Culturable microbiological profile of a non-sterile drugs pharmaceutical production environment

Abstract For places where non-sterile drug production occurs, regulatory bodies recommend monitoring of the environmental bioburden. This procedure provides information regarding possible microbiological risks to which the products may be exposed, so that subsequent action measures may be implemented. The aim of the present work was to quantify and characterize the microorganisms present in Grade D (ISO 8) cleanrooms of a Brazilian pharmaceutical industry, identifying any possible seasonal climatic influences on these environments. Sampling was performed by surface and air monitoring, over 12 months during the year 2019, in rooms that were in operation. For both sampling methods, no statistically significant differences in bacteria and fungi counts were found between months or seasonal periods. Microorganisms that presented higher incidence included Staphylococcus epidermidis (15%) and Micrococcus spp. (13%), common to the human microbiota, and the fungi Cladosporium sp. (23%) and Penicillium sp. (21%), typical of the external environment. The results showed that microbial contamination in the Grade D cleanrooms was within the permissible maximum levels and remained similar throughout the year. Microbiological quality control in the clean areas of the pharmaceutical industry investigated was considered effective, with regular maintenance being necessary to keep bioburden levels controlled.

Política industrial farmacéutica, un requisito clave para la autonomía sanitaria de Colombia / Pharmaceutical industrial policy, a key requirement for health autonomy in Colombia

Colombia depende de la importación de medicamentos, así como de gran parte de los materiales (principios activos y excipientes) requeridos para su elaboración; problemática que genera consecuencias sanitarias y macroeconómicas, las cuales se agudizan en el contexto de desindustrialización nacional y de disrupción tecnológica. De esta manera, se acepta que la disponibilidad y acceso a medicamentos y otras tecnologías sanitarias esenciales son un requisito fundamental para alcanzar la autonomía sanitaria de un país. Por lo tanto, resulta imprescindible coordinar esfuerzos entre diversos sectores sociales para desarrollar una agenda pública enfocada a la creación de condiciones que fortalezcan las capacidades científicas y tecnológicas de la industria farmacéutica local, y con ello, mejorar el suministro farmacéutico del país. En el presente documento se presentan conceptos teóricos y prácticos que deberían ser considerados en la definición y materialización de una política pública encaminada a fortalecer la industria farmacéutica y favorecer la autonomía sanitaria de Colombia.

Colombia has a notorious dependency on the importation of medicines, as well as a large part of the materials (active ingredients and excipients) required for their manufacture. This problem generates health and macroeconomic consequences, which are exacerbated in the context of national deindustrialization and technological disruption. In this way, it is accepted that the availability and access to medicines and other essential health technologies are a fundamental requirement to achieve the health autonomy of a country. Therefore, it is crucial to coordinate efforts between several social sectors to develop a public agenda focused on creating conditions that allow strengthening the scientific and technological capabilities of the local pharmaceutical industry, thereby, improving the country's pharmaceutical supply. This document presents conceptual and practical topics that should be considered to defining and materializing a public policy aimed at strengthening the local pharmaceutical industry and favoring Colombia's sanitary autonomy.

Premios Nobel Chain y Schatz evalúan la producción de penicilina en Chile en los años sesenta / Nobel Prize winners Chain and Schwartz evaluate the production of penicillin in Chile in the sixties

En los años sesenta el antiguo Instituto Bacteriológico de Chile obtuvo de la Universidad de Chile la ayuda de Albert Schatz, descubridor de la estreptomicina, para mejorar su producción de penicilina. Esta asesoría no fue aprovechada y la situación empeoró, hasta la llegada de Mario Miranda como Director, quien trajo a Sir Ernst Chain, Premio Nobel por el desarrollo de la penicilina, para que hiciese una evaluación de la planta de producción antes de decidir su cierre. El autor de estas líneas, quien puso fin a la producción en 1973, relata las visitas y las conclusiones de ambos asesores.

In the sixties the ancient Bacteriological Institute of Chile obtained from the University of Chile the transfer of Albert Schatz, discoverer of streptomycin, to improve its penicillin production. This advisory was wasted and the situation worsened until the arrival of Mario Miranda as the new Director, who brought Sir Ernst Chain, Nobel Prize for the development of penicillin, to make an evaluation of the production plant before deciding to continue or close it. The author of these lines, who ended production in 1973, recounts the visits and the conclusions of both advisors.

Mudanças na alimentação de estudantes de uma Universidade Pública, durante a pandemia de COVID-19 / Changes in the diet of students at a public university during the COVID-19 pandemic

A pandemia de Covid-19 teve implicações diretas na qualidade de vida, saúde e renda da população mundial. Grande parte dos brasileiros passou a ficar mais tempo em casa e a rotina dos estudantes universitários foi afetada pelo fechamento dos sistemas educacionais. O presente estudo buscou investigar se houve mudanças no consumo alimentar de estudantes universitários de uma universidade pública do Estado do Rio de Janeiro no primeiro ano da pandemia de Covid-19, e possíveis fatores associados. Os ingressantes na Universidade do Estado do Rio de Janeiro (UERJ) no ano de 2019 foi a população alvo. Os dados foram coletados através de questionário on-line, entre agosto de 2020 e março de 2021. Do total de 3.973 ingressantes com email, 771 responderam ao questionário (19,4%). Foram investigadas variáveis demográficas, socioeconômicas e de consumo alimentar. Mudanças no consumo alimentar de 29 itens: ovos, doces, bolos, chá, café, queijo, sucos naturais, legumes, frutas, pães, raízes, pipoca, verduras, arroz, refrigerantes, leite, biscoitos doces, macarrão, alimentos prontos para consumo, sucos industrializados, carnes, iogurte, feijão, enlatados, biscoitos salgados, oleaginosas, refrigerantes diet/zero, salgadinhos de pacote e bebidas alcoólicas, foram avaliadas pela frequência de aumento ou redução. Associações entre essas mudanças e sexo, status de peso, raça/cor de pele e alteração na renda familiar foram avaliadas por regressão logística ajustada por idade. As análises foram ponderadas considerando a taxa de resposta por curso e sexo. Ocorreram grandes mudanças na alimentação, sendo as principais, o aumento no consumo de doces (52,3%), ovos (49,3%) e bolos (44,0%) e a redução no consumo de bebidas alcoólicas (36,9%), salgadinhos de pacote (33,3%) e biscoitos doces (28,9%). Universitários com excesso de peso apresentaram menor chance de aumentar o consumo de sucos naturais (OR:0,6; IC:0,5-0,9) em relação aos sem excesso de peso. Universitários negros apresentaram maior chance de aumentar o consumo de sucos naturais (OR=1,3; IC:1,1-1,7) e leite (OR=1,4; IC:1,1-2,0) em relação aos brancos. Com exceção para poucos alimentos, não houve mudança associada aos fatores avaliados e, no geral, a alimentação parece ter melhorado com redução de um terço para bebidas alcoólicas, salgadinhos de pacote e biscoitos doces. AU.

The Covid-19 pandemic had direct implications for the quality of life, health and income of the world's population. Most Brazilians stayed home longer and the routine of college students was affected by the closure of educational systems. The present study evaluated changes in food consumption of college students in the first year of the Covid-19 pandemic, and possible associated factors. Freshman from the State University of Rio de Janeiro (UERJ) in the year 2019, was the target population. Data were collected through an online questionnaire from August 2020 to March 2021 including demographic, socioeconomic and food consumption variables. Of the total of 3,973 email entrants, 771 completed the questionnaire (19.4%). Demographic, socioeconomic, and food consumption variables were investigated. Changes in food consumption of 29 items: eggs, sweets, cakes, tea, coffee, cheese, natural juices, vegetables, fruits, breads, roots, popcorn, greens, rice, soft drinks, milk, sweet cookies, noodles, ready-to-eat foods, processed juices, meats, yogurt, beans, canned food, salty cookies, oilseeds, diet/zero sodas, packaged snacks and alcoholic beverages, were assessed by the increase or decrease in the daily frequency. Associations between dietary changes with sex, weight status, race/skin color, and change in household income were assessed using age-adjusted logistic regression. All analyses were weighted considering the response rate by course and sex. Major changes in diet were the increased consumption of sweets (52.3%), eggs (49.3%), and cakes (44.0%) and decreased consumption of alcoholic beverages (36.9%), packaged snacks (33.3%), and sweet cookies (28.9%). Overweight students did not increase their consumption of fruit juices (OR:0.6; CI:0.5-0.9) compared to those without overweight. Black students had higher odds to increase consumption of juice (OR=1.3; CI:1.1-1.7) and milk (OR=1.4; CI:1.1-2.0) compared to white students. Except for these few food groups, the factors studied were not associated with dietary changes, and overall, the diet improved with a one-third reduction for alcoholic beverages, packaged snacks and sweet cookies. AU

TDAH e Complexo Médico-Industrial: revisão narrativa sobre uma epidemia lucrativa / ADHD and Medical-Industrial Complex: narrative review about a profitable epidemic

O emprego de diagnósticos psiquiátricos alcançou uma importância social tamanha que o atual cenário aponta para um risco constante de epidemias diversas de transtornos mentais. Por essa razão, este estudo teve como objetivo compreender a complexa dinâmica de forças que edificam o caminho para uma condição da vida se tornar um problema médico e, a posteriori, um quadro epidêmico. Para tanto, através de uma revisão narrativa, esta pesquisa reconheceu os múltiplos aspectos da medicalização da vida; da dinâmica de um Complexo Médico-Industrial e Financeiro; e da epidemia de diagnósticos psiquiátricos. O estudo igualmente apreciou a evolução histórico-social do Transtorno do Déficit de Atenção com Hiperatividade (TDAH), como um meio para identificar as interinfluências envolvidas na consolidação de seu diagnóstico, o qual se tornou exponencialmente mais recorrente na atualidade. Além disso, o estudo examinou, em bases como SciELO, PubMed, MEDLINE, MeSH e Google Acadêmico, trabalhos que façam referência à evolução da produção e do consumo dos principais fármacos prescritos para seu tratamento, de modo a averiguar as possíveis repercussões socioeconômicas da inflação diagnóstica do TDAH. Com isso, este trabalho constatou que a alternância do protagonismo entre os atores que compõem o campo da saúde é atualmente definida pelo mercado, e, associada à fluidez dos diagnósticos psiquiátricos, as influências de tais forças passaram a ser determinantes no modo como um distúrbio é introduzido, modificado e/ou ampliado no meio social. Outrossim, a pesquisa mostrou que os transtornos psiquiátricos se tornaram cada vez mais passíveis de se transformarem em condições epidêmicas, especialmente em razão: das sucessivas alterações de seus critérios, o que permitiu ampliar o público-alvo dos diagnósticos; da cronificação das práticas em saúde mental, influenciadas pelo forte movimento reducionista do sofrimento humano à lógica biomédica; e da primazia da farmacoterapia, perpetuada por meio de um modelo de atenção gerenciada que preza pela redução dos custos e aumento dos lucros com a assistência. AU

The use of psychiatric diagnoses has reached such a social importance that the current scenario points to a constant risk of various epidemics of mental disorders. Hence, this study aimed to understand the complex dynamics of forces that build the path for a condition of life to become a medical problem and, subsequently, an epidemic. For this purpose, through a narrative review, this research recognized the multiple aspects of the medicalization of life; the dynamics of a Medical-Industrial and Financial Complex; and the epidemic of psychiatric diagnoses. The study also looked at the historical-social evolution of Attention Deficit Hyperactivity Disorder (ADHD) as a means to identify the inter-influences involved in the consolidation of its diagnosis, which has become exponentially more recurrent nowadays. In addition, the study examined SciELO, PubMed, MEDLINE, MeSH, and Google Scholar databases to determine the evolution of the production and consumption of the main drugs prescribed for the treatment of ADHD, in order to investigate the possible socioeconomic repercussions of ADHD diagnostic inflation. With this, this work has found that the alternation of the protagonism among the actors that compose the health field is currently defined by the market, and, associated with the fluidity of psychiatric diagnoses, the influences of such forces have become determinant in the way a disorder is introduced, modified and/or expanded in the social environment. Moreover, the research showed that psychiatric disorders have become increasingly likely to become epidemic conditions, especially for the following reasons: the successive changes in their criteria, which allowed the expansion of the target audience of the diagnoses; the chronification of mental health practices, influenced by the strong reductionist movement of human suffering to biomedical logic; and the primacy of pharmacotherapy, perpetuated through a model of managed care that focuses on ​​cost reduction and increasing profits with the care. AU

Medicalização do sofrimento psíquico na Atenção Primária à Saúde em um município do interior do Ceará / Medicalization of psychic suffering in Primary Health Care in a small town in the state of Ceara, Brazil

Resumo Este trabalho objetiva discutir como o fenômeno da medicalização do sofrimento psíquico se apresenta no discurso e na prática dos profissionais da Atenção Primária à Saúde. Foram realizadas observações sistemáticas e entrevistas semidiretivas com sete trabalhadores do município de Iguatu, Ceará, Brasil. A análise dos dados foi feita através da Análise de Conteúdo, de Bardin. Os resultados apontaram para uma centralidade no uso de medicação para atender o sofrimento psíquico que chega às unidades de saúde. Os profissionais discorreram sobre o medicamento enquanto uma estratégia rápida e eficiente, que, em consonância com a literatura pesquisada, pode ser utilizada como um dispositivo de controle do sujeito em adoecimento psíquico. Considera-se possível mobilizar, junto aos profissionais, espaços de discussão que apontem para o cuidado da pessoa com sofrimento psíquico através do uso de tecnologias leves, como escuta, vínculo e diálogo.

Abstract This paper aims to discuss how the phenomenon of the medicalization of psychological distress appears in the discourse and practice of Primary Health Care professionals. Systematic observations and semi-directive interviews were conducted with seven workers in the city of Iguatu, Ceará, Brazil. Data analysis was performed using Bardin's Content Analysis. The results pointed to a centrality in the use of medication to attend the psychological suffering that reaches the health units. The professionals spoke about the medication as a quick and efficient strategy, which, in line with the researched literature, can be used as a device to control the subject in psychic illness. It is considered possible to mobilize discussion spaces with professionals that point to the care of people with psychological distress through the use of light technologies, such as listening, bonding and dialogue.Resumo: Este trabalho objetiva discutir como o fenômeno da medicalização do sofrimento psíquico se apresenta no discurso e na prática dos profissionais da Atenção Primária à Saúde. Foram realizadas observações sistemáticas e entrevistas semidiretivas com sete trabalhadores do município de Iguatu, Ceará, Brasil. A análise dos dados foi feita através da Análise de Conteúdo, de Bardin. Os resultados apontaram para uma centralidade no uso de medicação para atender o sofrimento psíquico que chega às unidades de saúde. Os profissionais discorreram sobre o medicamento enquanto uma estratégia rápida e eficiente, que, em consonância com a literatura pesquisada, pode ser utilizada como um dispositivo de controle do sujeito em adoecimento psíquico. Considera-se possível mobilizar, junto aos profissionais, espaços de discussão que apontem para o cuidado da pessoa com sofrimento psíquico através do uso de tecnologias leves, como escuta, vínculo e diálogo.

Analysis of Lean Six Sigma Use in Pharmaceutical Production

Abstract Over the last years, pharmaceutical industries have adopted continuous improvement and operational excellence programs to optimize processes, improve quality and reduce operational costs. Worldwide, Lean Manufacturing (LM) and Six Sigma (SS), as well as the integration of the two methods: Lean Six Sigma (LSS) are the most used approaches in the continuous improvement of industries and services. This work aims to investigate the employment of the Lean Six Sigma methodology in the productive areas of pharmaceutical companies located in Brazil. Interviews were conducted with managers of pharmaceutical industries that apply the approach. The results indicated the greater use of Lean Manufacturing tools compared to Six Sigma and the influence of specific peculiarities of the pharmaceutical industry on the benefits that are achieved with the use of Lean Six Sigma. The approach is considered of great value as it provides substantial benefits to the pharmaceutical industry. It is concluded that the work corroborates to the theoretical and empirical knowledge about the methodology use in the context of Brazilian pharmaceutical industries, as well as contributes to the implementation, reformulation, and improvement of Lean Six Sigma programs in this industrial segment.

Current status, trends, and challenges of continuous manufacturing technology for oral traditional Chinese medicine solid preparations / 中国中药杂志

In recent years, continuous manufacturing technology has attracted considerable attention in the pharmaceutical industry. This technology is highly sought after for its significant advantages in cost reduction, increased efficiency, and improved productivity, making it a growing trend in the future of the pharmaceutical industry. Compared to traditional batch production methods, continuous manufacturing technology features real-time control and environmentally friendly intelligence, enabling pharmaceutical companies to produce drugs more efficiently. However, the adoption of continuous manufacturing technology has been slow in the field of traditional Chinese medicine(TCM) pharmaceuticals. On the one hand, there is insufficient research on continuous manufacturing equipment and technology that align with the characteristics of TCM preparations. On the other hand, the scarcity of talent with diverse expertise hampers its development. Therefore, in order to promote the modernization and upgrading of the TCM pharmaceutical industry, this article combined the current development status of the TCM industry to outline the development status and regulatory requirements of continuous manufacturing technology. At the same time, it analyzed the problems with existing TCM manufacturing models and explored the prospects and challenges of applying continuous manufacturing technology in the field of TCM pharmaceuticals. The analysis focused on continuous manufacturing control strategies, technical tools, and pharmaceutical equipment, aiming to provide targeted recommendations to drive the development of the TCM pharmaceutical industry.

Four critical engineering and technical problems in manufacturing measurement of traditional Chinese medicine / 中国中药杂志

Focusing on the development and quality improvement strategy of the traditional Chinese medicine(TCM) industry, the scientific and technological innovation of the new engineering of TCM should be paid attention to solve the "stuck neck" dilemma. Under the background of the ecological and industrial revolution of the scientific and technological innovation system, the super-scale information interaction and multi-dimensional integration will inevitably lead to profound changes in the manufacturing mode of TCM. Manufacturing measurement of TCM is formed on the basis of the reliability engineering theory of process control of TCM production. It is the development extension of system theory and system science ideas and a cross-fertilization discipline that combines theory with practice and adheres to the "four-oriented" re-epistemology improvement of the TCM discipline. In response to the problems of complex raw material sources, coarse process technology, unclear material basis, and poor applicability of equipment and technology in the manufacture of TCM, the transformation research mode of "aiming at the integration of pharmaceutical industry-developing intelligent production line-enabling industrial transformation" has been developed. This paper proposed the four key engineering technical problems, i.e., the identification of critical quality attributes(CQA) in the manufacture of TCM, the quality by design(QbD) and product development of the manufacturing process of TCM, the quality transfer principle and multivariate process capability index of TCM manufacturing, and the development of measurement technology and equipment of the manufacturing measurement of TCM, to achieve the systematization of quality control indicators, real-time process control, digitalization of manufacturing process, transparency of quality transfer, and intelligent whole-process control. In this paper, the new concepts, new theories, and new technologies provide a reference for the industrialization of TCM.

Lean strategy for data mining and continuous improvement of Chinese pharmaceutical process: a case study of sporoderm-removal Ganoderma lucidum spore powder / 中国中药杂志

In the digital transformation of Chinese pharmaceutical industry, how to efficiently govern and analyze industrial data and excavate the valuable information contained therein to guide the production of drug products has always been a research hotspot and application difficulty. Generally, the Chinese pharmaceutical technique is relatively extensive, and the consistency of drug quality needs to be improved. To address this problem, we proposed an optimization method combining advanced calculation tools(e.g., Bayesian network, convolutional neural network, and Pareto multi-objective optimization algorithm) with lean six sigma tools(e.g., Shewhart control chart and process performance index) to dig deeply into historical industrial data and guide the continuous improvement of pharmaceutical processes. Further, we employed this strategy to optimize the manufacturing process of sporoderm-removal Ganoderma lucidum spore powder. After optimization, we preliminarily obtained the possible interval combination of critical parameters to ensure the P_(pk) values of the critical quality properties including moisture, fineness, crude polysaccharide, and total triterpenes of the sporoderm-removal G. lucidum spore powder to be no less than 1.33. The results indicate that the proposed strategy has an industrial application value.

Methodology and application of process analytical technology (PAT) for traditional Chinese medicine manufacturing:a review / 中国中药杂志

Owing to the advancement in pharmaceutical technology, traditional Chinese medicine industry has seen rapid development. Preferring conventional manufacturing mode, pharmaceutical enterprises of traditional Chinese medicine have no effective process detection tools and process control methods. As a result, the quality of the final products mainly depends on testing and the quality is inconsistent in the same batch. Process analytical technology(PAT) for traditional Chinese medicine manufacturing, as one of the key advanced manufacturing techniques, can break through the bottleneck in quality control of medicine manufacturing, thus improving the production efficiency and product quality and reducing the material and energy consumption. It is applicable to the process control and real-time release of advanced manufacturing modes such as intelligent manufacturing and continuous manufacturing. This paper summarized the general idea of PAT for traditional Chinese medicine manufacturing. Through the analysis of the characteristics and status quo of the technology, we summed up the methodology for the continuous application and improvement of PAT during the whole life-cycle of traditional Chinese medicine. The five key procedures(process understanding, process detection, process modeling, process control, and continuous improvement) were summarized, and the application was reviewed. Finally, we proposed suggestions for the technical and regulatory challenges in implementing PAT in traditional Chinese medicine industry. This paper aims to provide a reference for development and application of PAT in advanced manufacturing, intelligent manufacturing, and continuous manufacturing of traditional Chinese medicine industry.

Caracterización de las aguas residuales generadas en la producción de conjugados monovalentes en el Instituto Finlay de Vacunas / Characterization of the wasteswater generated in the production of conjugated monovalent at the Finlay Vaccine Institute

En la actualidad la contaminación de las aguas terrestres es un grave problema ambiental. La industria farmacéutica es una de las que produce un mayor impacto por la gran variedad de químicos que aporta al agua; sus efluentes generalmente tienen asociadas elevadas cargas orgánicas no biodegradables. La preservación de la calidad de las aguas terrestres es un tema regulado por la legislación nacional, donde se exige la caracterización de las aguas residuales antes de su vertimiento con vistas a evaluar el impacto ambiental que producen y diseñar el sistema adecuado para su tratamiento. El Instituto Finlay de Vacunas, pertenece al grupo de BioCubaFarma, es una empresa de ciclo completo, cuenta con nueve instalaciones, cinco de ellas son generadoras de grandes volúmenes de aguas residuales industriales. El presente trabajo tiene el objetivo de presentar los resultados obtenidos en la evaluación de los parámetros físico-químico de los residuales líquidos del proceso productivo de conjugados monovalentes, para esto se muestrearon los residuales líquidos generados al final de cada etapa del proceso. Se determinaron los indicadores de contaminación: pH, temperatura, conductividad eléctrica, demanda química y bioquímica de oxígeno, fósforo total, nitrógeno total y sólidos sedimentables; los ensayos fueron realizados en el laboratorio de la Empresa Nacional de Servicios Técnicos de la Habana, acreditado para la realización de las caracterizaciones de aguas residuales. Los resultados fueron comparados con los límites máximos permisibles establecidos en la Norma Cubana NC-27:2012 de vertimiento de aguas residuales al alcantarillado, además se calculó el índice de biodegradabilidad. Se demostró que el pH, la conductividad eléctrica, demanda química de oxígeno y demanda bioquímica de oxígeno no cumplen con el vertido para la descarga al alcantarillado pudiendo impactar de manera negativa en los recursos hídricos(AU)

At present, the pollution of terrestrial waters is a serious environmental problem. The drug industry is one of those that produces a greater impact, due to the great variety of chemicals that can contribute to the water; its effluents generally have associated high non-biodegradable organic loads. The preservation of the quality of terrestrial waters is a subject regulated by legislation, where the characterization of wastewater is required before its discharge, since it allows evaluating the environmental impact it produces and designing the appropriate system for its treatment. The Finlay Vaccine Institute, belongs to the BioCubaFarma group, is a full cycle company, has nine facilities, five of them are generators of large volumes of industrial wastewater. The current work presents the results obtained in the evaluation of the physical-chemical parameters of the liquid waste from the production process of monovalent conjugates, for this the liquid waste generated at the end of each stage of the process was sampled. Pollution indicators were determined: pH, temperature, electrical conductivity, chemical and biochemical oxygen demand, total phosphorus, total nitrogen and sedimentable solids. The results were compared with the maximum permissible limits established in NC-27: 2012 for the discharge of wastewater. The biodegradability index was also calculated. It was shown that some of the determined parameters do not comply with the discharge to release to the sewer system, which could have a negative impact on water resources(AU)

Ensaios clínicos em congressos médicos: estudo sobre conflito de interesses / Clinical trials in medical congresses: a study on conflicts of interest / Ensayos clínicos en congresos médicos: un estudio sobre conflicto de intereses

Resumo Este artigo busca investigar conflitos de interesses envolvendo a apresentação de ensaios clínicos em congressos brasileiros de cinco especialidades médicas, ocorridos entre 2004 e 2018. Foram estudados 407 resumos em 22 anais. Após aplicar critérios de seleção, obteve-se um corpus de 77 ensaios. Detectou-se maior frequência de conflitos de interesses envolvendo ensaios com drogas para as quais não havia genéricos/similares ( p =0,000), sendo que em 48% daqueles em conflito de interesses não houve declaração. Os resultados favoráveis à droga-teste ocorreram em 90,9% do total de ensaios, mas em 48,6% deles não foi reportado valor de p . As categorias terapêuticas mais testadas foram imunossupressores e imunomoduladores, antidiabéticos e antineoplásicos, que, juntas, representaram 68,9% do total de drogas envolvidas. Os resultados apontam conflitos de interesses ocultos, supervalorização de resultados positivos de drogas-testes, nem sempre com evidências suficientes, e concentração de produção em drogas de alto custo.

Abstract This article seeks to investigate conflicts of interest involving the presentation of clinical trials in Brazilian congresses of five medical specialties between 2004 and 2018. A total of 407 abstracts in 22 annals were studied. After applying selection criteria, we reached a corpus of 77 essays. A higher frequency of conflicts of interest was found involving essays with drugs for which no generic/similar option was available (p=0.000), and 48% of those with a conflict of interest declared nothing. Favorable results to the test drug occurred in 90.9% of the total of essays, but 48.6% of them lacked the p-value. The most tested therapeutic categories were immunosuppressors and immunomodulators, antidiabetic, and antineoplastic, which, together, amounted to 68.9% of the total of the involved drugs. The results pointed to hidden conflicts of interest, overvaluing of positive results of test drugs, not always with sufficient evidence, and focus of production on high-cost drugs.

Resumen Este artículo analiza los conflictos de intereses en ensayos clínicos presentados en congresos brasileños de cinco especialidades médicas, realizados entre 2004 y 2018. Se analizaron 407 resúmenes de 22 anales. Tras aplicados los criterios de selección se obtuvo un corpus de 77 ensayos. Hubo una mayor frecuencia de conflictos de intereses en ensayos con medicamentos para los que no había medicaciones genéricas/similares ( p =0,000), y el 48% con conflictos no hubo su declaración. Los resultados favorables para droga prueba están en el 90,9% del total de ensayos, pero el 48,6% de ellos no informó el valor de p . Las categorías terapéuticas más probadas fueron inmunosupresores e inmunomoduladores, antidiabéticos y antineoplásicos, que juntas compusieron el 68,9% del total de fármacos. Los resultados apuntan a conflictos de intereses ocultos, sobreestimación de los resultados positivos de las drogas prueba, no siempre con evidencia suficiente, y concentración de la producción en medicamentos de alto costo.

As entidades empresariais do setor farmacêutico: o caso da Associação Brasileira da Indústria Farmacêutica, 1964-1988 / Business entities in the pharmaceutical sector: the Associação Brasileira da Indústria Farmacêutica, 1964-1988

Resumo O artigo analisa a Associação Brasileira da Indústria Farmacêutica, entidade empresarial do setor farmacêutico criada para amparar os interesses das indústrias e garantir posições estratégicas no aparelho do Estado, impulsionando políticas favoráveis. A fim de alcançar essa meta, atuou junto ao Estado, de forma lícita e ilícita, para influenciar a agenda pública e para que as pautas das políticas públicas beneficiassem os interesses das suas associadas. O texto tem como objetivo analisar os condicionantes que levaram a sua formação, suas articulações políticas, suas fissuras e tensões internas e sua pressão junto ao Estado restrito para inscrever suas demandas específicas.

Abstract This article analyzes the Associação Brasileira da Indústria Farmacêutica, an association created to represent Brazilian pharmaceutical manufacturers, pursue the interests of the sector, and ensure strategic stances within the government to advance favorable policy. To do so, the association worked with the government (through legal and non-legal means) to influence the public agenda so that public policies benefited the interests of its members. We examine the conditions that led to the creation of this organization, its political connections, schisms and internal tensions, as well as pressure on the limited government to take up its specific demands.

Pharmaceutical patent term extension and patent prosecution in Brazil (1997-2018) / Extensão do prazo de vigência e tramitação de patentes farmacêuticas no Brasil (1997-2018) / Extensión de la vigencia y tramitación de patentes farmacéuticas en Brasil (1997-2018)

In Brazil, if patent prosecution takes more than 10 years, this extra period is added to the regular 20-year term. This paper analyses all pharmaceutical patents granted by the Brazilian National Institute of Industrial Property (INPI) with term extension and later discusses some intellectual property and health policy implications. On average, pharmaceutical patent applications wait seven years after substantive examination is requested before being examined, which takes only three and a half years. Furthermore, the role of the Brazilian Health Regulatory Agency (Anvisa) in providing prior consent has a marginal effect in prolonging the prosecution. Therefore, the extension of pharmaceutical patents' term is caused by the number of pending applications per examiner, which halts the prosecution for double the time it takes to examine the applications. Thus, proper solutions should focus on reducing the backlog per examiner at the INPI, which has caused the extension of 92% of the pharmaceutical patents in three and a half years, on average. We concluded that the Brazilian pharmaceutical patenting policy is biased towards the patentee. This imbalance will only be effectively corrected when the INPI is financially and administratively autonomous to reduce the ratio between the pharmaceutical patent application backlog and the number of examiners.

No Brasil, quando a tramitação de uma patente demora mais de 10 anos, esse tempo adicional é acrescentado à vigência regular de 20 anos. Este artigo analisa todas as patentes farmacêuticas concedidas pelo Instituto Nacional de Propriedade Industrial (INPI) com prorrogação de prazo, e em seguida discute algumas implicações para políticas de propriedade intelectual e de saúde. Em média, os pedidos de patente farmacêuticas esperam sete anos entre o requerimento do exame e o início da análise, que leva apenas três anos e meio. Além do mais, o papel da Agência Nacional de Vigilância Sanitária (Anvisa) na anuência prévia tem efeito marginal sobre o período de tramitação. Portanto, a extensão da vigência das patentes farmacêuticas é provocada pelo alto número de pedidos pendentes por examinador, o que atrasa em até duas vezes o tempo que leva para examinar os pedidos. Logo, soluções adequadas devem focar na redução do acúmulo de pedidos pendentes por examinador no INPI, que causou a extensão de 92% das patentes farmacêuticas em três anos, em média. Conclui-se que a política brasileira para patentes farmacêuticas apresenta um viés em favor do titular da patente. Esse desequilíbrio só será sanado efetivamente quando o INPI tiver autonomia financeira e administrativa para reduzir a razão entre o backlog de pedidos de patentes farmacêuticas e o número de examinadores.

En Brasil, si la tramitación de una patente tarda más de 10 años, este período extra se añade a la vigencia regular de 20 años. Este trabajo analiza todas las patentes farmacéuticas otorgadas por la Oficina de Patentes Brasileña (INPI) con extensión de su vigencia, y discute posteriormente algumas implicaciones para las políticas de propriedade intelectual y de salud. En promedio, las solicitudes de patentes farmacéuticas esperan siete años desde el requerimiento del examen antes de ser examinadas, lo que tarda solamente tres años y medio. Asimismo, el rol de la Agencia Nacional de Vigilancia Sanitaria (Anvisa) al dar su consentimiento previo tiene un efecto marginal para prolongar la tramitación. Por ello, la extensión de la vigencia de las patentes farmacéuticas está provocada por el número de solicitudes pendientes por examinador, lo que paraliza la tramitación por el doble de período de tiempo que cuesta examinar las solicitudes. Así pues, las soluciones apropiadas deberían centrarse en reducir el acúmulo de solicitudes pendientes por examinador en el INPI, que ha provocado la extensión de la patente en un 92% de las solicitudes farmacéuticas en tres años y meio, en promedio. Se concluye que la política de patentes farmacéuticas brasileña está sesgada hacia el titular de la patente. Este desequilibrio solo se corregirá efectivamente cuando el INPI tenga autonomía financeira y administrativa para reducir la razón entre el backlog de solicitudes de patentes farmacéuticas y el número de examinadores.

Solid Phase Extraction and Simultaneous Chromatographic Quantification of some Non-steroidal Anti-inflammatory Drug Residues; an Application in Pharmaceutical Industrial Wastewater Effluent

Abstract Two sensitive and selective methods were developed for the simultaneous determination of four commonly used non-steroidal anti-inflammatory drugs (NSAIDs), namely; paracetamol (PCM), diclofenac sodium (DCF), ibuprofen (IBP), and indomethacin (IND) in wastewater effluents. The first method used HPLC for the determination of the studied drugs using a mobile phase consisting of phosphate buffer (pH 3.0) and acetonitrile at a flow rate of 1 mL/min. in gradient elution mode and detection at 220 nm. The separation process was performed on BDS Hypersil Cyano column (250 x 4.6 mm, 5 µm). The second method was a TLC-densitometric one which was performed using n-Hexane: ethyl acetate: acetic acid in the ratio (6:3.5:0.5) as a developing system. The proposed chromatographic methods were successfully applied for the selective determination of the four studied drugs in simulated and real pharmaceutical wastewater samples after their solid-phase extraction

Por que a Homeopatia incomoda? / Why Homeopathy bothers?

Escolhemos o título acima porque, como praticantes de uma atitude médico-filosófica que vê o ser humano como uma unidade e integrado ao todo, jamais conseguimos nos furtar ao diagnóstico sistêmico. É hábito do homeopata o diagnóstico em sua totalidade, das partes integradas ao todo, buscando o porquê em tudo, até em um simples artigo de um simples jornal de uma simples cidade que integra o nosso pequeno planeta, diga ele respeito ou não à homeopatia. Inicialmente a homeopatia começou incomodando as religiões, pois quando Hahnemann experimentou substâncias em humanos, observou o aparecimento de sintomas físicos e psíquicos, estes últimos eram tidos até então como instâncias da alma e portanto propriedade dos religiosos. Além de destruir o tácito acordo entre medicina e religião, onde médicos cuidavam dos males do corpo e os religiosos dos males da alma, resgatou também a unidade que é o ser. Foi a primeira prova testemunhal na medicina ocidental da comprovação dessa unidade. (AU)

Considerations on Clinical Development and Regulatory of the Oversea License-in Anti-tumor Drugs / 中国肺癌杂志

With the boom of China's innovative pharmaceutical industry, licensing-in model has gradually become an important research and development model for innovative pharmaceutical companies. The in-licensed drugs at different stages need different research and development (R&D) strategy in China. The pharmaceutical companies take the responsibility to comprehensively collate the oversea clinical data and conduct a detailed analysis of clinical pharmacology, safety, efficacy and ethnic sensitivity. Clinical R&D strategy should be made based on the results of the above data and analysis. We encourage high-quality drugs which fill unmet clinical needs licensed in, and as early as possible, so as to conduct multi-regional clinical trials (MRCTs). The clinical R&D strategy in China is particularly important for the drug's approval. Guidelines published by the National Medical Products Administration (NMPA) and clinical associations should be followed. Communications about clinical R&D strategy with Center of Drug Evaluation (CDE) are encouraged.
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Category of Chinese medicine registration:historical evolution,current status,and problems / 中国中药杂志

The development of traditional Chinese medicine(TCM) has always been highly valued and supported since 1949. However, Chinese medicine industry still faces great challenges in view of the current status of the industry and registration and approval of new products in recent years. Related policies also directly influence the development of the industry. The latest version of the Provisions for Drug Registration and Requirement on Registration Classification and Application Information of Traditional Chinese Medicines have been put into practice since 2020. Registration classification is the core content of the Chinese medicine registration management system, as it is closely related to the research, development, and registration of Chinese medicine and the innovative development of the industry. This article aims to systematically review the historical evolution of the category of Chinese medicine registration and analyze the current status and problems, which is expected to provide a reference for the formulation of supporting documents according to related laws and regulations.