Counterfeit medicines: relevance, consequences and strategies to combat the global crisis

Abstract Counterfeiting of medicines, also known as "falsification" or "adulteration", is the process in which the identity, origin, or history of genuine medicines are intentionally modified. Currently, counterfeit medicines are a global crisis that affects and is mostly caused by developing countries in Asia, Africa and Latin America. These countries lack strict law enforcement against this practice and have low-income populations with medicinal needs. Lately, the crisis has escalated, impacting developed countries as well, e.g., the US and the EU, mainly via the Internet. Despite this extension, some current laws aim to control and minimize the crisis' magnitude. Falsification of medicines maintains an illegitimate supply chain that is connected to the legitimate one, both of which are extremely complex, making such falsification difficult to control. Furthermore, political and economic causes are related to the crisis' hasty growth, causing serious consequences for individuals and public health, as well as for the economy of different countries. Recently, organizations, technologies and initiatives have been created to overcome the situation. Nevertheless, the development of more effective measures that could aggregate all the existing strategies into a large functioning network could help prevent the acquisition of counterfeit medicines and create awareness among the general population.

Regulamentação e criminalização das drogas no Brasil / Drug regulation and criminalization in Brazil

O presente estudo visa avaliar, através de uma revisão narrativa da literatura, como o controle do Estado exerceu ao longo da história do Brasil a regulamentação do uso de drogas. Método Foram consultados livros, artigos de periódicos acadêmicos indexados, trabalhos completos apresentados em congressos e documentos históricos disponíveis na internet relativos ao tema. Resultados A primeira legislação penal em relação ao uso de drogas surge apenas no Brasil império. Nesse período começam a surgir também os primeiros problemas devido ao uso de drogas. A criação de cursos superiores nas áreas de saúde e de ciências naturais veio a formar profissionais capacitados na manipulação e fiscalização de produtos químicos e farmacêuticos. Com o tempo, observando-se os efeitos, algumas substâncias passam a ser proscritas. Conclusão Por toda história do país, o uso e a regulação das drogas, permearam todas as épocas influenciando na cultura, educação e no modo de vida da população. Atualmente há um grande debate acerca das políticas sobre drogas no Brasil, principalmente sobre a maconha e seus usos terapêuticos, mostrando novamente a influência do Estado sobre a saúde e a segurança da população.

The present study aims to evaluate, through a narrative review of the literature, how State's control has exercised regulation of drug use throughout the history of Brazil. Method Books, articles from indexed academic journals, complete works presented at conferences and historical documents available on the internet relating to the topic were consulted. Results The first criminal legislation related to drug use only appeared in Imperial Brazil. During this period, the first problems due to drug use also begin to appear. The creation of higher education courses in the areas of health and natural sciences resulted in the training of professionals capable of handling and supervising chemical and pharmaceutical products. Over time, observing the effects, some substances become proscribed. Conclusion Throughout the country's history, the use and regulation of drugs has permeated all eras, influencing culture, education and the population's way of life. There is currently a great debate about drug policies in Brazil, mainly regarding marijuana and its therapeutic uses, once again showing the influence of the State on the health and safety of the population.

A política para a cannabis no Brasil entre o direito penal e a saúde pública: da construção do discurso proibicionista às possibilidades de legalização / Cannabis policy in Brazil between criminal law and public health: from the construction of the prohibitionist discourse to the possibilities of legalization

A Cannabis sativa L tem acompanhado a trajetória da humanidade há milênios com destacado papel histórico no desenvolvimento das sociedades humanas. Por suas propriedades singulares e versatilidade é uma das mais antigas plantas cultivadas do mundo e também uma das primeiras plantas a ser utilizada como medicamento e sublimação em rituais religiosos. Durante o século XX, interesses políticos e ideológicos internacionais exacerbaram os atributos psicoativos da planta, tornando-a, proscrita e proibida inclusive ao uso medicinal. No Brasil, ao discurso proibicionista adicionou-se ainda o viés racista, imputando à pessoa escravizada a culpa pela introdução e fumo da erva assassina. Com as notáveis descobertas científicas sobre a cannabis o discurso proibicionista tem perdido força, iniciando-se um movimento global pela legalização que representa o início de uma nova era do entendimento sobre a planta e da concepção sobre o uso de substâncias psicoativas que não mais poderá ser contido pela repressão.

Cannabis sativa L has followed the trajectory of humanity for millennia with an outstanding historical role in the development of human societies. Due to its unique properties and versatility, it is one of the oldest cultivated plants in the world and also one of the first plants to be used as medicine and sublimation in religious rituals. During the 20th century, international political and ideological interests exacerbated the psychoactive attributes of the plant, making it proscribed and prohibited even for medicinal use. In Brazil, the prohibitionist discourse also added a racist bias, blaming slaves for the introduction and smoking of the killer herb. With the remarkable scientific discoveries about cannabis, the prohibitionist discourse has lost strength, starting a global movement for legalization that represents the beginning of a new era of understanding about the plant and the conception of the use of psychoactive substances that can no longer be contained by repression.

Caracterización de casos judicializados por medicamentos no autorizados a prescripción en un hospital público / Characterization of cases prosecuted for unauthorized prescription drugs in a public hospital

INTRODUCCIÓN. La salud, un derecho establecido en la Carta Magna de los países, obliga y garantiza este servicio. Paciente insatisfecho por no acceso o cobertura de medicamentos promueve litigios que vulnera la administración gerencial, su conocimiento, es indispensable. OBJETIVO. Describir el perfil demográfico y epidemiológico de los pacientes y de los casos judicializados por medicamentos no autorizados a prescripción. MATERIALES Y MÉTODOS. Estudio retrospectivo con universo y muestra conocida de 36 pacientes. Criterios de inclusión: todo año de edad y sexo, con proceso judicializado por medicamentos en el Hospital de Especialidades Carlos Andrade Marín del Instituto Ecuatoriano de Seguridad Social, período octubre 2016 a septiembre 2019. Datos obtenidos del Sistema AS400 y áreas administrativas, analizados en los programas Excel y SPSS versión 23.0. RESULTADOS. Predominó el sexo hombre 61,0% (22; 36), Alfa de Cronbach de 07, rango de edad de 3 - 77 años y media de 44. Medicamentos más judicializados: omalizumab 33,3% (12; 36) y atalureno 13,9% (5; 36). Las enfermedades prevalentes: Asma Persistente, Distrofia Muscular y Cáncer de Pulmón predominaron. Vivieron 86,1% (31; 36) pacientes. La instancia judicial por Fiscalía 44,4% (16; 36) fue medida cautelar y ganó el juicio. CONCLUSIÓN. La judicialización fue una opción de los pacientes que garantizó su derecho a la salud ante las enfermedades catastróficas, raras o huérfanas, logró acceso y cobertura de medicamentos no disponibles, ni autorizada su prescripción, ocasionó un costo extrapresupuestario y vulneró la administración gerencial del hospital.

INTRODUCTION. Health, a right established in the Magna Carta of the countries, obliges and guarantees this service. Patient dissatisfied with non-access or medications coverage promotes litigation that violates the management administration, his knowledge is essential. OBJECTIVE. Describe the demographic and epidemiological profile of patients and cases prosecuted for drugs not authorized by prescription. MATERIALS AND METHODS. Retrospective study with universe and known sample of 36 patients. Inclusion criteria: all years of age and sex, with a judicial process for medications at the Carlos Andrade Marín Specialities Hospital of the Ecuadorian Social Security Institute, period October 2016 to September 2019. Data obtained from the AS400 System and administrative areas, analyzed in Excel and SPSS version 23.0 programs. RESULTS. The male sex predominated 61,0% (22; 36), Cronbach's Alpha 07, age range 3 - 77 years and a half of 44. More judicialized medications: omalizumab 33,3% (12; 36) and atalureno 13, 9% (5; 36). The prevalent diseases: Persistent Asthma, Muscular Dystrophy and Lung Cancer predominated. 86,1% (31; 36) patients lived. The judicial instance by the Prosecutor, 44,4% (16; 36) was a precautionary measure and won the trial. CONCLUSION. Judicialization was an option for patients who guaranteed their right to health in the face of catastrophic, rare or orphan diseases, achieved access to and coverage of unavailable medications, or authorized their prescription, caused an extra-budgetary cost and violated the hospital's management administration.

High rates of incarceration due to drug trafficking in the last decade in southern Brazil

Abstract Introduction Drug-related crimes, especially drug trafficking, account for a large part of incarcerations not only in Brazil, but also worldwide. It is not clear whether the change in the drug law has contributed to the increase in the number of drug trafficking prisoners. Few studies have investigated gender differences and the growth of drug trafficking offenses in the Brazilian southern state of Rio Grande do Sul. Objective To investigate the growth of the prison population in the state of Rio Grande do Sul, emphasizing incarcerations for drug trafficking and gender differences. Method This was an ecological study using secondary data collected from official databases of the Brazilian National Penitentiary Department (Departamento Penitenciário [DEPEN]), affiliated with the Brazilian Ministry of Justice. Results Between 2006 and 2015, incarcerations increased by 27% (25% men, 83% women). Incarcerations for drug trafficking accounted for 11% of total arrests in 2006 (11% men, 20% women) and 45% in 2015 (47% men, 91% women), corresponding to an increase of 427% (415% among men, 723% among women). Conclusions Imprisonment for drug trafficking has increased considerably, especially among women. This may be due to factors such as: increase of drug trafficking, increase in the numbers of gangs in the state, and changes in the Brazilian drug law. These results highlight an emerging challenge in public health from the perspective of human rights and gender.

Mercado del Cannabis medicinal en Colombia: una oportunidad para el sector salud que requiere lineamientos estratégicos del gobierno nacional y la academia / Medical Marijuana market in Colombia: an opportunity for the health sector that requires strategic guidelines from the national government

Resumen Los resultados de las investigaciones sobre cannabis medicinal han traído a las mesas de gobierno discusiones sobre su potencial terapéutico y las medidas a tomar para controlar su producción, comercialización y utilización. En Colombia, desde el 2017, el mercado del cannabis medicinal se encuentra regulado; sin embargo, existen brechas entre la norma, disponibilidad y acceso de los pacientes a productos farmacéuticos con derivados del cannabis, aprobados por el ente regulatorio y que cumplan con los estándares de calidad. Desde esta perspectiva, se considera necesario que el gobierno nacional lidere, en coordinación con la academia y el sector productivo, el desarrollo de preparados farmacéuticos a base de cannabis; además de establecer e implementar medidas estratégicas y concertadas, orientadas a mejorar el acceso y la utilización adecuada de los productos farmacéuticos de cannabis medicinal, en especial para los casos en los que se pueda establecer una clara relación riesgo/beneficio. Con ello, se contribuye a mejorar las condiciones de salud de pacientes que se pueden beneficiar de estas opciones, al igual que al desarrollo y consolidación de un sector promisorio para el país. MÉD. UIS.2020;33(1):53-8.

Abstract The results of medical marijuana research have brought to the government tables discussions about their therapeutic potential and the measures to be taken to control their production, commercialization and use. In Colombia, since 2017, the medical cannabis market is regulated; however, there are gaps between the laws, availability and the access of patients to pharmaceutical products with cannabis derivatives approved by the regulatory entity and that comply with the standards of quality. From this perspective, it is necessary for the national government to lead, in coordination with the academy and the productive sector, the development of pharmaceutical preparations based on cannabis and to establish and implement strategic and concerted measures, aimed to improve access and proper use of medical marijuana pharmaceutical products, mainly for cases in which a clear risk/benefit relationship can be established. This would help to improve the health conditions of patients who can get benefits from these options, as well as the development and consolidation of a promising sector for the country. MÉD.UIS.2020;33(1):53-8.

Cannabis medicinal: riesgos relacionados con la indicación previa a su aprobación / Medical cannabis: Risks related to its indication prior to approval

En los últimos años, se ha observado un incremento significativo en el interés por la prescripción del cannabis medicinal. En el siguiente artículo, se informa acerca de la escasa base científica que avala la prescripción de estos compuestos en un listado amplio y diverso de patologías médicas. Se considera fundamental que cualquier sustancia que vaya a ser utilizada en humanos siga un protocolo de aprobación estricto y científico, que pueda desligarse de modas o de resultados individuales. Es necesario que, antes de la prescripción de una droga en personas, deba tenerse un panorama claro de cuáles son los usos del compuesto en cuestión, pero, sobre todo, de su seguridad, que es prácticamente desconocida en el cannabis medicinal.

In recent years, the interest in medical cannabis prescription has increased significantly. This article provides information about the little scientific basis supporting the prescription of these products for a wide and diverse range of medical conditions. It is critical for any substance to be used in human beings to follow a strict scientific approval protocol, detached from any trend or individual outcome. Before prescribing any drug to human beings, it is necessary to have a clear picture of its uses, especially its safety, which is practically unknown in the case of medical cannabis.

Chemical Characteristics, Therapeutic Uses, and Legal Aspects of the Cannabinoids of Cannabis sativa: A Review

Abstract Marijuana (Cannabis sativa) is an important annual medicinal plant that belongs to the Cannabaceae family. It contains 421 substances of 18 chemical types-the most significant compound is δ-9-tetrahydrocannabinol, which causes several effects, both in the Central Nervous System and in several peripheral locations in the organism. The objectives of this scientific review are to mention the anatomical distribution, chemical characteristics and biosynthesis of cannabinoids, as well as its actions mechanisms. The endogenous cannabinoid system, the therapeutic properties of C. sativa and its action on the nociceptive control are described. Finally, the modulators of the cannabinoid system in clinical use are indicated, together with marijuana legalization benefits.

Conceptos fundamentales de bioequivalencia y biosimilitud en la normativa chilena y controversias sobre intercambiabilidad / Chilean legislation on bioequivalence and biosimilarity and current controversies related to drug interchangeability

Los medicamentos constituyen un bien económico que forma parte del gasto público y privado y de la toma de decisiones en salud. El aseguramiento de su calidad, eficacia y seguridad resulta fundamental. Sin embargo, la variada oferta disponible en el mercado chileno, donde se reconocen productos innovadores y genéricos, constituye un escenario confuso para consumidores y proveedores en salud. En esta revisión pretendemos aclarar los conceptos de fármacos bioequivalentes (aplicable a compuestos de tamaño molecular pequeño) y fármacos biosimilares (para compuestos biológicos de mayor complejidad molecular). En ambos casos, el comportamiento en el organismo del principio activo debe ser demostrado mediante estudios realizados para este fin. Una aplicación directa del concepto de bioequivalencia es la intercambiabilidad, definida como la posibilidad de utilizar un producto de un mismo principio activo, mientras la forma farmacéutica y esquema de dosificación sean iguales. Las normas relativas a esta materia y los organismos públicos encargados, no solo debieran garantizar la seguridad y la eficacia en el intercambio entre productos, sino también aspectos relacionados con el costo, la accesibilidad a los fármacos y la implementación de una guía de homogeneización de conceptos y criterios de intercambiabilidad basados en la evidencia, lo cual impactaría en una mejor educación para los usuarios, reduciendo la asimetría de información entre el usuario y la industria. La importancia de la intercambiabilidad destaca en Chile en el contexto del Plan de Garantías Explícitas en Salud (GES) y la Ley de Protección Financiera para Diagnósticos y Tratamientos de Alto Costo en Salud (Ley Ricarte Soto). Sin embargo, no es posible garantizar que todos los productos alternativos al innovador presentes en el mercado chileno son bioequivalentes. El conocimiento disponible en esta temática puede impactar y contribuir a la toma de decisiones en los prescriptores y usuarios, así como en la elaboración de políticas públicas en torno a los productos farmacéuticos bioequivalentes y biosimilares en nuestro país.

Medicines are an economic good and a fundamental component of public and private health spending and decision-making. Assurance of their quality, efficiency, and safety is essential. In Chile, the wide variety of available drugs, including innovator products, and generics­some of which are certified as bioequivalent, while others are not­creates a potentially confusing scenario for both consumers and health providers. In this review, we intend to shed light on the concepts of bioequivalency (the standard permitting interchangeability for small-molecule drugs) and biosimilarity (the standard permitting interchangeability for biological compounds of greater molecular complexity). In both cases, how the active substance interacts with the host organism must be demonstrated by studies designed and carried out for this purpose. Interchangeability is defined as the possibility of using a product of the same active principle, as long as the pharmaceutical form and dosage scheme are the same. Regulations related to bioequivalence and biosimilarity must not only guarantee safety and efficacy when products are interchanged but also facilitate cost savings and access to medicines. Implementation of evidence-based guidelines that standardize concepts of interchangeability could lead to more educated usage and reduced information asymmetry between patients (users) and industry. Drug interchangeability is particularly relevant in two government health initiatives in Chile: the Explicit Guarantees in Health Care (GES) plan, and the Law on Financial Protection for High-Cost Diagnostics and Treatment in Health Care (also known as the "Ricarte Soto Law"). Nonetheless, it is not possible to guarantee that all alternative drug products on the Chilean market are bioequivalents of the reference product. Synthesis of the available knowledge on bioequivalent and biosimilar pharmaceutical products in Chile could facilitate and contribute to stakeholder decision-making and the development of better health policies.

Thoughts and suggestions on registration and classification of traditional Chinese medicines / 中国中药杂志

In this paper, we reviewed the history of the registration and classification changes of traditional Chinese medicines(TCM) since the establishment of China's drug regulatory agency, and put forward relevant suggestions. Although China's drug regulatory agency has gone through 22 years, the whole regulatory system was gradually built on the basis of the generic pharmaceutical industry at that time and through continuous exploration and summary of simply experience from foreign regulatory agencies. To a certain extent, the supervision of TCM drugs was also affected by some immature supervision ideas during this period. Based on the newly issued Drug Administration Law and Provisions for Drug Registration, the author puts forward some personal thoughts on the classifications of TCM drug registration. It is hoped that experts in the industry and regulatory agencies will work together to explore and improve the relevant system of TCM registration administration.

Análisis y reflexiones sobre la iniciativa de reforma a la Ley General de Salud de México 2019 / Analysis and reflections on the 2019 initiative that reforms Mexico's Ley General de Salud

Resumen: La iniciativa con Proyecto de Decreto por el que se reforma la Ley General de Salud de México presentada en 2019 ante el Congreso de la Unión propone la creación de un sistema de acceso universal y gratuito a los servicios de salud y a medicamentos asociados para la población sin seguridad social y la creación del Instituto de Salud para el Bienestar. Este artículo analiza algunos aspectos sustantivos del Proyecto de Decreto con el objetivo de motivar la reflexión sobre la reforma propuesta y sus componentes más importantes para contribuir a su propósito. Se concluye que los principales temas del proyecto requieren precisión en rubros relevantes, como la transformación del esquema de financiamiento para la atención, el fortalecimiento de la rectoría y gobernanza, la responsabilidad en la provisión de servicios y la regulación y acceso a medicamentos. Las aportaciones de académicos, tomadores de decisiones y organizaciones sociales serán indispensables para una política pública de salud basada en evidencia y con equidad social.

Abstract: The initiative including an Act Project for reforming the Ley General de Salud of Mexico, submitted in 2019 to the Congress of the Union, proposes the creation of a system of universal and free access to health services and associated medicines for the population lacking of social security benefits, and the creation of the Instituto de Salud para el Bienestar. This article analyzes the substantive aspects of the project, with the aim of motivating the reflection of the proposed reform and its most important components, to contribute to achieving its aim. The conclusion is that the main themes of the Project require precision in relevant areas, such as the transformation of the financing scheme for care, the strengthening of stewardship and governance, the responsibility in the provision of services, and the regulation and access to medicines. The contributions of academics, decision makers and social organizations will be essential to create a public health policy based on evidence and social equity.

Challenges to regulate products containing bisphenol A: Implications for policy / Desafíos para regular los productos que contienen bisfenol A: implicaciones para la política

Abstract: Bisphenol A (BPA), found in plastics and epoxy resins, is one of the most studied chemicals. BPA is regarded as an endocrine disruptor and has been related to adverse health effects in humans. However, some regulatory agencies around the world have concluded that BPA is safe at current human exposure levels. As the scientific community attempts to settle the debate on BPA's health effects, regulatory agencies have been put into a challenging public health policy situation. The United States has implemented no regulatory actions due to safety concerns, while Europe has used the precautionary principle to guide its regulation in the face of scientific uncertainty. In this paper, we explore the debate surrounding BPA regulation and the possibility for countries to introduce guidelines, using Mexico as an example. Policy change determinants analysis suggest that countries can and should impose regulations on BPA.

Resumen: El bisfenol A (BPA), presente en plásticos y resinas epoxi, es uno de los químicos más estudiados. Se considera un disruptor endocrino y se ha relacionado con efectos adversos para la salud humana. Algunas agencias regulatorias en el mundo han concluido que el BPA es seguro a los niveles de exposición humana actuales. Mientas la comunidad científica intenta resolver el debate sobre dichos efectos, las agencias regulatorias enfrentan una difícil situación de política pública. Los Estados Unidos de América no han implementado acciones reglamentarias por razones precautorias, mientras que Europa ha utilizado el principio precautorio para guiar su regulación ante la incertidumbre científica. En este documento exploramos el debate que rodea la regulación del BPA y la posibilidad de que los países introduzcan directrices, usando a México como ejemplo. El análisis de los determinantes del cambio de políticas sugiere que los países pueden y deben regular el BPA.

Revisão da literatura sobre implicações para assistência de usuários de drogas da descriminalização em Portugal e Brasil / Literature review on the implications of decriminalization for the care of drug users in Portugal and Brazil

Resumo Os problemas relacionados ao uso de drogas se mantêm como foco de preocupação em países que têm uma história em comum e trajetórias distintas como Brasil e Portugal. Objetivo: descrever os achados na literatura científica sobre os impactos das mudanças na legislação sobre drogas na assistência a estas pessoas nos dois países. Método: revisão integrativa da literatura, por meio de critérios de inclusão e exclusão, seleção da amostra, análise e categorização dos estudos com a escolha de 21 artigos publicados nas bases PubMed, SciELO e Biblioteca do Conhecimento on-line, mais portarias e leis referentes ao tema. Resultados: Observa-se que é escassa a produção sobre as repercussões das mudanças da legislação para a assistência. Nos dois países, o álcool e o tabaco se mantêm como foco de preocupação. Em Portugal, a preocupação com os problemas relacionados ao uso de heroína diminuiu nos últimos anos, mas as taxas de prevalência do uso de opióides se mantêm muito acima das do Brasil. Os problemas com o crack configuram uma realidade brasileira sem paralelo em Portugal. Em ambos os casos, há iniciativas para a mudança da política em direção à diminuição da abordagem repressiva, com a diferenciação entre usuários e traficantes, o aumento da punição dos traficantes e abrandamento da punição dos usuários.

Abstract Introduction: Substance use problems remain at the core of public concern in countries sharing a common culture and a distinct history like Brazil and Portugal. Objective: To describe findings of scientific literature about the implications of drug legislation change for the care of drug users in Brazil and Portugal. Methods: This is an integrative review of literature that considers inclusion and exclusion criteria, sample selection, analyses and categorization of 21 articles selected that were published in databases PubMed, SciELO and Biblioteca do Conhecimento on-line (B-ON) and included ordinances and laws related to the subject. Results: We observed that production on the repercussions of changes of legislation on care is scarce. Alcohol and tobacco are still a matter of concern in both countries. In Portugal, concerns about heroin-related issues have declined in recent years, but opioids use prevalence rates remain well above those of Brazil. Crack-related problems are a Brazilian reality without parallel in Portugal. In both cases, some actions are in place to change the policy in favor of a reduced repressive approach, with differentiation between users and drug dealers, increased punishment of dealers and reduced punishment of drug users.

Revisão dos dispositivos legais e normativos internacionais e nacionais sobre gestão de medicamentos e de seus resíduos / Review of national and international legal and regulatory mechanisms on the management of drugs and the residues thereof

Resumo Este trabalho apresenta uma revisão descritiva de leis e normas adotadas pelos países da Europa, das Américas e Austrália sobre gestão de medicamentos e de seus resíduos. Esta revisão integra pontos relevantes de documentos oficiais das agências reguladoras desses países, bem como de trabalhos científicos importantes. Todos os países pesquisados realizam gestão de medicamentos concomitantemente com a gestão de seus resíduos, atuando desde programas de conscientização sobre o uso racional e os riscos dos medicamentos até na coleta e disposição segura de seus resíduos. A Alemanha, os EUA e a Suécia exigem uma avaliação prévia do impacto ambiental provocado pelo medicamento como critério de seu registro. Em destaque, a Suécia que periodicamente atualiza uma lista de medicamentos essenciais baseada na avaliação do risco e do perigo ambiental de seus resíduos. No Brasil, as medidas legais propostas como prescrição racional e logística reversa ainda não foram efetivamente implementadas. A avaliação prévia de impacto ambiental resguarda os riscos à saúde humana e da biota selvagem causados pela exposição aos resíduos de medicamentos. Portanto, esses modelos internacionais poderiam servir de base para discussões e/ou alterações legais e normativas no Brasil.

Abstract This paper presents a descriptive review of laws and regulations on the management of drugs and the residues thereof adopted by countries in Europe, the Americas and Australia. This review integrates relevant points of official documents of regulatory agencies in these countries, as well as important scientific works. All countries surveyed carry out drug management concomitant with the management of the residues thereof, ranging from awareness programs on the rational use and the risks of drugs through to the collection and safe disposal of such residues. Germany, the USA and Sweden demand a prior assessment of the environmental impact caused by a given drug as a criterion for its registration. Sweden is noteworthy in that it periodically updates a list of essential drugs based on risk assessment and the environmental risks posed by the residues thereof. In Brazil, the legal measures proposed including rational prescription and reverse logistics have not yet been effectively implemented. Prior environmental impact assessment safeguards the risks to human health and the wild biota caused by exposure to drug residues. Therefore, these international models could serve as a basis for discussion and/or legal and regulatory changes in Brazil.

Intercambialidade de produtos biológicos no Sistema Único de Saúde (SUS): principais desafios regulatórios / Interchangeability of biological products in the Brazilian Unified National Health System (SUS): the main regulatory challenges / Intercambiabilidad de productos biológicos en el Sistema Único de Salud (SUS): principales desafíos regulatorios

Resumo: Produtos biológicos revolucionaram a terapêutica mundial. O alto custo desses medicamentos, no entanto, ameaça a sustentabilidade dos sistemas de saúde. O desenvolvimento de cópias é tido como uma alternativa econômica, mas devido à complexidade desses produtos, muitos conceitos utilizados para os medicamentos genéricos não se aplicam. A intercambialidade entre produtos biológicos representa um desafio regulatório a ser superado. Este ensaio discute os principais desafios regulatórios relacionados ao estabelecimento de critérios para intercambialidade entre produtos biológicos novos e suas cópias no âmbito do Sistema Único de Saúde (SUS), considerando as diretrizes adotadas pelas principais agências reguladoras de medicamentos do mundo sobre a intercambialidade e o arcabouço regulatório vigente no Brasil para esta questão. Preocupações relacionadas à intercambialidade de produtos biológicos incluem substituição automática, nomenclatura, farmacovigilância, imunogenicidade e extrapolação das indicações terapêuticas e dos dados clínicos de produtos biológicos novos para suas cópias. Embora o sucesso clínico e os benefícios econômicos da alternância entre alguns produtos biológicos novos e seus biossimilares já tenham sido observados, a heterogeneidade das barreiras regulatórias para aprovação das cópias de produtos biológicos entre diferentes países deve ser considerada para a regulamentação da intercambialidade de produtos biológicos no Brasil.

Abstract: Biological products have sparked a worldwide therapeutic revolution. However, the high cost of these products threatens health systems' sustainability. The development of copies is considered an economic alternative, but due to the products' complexity, many concepts used in generic drugs do not apply. Interchangeability between biologicals poses a regulatory challenge. This essay discusses the main regulatory challenges for establishing criteria for interchangeability between new biologicals and their copies in the scope of the Brazilian Unified National Health System (SUS), considering the guidelines adopted by the world's main drug regulatory agencies concerning interchangeability and the prevailing Brazilian regulatory framework on this issue. Concerns related to the interchangeability of biologicals include automatic substitution, nomenclature, pharmacovigilance, immunogenicity, and extrapolation of therapeutic indications and clinical data from new biologicals to their copies. While the clinical success and economic benefits of switching from new biologicals to their biosimilars have already been observed, the heterogeneity between countries in the regulatory barriers to the approval of copies of biologicals should be taken into consideration during the regulation of interchangeability of biologicals in Brazil.

Resumen: Los productos biológicos revolucionaron la terapéutica mundial. El alto coste de estos medicamentos, no obstante, amenaza la sostenibilidad de los sistemas de salud. El desarrollo de copias se considera como una alternativa económica, pero debido a la complejidad de estos productos, muchos conceptos utilizados para los medicamentos genéricos no se aplican a los mismos. La intercambiabilidad entre productos biológicos representa un desafío regulatorio que se debe superar. Este trabajo discute los principales desafíos regulatorios, relacionados con el establecimiento de criterios para la intercambiabilidad entre productos biológicos nuevos y sus copias en el ámbito del Sistema Único de Salud (SUS), considerando las directrices adoptadas por las principales agencias regulatorias de medicamentos del mundo sobre la intercambiabilidad y el armazón regulatorio vigente en Brasil para esta cuestión. Las preocupaciones relacionadas con la intercambiabilidad de productos biológicos incluyen la sustitución automática, nomenclatura, farmacovigilancia, inmunogenicidad y extrapolación de las indicaciones terapéuticas, así como de los datos clínicos de productos biológicos nuevos para sus copias. A pesar de que el éxito clínico y los beneficios económicos de la alternancia entre algunos productos biológicos nuevos y sus biosimilares, ya se han observados, la heterogeneidad de las barreras regulatorias para la aprobación de las copias de productos biológicos entre los diferentes países debe ser considerada para la regulación de la intercambiabilidad de productos biológicos en Brasil.

Biosimilares: consenso de expertos de la Sociedad Latinoamericana de Psoriasis (SOLAPSO) en Argentina / Biosimilars: Expert consensus of the Latin American Society of Psoriasis (SOLAPSO) in Argentina

Con la aparición de los tratamientos biológicos, se ha modificado la terapéutica de muchas enfermedades, en especial las reumatológicas, dermatológicas y oncológicas. Debido al alto costo de estos productos y el vencimiento de las patentes, la industria farmacológica desarrolla los biosimilares, fármacos que son una versión (copia) de la sustancia de un medicamento biológico original, y que pueden facilitar el acceso a estos tratamientos. Son elaborados de acuerdo a exigencias específicas de organismos reguladores en cuanto a calidad, eficacia y seguridad, y debe demostrarse que son comparables al medicamento de referencia. Este trabajo revisa las normativas regulatorias internacionales y nacionales, las controversias que rodean a los biosimilares y presenta la posición de un grupo de expertos con respecto al uso de biosimilares.

With the appearance of biological treatments, therapeutics has changed in many rheumatological, dermatological and oncological diseases. Due to the high cost of these biological medicaments and the expiration of patents, the pharmacological industry develops biosimilars, drugs that are a version (copy) of the substance of the original biological medicine, with the aim of facilitating access to these treatments. These biosimilars are prepared according to the specific requirements of regulatory bodies in terms of quality, efficacy and safety, and must be shown they are comparable to the reference product. This paper reviews the international and national regulatory framework, the controversies surrounding biosimilars, and presents the position of a group of experts regarding the use of biosimilars.

A Visão Jurídica do Uso do Medicamento off label no âmbito da Saúde Suplementar / The Legal View of the Use of the off-label Drug in the scope of Supplementary Health

Objetivo: Este artigo tem o objetivo analisar do ponto de vista sobre o tema do uso do medicamento off label no âmbito da Saúde Suplementar. Metodologia: foi realizado uma revisão da legislação pátria, consultando o inteiro teor das leis e normas que constituem o tema. Foram consultadas as bases de dados legislativos do Senado Federal, bem como a base legal da Agência Nacional de Vigilância Sanitária e a Agência Nacional de Saúde Suplementar. Resultados: há fartura de normas legais para a regulamentação da matéria, sendo que toda a política de tratamento deste tema está consubstanciada na base da pirâmide hierárquica de leis, ou seja, nas portarias e instruções normativas. Conclusão: A existência de previsão de cobertura da doença ou patologia no contrato, há liberdade de prescrição de medicamentos off label pelo médico assistente se aplica. (AU)

Objective: This article aims to analyze from the point of view on the subject of the use of the off label drug in the scope of Supplementary Health. Methods: a review of the national legislation has been carried out, consulting the entire content of the laws and norms that constitute the theme. The legislative databases of the Federal Senate were consulted, as well as the legal basis of the National Sanitary Surveillance Agency and the National Supplementary Health Agency. Results: There are plenty of legal norms for the regulation of the matter, and the whole treatment policy of this theme is based on the hierarchical pyramid of laws, that is, in ordinances and normative instructions. Conclusion: The existence of predicted coverage of the disease or pathology in the contract, there is freedom of prescription of off-label medications by the attending physician applies. (AU)

Objetivo: Este artículo tiene el objetivo de analizar desde el punto de vista sobre el tema del uso del medicamento off label en el ámbito de la Salud Suplementaria. Medotología: se realizó una revisión de la legislación patria, consultando el entero contenido de las leyes y normas que constituyen el tema. Se consultaron las bases de datos legislativos del Senado Federal, así como la base legal de la Agencia Nacional de Vigilancia Sanitaria y la Agencia Nacional de Salud Suplementaria. Resultados: hay abundancia de normas legales para la reglamentación de la materia, siendo que toda la política de tratamiento de este tema está consubstanciada en la base de la pirámide jerárquica de leyes, o sea, en las ordenanzas e instrucciones normativas. Conclusión: La existencia de previsión de cobertura de la enfermedad o patología en el contrato, hay libertad de prescripción de medicamentos fuera de etiqueta por el médico asistente se aplica. (AU)

Lei da fosfoetanolamina sintética no Brasil / Synthetic phosphoethanolamine law in Brazil / Ley de la fosfoetanolamina sintética en Brasil

Objetivo: O objetivo foi analisar o contexto em que foi proposto e aprovado o diploma legal que autorizou o fornecimento da fosfoetanolamina sintética à luz da legislação brasileira. Metodologia: Tratou-se de um estudo descritivo-analítico, considerando que foi feita uma revisão teórica das informações disponíveis sobre o projeto de Lei da Câmara PL nº 4.639/2016, no Senado Federal PLC nº 3/2016 e da Lei da Fosfoetanolamina, Lei nº 13.269, de 13 de abril de 2016, além da revisão normativa das atribuições e competências da Agência Nacional de Vigilância Sanitária. Resultados: Ocorreu uma substituição de todo o arcabouço jurídico por legislação ordinária de efeitos concretos. Conclusão: A atuação da Agência Nacional de Vigilância Sanitária foi desconsiderada, já que cabe à agência realizar todos os testes e, posteriormente, liberar o medicamento para o consumo

Objective: The objective was to analyze the context in which the aforementioned law was proposed and approved, in light of Brazilian legislation. Methodology: This was a descriptive-analytical study, considering that a theoretical review of the information available on the House Bill PL 4.639 / 2016, Federal Senate PLC No. 3/2016 and the Law of Phosphoethanolamine, Law 13,269, of April 13, 2016, in addition to the normative review of the attributions and competencies of Brazilian Health Surveillance Agency. Results: It is clear that a whole legal framework has been replaced by ordinary legislation with concrete effects. Conclusions: In the case in question, Brazilian Health Surveillance Agency performance was disregarded, since it is up to the Agency to carry out all the tests and subsequently release the product for consumption

Objetivo: El objetivo fue analizar el contexto en que se propuso y aprobó el referido diploma legal, a la luz de la legislación brasileña. Metodología: En el caso de que se trate de un estudio descriptivo-analítico, considerando que se hizo una revisión teórica de las informaciones disponibles sobre el proyecto de Ley de la Cámara PL nº 4.639 / 2016, en el Senado Federal PLC nº 3/2016 y de la Ley de la Fosfoetanolamina, Ley nº 13.269, de 13 de abril de 2016, además de la revisión normativa de las atribuciones y competencias de Agencia Nacional de Vigilancia Sanitaria. Resultados: Ocurrió una sustitución de todo un marco jurídico por legislación ordinaria de efectos concretos. Conclusiones: En el caso en cuestión, la actuación de la Agencia Nacional de Vigilancia Sanitaria fue desconsiderada, ya que corresponde a la Agencia realizar todas las pruebas y, posteriormente, liberar el medicamento para el consumo