Drug prices and trends before and after requesting compulsory licenses: the Ecuadorian experience.

Introduction: The Ecuadorian Institute of Intellectual Property (IEPI) granted several compulsory licenses between 2011 and 2017. In 2009, the President of Ecuador signed a decree that was intended to facilitate the request of compulsory licenses (CL) in the country, not only for Enfarma EP but for any privately owned local company in order to produce more accessible medicines. Areas covered: The national and international regulatory framework of pharmaceutical patents and the local applicability of CL in Ecuador. The authors also analyzed the results of requesting unplanned and epidemiologically unnecessary CL at a national level. Finally, the authors reviewed the effects of requesting, granting or denying CL on price per unit in the last 7 years of available data. Expert opinion: The authors think that compulsory licenses are useful tools when negotiating drug prices or when the demand cannot be satisfied due to economic constrain within the local health system. However, the authors' experience suggests that Ecuador did not have an established and reliable production system neither an adequate plan before requesting CL, therefore the positive effects of this measure were not clearly established.

Expedited pharma patenting in Brazil.

This article has the purpose of bringing an updated landscape on expedited protection of pharmaceutical patent applications in Brazil. The serious backlog of examination of patent applications in Brazil is a fact well known worldwide for a long time. In 2017, said backlog related to pharmaceutical patent applications achieved a mean time of about 11-13 years. On the other hand, there are alternatives to attempt to surpass such huge delay, based on official regulations for expediting examination, which have shown to be quite effective. Actual examples of pharmaceutical patents beneficiated from such fast track rules have received grant decisions within about 0.5-3.5 years counted from request for accelerated examination.

Participants' awareness of ethical compliance, safety and protection during participation in pharmaceutical industry clinical trials: a controlled survey.

BACKGROUND: The rapid increase of industry-sponsored clinical research towards developing countries has led to potentially complex ethical issues to assess. There is scarce evidence about the perception of these participants about the ethical compliance, security, and protection. We sought to evaluate and contrast the awareness and perception of participants and non-participants of industry-sponsored research trials (ISRT) on ethical, safety, and protection topics. METHODS: A Cases-control survey conducted at twelve research sites in México. Previous and current participants of ISRT (cases) as well as non-participants (controls) with one of four chronic diseases, were asked to complete the survey which focused on ethical compliance and protection issues of ISRT, and the perception of participating in a trial. RESULTS: A total of 604 cases and 604 controls were surveyed. Cases significantly answered that ethics committees are aware of what is happening in studies (50.5% vs. 33.8%, P = ≤ 0.001), and that medical care of industry-sponsored research trials is better than their usual medical care (77.2% vs. 38.2%, P = < 0.001). The same proportion of cases and controls thought patients must receive economical reimbursement for participating in a research study (49.5% vs. 53.1%, P = 0.205). The informed consent of the pharmaceutical clinical trial was fully read by 90.4% of the cases. Most cases were satisfied or very satisfied with their overall study participation (35.6 and 62.3%, respectively). CONCLUSION: Previous and current participants of industry-sponsored research trials have a more positive attitude towards ethics committees, the quality of medical care of the research trials, and the main purpose of economical reimbursements, when compared to non-participants.

Biosimilars: An Approach to some Current Worldwide Regulation Frameworks.

Developing new biologics has led to regulations and norms aimed at guaranteeing their safety, quality and effectiveness, in terms of marketing, prescription, use, interchangeability and switching. Biologics are of great importance in treating patients suffering from rheumatic, autoimmune, inflammatory and neoplastic diseases. The expiry/lapse of reference biologics or originators' patents has meant that developing biosimilars involves accompanying legal requirements for their approval in countries worldwide. This paper has thus approached the situation of biosimilar regulation worldwide, the pertinent technical concepts and regulatory differences in some countries of interest.

Where Is the Opioid Use Epidemic in Mexico? A Cautionary Tale for Policymakers South of the US-Mexico Border.

In North America, opioid use and its harms have increased in the United States and Canada over the past 2 decades. However, Mexico has yet to document patterns suggesting a higher level of opioid use or attendant harms.Historically, Mexico has been a country with low-level use of opioids, although heroin use has been documented. Low-level opioid use is likely attributable to structural, cultural, and individual factors. However, a range of dynamic factors may be converging to increase the use of opioids: legislative changes to opioid prescribing, national health insurance coverage of opioids, pressure from the pharmaceutical industry, changing demographics and disease burden, forced migration and its trauma, and an increase in the production and trafficking of heroin. In addition, harm-reduction services are scarce.Mexico may transition from a country of low opioid use to high opioid use but has the opportunity to respond effectively through a combination of targeted public health surveillance of high-risk groups, preparation of appropriate infrastructure to support evidence-based treatment, and interventions and policies to avoid a widespread opioid use epidemic.

Quality of medicines: Deficiencies found by Brazilian Health Regulatory Agency (ANVISA) on good manufacturing practices international inspections.

The circulation of poor quality medicines, especially in the developing countries, is a public health concern. Compliance with good manufacturing practices (GMP) is essential to ensure the quality, efficacy, and safety of medicines. This study evaluated the outcomes of the Brazilian Health Regulatory Agency's (ANVISA) international inspections of two years (2015 and 2016) and compared these to those of other regulatory authorities. The information from 255 inspection reports was analyzed, and the type and extent of deficiencies were collected. In the period evaluated, 62.75% of ANVISA-inspected companies were classified as GMP "satisfactory," 24.71% were classified as having "on demand" status, and 12.55% of inspections concluded that the company did not comply with Brazilian GMP regulations ("unsatisfactory"). The most common areas of deficiency were documentation (28.63%) and premises (26.27%). The pattern of deficiencies was similar to the findings of other regulatory agencies. However, ANVISA detected a more significant number of non-compliance results than other authorities, which may be caused by differences in classifications adopted by each Agency. Furthermore, manufacturers inspected by ANVISA may follow different standards and practices for products manufactured for the Brazilian market. Disclosure of main GMP deficiencies found can be useful for encouraging the industry to comply with GMP, and additional guidelines in the specific areas where deficiencies are often identified may be useful to industry to improve GMP compliance. Harmonization of GMP guidelines and inspection procedures are the key steps to avoid duplicate work, but regulatory authorities also need to work together to enforce the proper level of GMP compliance by pharmaceutical manufacturers, assuring high quality and safe medicines supply.

Patent portfolio management: literature review and a proposed model.

INTRODUCTION: Patents and patent portfolios are gaining attention in the last decades, from the called 'pro-patent era' to the recent billionaire transactions involving patent portfolios. The field is growing in importance, both theoretically and practically and despite having substantial literature on new product development portfolio management, we have not found an article relating this theory to patent portfolios. AREAS COVERED: The paper develops a systematic literature review on patent portfolio management to organize the evolution and tendencies of patent portfolio management, highlighting distinctive features of patent portfolio management. Interview with IP manager of three life sciences companies, including a leading multinational group provided relevant information about patent portfolio management. EXPERT OPINION: Based on the systematic literature review on portfolio management, more specifically, on new product development portfolio theory, and interview the paper proposes the paper proposes a reference model to manage patent portfolios. The model comprises four stages aligned with the three goals of the NPD portfolio management: 1 - Linking strategy of the Company's NPD Portfolio to Patent Portfolio; 2 - Balancing the portfolio in buckets; 3 - Patent Valuation (maximizing valuation); 4 - Regularly reviewing the patent portfolio.

A judicialização da Saúde na percepção de médicos prescritores / La judicialización de la salud en la percepción de los médicos prescriptores / The judicialization of Health in the perception of physician's prescribing

Este artigo analisa a possível interferência da indústria farmacêutica nas prescrições de medicamentos usadas em ações judiciais contra o Sistema Único de Saúde (SUS). Apresenta-se o levantamento que deu origem ao banco de dados com ações judiciais por medicamentos, procedimentos e equipamentos para o tratamento de diversas doenças contra o Estado de Minas Gerais. Justifica-se a análise da percepção dos prescritores, com intuito de conhecer as suas respectivas posições em relação ao tema da interferência da indústria farmacêutica nas tomadas de decisões relativas às ações judiciais. O modelo teórico e metodológico utilizado destaca os perfis dos entrevistados. Por fim, expõe-se, em detalhes, a análise das percepções dos prescritores, correlacionando-as com o tema da influência da indústria farmacêutica no atual crescimento das ações judiciais.(AU)

Este artículo analiza la posible interferencia de la industria farmacéutica en las prescripciones de medicamentos, utilizadas en acciones judiciales contra el Sistema Único de Salud (SUS). Se presenta el levantamiento que dio origen al banco de datos con procesos judiciales por medicamentos, procedimientos y equipos para el tratamiento de diversas enfermedades contra el Estado de Minas Gerais. Se justifica el análisis de la percepción de los prescriptores con el objetivo de conocer sus respectivas posiciones con relación al tema de la interferencia de la industria farmacéutica en las tomas de decisión relativas a los procesos judiciales. El modelo teórico y metodológico utilizado destaca los perfiles de los entrevistados. Finalmente, se expone en detalles el análisis de las percepciones de los prescriptores, correlacionándolas con el tema de la influencia de la industria farmacéutica en el crecimiento actual de los procesos judiciales.(AU)

This paper analyzes the possible interference of the pharmaceutical industry in prescriptions drugs used in lawsuits against the Brazilian National Health System (SUS). It presents the survey used to build the database with lawsuits by drugs, procedures and equipment for the treatment of various diseases against the State of Minas Gerais. It is the analysis of the perception of the prescribers in order to know their respective positions in relation to the theme of the interference of the pharmaceutical industry in decisionmaking relating to lawsuits. The theoretical model and methodology used highlights the profile of the interviewees. Finally, it exposes in detail the analysis of the perceptions of prescribers, correlating them with the topic of the influence of the pharmaceutical industry in the current growth of lawsuits.(AU)

[Dosing regimens in second medical use patents]. / Regimes de dosagem em patentes de segundo uso médico.

: In the pharmaceutical field, the development of new drugs requires sophisticated understanding of pathophysiological mechanisms in order to identify and characterize potential biomolecular targets and proceed with clinical trials. In this context, protection of research and development results is a vital stage for guaranteeing financial return on the heavy investments in the area. One strategy to achieve this objective is to exploit second-use patents, usually drafted in the format "use of compound X characterized by the fact that it is used in preparing a drug for disease Y". Considering the possible social impact and lack of specific guidelines in Brazil, this article reviews the principal cases related to dosing regimens in Europe and analyzes the positions of the European Patent Office (EPO) and German and UK judiciary systems on the requirements for patentability and scope of protection, aimed at contributing to the technical debate on the topic.

No campo farmacêutico, o desenvolvimento de novos fármacos exige um grau sofisticado de entendimento de mecanismos fisiopatológicos, a fim de identificar e caracterizar potenciais alvos biomoleculares e prosseguir com os estudos clínicos. Dentro desse contexto, a proteção dos resultados de Pesquisa & Desenvolvimento é uma etapa vital para garantir o retorno financeiro dos pesados investimentos na área. Uma das estratégias para atingir tal objetivo consiste na exploração de patentes de segundo uso médico, usualmente redigidas no formato "uso do composto X caracterizado pelo fato de ser empregado no preparo de medicamento para a doença Y". Considerando o possível impacto social e a ausência de diretrizes específicas no Brasil, o presente artigo revisa os principais casos relacionados a regimes de dosagem na Europa e analisa os posicionamentos do Escritório Europeu de Patentes (EPO) e judiciários alemão e do Reino Unido sobre os requisitos de patenteabilidade e escopo de proteção, visando a contribuir com o debate técnico sobre o assunto.

En el campo farmacéutico, el desarrollo de nuevos fármacos exige un grado de sofisticación en la comprensión de los mecanismos fisiopatológicos, con el fin de identificar y caracterizar potenciales objetivos biomoleculares y proseguir con los estudios clínicos. Dentro de este contexto, la protección de los resultados de Investigación y Desarrollo es una etapa vital para garantizar el retorno financiero de las costosas inversiones en este área. Una de las estrategias para alcanzar tal objetivo consiste en la explotación de patentes de segundo uso médico, habitualmente redactadas en el formato "uso del compuesto X, caracterizado por el hecho de ser empleado en la preparación del medicamento para la enfermedad Y". Considerando el posible impacto social, y la ausencia de directrices específicas en Brasil, el presente artículo revisa los principales casos relacionados con los regímenes de dosificación en Europa y analiza las posiciones adoptadas por la Oficina Europea de Patentes (EPO) y los sistemas judiciales alemanes y del Reino Unido sobre los requisitos de patentabilidad y alcance de la protección, con el objetivo de contribuir al debate técnico sobre este asunto.

[How much does the backlog on drug patents cost for health in Brazil?] / Quanto custa o atraso na concessão de patentes de medicamentos para a saúde no Brasil?

The backlog in processing patent applications in Brazil has persisted since the enactment of Law 9,279/1996, when the country resumed granting patents on drugs. The agencies responsible for granting such patents, namely the Brazilian National Patent and Trademark Office (INPI) and the Brazilian National Health Surveillance Agency (Anvisa) cite technical and administrative reasons for the backlog. However, little research has focused on the economic impacts for health due to the inefficiency of the Brazilian patent system. The current study thus proposes a methodology to estimate the extent to which government procurement of medicines is burdened by the backlog in drug patent applications. According to the results, a total of more than BRL 14 million (USD 4.5 million) is spent unnecessarily per year by the Federal Government on just one antiretroviral drug due to the extension of the respective patent's life. Measures to resolve this situation are urgently needed in the three branches of government. These include hiring more staff for the INPI, analysis of bills of law under review in the two houses of the Brazilian Congress to amend the Industrial Property Law, and ruling on direct class action claims of unconstitutionality to suppress the legal mechanisms that allow extending the life of patents.

The Brazilian phytotherapics industry: challenges and opportunities. / A indústria de fitoterápicos brasileira: desafios e oportunidades.

The purpose of this article is to discuss and analyze the development challenges of the medicinal plants and phytotherapics industry in Brazil. This industry represents an excellent alternative to face the paradox of abundance that exists in the health area. The methodology adopted was a field research, using semi-structured questionnaires with companies, researchers and public managers to evaluate their development between 2009 and 2015 and to point out the most serious problems faced. The results observed indicate that the main challenges found were the regulation of law on the access to the genetic patrimony in the research area, and to bring into harmony the rules in the entire chain of medicinal plants and phytotherapics production area. The slow implementation pace of public policies for the industry shows a setback regarding both productive and research activities with medicinal plants and phytotherapics in the period.

A indústria de fitoterápicos brasileira: desafios e oportunidades / The Brazilian phytotherapics industry: challenges and opportunities

Resumo O objetivo deste artigo é discutir e analisar os desafios do desenvolvimento da indústria de plantas medicinais e de fitoterápicos no Brasil. Esta indústria representa uma excelente alternativa para responder ao paradoxo da abundância na área de saúde. A metodologia adotada foi uma pesquisa de campo, utilizando-se questionários semiestruturados, com empresas, pesquisadores e gestores públicos para avaliar seu desenvolvimento entre 2009 e 2015 e apontar seus principais problemas. Os resultados observados indicam que os principais desafios são, na pesquisa, a regulamentação da lei de acesso ao patrimônio genético e, na produção, a harmonização da regulamentação em toda a cadeia produtiva da indústria de plantas medicinais e fitoterápicos. A morosidade da implantação das políticas públicas voltadas para a indústria mostra um retrocesso tanto das atividades produtivas com fitoterápicos, quanto das atividades de pesquisa com plantas medicinais no período.

Abstract The purpose of this article is to discuss and analyze the development challenges of the medicinal plants and phytotherapics industry in Brazil. This industry represents an excellent alternative to face the paradox of abundance that exists in the health area. The methodology adopted was a field research, using semi-structured questionnaires with companies, researchers and public managers to evaluate their development between 2009 and 2015 and to point out the most serious problems faced. The results observed indicate that the main challenges found were the regulation of law on the access to the genetic patrimony in the research area, and to bring into harmony the rules in the entire chain of medicinal plants and phytotherapics production area. The slow implementation pace of public policies for the industry shows a setback regarding both productive and research activities with medicinal plants and phytotherapics in the period.

Quanto custa o atraso na concessão de patentes de medicamentos para a saúde no Brasil? / How much does the backlog on drug patents cost for health in Brazil? / ¿Cuánto cuesta el atraso en las patentes de medicamentos para la salud en Brasil?

Resumo: O backlog na análise de pedidos de patentes é um problema que persiste desde a promulgação da Lei nº 9.279/1996, quando o Brasil passou a conceder patentes para medicamentos novamente. Os órgãos responsáveis pela concessão dessas patentes, Instituto Nacional da Propriedade Industrial (INPI) e Agência Nacional de Vigilância Sanitária (Anvisa), alegam motivos técnico-administrativos para justificar o atraso. No entanto, os impactos econômicos para a saúde devido à ineficiência do sistema de patentes brasileiro ainda foram pouco investigados. Assim sendo, este trabalho propõe uma metodologia para estimar o quanto as compras públicas de medicamentos são oneradas em função da morosidade na análise dos pedidos de patentes no país. Os resultados mostram que mais de R$ 14 milhões são gastos desnecessariamente anualmente pelo Governo Federal com apenas um medicamento antirretroviral por causa da extensão da vigência das patentes. Conclui-se que medidas governamentais de controle dessa situação são prementes no âmbito dos Três Poderes. Dentre elas, destacam-se a contratação de servidores para o INPI, análise dos projetos de lei que tramitam na Câmara dos Deputados e Senado Federal para a alteração da Lei da Propriedade Industrial, e julgamento das Ações Diretas de Inconstitucionalidade para a supressão do dispositivo legal que possibilita a extensão da vigência das patentes.

Abstract: The backlog in processing patent applications in Brazil has persisted since the enactment of Law 9,279/1996, when the country resumed granting patents on drugs. The agencies responsible for granting such patents, namely the Brazilian National Patent and Trademark Office (INPI) and the Brazilian National Health Surveillance Agency (Anvisa) cite technical and administrative reasons for the backlog. However, little research has focused on the economic impacts for health due to the inefficiency of the Brazilian patent system. The current study thus proposes a methodology to estimate the extent to which government procurement of medicines is burdened by the backlog in drug patent applications. According to the results, a total of more than BRL 14 million (USD 4.5 million) is spent unnecessarily per year by the Federal Government on just one antiretroviral drug due to the extension of the respective patent's life. Measures to resolve this situation are urgently needed in the three branches of government. These include hiring more staff for the INPI, analysis of bills of law under review in the two houses of the Brazilian Congress to amend the Industrial Property Law, and ruling on direct class action claims of unconstitutionality to suppress the legal mechanisms that allow extending the life of patents.

Resumen: El atraso en el procesamiento de solicitudes de patentes en Brasil ha persistido desde la promulgación de la Ley 9.279/1996, cuando el país reanudó la concesión de patentes sobre drogas. Los organismos encargados de otorgar las patentes, a saber, la Oficina Nacional de Patentes y Marcas (INPI) y la Agencia Nacional de Vigilancia Sanitaria (Anvisa), alegan motivos técnico-administrativos para justificar el retraso. Sin embargo, poca investigación se ha centrado en los impactos económicos para la salud debido a la ineficiencia del sistema brasileño de patentes. El presente estudio propone una metodología para estimar el grado en que la contratación pública de medicamentos está cargada con el atraso en las solicitudes de patente de medicamentos. De acuerdo con los resultados, el gobierno federal gasta innecesariamente un total de más de BRL 14 millones (USD 4.5 millones) por un solo medicamento antirretroviral debido a la extensión de la vida de la respectiva patente. Las medidas para resolver esta situación son urgentemente necesarias en las tres ramas del gobierno. Estos incluyen la contratación de más personal para la INPI, el análisis de los proyectos de ley en revisión en las dos cámaras del Congreso brasileño para enmendar la Ley de Propiedad Industrial, y la decisión sobre demandas de acción colectiva directa de inconstitucionalidad para suprimir los mecanismos legales que permiten extender la vida de las patentes.

Postmarketing Surveillance Studies-An Industry Perspective on Changing Global Requirements and Implications.

PURPOSE: This article describes postmarketing surveillance (PMS) study regulations and expectations of the regulatory agencies in 5 countries. With a focus on postapproval drug safety, there is a continuous need for understanding the benefit-risk profile of an approved drug. In addition to spontaneous adverse-event reporting, regulatory agencies seem to be more reliant on PMS studies. The opportunity to systematically monitor use in special populations, such as elderly patients and those with comorbid conditions, also presents itself during postmarketing use. Regulatory agencies in Japan, the Republic of Korea, and Mexico are requiring such studies as standards or conditions of drug approvals and license renewals. These studies are meant to be observational and noninterventional, over specified time periods. Studies are required specifically for following up treated patients in clinical practice, with the main objective of collecting safety data to further characterize the benefit-risk profile that was established during clinical trials and particularly in the country-specific population. METHODS: We reviewed and compared the published PMS guidelines and requirements in Japan, the Republic of Korea, the People's Republic of China, India, and Mexico. Interpretations of the guidelines and requirements are included and are based on direct interactions with the different regulatory agencies. FINDINGS: We note that the different country PMS guidelines are at varying points in development. While some countries have more comprehensive guidelines, in others, the guidelines are still evolving. The similarities among guidelines include the requirements of the content and format of protocols, periodic reports, and interim reports of PMS studies. The differences in the requirements of PMS studies, such as sample size and study duration, are noticeable. These protocols are to be submitted, together with the respective risk-management plans, for approval by the regulatory authority prior to implementation of the study. IMPLICATIONS: Conventional drug discovery and approval processes are well understood, and there are ample regulatory guidelines and International Conference of Harmonisation-based reference documents for understanding the path of the drug-approval process. Limited information is currently available with regard to the regulations and how PMS studies should be developed and evaluated. Some of the country-specific elements included can inform readers while they prepare to develop and implement PMS study protocols.

Main Reasons for Registration Application Refusal of Generic and Similar Pharmaceutical Drug Products by the Brazilian Health Regulatory Agency (ANVISA).

Objective. The marketing authorization of generic and similar pharmaceutical drug products involves the analysis of proposing company's administrative aspects as well as drug product technical description and scientific evaluations. This study evaluated the main reasons for registration refusal of generic and similar pharmaceutical drug products in Brazil. The aim is to help future applicants to better organize the proposal. Methods. A retrospective search of drug products registration processes was performed on the Brazilian Government Official Gazette from January 1, 2015, and December 31, 2015. Results. Drug product quality control, drug product stability study, deadline accomplishment, API quality control made by drug manufacturer, active pharmaceutical ingredient (API), and production report were the main reasons for marketing authorization application refusal of generic and similar pharmaceutical drug products in 2015. Conclusion. Disclosure of the reasons behind failed applications is a step forward on regulatory transparency. Sharing of experiences is essential to international regulatory authorities and organizations to improve legislation requirements for the marketing authorization of generic and similar pharmaceutical drug products.

Evaluating the Usefulness of Compulsory Licensing in Developing Countries: A Comparative Study of Thai and Brazilian Experiences Regarding Access to Aids Treatments.

While compulsory licensing (CL) is described in the TRIPS agreement as flexibility to protect public health by improving access to medicines in developing countries, a recent literature contends adversely that CL may harm public health. Therefore, this article intends to evaluate the usefulness of CL in the South through the prism of obligations and goals entrusted to patent holders (the effective and non-abusive exploitation of patents in order to achieve industrial and health developments) and in light of experiences in Thailand and Brazil regarding access to antiretroviral drugs. In this way, it shows that the obligations assigned to patent holders were better served by the recipients of CL and brought significant health and industrial benefits in the two high middle-income countries. In particular, CL allowed the scaling-up of free and universal access to antiretroviral drugs by assuring the financial sustainability of these public health programs endangered by monopolistic practices from patent holders.