o desenvolvimento tecnológico e a produção industrial e a regulação ética. Com fortes componentes regulatórios e tendo a política nacional de medicamentos como eixo estruturante, as três décadas do SUS são confrontadas entre avanços e retrocessos, considerando a complexidade nacional, as mudanças políticas, econômicas e sociais que impactaram políticas públicas e o acesso a medicamentos, tema que hoje mostra sua importância mesmo nas economias mais ricas do mundo, a partir de foros de discussão relacionados com Saúde Global. As conquistas ao longo do tempo são destacadas, considerando a preocupação decorrente do regime fiscal que compromete as áreas sociais.

[Evolution of the international intellectual property rights system: patent protection for the pharmaceutical industry and access to medicines]. / A evolução do sistema internacional de propriedade intelectual: proteção patentária para o setor farmacêutico e acesso a medicamentos.

This article discusses the evolution of the international intellectual property rights system in three phases and the implications for public health, especially for the implementation of policies for access to medicines. During the first phase, characterized by the Paris and Berne Convention, signatory countries defined which technological fields should be protected (or not). Under the second phase, with the enforcement of the WTO TRIPS Agreement, countries are obliged to grant patent protection for all technological fields, including for the pharmaceutical industry. Within their national legislations, countries also have the opportunity to implement access to TRIPS flexibilities for medicines. With the third phase, characterized by the negotiation and signing of bilateral and regional free trade agreements, countries will have to implement TRIPS-plus provisions which may have negative implications for the TRIPS flexibilities as well as for policies for access to medicines. The authors conclude that the currently proposed international intellectual property rights system favors patent-holder rights and that a balance is needed between patent holders' and health rights.

[Uncomplicated Plasmodium vivax and P. falciparum malaria in Brazil: evidence on single and combined drug treatments recommended by official guidelines]. / Malária não complicada por Plasmodium vivax e P. falciparum no Brasil: evidências sobre fármacos isolados e associações medicamentosas empregados em esquemas terapêuticos recomendados pelo protocolo terapêutico oficial.

Malaria is the most important endemic parasitic disease in the world. Conditions are favorable for transmission of the disease in 60% of Brazil's territory. Over 500,000 cases per year are recorded in the country. However, the geographic distribution is uneven, which may explain differences in the efficacy and effectiveness of antimalarial drugs. We conducted an extensive literature review of antimalarial treatment in Brazil from 1980 to 2005 in order to identify evidence that might have been available for the 2001 Edition of the Malaria Treatment Manual, the official Ministry of Health guidelines. Only a few studies, of low methodological quality, were identified by the search. None of the studies would have been capable of generating evidence-based guidelines according to the current classification of levels of pharmacological and clinical evidence. Studies published after 2001 drew on more evidence and are expected to provide the basis for the next edition of the manual, due in 2007. References in the 2001 Edition were outdated, possibly perceived as traditional references in the field, but lacking in specificity for region, population, and/or type of malaria.

Public procurement of hepatitis C medicines in Brazil from 2005 to 2015. / Compras públicas de medicamentos para hepatite C no Brasil no período de 2005 a 2015.

This paper analyzes the Minister of Health's (MoH) procurement of medicines for hepatitis C from 2005 to 2015. Data sources were the Integrated General Services Administration (SIASG), to estimate annual expenditure for selected medicines of the MoH Clinical Protocols and Therapeutic Guidelines (PCDT) for Hepatitis C. All presentations and strengths recorded on SIASG were included. The unit prices were estimated based on the purchase with the highest volume each year. There was a 159.5 fold increase in expenditure of the selected medicines from 2005 to 2006, because procurement of those medicines became centralized. In 2007 there was 730% increase in spending due to the incorporation of pegainterferons alfa 2a and 2b. In 2012 the purchase of only two new direct-acting antivirals (DAA) accounted for 99% of total annual expenditure. In 2015 the adoption of a new DAA led to an increase of 230% (R$945 million) in MoH spending. The significant increase of MoH expenditure on medicines for hepatitis C from 2005 to 2015 was due to the increase of volumes purchased as well as the incorporation of alfapeginterferon and new DAAs. Ensuring universal access to treatment for hepatitis C will depend on the implementation of strategies that strengthen the MoH's bargaining power in price reduction negotiations with the manufacturers of monopoly medicines.

Challenges in a product development partnership: a malaria treatment case study. / Desafios de uma parceria para o desenvolvimento de produtos: o caso de um tratamento para malária.

This paper examines the development of a treatment - a fixed-dose combination of artesunate and mefloquine - in Brazil, from three points of view: in terms of access to medication; to record and report successes; and to look at the lessons learned. This product development took place in the ambit of a public-private partnership. Semi-structured interviews were held with key actors involved in the different phases of the development, and documents were analyzed. Two important points of reference orienting the design of the study and analysis were: a logical model for access to medication; and evaluation of programs. It is concluded that there were several successes over the course of the project, but insufficient attention was given in the project's architecture to planning of adoption of the product: irregularities in demand caused difficulties in planning and production, and adoption of the product was irregular in the Americas. It is concluded that the project can be considered to have been successful: the product was created, and the aims were met - strengthening of institutional and individual capacities and alliances, and advocacy. However, there were weaknesses in the process, which need to be mitigated in future projects of the same type.

National Medicines Policy in retrospective: a review of (almost) 20 years of implementation. / Política Nacional de Medicamentos em retrospectiva: um balanço de (quase) 20 anos de implementação.

Pharmaceutical services and the formulation of a medicines policy are SUS areas ensured by the organic health care law 8,080/90. Thus, after a widely participative process, involving stakeholders, the National Medicines Policy (NMP) was approved in 1998 by Ordinance 3,916.The NMP presents directives and priorities, aligned with organic health care law, which should guide the federal, states and municipals entities actions to achieve the policy goals. Considering almost 20 years of the NMP, this paper took stock discussed some of the directives in light of the SUS principles. It was not the objective to provide an exhaustive review of all the activities performed during this period. The authors tried to get close to those that have brought advances and dilemmas, with potential risk of regression. Efforts to implement an ambitious agenda applied to pharmaceutical services were identified. This agenda tried to deal with different challenges like the dynamics of the pharmaceutical market and the operation of pharmaceutical services to guarantee the supply of medicines aligned with principles and directives of SUS.

Farmácia Popular Program: pharmaceutical market analysis of antihypertensive acting on the renin-angiotensin system medicines.

This paper aims to analyse changes in the retail pharmaceutical market following policy changes in the Farmácia Popular Program (FP), a medicines subsidy program in Brazil. The retrospective longitudinal analyses focus on therapeutic class of agents acting on the renin-angiotensin system. Data obtained from QuintilesIMS (formerly IMS Health) included private retail pharmacy sales volume (pharmaceutical units) and sales values from 2002 to 2013. Analyses evaluated changes in market share following key FP policy changes. The therapeutic class was selected due to its relevance to hypertension treatment. Market share was analysed by therapeutic sub-classes and by individual company. Losartan as a single product accounted for the highest market share among angiotensin II antagonists. National companies had higher sales volume during the study period, while multinational companies had higher sales value. Changes in pharmaceutical market share coincided with the inclusion of specific products in the list of medicines covered by FP and with increases in or exemption from patient copayment.

Initiatives to challenge patent barriers and their relationship with the price of medicines procured by the Brazilian Unified National Health System. / Iniciativas de enfrentamento da barreira patentária e a relação com o preço de medicamentos adquiridos pelo Sistema Único de Saúde.

Since 1996, when antiretroviral (ARV) treatments started being guaranteed to people living with HIV in Brazil, the government has faced the challenge of ensuring sustainability of this policy within a context of incorporating patented medicines. This article sought to analyze the historical series of the price of lopinavir/ritonavir (LPV/r) in Brazil and in the international market also considering the initiatives to challenge patent barriers between 2001 and 2012. The methods used were mapping initiatives to challenge LPV/r patent barriers and the analysis of historical series of its price in Brazil and in the international market. Results show that, between 2001 and 2003, there were efforts to use compulsory licensing as a threat. From 2005 to 2007, initiatives by different satkeholders were identified: declaration of public interest, pre-grant opposition ("support to examination") and civil action. From 2006 to 2008, compulsory licensing initiatives in other countries resulted in a price reduction in Brazil. Between 2009 and 2012, there was a 30% reduction in the Brazilian purchasing price.

[Induction of hospital indebtedness due to medicine purchases under monopoly conditions: the case of imatinib mesylate]. / Indução de endividamento hospitalar na compra de medicamento em situação de monopólio: o caso do mesilato de imatinibe.

Medicine expenditures consume a large share of the health budget, so knowledge on the use of these funds is essential for decision-making in public health and improvement of pharmaceutical care. This study analyzed the indebtedness of a high-complexity university hospital due to increased spending on imatinib mesylate. The descriptive study was based on analysis of documents and records in the Hospital Information System (SIH) from 2002 to 2010. Starting with inclusion of the medicine in the budget, the study mapped strategies by the pharmaceutical industry and government, as well as government responses to reduce the product's price. The systematization and publication of information stored in files and electronic databases can help monitor the results of programs funded by the Brazilian Ministry of Health.

Strategies for price reduction of HIV medicines under a monopoly situation in Brazil.

OBJECTIVE: To analyze Government strategies for reducing prices of antiretroviral medicines for HIV in Brazil. METHODS: Analysis of Ministry of Health purchases of antiretroviral medicines, from 2005 to 2013. Expenditures and costs of the treatment per year were analyzed and compared to international prices of atazanavir. Price reductions were estimated based on the terms of a voluntary license of patent rights and technology transfer in the Partnership for Productive Development Agreement for atazanavir. RESULTS: Atazanavir, a patented medicine, represented a significant share of the expenditures on antiretrovirals purchased from the private sector. Prices in Brazil were higher than international references, and no evidence was found of a relationship between purchase volume and price paid by the Ministry of Health. Concerning the latest strategy to reduce prices, involving local production of the 200 mg capsule, the price reduction was greater than the estimated reduction. As for the 300 mg capsule, the amounts paid in the first two years after the Partnership for Productive Development Agreement were close to the estimated values. Prices in nominal values for both dosage forms remained virtually constant between 2011 (the signature of the Partnership for Productive Development Agreement), 2012 and 2013 (after the establishment of the Partnership). CONCLUSIONS: Price reduction of medicines is complex in limited-competition environments. The use of a Partnership for Productive Development Agreement as a strategy to increase the capacity of local production and to reduce prices raises issues regarding its effectiveness in reducing prices and to overcome patent barriers. Investments in research and development that can stimulate technological accumulation should be considered by the Government to strengthen its bargaining power to negotiate medicines prices under a monopoly situation.

Resistência a Antimicrobianos: a formulação da resposta no âmbito da saúde global / Antimicrobial Resistance: formulation of the response in the global health context

RESUMO A Resistência a Antimicrobianos (AMR) tem se revelado como um dos maiores problemas para a saúde pública no nível global. O objetivo deste artigo foi analisar a formulação da resposta à AMR negociada no âmbito da Organização Mundial da Saúde (OMS) por seus Estados-Membros. Foram analisados os relatórios e resoluções produzidos na Assembleia Mundial da Saúde no período de 1998 a 2019. Os achados indicam que, a partir de 2014, foram estabelecidas condições de possibilidade para a aprovação do Plano de Ação Global em AMR de forma mais robusta, abrangendo o conceito de Saúde Única e envolvendo outras instâncias internacionais (FAO, OIE, OMC e PNUMA). A análise dos conteúdos e o uso de diferentes referenciais analíticos, considerando dois setores econômicos - agropecuária e indústria farmacêutica -, mostraram-se relevantes para ilustrar a complexidade da temática, reforçando sua relevância global, reconhecendo a dimensão do uso de antibióticos em animais e as lacunas em inovação tecnológica. Como a OMS, além de ser um importante agente mobilizador para a resposta à AMR no nível global, tem garantido orçamento para ações nessa área mesmo em um contexto de desfinanciamento, conclui-se que a perspectiva da saúde pública deve prevalecer na resposta à AMR.

ABSTRACT Antimicrobial Resistance (AMR) has proved to be a major public health problem at the global level. This paper examined the formulation of the response to AMR negotiated through the World Health Organization (WHO) by its Member States. Related WHO reports and resolutions from 1998 to 2019 were analysed. The findings indicate that, from 2014 on, more robust conditions were established for approval of a Global Action Plan on AMR, encompassing the concept of One Health and involving other international entities (FAO, OIE, WTO and Unep). Content analysis and various analytical frameworks, considering two economic sectors (the livestock and pharmaceutical industries), proved relevant to illustrating the complexity of the issue, reinforcing its global importance and acknowledging the extent of antibiotic use in animals and the gaps in technological innovation. As the WHO is not only an important agent for mobilizing the response to AMR at the global level, but - despite a context of de-funding - has guaranteed a budget for action in this area, it is concluded that the public health perspective should prevail in the response to AMR.

Desabastecimento de medicamentos na literatura científica da saúde: uma revisão narrativa / Medicines shortage in medical scientific journals: a literature review

Resumo O desabastecimento de medicamentos já é considerado um problema de saúde pública e representa um obstáculo importante para a garantia do acesso a eles e, consequentemente, do direito à saúde. Sendo assim, com o intuito de compreender melhor esse fenômeno, este artigo buscou identificar, descrever e caracterizar as publicações científicas da saúde que versam sobre o tema de desabastecimento de medicamentos e identificar as lacunas de pesquisa. Para tanto, realizou-se revisão narrativa da literatura científica na base de dados PubMed. Os resultados foram selecionados de acordo com o título e resumo, e os dados foram extraídos do texto completo. Além de uma análise quantitativa, também foi realizada uma síntese qualitativa dos estudos, explicitando as principais causas, estratégias de enfrentamento, discussões conceituais e a descrição do problema contido nas publicações incluídas. Foram analisados 98 artigos, a maioria foi publicada a partir do ano de 2011, nos EUA, citando diversos medicamentos e com o foco na descrição do problema. Os resultados deste estudo sugerem a contemporaneidade do problema, o uso da literatura científica como denúncia e a falta de estudos sobre o tema em países de baixa e média renda e que se voltem a compreender suas causas.

Abstract The shortage of medicines is already considered a public health problem that affects several regions worlwide and is a major obstacle to ensure access to medicines and, consequently, the right to health. Thus, in order to better understand this phenomenon, this article sought to identify, describe and characterize the medical scientific publications that deal with the issue of medicines shortages and to identify the gaps on this theme. For that, a narrative review of the medical scientific literature was carried out in the PubMed database. The results were selected according to the title and abstract, and the data were extracted from the full text. In addition to quantitative analysis, a qualitative synthesis of the studies was also performed, identifying the mentioned causes, coping strategies, conceptual discussions and problem description. We analyzed 98 papers, most of them published since the year 2011, in the United States, citing various drugs and with a focus on describing the problem. The results of this study suggest the contemporaneous of the problem, the use of scientific literature as drug shortages denunciation, the lack of studies in low- and middle-income settings, and a gap in studies that investigates the causes of medicines shortages.

Redução de preço de medicamento em situação de monopólio no Sistema Único de Saúde: o caso do Tenofovir / Price reduction of monopoly medicine in the Unified Health System: the case of Tenofovir

Resumo O objetivo do estudo é analisar a evolução do preço do tenofovir (TDF) no Brasil à luz das diferentes iniciativas para sua redução. Os critérios para a seleção do caso foram: ter sido objeto de pelo menos uma estratégia de enfrentamento da barreira patentária, que no caso foi o subsídio ao exame do pedido da patente (oposição à patente); e ter sido objeto de uma Parceria para Desenvolvimento Produtivo (PDP) para produção local. Os principais resultados sugerem que os subsídios ao exame apresentados em 2005 e 2006 contribuíram para a decisão de indeferimento do pedido de patente em 2009. Estima-se que o Brasil pagou cerca de US$ 200 milhões a mais pelo monopólio gerado a partir de um pedido de patente pendente. Houve uma redução do preço do TDF entre 2003 e 2013, inclusive durante a vigência da PDP (2011 a 2013). Em 2010, após o anúncio da PDP, também houve uma diminuição de 40% no preço do TDF ofertado pela Gilead, que refletiu no preço de oferta do produto PDP. No entanto, o preço pago no Brasil para o produto nacional foi cerca de dez vezes mais caro que o genérico ofertado internacionalmente.

Abstract This study aimed to analyze the evolution of the price of tenofovir (TDF) in Brazil considering the different initiatives for its reduction. The selection criteria for the case were: to have been subject to at least one strategy to overcome patent barrier, which in the case was the support to examination of the patent application (patent opposition); and have been subject of a local production Partnership for Productive Development (PDP). The main results suggest that patent opposition presented in 2005 and 2006 contributed to the decision to reject the patent application in 2009. Brazil is estimated to have paid around US$ 200 million more for the monopoly due to the patent pending application period. There was a reduction in the price of TDF between 2003 and 2013, including during the PDP (2011 to 2013). In 2010, after the PDP announcement, there was an additional 40% decrease in the price of the TDF offered by Gilead, which reflected in the price offered by the PDP. However, the price paid in Brazil for the national product was about ten times higher than the generic offered internationally.

Assistência Farmacêutica nos 30 anos do SUS na perspectiva da integralidade / Pharmaceutical Services and comprehensiveness 30 years after the advent of Brazil's Unified Health System

Resumo Os autores analisam a Assistência Farmacêutica (AF) e o acesso a medicamentos no Brasil na perspectiva do princípio da integralidade nos 30 anos do SUS. A partir da sua inclusão no movimento de reforma sanitária, foram selecionados temas relevantes, incluindo a reorientação da AF, a questão de recursos humanos, o conceito de medicamentos essenciais, o uso apropriado de medicamentos, o desenvolvimento tecnológico e a produção industrial e a regulação ética. Com fortes componentes regulatórios e tendo a política nacional de medicamentos como eixo estruturante, as três décadas do SUS são confrontadas entre avanços e retrocessos, considerando a complexidade nacional, as mudanças políticas, econômicas e sociais que impactaram políticas públicas e o acesso a medicamentos, tema que hoje mostra sua importância mesmo nas economias mais ricas do mundo, a partir de foros de discussão relacionados com Saúde Global. As conquistas ao longo do tempo são destacadas, considerando a preocupação decorrente do regime fiscal que compromete as áreas sociais.

Abstract This article examines pharmaceutical services and access to essential medicines in Brazil during the 30 years since the advent of Brazil's Unified Health System from a comprehensiveness perspective. The following topics are addressed: the "realignment" of pharmaceutical services; human resources in pharmaceutical services; the essential medicines concept; the rational use of medicines; technological advances and drug manufacturing; and ethical regulation. With a strong regulatory focus and a structural framework centered on the National Medicines Policy, the past three decades represent a mixture of progress and setbacks, considering the national complexities of the healthcare system and the political, economic and social changes that have influenced policy and access to medicines, which is a key concern even in the world's richest countries, as the forums of discussion on global health have demonstrated. We show that major steps forward have been taken, highlighting that the recent fiscal austerity measures imposed by the government threaten to seriously undermine social progress.

Assistência Farmacêutica nos 30 anos do SUS na perspectiva da integralidade / Pharmaceutical Services and comprehensiveness 30 years after the advent of Brazil's Unified Health System

Os autores analisam a Assistência Farmacêutica (AF) e o acesso a medicamentos no Brasil na perspectiva do princípio da integralidade nos 30 anos do SUS. A partir da sua inclusão no movimento de reforma sanitária, foram selecionados temas relevantes, incluindo a reorientação da AF, a questão de recursos humanos, o conceito de medicamentos essenciais, o uso apropriado de medicamentos, o desenvolvimento tecnológico e a produção industrial e a regulação ética. Com fortes componentes regulatórios e tendo a política nacional de medicamentos como eixo estruturante, as três décadas do SUS são confrontadas entre avanços e retrocessos, considerando a complexidade nacional, as mudanças políticas, econômicas e sociais que impactaram políticas públicas e o acesso a medicamentos, tema que hoje mostra sua importância mesmo nas economias mais ricas do mundo, a partir de foros de discussão relacionados com Saúde Global. As conquistas ao longo do tempo são destacadas, considerando a preocupação decorrente do regime fiscal que compromete as áreas sociais.