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.

Government spending on antiretrovirals in Brazil and its main determinants / Gastos governamentais com antirretrovirais no Brasil e seus principais determinantes

The construction of public policies for the prevention and treatment of HIV/AIDS in Brazil is a history of struggle that unites sanitarians, researchers and activists since the 1980s. An important part of this path is linked to the production and distribution of antiretroviral drugs (ARV), initiatives to reduce the price of ARVs and civil society mobilizations for the guarantee of rights, which contributed to create one of the most successful programs to combat the disease in the country. world. Based on this history, this study aimed to analyze government spending on the acquisition of selected ARVs in the period between 2005 and 2020, making a comparison with international prices, in the light of determinants related to patent disputes, voluntary licensing, PDPs and ARV price reduction initiatives. Among other results, it was possible to observe that there was no immediate relationship between the end of the patent concession and the reduction of prices. Filings of other patent applications and the lack of nationally registered competitors, even after patent expiration, can be significant factors in maintaining high prices.

A construção de políticas públicas para a prevenção e tratamento do HIV/Aids no Brasil é uma história de luta que une sanitaristas, pesquisadores e ativistas desde os anos 1980. Parte importante desse caminho está ligado à produção e distribuição de medicamentos antirretrovirais (ARV), iniciativas de redução do preço dos ARV e mobilizações da sociedade civil pela garantia de direitos, que contribuíram para criar um dos programas mais bem-sucedidos de combate à doença no mundo. Com base nesse histórico, este trabalho teve por objetivo analisar os gastos governamentais na aquisição de ARV selecionados no período entre 2005 e 2020, fazendo uma comparação com preços internacionais, à luz dos determinantes relacionados às disputas patentárias, ao licenciamento voluntário, às PDPs e às iniciativas para redução de preços de ARVs. Entre outros resultados, foi possível observar que não houve uma relação imediata entre o fim da concessão patentária e a redução de preços. Depósitos de outros pedidos de patente e a inexistência de concorrentes registrados nacionalmente, mesmo após a expiração da patente, podem ser fatores significativos para a manutenção de altos preços.

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.

Iniciativas de enfrentamento da barreira patentária e a relação com o preço de medicamentos adquiridos pelo Sistema Único de Saúde / Iniciativas para enfrentarse a la barrera patentaria y su relación con el precio de medicamentos adquiridos por el Sistema Único de Salud / Initiatives to challenge patent barriers and their relationship with the price of medicines procured by the Brazilian Unified National Health System

Resumo: Desde 1996, com a consolidação da oferta do tratamento antirretroviral (ARV) às pessoas vivendo com HIV no Brasil, o governo tem como desafio assegurar a sustentabilidade desta oferta num contexto de incorporação de medicamentos patenteados. O artigo teve como objetivo analisar a série histórica do preço do lopinavir/ritonavir (LPV/r) no Brasil e no mercado internacional à luz de iniciativas de enfrentamento da barreira patentária no período de 2001 a 2012. A metodologia consistiu em mapeamento de iniciativas de enfrentamento da barreira patentária para o LPV/r e análise da série histórica do preço no Brasil e no mercado internacional. Os resultados encontrados apontam que, entre 2001 e 2003, identificaram-se esforços de ameaça de licença compulsória. De 2005 a 2007, identificaram-se iniciativas por diferentes atores: declaração de interesse público, subsídios ao exame e ação civil pública. De 2006 e 2008, iniciativas internacionais de licença compulsória resultaram na redução do preço no Brasil. Entre 2009 e 2012, observa-se uma redução do preço de aquisição pelo Brasil de 30%.

Resumen: Desde 1996, con la consolidación de la oferta de tratamiento antirretroviral (ARV) para las personas viviendo con VIH, el Gobierno de Brasil tiene el desafío de asegurar la sostenibilidad de dicha oferta en un contexto de incorporación de medicamentos patentados. El objetivo de este artículo es analizar la serie histórica del precio del lopinavir/ritonavir (LPV/r) en Brasil y en el mercado internacional, a la luz de iniciativas para enfrentar la barrera patentaria durante el período de 2001 a 2012. La metodología consistió en un mapeo de iniciativas para hacer frente a la barrera patentaria del LPV/r y el análisis de la serie histórica de sus precios de adquisición por el SUS y en el mercado internacional. Entre 2001 y 2003 se identificaron esfuerzos por obtener reducciones de precio de LPV/r, mediante la amenaza de expedición de licencia obligatoria. De 2005 a 2007, se identificaron varias iniciativas de diferentes actores, tales como, la expedición de declaración de interés público, preseentación de subsidios para el examen de solicitudes de patente de este medicamento y la interpesición de acción civil pública. Entre 2006 y 2008, la expedición de licencias obligatorias en el marco de iniciativas internacionales, propiciaron reducciones de precio de LPV/r en Brasil. La reducción promedio del precio de adquisición por parte SUS fue de 30% entre 2009 y 2012.

Abstract: 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.

Indução de endividamento hospitalar na compra de medicamento em situação de monopólio: o caso do mesilato de imatinibe / Induction of hospital indebtedness due to medicine purchases under monopoly conditions: the case of imatinib mesylate / Inducción de la deuda hospitalaria en la compra de medicamentos en monopolio: el caso de mesilato de imatinib

Os gastos com medicamentos correspondem a uma grande parcela do orçamento em saúde. Sendo assim, a produção de conhecimento sobre o uso desses recursos é essencial na tomada de decisão em saúde pública e melhoria da assistência farmacêutica. Este estudo teve como objetivo analisar o processo de endividamento em um hospital universitário de alta complexidade devido ao gasto crescente com a aquisição de mesilato de imatinibe. Por meio de análise documental e registros no Sistema de Informações Hospitalares (SIH) entre 2002 e 2010, realizou-se um estudo descritivo. A partir do caminho da incorporação do medicamento, foram mapeadas as estratégias da indústria farmacêutica e do governo, assim como as respostas governamentais de redução do preço. A sistematização e publicação de informações guardadas em arquivos e na memória podem contribuir para o acompanhamento dos resultados dos programas mantidos pelo Ministério da Saúde.

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.

Los gastos en medicamentos representan una gran proporción del presupuesto de salud, por lo que la producción de conocimiento sobre el uso de estos recursos es esencial en la toma de decisiones en salud pública y la mejora de la atención farmacéutica. Este estudio tuvo como objetivo analizar el proceso de endeudamiento en un hospital universitario de alta complejidad, debido al aumento de los gastos en la adquisición de mesilato de imatinib. A través del análisis de los documentos y registros en el Sistema de Información Hospitalaria (SIH) entre 2002 y 2010, se realizó un estudio descriptivo. A partir de la incorporación del medicamento, se mapearon las estrategias de la industria farmacéutica y del gobierno, así como las respuestas del gobierno para reducir el precio. La sistematización y publicación de la información almacenada en los archivos y su memoria puede contribuir para el seguimiento de los resultados de los programas mantenidos por el Ministerio de Salud.

Analysis of clinical pharmacist interventions in a tertiary teaching hospital in Brazil.

OBJECTIVE: To analyze the clinical pharmacist interventions performed during the review of prescription orders of the Adult Intensive Care, Cardiologic Intensive Care, and Clinical Cardiology Units of a large tertiary teaching hospital in Brazil. METHODS: The analysis took place daily with the following parameters: dose, rate of administration, presentation and/or dosage form, presence of inappropriate/unnecessary drugs, necessity of additional medication, more proper alternative therapies, presence of relevant drug interactions, inconsistencies in prescription orders, physical-chemical incompatibilities/solution stability. From this evaluation, the drug therapy problems were classified, as well as the resulting clinical interventions. RESULTS: During the study, a total of 6,438 drug orders were assessed and 933 interventions were performed. The most prevalent drug therapy problems involved ranitidine (28.44%), enoxaparin (13.76%), and meropenem (8.26%). The acceptability of the interventions was 76.32%. The most common problem found was related to dose, representing 46.73% of the total. CONCLUSION: Our study showed that up to 14.6% of the prescriptions reviewed had some drug therapy problem and the pharmacist interventions have promoted positive changes in seven to ten of these prescriptions.

Análise das intervenções de farmacêuticos clínicos em um hospital de ensino terciário do Brasil / Analysis of clinical pharmacist interventions in a tertiary teaching hospital in Brazil

OBJECTIVE: To analyze the clinical pharmacist interventions performed during the review of prescription orders of the Adult Intensive Care, Cardiologic Intensive Care, and Clinical Cardiology Units of a large tertiary teaching hospital in Brazil. METHODS: The analysis took place daily with the following parameters: dose, rate of administration, presentation and/or dosage form, presence of inappropriate/unnecessary drugs, necessity of additional medication, more proper alternative therapies, presence of relevant drug interactions, inconsistencies in prescription orders, physical-chemical incompatibilities/solution stability. From this evaluation, the drug therapy problems were classified, as well as the resulting clinical interventions. RESULTS: During the study, a total of 6,438 drug orders were assessed and 933 interventions were performed. The most prevalent drug therapy problems involved ranitidine (28.44%), enoxaparin (13.76%), and meropenem (8.26%). The acceptability of the interventions was 76.32%. The most common problem found was related to dose, representing 46.73% of the total. CONCLUSION: Our study showed that up to 14.6% of the prescriptions reviewed had some drug therapy problem and the pharmacist interventions have promoted positive changes in seven to ten of these prescriptions.

OBJETIVO: Analisar as intervenções realizadas por farmacêuticos clínicos durante a revisão de prescrições médicas das Unidades de Terapia Intensiva Adulto, Terapia Intensiva Cardiológica e de Cardiologia Clínica de um hospital universitário terciário do Brasil. MÉTODOS: A análise de prescrições foi realizada diariamente com avaliação dos seguintes parâmetros: dose, intervalo de administração, apresentação e/ou forma farmacêutica, presença de medicamentos inapropriados/desnecessários, necessidade de medicamento adicional, alternativas terapêuticas mais adequadas, presença de interações medicamentosas relevantes, inconsistências nas prescrições, incompatibilidades físico-químicas/estabilidade da solução. A partir dessa avaliação, os problemas relacionados aos medicamentos foram classificados, bem como as intervenções farmacêuticas resultantes, conforme estabelecido pelo manual de farmácia clínica do hospital. RESULTADOS: Durante o estudo, um total de 6.438 prescrições foi avaliado e foram realizadas 933 intervenções farmacêuticas. Os medicamentos mais envolvidos nos problemas foram: ranitidina (28,44%), enoxaparina (13,76%) e meropenem (8,26%). A aceitação das intervenções foi de 76,32%. O problema mais comumente encontrado foi relacionado à dose, representando 46,73% do total. CONCLUSÃO: Até 14,6% das prescrições avaliadas apresentaram algum problema relacionado a medicamentos. As intervenções farmacêuticas promoveram mudanças positivas em sete a cada dez dessas prescrições.