Fatty acids analysis by capillary electrophoresis: Fundamentals, advantages and applications.

This review covers the know-how of the Grupo de Química Analítica e Quimiometria regarding the analysis of fatty acids by capillary electrophoresis acquired over its 20 years of existence. Therefore, the fundamentals, advantages, and applications of this technique for analyzing different fatty acids in samples such as food, oils, cosmetics, and biological matrices are presented and discussed. Capillary electrophoresis is, thus, shown as an interesting and valuable separation technique for the target analysis of these analytes as an alternative to the gas chromatography coupled to flame ionization detection, as it offers advantages over the latter such as low analysis times, low sample and reagent consumption, the use of a nondedicated column, and simpler sample preparation. In addition, the methods shown in this literature review can be useful for quality control, adulteration, and health-related research by regulatory agencies.

Mesenchymal Stem Cell Therapies Approved by Regulatory Agencies around the World.

Cellular therapy has used mesenchymal stem cells (MSCs), which in cell culture are multipotent progenitors capable of producing a variety of cells limited to the mesoderm layer. There are two types of MSC sources: (1) adult MSCs, which are obtained from bone marrow, adipose tissue, peripheral blood, and dental pulp; and (2) neonatal-tissue-derived MSCs, obtained from extra-embryonic tissues such as the placenta, amnion, and umbilical cord. Until April 2023, 1120 registered clinical trials had been using MSC therapies worldwide, but there are only 12 MSC therapies that have been approved by regulatory agencies for commercialization. Nine of the twelve MSC-approved products are from Asia, with Republic of Korea being the country with the most approved therapies. In the future, MSCs will play an important role in the treatment of many diseases. However, there are many issues to deal with before their application and usage in the medical field. Some strategies have been proposed to face these problems with the hope of reaching the objective of applying these MSC therapies at optimal therapeutic levels.

A Proposal of a Combined Convergence Regulatory Strategy Applied to Post-approval Changes by Latin American Countries, Reducing Workload and Allowing Continuous Improvement to Guarantee the Quality, Safety, and Efficacy of Medicines.

In recent years, post-approval changes (PACs) for medicinal products have increased faster than the national regulatory agencies can attend to without causing any negative impact. This study presents a proposal for regulatory management based on our analysis of the data available from the national regulatory agencies of Latin America on the total post-approval changes evaluated, and the time spent in the process. A retrospective search on the official websites of competent national regulatory authorities (NRAs) of 14 Latin American countries (México, Guatemala, Nicaragua, Honduras, El Salvador, Panamá, Costa Rica, Venezuela, Colombia, Ecuador, Peru, Argentina, Chile and Brazil) was conducted to collect data on post-approval changes in the last 4-6 years, up to January 2021. The NRAs considered were Brazil, México, Colombia, and Costa Rica. Our analysis was focused on the post-approval changes that required approval before implementation, those that were submitted, and those that were submitted and approved for small molecules, biologics, and biotechnological products. The results indicated differences in the regulatory processes and procedures applied by the different agencies. We also found that the implementation of the PACs was directly impacted by limited resources, which puts the medication supply for chronic treatments at risk resulting in serious consequences for patients. For local decision-making, Latin American NRAs should implement regulatory pathways already made by regulatory agencies included in the World Health Organization Listed Authorities on PAC approval to optimize their resources and to ensure the continuity of medicine supply for their patients.

As agências reguladoras em resposta à crise da COVID-19 / Las agencias reguladoras en respuesta a la crisis de la COVID-19 / Regulatory agencies in response to the COVID-19 crisis

Resumo Este artigo tem por objetivo analisar as respostas das agências reguladoras federais para o enfrentamento da crise de saúde pública gerada pelo novo coronavírus. Parte-se do entendimento de que a avaliação empírica dos padrões de resposta evidenciados pelas agências durante a crise da COVID-19 cumpre um papel importante no aprimoramento da função pública. Em primeiro lugar, porque oferece subsídios para que a própria atividade regulatória se adapte de forma mais célere às necessidades do atual momento de crise. Em segundo, porque o contexto excepcional gerado pela pandemia coloca em evidência alguns traços essenciais da atividade regulatória: suas condições de exercício e funcionalidades, suas limitações e potencialidades e, sobretudo, sua importância para a minimização de danos em cenários marcados por instabilidade estrutural. Os dados utilizados no presente estudo foram extraídos do Diário Oficial da União (DOU) e dos sítios eletrônicos das 11 agências reguladoras federais. Para a presente análise, foram selecionadas apenas as medidas com efetivo impacto regulatório sobre o setor regulado. Identificamos uma significativa heterogeneidade no volume de respostas das agências, em parte relacionada a diferenças setoriais, mas sobretudo decorrente de assimetrias na capacidade institucional desses órgãos. Identificamos também uma heterogeneidade no conteúdo das respostas das agências a problemas regulatórios semelhantes, evidenciando falhas de coordenação regulatória que precisam ser urgentemente solucionadas.

Resumen El objetivo de este artículo es analizar las respuestas de las agencias reguladoras federales para enfrentar la crisis de salud pública creada por el nuevo coronavirus. Entendemos que la evaluación empírica de los protocolos de respuesta llevados a cabo por las agencias durante la crisis de la COVID-19 cumple un papel importante para perfeccionar la función pública. En primer lugar, porque colabora a que la propia actividad regulatoria se adapte de forma más rápida a las necesidades del momento actual de crisis. En segundo lugar, porque el contexto excepcional producido por la pandemia pone en evidencia algunos rasgos esenciales de la actividad regulatoria: sus condiciones de ejercicio y operaciones, sus limitaciones y potencialidades y, sobre todo, su importancia para la minimización de daños en momentos de inestabilidad estructural. Los datos utilizados en el presente estudio provienen del Diário Oficial da União (DOU), así como de los sitios web de las once agencias reguladoras federales. Hemos seleccionado para este análisis solamente las medidas de impacto regulatorio efectivo sobre el sector regulado. Identificamos una heterogeneidad significativa en el volumen de respuestas de las agencias, que se relaciona, en parte, con diferencias sectoriales, pero sobre todo resultante de asimetrías en la capacidad institucional de esos órganos. Identificamos también una heterogeneidad de contenido en las respuestas de las agencias ante algunos problemas regulatorios semejantes, lo que demuestra deficiencias en la coordinación regulatoria que deben solucionarse urgentemente.

Abstract This article aims to examine the responses of federal regulatory agencies to the public health crisis - the COVID-19 pandemic. We adhere to the understanding that an empirical evaluation of the patterns of response manifested by the agencies during the pandemic plays an important role in the improvement of public function. First, because it aids the task of adapting regulatory activities more quickly to the needs of the current situation. Secondly, because the context of exceptionality created by the pandemic highlights essential features of the regulatory activity in itself: its conditions of execution and functionalities, limitations and potentialities, and, most of all, its importance for minimizing losses in scenarios of structural instability. The data used in this study was gathered from the Official Gazette Diário Oficial da União (DOU) and the websites of the eleven regulatory federal agencies. In our analysis, we only selected measures with an impact on the regulated sector. We found significant heterogeneity in the number of agency responses, partly related to sectorial differences, but mostly arising from asymmetries of institutional capability among these bodies. We also found heterogeneity of content in the responses given by agencies to similar regulatory problems, which suggests the existence of failures in regulatory coordination in urgent need of a solution.

A Baseline Analysis of Regulatory Review Timelines for ANVISA: 2013-2016.

BACKGROUND: The Brazilian health regulatory agency (Agência Nacional de Vigilância Sanitária, ANVISA) has embarked on transformational initiatives to fulfill its mandate to provide timely access to safe, effective, and quality therapeutics. A new Brazilian law was enacted to provide the agency with greater flexibility. Optimizing Efficiencies in Regulatory Agencies (OpERA) is a regulatory-strengthening program that seeks to provide benchmarking data that can be used to define performance targets and focus performance improvement. The objective of this study was to use OpERA methodology to undertake a retrospective analysis of the timelines associated with important components of the ANVISA regulatory review process to establish a baseline against which the influence of the new law could be measured. METHODS: The OpERA tool was used to collect specific milestone data that identify time periods, review stages, and data points for products approved by ANVISA 2013-2016. RESULTS: For the 138 products approved in this cohort, the overall median approval time was 795 days. ANVISA and submitting companies will need to reduce their review and response times by approximately half in order to meet the total time goal of 365 days. CONCLUSIONS: The observations from this baseline study have identified opportunities for ANVISA and sponsor companies to collaborate to reduce regulatory assessment times while assuring the timely approval of safe and effective, quality medicines. These analyses will be repeated to determine how the provisions of the new Law will impact the activities of ANVISA and the extent of sponsors' contributions to this effort.

On Innovation.

Innovation has become an increasingly common topic in healthcare. Private companies, developers, payers, and regulators are devoting attention toward innovative products and processes as a crucial component of their interests in and occupation with healthcare services. Even when there is no consensus as to its definition, "innovation" -as opposed to "invention"- is broadly understood to refer turning a good idea into a practical solution. Adoption and applicability are key components of implementation that are sustained not only on innovation's attributes themselves but also in the characteristics of providers, users, and implementing organizations, as well as the external environment. Regulatory agencies often face the need to make decisions about proposed innovations with obsolete or inadequate normative frameworks and with a high degree of uncertainty about its eventual performance or its risks. Early interaction between developers and dedicated multidisciplinary teams at regulatory agencies may prove instrumental for speeding up the time required for proper evaluation and product registration, as well as the establishment of quality validation mechanisms. Community involvement both in the adoption and vigilance on innovative products and processes is crucial for completing the process of defining their roles and uses.

Diffusion and adaptation of the regulatory agency model in Brazil / Difusión y adaptación del modelo de agencia reguladora en Brasil / Difusão e adaptação do modelo de agência reguladora no Brasil

Abstract This article examines the diffusion of independent regulatory agencies (IRAs) in Brazil, demonstrating how important domestic factors interplayed with traditional mechanisms of diffusion lead to an expressive process of agencification. Although top-down, bottom-up and horizontal mechanisms played an important role in the Brazilian agencification process, they fail to explain the creation of IRAs in unexpected sectors or the frequent modifications that occurred at subnational levels in a short period of time. To understand how local political actors adapted the regulatory agency model to the Brazilian institutional legacies, field research was conducted, based on bibliographical, documental, and interviews with key political actors. The specificities of Brazilian federalism and the strategic role of the film industry, bureaucrats and politicians in (re)interpreting the agency model helped to boost the diffusion of IRAs in Brazil.

Resumo Este artículo examina la difusión de agencias reguladoras independientes en Brasil, demostrando de qué forma la interacción entre variables contextuales y mecanismos de difusión llevaron a un significativo proceso de agencialización. Aunque los mecanismos top-down, bottom-up y horizontales han desempeñado un papel importante en la difusión de las agencias reguladoras brasileñas, son insuficientes para explicar la creación de agencias en sectores inusitados o las frecuentes modificaciones ocurridas en los niveles subnacionales. Para entender la adaptación del modelo de agencia al contexto local, se realizó una investigación de campo, basada en bibliografía, documentación oficial y entrevistas con actores clave. Las especificidades del federalismo brasileño y el papel estratégico desempeñado por actores de la industria cinematográfica, burócratas y políticos en la reinterpretación del modelo de agencia contribuyeron a apalancar la difusión de agencias reguladoras independientes en Brasil.

Resumo Este artigo examina a difusão de agências reguladoras independentes no Brasil, demonstrando de que forma a interação entre variáveis relacionadas ao contexto local e mecanismos tradicionais de difusão levaram a um expressivo processo de agencificação. Embora mecanismos top-down, bottom-up e horizontais tenham desempenhado um papel importante na difusão das agências reguladoras brasileiras, eles são insuficientes para explicar a criação de agências em setores inusitados ou as frequentes modificações ocorridas nos níveis subnacionais. Para entender a adaptação do modelo de agência ao contexto local, foi realizada uma pesquisa de campo, baseada em bibliografia, documentação oficial e entrevistas com atores-chave. As especificidades do federalismo brasileiro e o papel estratégico desempenhado por atores da indústria cinematográfica, burocratas e políticos na reinterpretação do modelo de agência contribuíram para alavancar a difusão de agências reguladoras independentes no Brasil.

El desafío de la innovación desde la perspectiva regulatoria / The challenge of innovation from a regulatory perspective

Actualmente, la innovación está en la agenda de diferentes actores del sistema de salud. Tanto empresas privadas como pequeños desarrolladores, pagadores y reguladores interpretan de manera creciente a la innovación como un componente esencial de su desarrollo. Cada uno de los interesados debe identificar el aspecto innovador de un nuevo producto o desarrollo en relación a su área de competencia. Aun cuando no exista una definición consensuada sobre innovación, se entiende que ésta -a diferencia de la invención- se refiere a la transformación de una buena idea en una solución práctica. En este sentido, la implementación de una innovación requiere de la adopción (decisión) y de la aplicabilidad, sustentadas no solamente en los atributos del desarrollo en sí, sino también en las características de los proveedores, usuarios y organizaciones adoptantes, y en las del ambiente externo. Muchas veces, las agencias reguladoras se enfrentan a las innovaciones con normativas que resultan obsoletas o insuficientes, y con mayor grado de incerteza respecto de su desempeño. La interacción temprana entre los desarrolladores y equipos multidisciplinarios establecidos a tal fin en las agencias reguladoras puede resultar un instrumento fundamental a los fines de acortar los plazos de evaluación y registro, y de establecer mecanismos adecuados de evaluación de calidad. La participación de la comunidad tanto en la adopción como en la vigilancia de desarrollos innovadores completa el proceso de definición de sus potenciales usos y roles.

Innovation has become an increasingly common topic in healthcare at present. Private companies, developers, payers and regulators think of innovation as a crucial component of their development. Each one of the interested parties may identify the innovative aspect of a new product or development related to their disciplinary field. Even when there is no definition agreement on innovation, it is understood -as opposite to invention- that it refers to turning a good idea into a practical solution. Implementation recognizes adoption and applicability as key components in which not only the innovation attributes are considered but also the characteristics of the providers, users and implementing organizations, as well as the external environment. Regulatory agencies often face innovations with obsolete or inadequate normative framework, and also, high degrees of uncertainty regarding its performance. Early interaction between developers and multidisciplinary teams established to that effect at regulatory agencies may become a fundamental instrument to speed up the times of evaluation and registration, and establish suitable mechanisms for quality evaluation. Involvement of the community in both the adoption and vigilance of innovative developments complete the process of defining its potential roles and uses.

A comparative analysis of the pharmacovigilance systems of Brazil, Spain, the European Union and the United States based on the information provided by their regulatory agency websites.

BACKGROUND: Pharmacovigilance (PV) plays an essential role in monitoring and raising awareness of adverse drug reactions (ADRs). Increasingly, ADRs are reported and PV information and activities are circulated via the Internet. PV actions are carried out by the Regulatory Agencies (RAs) responsible for medicinal products in each country. OBJECTIVE: The objective of this study is to ascertain and assess the operation and areas of competence of the PV system in Brazil and to compare them with those of Spain, the European Union (EU) and the United States (USA), through the information available on the websites of the RAs in each country. METHODS: A search of the information provided on the websites of these countries' RAs, establishing indicators to assess how far the information is available and accessible. RESULTS: The RAs we studied are similarly organised and they complied with most of the 38 indicators we defined to obtain and assess the information they provide on PV procedures and their systems for electronic reporting of ADRs. Brazil's RA, ANVISA, complied with 100% of the areas of competence analysed and with 92.11% of the indicators established for the study. CONCLUSIONS: Brazil's PV system, through ANVISA, achieves a good level of performance, both in itself and compared to the other RAs. There is room for improvement in three of the indicators analysed.

Medicamentos biosimilares en Colombia: una revisión desde el consumo informado / Biosimilar Medicines in Colombia: An Approach from the Informed Consumption / Medicamentos biossimilares na Colômbia: uma revisão desde o consumo informado

Resumen Introducción: este artículo presenta un análisis sobre medicamentos biosimilares en Colombia con miras a establecer si existe un consumo informado respecto de estos fármacos, teniendo en cuenta la calidad y cantidad de información que circula en relación con su disponibilidad y acceso económico (precios). Desarrollo: el tipo de estudio es cualitativo con un diseño documental a partir de la revisión en bases de datos como Pubmed, Scopus, Scielo, Vlex y Redalyc, bases de información de registros sanitarios de agencias reguladoras de medicamentos (FDA, EMA e Invima) y el Sistema de Información de Vademecum Med Informática. Uno de los biosimilares autorizados en FDA y cuatro de la EMA se encuentran registrados en el Invima; sin embargo, son más los biosimilares no autorizados ni en FDA ni en EMA que se encuentran registrados en el Invima, los cuales aún no aparecen con esta clasificación de biosimilares ni en la agencia reguladora colombiana ni en ningún otro medio oficial o comercial. De los medicamentos biológicos de referencia de estos biosimilares, 12 tienen control de precios y 7 han sido autorizados al menos una vez vía judicial a los usuarios del sistema. Conclusiones: si bien, la reglamentación ha sido de gran avance en relación con el acceso a biosimilares y, en consecuencia, a sus biológicos pioneros, el sistema aún tiene barreras jurídicas, de información, disponibilidad y acceso que dificultan la protección y efectividad del derecho a la salud de la población en términos de un consumo informado de estos.

Abstract Introduction: This article presents an analysis of biosimilar drugs in Colombia, aiming at critically analyzing whether the consumption of biosimilar drugs in Colombia is fully informed or if it rather is characterized for its lack of information. Informed consumption in the sense of taking into account the quality and quantity of the information circulating in relation to the availability and affordability (prices) of biosimilar drugs. Development: This is a qualitative documentary analysis, based on the review of databases such as Pubmed, Scopus, Scielo, Vlex and Redalyc, and sanitary databases of drugs regulatory agencies (FDA, EMA and the Colombian Invima) and the Vademecum Med Informatica. One of the biosimilars authorized by FDA and four of those by EMA were also registered before by the Invima. However, the number of Invima authorized biosimilars is higher than that authorized by FDA and EMA. It is also important to highlight the fact that any biosimilar is not registered as such neither before the Invima nor before any other official or commercial source. Out of the biological reference products with biosimilars, twelve have regulated price and seven have been authorized at least once via court ruling. Conclusions: Although the regulations are progressive in relation to the access to biosimilars and, consequently, to their biological pioneers, the system still has legal, availability and information barriers that undermine the protection and effectiveness of the right to health.

Resumo Introdução: este artigo apresenta uma análise sobre medicamentos biossimilares na Colômbia com vista a estabelecer se existe um consumo informado respeito destes fármacos, tendo em conta a qualidade e quantidade de informação que circula em relação com a sua disponibilidade e acesso econômico (preços). Desenvolvimento: o tipo de estudo é qualitativo com um desenho documental a partir da revisão em bases de dados como Pubmed, Scopus, Scielo, Vlex e Redalyc, bases de informação de registros sanitários de agências reguladoras de medicamentos (FDA, EMA e Invima) e o Sistema de Informação de Vademecum Med Informática. Um dos biossimilares autorizados em FDA e 4 da EMA, se encontram registrados no Invima, no entanto são mais os biossimilares não autorizados nem na FDA nem na EMA que se encontram registrados no Invima, os quais ainda não aparecem com esta classificação de biossimilares nem na agência reguladora colombiana, nem em nenhum outro meio oficial ou comercial. Dos medicamentos biológicos de referência destes biossimilares, 12 têm controle de preços e 7 têm sido autorizados pelo menos uma vez via judicial aos usuários do sistema. Conclusões: se bem a regulamentação tem sido de grande avanço em relação com o acesso a biossimilares e, consequentemente, a seus biológicos pioneiros, o sistema ainda tem barreiras jurídicas, de informação, disponibilidade e acesso que dificultam a proteção e efetividade do direito à saúde da população em termos de um consumo informado dos mesmos.

Safety assessment of FDA-approved (orlistat and lorcaserin) anti-obesity medications.

INTRODUCTION: Options for treating obesity remain limited despite it being a chronic, recurrent and morbid condition. New drugs that are proposed for its treatment encounter strong reluctance by regulatory agencies and many doctors. AREAS COVERED: This review will focus on the safety of an older drug, orlistat (the only one still approved in the European Union) and a newer recently FDA-approved one, lorcaserin. Both are approved as long-term monotherapy for obesity in the United States of America and they have demonstrated median weight loss of nearly 3% over placebo. EXPERT OPINION: Research, development and approval of new anti-obesity drugs are necessary for improved management of this chronic condition. Orlistat and lorcaserin are two FDA-approved drugs with limited overall efficacy. Nevertheless they are useful weapons for at least some obese individuals. Orlistat has a long and solid safety profile, whereas the safety of lorcaserin is still a matter of debate, mainly due to a lack of long-term data. However, lorcaserin's selective agonism on 5HT2c serotonin receptors diminishes concerns about valvulopathy associated with other serotonin agonists, such as fenfluramine.

Estrategia para la preparación de unidades de salud en buenas prácticas clínicas / Strategy for the preparation of health units for good clinical practices

Introducción: El entorno regulatorio mundial es cada vez más exigente para establecer, implementar y mantener el cumplimiento de las buenas prácticas clínicas (BPC). En Cuba, una respuesta necesaria derivada del desarrollo creciente de la industria farmacéutica y biotecnológica nacional fue la creación del Centro Nacional Coordinador de Ensayos Clínicos (CENCEC). Una de las misiones del CENCEC es preparar a las unidades-sitios clínicos seleccionados que realizan investigaciones clínicas, para su posterior certificación en BPC por la autoridad reguladora nacional, con la finalidad de avalar la calidad que corresponde al proceso de investigación clínica que redunda en una esmerada atención y protección al paciente objeto de estudio. Objetivo: Describir la estrategia del CENCEC para la preparación en BPC de los sitios clínicos seleccionados del Sistema Nacional de Salud (SNS) que participan en ensayos clínicos. Métodos: Se revisan más de 250 documentos normativos emitidos por Europa, Estados Unidos, Japón y los países nórdicos relacionados con aspectos prácticos y éticos para la implementación de las BPC...

Background: The global regulatory environment is increasingly demanding to establish, implement, and maintain the compliance with Good Clinical Practices (GCP). In Cuba, The National Coordinating Center for Clinical Trials (CENCEC) was created as a necessary response derived from the increasing development of the national pharmaceutical and biotechnological industry. One of the missions of the CENCEC is to prepare selected clinical units/sites that conduct clinical research for a further certification in GCP by the national regulatory authority in order to guarantee the quality that corresponds to the process of clinical research, resulting in a careful attention and protection of the patient under study. Objective: To describe the strategy of the CENCEC for the preparation of good clinical practices in the selected clinical sites of the National Health System (SNS) that participate in clinical trials. Methods: More than 250 regulatory documents issued by Europe, the United States, Japan and the Nordic countries, related to ethical and practical aspects for the implementation of good clinical practices, were reviewed...

O quadro de trabalhadores federais em saúde no Brasil: uma análise no contexto dos anos 2000 / The federal health work force in Brazil: an analysis in the context of the 2000's

O artigo analisa o quadro de trabalhadores do Ministério da Saúde e entidades vinculadas - agências reguladoras da saúde e Fundação Oswaldo Cruz - de 2000 a 2008, relacionando a evolução quantitativa e o perfil dos vínculos dos trabalhadores federais da saúde com os condicionantes históricos e as políticas para o funcionalismo. As estratégias metodológicas da pesquisa foram: revisão bibliográfica, análise documental e de dados primários e secundários. Os resultados sugerem que a partir de 2003 houve uma recomposição parcial de quadros na administração pública federal, por meio de concursos públicos. Tal movimento foi heterogêneo entre áreas, sendo que a saúde apresentou um aumento de servidores ativos inferior à média federal. Observaram-se diferenças na situação do quadro de trabalhadores do Ministério da Saúde e entidades vinculadas. O nível central do Ministério foi pouco beneficiado com a realização de concursos, mantendo baixa proporção de servidores e alta dependência de consultores, terceirizados e contratos temporários. As agências reguladoras da saúde receberam servidores concursados a partir de 2005, mas em 2008 ainda apresentavam trabalhadores com outros tipos de vínculos. Na Fiocruz, observou-se um incremento do número de servidores, porém um aumento maior dos terceirizados. Por fim, discutem-se os desafios de conformação de uma adequada força de trabalho no Ministério da Saúde e entidades vinculadas, visto que no Brasil a esfera federal mantém um papel estratégico para a consolidação do Sistema Único de Saúde.

This paper analyzes the work force of the Brazilian Ministry of Health and associated entities -the health regulatory agencies and the Oswaldo Cruz Foundation -from 2000 to 2008, focusing on the quantitative evolution and types of employment relation. The methods involved a bibliographical review, documental analysis and analysis of primary and secondary data. The results suggest that since 2003, there has been an increase in civil service admissions. However, the increase in active federal health workers was lower than the average increase of the Federal Executive. Differences were found in the staffing situations of the Ministry of Health and of the associated entities. The central office of the Ministry benefitted only slightly from the civil service admissions and remained dependent on professionals hired as consultants or by temporary contracts. The health regulatory agencies have benefitted from civil service admission examinations since 2005, but at the end of the period there was still a large proportion of workers employed under alternative types of engagement. Meanwhile at Fiocruz, despite the increase in the number of civil servants, there was a greater increase in the number of workers employed under other types of contracts. Finally, the challenges involved in forming a stable and adequate federal work force are discussed, considering that in Brazil the federal government plays a fundamental role in consolidating the Unified Health System (SUS).