ABSTRACT
The establishment of core indicators for assessment plays an important role in carrying out the lifecycle value assessment of Chinese patent medicine, which are developed based on the concepts such as clinical value oriented, paying attention to the human use experience, and whole process quality control. To this end, the Specialty Committee of Data Monitoring and Decision Making of the World Federation of Chinese Medicine Societies organized experts to draft the Expert Consensus on Core Indicators for Lifecycle Value Assessment of Chinese Patent Medicine based on the research including Chinese Medicine Registration Review Evidence System in Combination of Traditional Chinese Medicine Theory, Human Use Experience, and Clinical Trials(GZY-FJS-2022-206) by National Administration of Traditional Chinese Medicine. This consensus proposed 92 core indicators from four stages, including new drug R&D project approval, pre-clinical research, new drug marketing authorization, and post-marketing, combining the assessment purposes and needs of different stakeholders from different dimensions such as clinical needs, clinical positioning, human use experience, effectiveness, safety, quality control, innovation, accessibility, and suitability. This consensus also interpreted the indicators to clearly elucidate the core elements of the value assessment of Chinese patent medicine in different R&D stages and guided the stakeholders to identify, analyze, and assess the value of Chinese patent medicine in the R&D and use process based on the core indicators in a scientific, objective, and standardized approach. This consensus is expected to play an important role in the high-quality new drug development, drug pricing and compensation of Chinese patent medicine, the development of clinical pathways, and rational clinical application.
Subject(s)
Humans , Nonprescription Drugs/therapeutic use , Consensus , Medicine, Chinese Traditional , Quality Control , Drug Approval , Drugs, Chinese Herbal/therapeutic useABSTRACT
This study aims to analyze the new drugs registered in Brazil from 2003 to 2013 from the perspective of childcare needs, drug safety and considering the disease burden of the country. This is a retrospective cohort study including new drugs registered in Brazil between 2003 and 2013. Drug indications were related to the Disability-Adjusted Life Year (DALY) of the 2015 Global Burden of Disease Study. Association between the number of new drugs and DALY was determined by Spearman's coefficient. Post-marketing safety alerts specific to the pediatric population have been identified in the WHO Drug Information Bulletin and on websites of drug regulatory agencies. A total of 134 new drugs were included in the cohort and 46 (34.3%) had a pediatric indication. There was no evidence of an association between the disease burden in children in Brazil and the number of pediatric drugs. The safety alert data associated with the pediatric population published after registration of the new drugs were scarce. The number of new drugs launched in Brazil with a pediatric indication was small, reflecting the international challenges of developing effective and safe medicines for children. No association was found between the number of new drugs and the disease burden.
Subject(s)
Brazil/ethnology , Pharmaceutical Preparations/analysis , Drug Approval/legislation & jurisprudence , World Health Organization , Child Care/methods , Child Health/classification , Cohort Studies , Reference Drugs , Health Services Needs and Demand/classificationABSTRACT
On the basis of introducing FDA's regulatory measure and relevant requirement for life-cycle management of combination product, this paper aims to discuss corresponding countermeasure for supervision system construction in consideration of domestic drug-device combination product's current situation, in order to promote innovative development of relevant industries.
Subject(s)
Device Approval , Drug Approval , United States , United States Food and Drug AdministrationABSTRACT
ABSTRACT Objective. To describe the current status of regulatory reliance in Latin America and the Caribbean (LAC) by assessing the countries' regulatory frameworks to approve new medicines, and to ascertain, for each country, which foreign regulators are considered as trusted regulatory authorities to rely on. Methods. Websites from LAC regulators were searched to identify the official regulations to approve new drugs. Data collection was carried out in December 2019 and completed in June 2020 for the Caribbean countries. Two independent teams collected information regarding direct recognition or abbreviated processes to approve new drugs and the reference (trusted) regulators defined as such by the corresponding national legislation. Results. Regulatory documents regarding marketing authorization were found in 20 LAC regulators' websites, covering 34 countries. Seven countries do not accept reliance on foreign regulators. Thirteen regulatory authorities (Argentina, Colombia, Costa Rica, Dominican Republic, Ecuador, El Salvador, Guatemala, Mexico, Panama, Paraguay, Peru, Uruguay, and the unique Caribbean Regulatory System for 15 Caribbean States) explicitly accept relying on marketing authorizations issued by the European Medicines Agency, United States Food and Drug Administration, and Health Canada. Ten countries rely also on marketing authorizations from Australia, Japan, and Switzerland. Argentina, Brazil, Chile, and Mexico are reference authorities for eight LAC regulators. Conclusions. Regulatory reliance has become a common practice in the LAC region. Thirteen out of 20 regulators directly recognize or abbreviate the marketing authorization process in case of earlier approval by a regulator from another jurisdiction. The regulators most relied upon are the European Medicines Agency, United States Food and Drug Administration, and Health Canada.
RESUMEN Objetivo. Describir el estado actual de la utilización de las decisiones de autoridades regulatorias de otras jurisdicciones en América Latina y el Caribe mediante la evaluación de los marcos regulatorios nacionales para la aprobación de nuevos medicamentos y establecer los organismos regulatorios extranjeros que se consideran autoridades regulatorias confiables para cada país. Métodos. Se realizaron búsquedas en los sitios web de las autoridades regulatorias de América Latina y el Caribe para identificar las regulaciones oficiales para la aprobación de nuevos medicamentos. La recopilación de datos se llevó a cabo en diciembre del 2019 y se completó en junio del 2020 para los países del Caribe. Dos equipos independientes recopilaron información sobre el reconocimiento directo o los procedimientos abreviados para la aprobación de nuevos medicamentos y los autoridades regulatorias de referencia (confiables) así definidos en la legislación nacional correspondiente. Resultados. Se encontraron documentos regulatorios sobre la aprobación de nuevos productos en los sitios web de veinte organismos regulatorios de América Latina y el Caribe, que abarcaban 34 países. Siete países no aceptan la utilización de decisiones de autoridades regulatorias extranjeras. Trece autoridades regulatorias (Argentina, Colombia, Costa Rica, Ecuador, El Salvador, Guatemala, México, Panamá, Paraguay, Perú, República Dominicana, Uruguay y el sistema regulador único para quince Estados del Caribe) aceptan de manera explícita confiar las decisiones para aprobación de nuevos medicamentos emitidas por la Agencia Europea de Medicamentos, la Administración de Alimentos y Medicamentos de Estados Unidos y Salud Canadá. Diez países aceptan también utilizar las autorizaciones para la comercialización de Australia, Japón y Suiza. Argentina, Brasil, Chile y México son autoridades de referencia para ocho autoridades regulatorias en la región. Conclusiones. La utilización de las decisiones de autoridades regulatorias de otras jurisdicciones se han convertido en una práctica común en América Latina y el Caribe. Trece de veinte autoridades regulatorias reconocen directamente o abrevian el proceso de aprobación de nuevos medicamentos en caso de que hayan recibido previamente la aprobación por parte de un organismo regulatorio de otra jurisdicción. La Agencia Europea de Medicamentos, la Administración de Alimentos y Medicamentos de Estados Unidos y Salud Canadá son las autoridades regulatorias de otras jurisdicciones en las cuales los reguladores de América Latina y el Caribe confían más.
RESUMO Objetivo. Descrever a prática atual de uso de decisões regulatórias de outras jurisdições na América Latina e no Caribe (ALC) mediante avaliação os marcos regulatórios dos países para aprovação de novos medicamentos e verificar, para cada país, quais entidades reguladoras estrangeiras são consideradas autoridades reguladoras de confiança por cada país. Métodos. Foi realizada uma pesquisa nos sites das autoridades reguladoras da ALC para identificar as regulamentações oficiais para aprovação de novos medicamentos. A coleta de dados foi feita em dezembro de 2019 e concluída em junho de 2020 para os países do Caribe. Dois grupos independentes coletaram informações sobre o reconhecimento direto ou o procedimento abreviado para aprovação de novos medicamentos e as autoridades reguladoras de referência (de confiança) definidas como tal pela respectiva legislação nacional. Resultados. Documentos regulatórios relacionados à aprovação de novos produtos foram obtidos de 20 sites de órgãos reguladores da ALC, abrangendo 34 países. Sete países não admitem o uso de decisões regulatórias de entidades reguladoras externas. Treze autoridades reguladoras (na Argentina, Colômbia, Costa Rica, El Salvador, Equador, Guatemala, México, Panamá, Paraguai, Peru, República Dominicana, Uruguai e o Sistema Regulador do Caribe unificado para 15 Estados caribenhos) admitem explicitamente a admissibilidade de decisões regulatórias para aprovação de novos medicamentos de outras jurisdições, quais sejam: Agência Europeia de Medicamentos (EMA), Agência Reguladora de Alimentos e Medicamentos (FDA) dos EUA e Health Canada. Dez países também aceitam decisões para autorização de comercialização da Austrália, Japão e Suíça. Argentina, Brasil, Chile e México são autoridades de referência para oito agências reguladoras. Conclusões. O uso de decisões regulatórias de outras jurisdições tornou-se prática comum na América Latina e Caribe. Treze das 20 agências reguladoras reconhecem diretamente ou abreviam o procedimento de aprovação de novos medicamentos no caso de tal aprovação já haver sido concedida por uma autoridade reguladora de outra jurisdição. A EMA, a FDA e a Health Canada são as autoridades estrangeiras nas quais as agências reguladoras da América Latina e Caribe mais confiam.
Subject(s)
Drug Approval/legislation & jurisprudence , Government Regulation , Cross-Sectional Studies , Caribbean Region , Latin AmericaABSTRACT
BACKGROUND@#Medicines for the treatment of 2019-novel coronavirus (2019-nCoV) infections are urgently needed. However, drug screening using live 2019-nCoV requires high-level biosafety facilities, which imposes an obstacle for those institutions without such facilities or 2019-nCoV. This study aims to repurpose the clinically approved drugs for the treatment of coronavirus disease 2019 (COVID-19) in a 2019-nCoV-related coronavirus model.@*METHODS@#A 2019-nCoV-related pangolin coronavirus GX_P2V/pangolin/2017/Guangxi was described. Whether GX_P2V uses angiotensin-converting enzyme 2 (ACE2) as the cell receptor was investigated by using small interfering RNA (siRNA)-mediated silencing of ACE2. The pangolin coronavirus model was used to identify drug candidates for treating 2019-nCoV infection. Two libraries of 2406 clinically approved drugs were screened for their ability to inhibit cytopathic effects on Vero E6 cells by GX_P2V infection. The anti-viral activities and anti-viral mechanisms of potential drugs were further investigated. Viral yields of RNAs and infectious particles were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and plaque assay, respectively.@*RESULTS@#The spike protein of coronavirus GX_P2V shares 92.2% amino acid identity with that of 2019-nCoV isolate Wuhan-hu-1, and uses ACE2 as the receptor for infection just like 2019-nCoV. Three drugs, including cepharanthine (CEP), selamectin, and mefloquine hydrochloride, exhibited complete inhibition of cytopathic effects in cell culture at 10 μmol/L. CEP demonstrated the most potent inhibition of GX_P2V infection, with a concentration for 50% of maximal effect [EC50] of 0.98 μmol/L. The viral RNA yield in cells treated with 10 μmol/L CEP was 15,393-fold lower than in cells without CEP treatment ([6.48 ± 0.02] × 10vs. 1.00 ± 0.12, t = 150.38, P < 0.001) at 72 h post-infection (p.i.). Plaque assays found no production of live viruses in media containing 10 μmol/L CEP at 48 h p.i. Furthermore, we found CEP had potent anti-viral activities against both viral entry (0.46 ± 0.12, vs.1.00 ± 0.37, t = 2.42, P < 0.05) and viral replication ([6.18 ± 0.95] × 10vs. 1.00 ± 0.43, t = 3.98, P < 0.05).@*CONCLUSIONS@#Our pangolin coronavirus GX_P2V is a workable model for 2019-nCoV research. CEP, selamectin, and mefloquine hydrochloride are potential drugs for treating 2019-nCoV infection. Our results strongly suggest that CEP is a wide-spectrum inhibitor of pan-betacoronavirus, and further study of CEP for treatment of 2019-nCoV infection is warranted.
Subject(s)
Humans , Betacoronavirus , Genetics , Cell Line , Clinical Laboratory Techniques , Coronavirus Infections , Diagnosis , Drug Therapy , Drug Approval , Pandemics , Pneumonia, Viral , Diagnosis , Drug Therapy , RNA, Small Interfering , Genetics , Real-Time Polymerase Chain Reaction , Viral LoadABSTRACT
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.
Subject(s)
Humans , Biological Products , Biosimilar Pharmaceuticals , Legislation, Drug , Brazil , Therapeutic Equivalency , Drugs, Generic , Drug Approval , Pharmacovigilance , Legislation, Pharmacy , National Health ProgramsABSTRACT
RESUMEN En Argentina, los nuevos medicamentos pueden ser autorizados presentando el certificado de aprobación en al menos uno de los 15 países considerados de alta vigilancia sanitaria, sin necesidad de realizar una evaluación propia de eficacia, seguridad o valor terapéutico agregado por el nuevo producto. En este artículo, evaluamos los nuevos medicamentos comercializados en Argentina en el año 2016, utilizando diferentes enfoques: su aprobación por otras agencias reguladoras, demostración de eficacia en ensayos clínicos aleatorizados, tipo de desenlaces estudiados, calificación del valor terapéutico agregado por medio de dos escalas reconocidas y el precio de venta al público. Se concluye que, como reflejo de lo que ocurre en los países desarrollados, los nuevos medicamentos ingresan con precios exorbitantes, pero la mayoría no representa un avance terapéutico significativo. El resultado es un aumento de riesgos para los pacientes y una sobrecarga para los sistemas de financiación públicos y privados.
ABSTRACT In Argentina, new drugs can be authorized by presenting the drug's certificate of approval in at least one of 15 countries considered to have rigorous health surveillance, without needing to carry out a local evaluation of the efficacy, safety or added therapeutic value of the new product. In this article, we evaluate the new drugs commercialized in Argentina in 2016 using different approaches: their approval by other regulatory agencies, the demonstration of their efficacy in randomized clinical trials, types of outcomes studied, rating of their added therapeutic value using two widely recognized scales, and their sale price to the public. It is concluded that, as a reflection of what occurs in developed countries, new drugs enter the market at exorbitant prices, but the majority do not represent a significant therapeutic advancements. The result is increased risks to patients and an overburdening of the public and private funding systems.
Subject(s)
Humans , Drug Costs/statistics & numerical data , Cost-Benefit Analysis/statistics & numerical data , Drug Approval , Drug Evaluation , Argentina , Randomized Controlled Trials as TopicABSTRACT
Patients with hyperglycemia are at a high risk of cardio- and cerebrovascular diseases. Diabetes patients also have poor outcomes after cerebrovascular disease development. Several classes of drugs are used for diabetes management in clinical practice. Thiazolidinedione (TZD) was introduced in the late 1990s, and new antidiabetic agents have been introduced since 2000. After issues with rosiglitazone in 2007, the U.S. Food and Drug Administration strongly recommended that trials investigating cardiovascular risk associated with new antidiabetic medications should be conducted before drug approval in the United States, to prove the safety of these new drugs and to determine their superiority to previous medications. Currently, results are available from two studies with TZD focusing on cardiovascular diseases, including stroke, and from 12 cardiovascular outcome trials focusing on major adverse cardiovascular events associated with new antidiabetic agents (four with dipeptidyl peptidase-4 inhibitors, three with sodium-glucose cotransporter-2 inhibitors, and five with glucagon-like peptide-1 analogues). These studies showed different results for primary cardiovascular outcomes and stroke prevention. It is important to determine whether prescription of TZD or new antidiabetic medications compared to conventional treatment, such as sulfonylurea or insulin, is better for stroke management. Furthermore, it is unclear whether drugs in the same class show greater safety and efficacy than other drugs for stroke management.
Subject(s)
Humans , Cardiovascular Diseases , Cerebrovascular Disorders , Diabetes Mellitus , Dipeptidyl-Peptidase IV Inhibitors , Drug Approval , Glucagon-Like Peptide 1 , Hyperglycemia , Hypoglycemic Agents , Insulin , Prescriptions , Stroke , Thiazolidinediones , United States , United States Food and Drug AdministrationABSTRACT
Resumo: Os anticorpos monoclonais (mABs) têm sido indicados como tecnologia inovadora para o tratamento de alguns tipos de câncer, por serem capazes de alvejar e matar seletivamente células tumorais. Contudo, os altos custos dessas terapias colocam em questão a sustentabilidade do acesso. Este trabalho teve como objetivo identificar as principais características dos anticorpos monoclonais, destinados ao tratamento de câncer, com registro sanitário ativo, no Brasil, em 2016. Tratou-se de uma análise descritiva retrospectiva a partir de consulta à página de Internet da Agência Nacional de Vigilância Sanitária (Anvisa), em que esses mABs foram caracterizados de acordo com antígeno-alvo, tipo de anticorpo, ano de registro, indicações terapêuticas e empresa detentora do registro. Foram identificados 14 anticorpos com ação em sete antígenos-alvo diferentes. No que diz respeito às indicações clínicas, houve uma maior frequência de linfomas, leucemias, câncer de mama e câncer colorretal. Quanto ao tipo, foram identificados três anticorpos quiméricos, seis humanizados e cinco humanos. A Roche apareceu como a empresa detentora do registro de 6 dos 14 mABs, o que representa 43% dos registros sanitários. Foi possível, a partir desses dados, discutir a ideia de medicamentos me-too no mercado de biológicos, assim como pensar as tensões existentes nesse mercado e a ideia de oligopólio diferenciado. Apesar do desenvolvimento de novos produtos, ainda que para atuar em um mesmo alvo, representar a possibilidade de um incremento competitivo e, com isso, de uma diminuição dos preços praticados pelas empresas torna-se um problema quando é a mesma empresa que lança no mercado novos anticorpos direcionados ao mesmo alvo, sem mudanças relevantes.
Abstract: Monoclonal antibodies (mABs) have been indicated as an innovative technology for the treatment of some types of cancer, since they are capable of targeting and selectively killing tumor cells. However, the high costs of these therapies raise questions as to the sustainability of access. This study aimed to identify the principal characteristics of monoclonal antibodies used in cancer treatment with active marketing authorization in Brazil as of 2016. This was a descriptive retrospective analysis based on consultation of the Brazilian Health Regulatory Agency (Anvisa) website, in which these mABs were characterized according to the target antigen, type of antibody, year of registration, therapeutic indications, and applicant. A total of 14 antibodies were identified with action on seven different target antigens. The most frequent clinical indications were for lymphomas, leukemias, breast cancer, and colorectal cancer. As for type, the study identified three chimeric, six humanized, and five human antibodies. Roche was the applicant in 6 of the 14 mABs, or 43% of the marketing authorization. It was possible to discuss the idea of me-too medicines in the biological market and the idea of a differentiated oligopoly, as well as to think about the tensions in this kind of market. It is expected that the development of new products, although to act on the same biological target, represent the possibility of a competitive increase and, as a result, a decrease in prices practiced by companies. However, this becomes a problem when it is the same pharmaceutical industry that launches on the market new antibodies directed to the same target, with no relevant changes.
Resumen: Los anticuerpos monoclonales (mABs) han sido señalados como una tecnología innovadora para el tratamiento de algunos tipos de cáncer, por ser capaces de apuntar y matar selectivamente células tumorales. No obstante, los altos costes de estas terapias ponen en cuestión la sostenibilidad del acceso. El objetivo de este trabajo fue identificar las principales características de los anticuerpos monoclonales, destinados al tratamiento de cáncer, con registro sanitario activo, en Brasil, en 2016. Se trató de un análisis descriptivo retrospectivo, a partir de la consulta a la página web de la Agencia Nacional de Vigilancia Sanitaria (Anvisa), donde esos mABs se caracterizaron conforme el antígeno objetivo, tipo de anticuerpo, año de registro, indicaciones terapéuticas y empresa detentora de su registro. Se identificaron 14 anticuerpos con acción en siete antígenos-objetivo diferentes. En lo referente a las indicaciones clínicas, hubo una mayor frecuencia de linfomas, leucemias, cáncer de mama y cáncer colorrectal. En cuanto al tipo, se identificaron tres anticuerpos quiméricos, seis humanizados y cinco humanos. Roche apareció como la empresa detentora del registro de 6 de los 14 mABS, lo que representa un 43% de los registros sanitarios. Fue posible, a partir de esos datos, discutir la idea de medicamentos me-too en el mercado de biológicos, así como reflexionar sobre las tensiones existentes en ese mercado y la idea de oligopolio diferenciado. El desarrollo de nuevos productos, aunque sean para actuar en un mismo objetivo, representa la posibilidad de un incremento competitivo y, con ello, de una disminución de los precios practicados por las empresas. Esto se convierte en un problema cuando es la misma empresa que lanza en el mercado nuevos anticuerpos, dirigidos al mismo objetivo, sin cambios relevantes.
Subject(s)
Humans , Antibodies, Monoclonal/economics , Antibodies, Monoclonal/therapeutic use , Neoplasms/therapy , Brazil , Retrospective Studies , Health Care Costs , Drug Approval , Health Care Sector , Drug Industry , Government Agencies , Antibodies, Monoclonal/classificationABSTRACT
ABSTRACT The manufacturing process for biological products is complex, expensive and critical to the final product, with an impact on their efficacy and safety. They have been increasingly used to treat several diseases, and account for approximately 50% of the yearly budget for the Brazilian public health system. As the patents of biological products expire, several biosimilars are developed. However, there are concerns regarding their efficacy and safety; therefore, the regulatory agencies establish rules to approve and monitor these products. In Brazil, partnership programs between national government-owned companies and private technology holders have been implemented, aiming at knowledge sharing, capacity-building and technological transfer. Such partnerships locally promote manufacturing of these strategic drugs at reduced costs to the public health system. These agreements offer mutual advantages to both the government and patent holders: for the former, a biotechnological development flow is established and enables potential cost reduction and self-sufficient production; whereas for the latter, exclusive sales of the product are ensured during technological transfer, for a fixed period.
RESUMO O processo de manufatura de produtos biológicos é complexo, oneroso e crítico para o produto final, com impacto em sua eficácia e segurança. Seu uso está sendo cada vez mais ampliado no tratamento de diversas doenças, e cerca de 50% do orçamento anual do sistema de saúde público brasileiro é consumido por tais produtos. Com o término da proteção de patentes de produtos biológicos diversos, estão sendo desenvolvidos os biossimilares. Porém, há preocupações relacionadas com sua eficácia e segurança, fazendo com que os órgãos reguladores criem regulamentações para sua aprovação e monitoramento. No Brasil, estão sendo implantados programas de parceria entre laboratórios públicos nacionais e laboratórios detentores de tecnologia, objetivando a obtenção de conhecimento, capacitação profissional e transferência desta tecnologia. Tais parcerias visam à produção local destes medicamentos estratégicos a um custo reduzido para o Sistema Único de Saúde. Os acordos oferecem vantagens mútuas para o governo e o laboratório detentor da patente do produto biológico: ao primeiro, estabelece-se um fluxo de desenvolvimento biotecnológico, que possibilita potencial redução de custos e autossuficiência na produção, enquanto ao segundo garante-se a exclusividade da venda do produto durante a transferência da tecnologia por um prazo estabelecido.
Subject(s)
Humans , Public-Private Sector Partnerships/trends , Biosimilar Pharmaceuticals/standards , Patents as Topic , Brazil , Technology, Pharmaceutical/trends , Technology, Pharmaceutical/statistics & numerical data , Drug Approval/legislation & jurisprudence , Biosimilar Pharmaceuticals/economicsABSTRACT
Nonprescription drugs have become increasingly important in Korean healthcare. By leveraging lower-cost drugs and reducing expenditure associated with fewer physician visits, the nonprescription segment can deliver tremendous value to individual consumers and the Korean healthcare system. Many countries have provided simpler and more rapid routes to market entry for qualifying nonprescription drug products, using the established data on drug safety and efficacy, as well as public and professional opinion. In US, the FDA waived the pre-approval process for over-the-counter (OTC) drugs marketed through the OTC Monograph Process. In Australia and Canada, different OTC product application levels are defined, with a reduced level of assessment required when the risks to consumers are considered low. Japan established a new OTC evaluation system in 2014 to facilitate the Rx-to-OTC switch process. The legislative framework for medicinal products in the European Union allows for drugs to be approved with reference to appropriate bibliographic data for old active substances with well-established uses. Through a comparison of the regulatory framework and the requirements for nonprescription approval process in different countries, several ways to improve regulatory practice for the evaluation of nonprescription drugs in Korea have been suggested.
Subject(s)
Australia , Canada , Delivery of Health Care , Drug and Narcotic Control , Drug Approval , European Union , Health Expenditures , Japan , Korea , Nonprescription DrugsABSTRACT
ABSTRACT Gout is considered the most common form of inflammatory arthritis in men over 40 years. The authors present a brief review of the current treatment of gout and discuss the existing pharmacological limitations in Brazil for the treatment of this disease. Although allopurinol is still the main drug administered for decreasing serum levels of uric acid in gout patients in this country, the authors also present data that show a great opportunity for the Brazilian drug market for the treatment of hyperuricemia and gout and especially for patients using private and public (SUS) health care systems.
RESUMO A gota é considerada a forma mais comum de artrite inflamatória em homens acima de 40 anos. Os autores apresentam uma breve revisão sobre o tratamento atual da gota e discutem as limitações farmacológicas existentes no Brasil para o tratamento dessa enfermidade. Apesar de o alopurinol ainda ser a principal medicação para a redução dos níveis de uricemia de pacientes com gota no país, os autores também apresentam dados que apontam para uma grande oportunidade para o mercado farmacológico brasileiro em relação ao tratamento da hiperuricemia e da artrite gotosa e especialmente para pacientes usuários de sistemas privados de saúde e do SUS (Sistema Único de Saúde).
Subject(s)
Humans , Uric Acid/blood , Gout Suppressants/therapeutic use , Hyperuricemia/drug therapy , Gout/drug therapy , Brazil/epidemiology , Incidence , Drug Approval , Hyperuricemia/blood , Hyperuricemia/epidemiology , Gout/blood , Gout/epidemiologyABSTRACT
Abstract Since the enforcement of Generics Act (1999), three types of pharmaceutically equivalent products are marketed in Brazil: innovative reference (REF), "similar" (S) and generic (G) drugs. The S (brand name) and G (generic name) borrow from REF (brand name) clinical data on safety and efficacy and dosage regimen. G (but not S) is bioequivalent to and interchangeable with REF. Starting in 2003, Brazilian Sanitary Surveillance Agency (Anvisa) has required data on relative bioavailability tests (with REF) to approve (or renew registration of) S drugs. In 2014, Anvisa extended interchangeability notion to similar drugs with a "comparable" bioavailability, i.e., an "equivalent" similar drug (EQ). Drugs for chronic diseases and "critical dose medicines" are listed among the EQ drugs approved. Interchangeability of nonbioequivalent medicines raises deep concerns regarding therapeutic failures and adverse events. Concerns are even more worrisome if patients switch from one drug to another during an ongoing treatment for illnesses such as epilepsy, congestive heart failure, hypertension, diabetes and/or substitutable drugs have a narrow therapeutic index.
Resumo A partir da vigência da lei dos genéricos (1999), três tipos de produtos farmaceuticamente equivalentes são comercializados no Brasil: o medicamento inovador de refência (REF), o produto "similar" (S), e o genérico (G). O similar (nome de fantasia) e o genérico (nome genérico) tomam de empréstimo do REF (nome de fantasia) os dados clínicos de segurança e eficácia e a posologia. G (mas não S) é bioequivalente ao, e intercambiável com REF. Desde 2003, a Agência Nacional de Vigilância Sanitária (Anvisa) exige dados de testes de biodisponibilidade relativa para registrar (ou renovar o registro de) medicamentos S. Em 2014, a Anvisa estendeu o conceito de intercambialidade aos medicamentos similares com biodisponibilidade "comparável", i.e., um medicamento similar "equivalente" (EQ). Medicamentos para doenças crônicas e "fármacos de dose crítica" estão listados entre os produtos EQ aprovados. A intercambialidade de medicamentos não-bioequivalentes suscita grande preocupação quanto a falhas terapêuticas e eventos adversos. Os receios são ainda maiores se os pacientes trocam um medicamento por outro durante o tratamento de doenças como epilepsia, insuficiência cardíaca, hipertensão, diabetes e/ou os produtos farmacêuticos substituídos tem um índice terapêutico estreito.
Subject(s)
Humans , Drugs, Generic/administration & dosage , Prescription Drugs/administration & dosage , Drug Substitution/methods , Legislation, Drug , Brazil , Biological Availability , Therapeutic Equivalency , Drugs, Generic/adverse effects , Drugs, Generic/pharmacokinetics , Treatment Failure , Drug Approval/legislation & jurisprudence , Prescription Drugs/adverse effects , Prescription Drugs/pharmacokinetics , Drug Substitution/adverse effects , Patient Safety , Therapeutic IndexABSTRACT
Resumo Norplant® é a marca do primeiro implante hormonal subdérmico contraceptivo registrado no mundo, desenvolvido nos laboratórios do Population Council, organização internacional direcionada ao tema da fertilidade e crescimento populacional. O artigo revisita a trajetória deste contraceptivo no Brasil desde sua chegada, através de pesquisas clínicas, até sua proibição em 1986 pelo órgão brasileiro responsável por medicamentos na ocasião. Sua circulação gerou controvérsias relacionadas a práticas de pesquisa, efeitos colaterais e usos políticos do método. Este artigo concentra sua análise nas divergências relacionadas com as práticas de pesquisa. Utilizou-se a técnica de análise de controvérsia, revisitando as versões dos envolvidos, investigando suas compreensões e os efeitos que este objeto produziu em suas redes. O Norplant® provocou deslocamentos e associações entre grupos da sociedade, autoridades do Estado, cientistas e médicos, indústria, produtos farmacêuticos, procedimentos de pesquisas, instrumentos burocráticos, usuárias de contraceptivos. Estilos de pensamento médico científicos foram sacudidos e novas formas de pensar autonomia científica começaram a ser discutidas no país.
Abstract Norplant® is the brand name of the world's first registered subdermal hormonal contraceptive implant, developed by the laboratories of the Population Council, an international organisation working in the area of fertility and population growth. The article revisits the trajectory of this contraceptive in Brazil from its arrival through clinical trials to its eventual ban in 1986 by the Brazilian regulatory agency responsible for approving medications at the time. Its circulation generated controversies related to research practices, side effects and political uses of the drug as a birth control method. This article focuses its analysis on the divergences related to research practices. It uses a controversy analysis technique, reviewing the versions of those involved, investigating their understandings and the effects that this object generated in their networks. Norplant® provoked displacements and associations between civil society groups, State authorities, scientists and physicians, industry, pharmaceutical products, research procedures, bureaucratic instruments, and the female users of the contraceptives. Scientific styles of medical thought were shaken up and new forms of thinking about scientific autonomy began to be discussed in the country.
Subject(s)
Humans , Female , Levonorgestrel/administration & dosage , Drug Approval , Contraceptive Agents, Female/administration & dosage , Biomedical Research/standards , Politics , Brazil , Levonorgestrel/adverse effects , Contraceptive Agents, Female/adverse effects , Biomedical Research/ethics , Ethics, Research , Drug ImplantsABSTRACT
Resumo: No campo farmacêutico, o desenvolvimento de novos fármacos exige um grau sofisticado de entendimento de mecanismos fisiopatológicos, a fim de identificar e caracterizar potenciais alvos biomoleculares e prosseguir com os estudos clínicos. Dentro desse contexto, a proteção dos resultados de Pesquisa & Desenvolvimento é uma etapa vital para garantir o retorno financeiro dos pesados investimentos na área. Uma das estratégias para atingir tal objetivo consiste na exploração de patentes de segundo uso médico, usualmente redigidas no formato "uso do composto X caracterizado pelo fato de ser empregado no preparo de medicamento para a doença Y". Considerando o possível impacto social e a ausência de diretrizes específicas no Brasil, o presente artigo revisa os principais casos relacionados a regimes de dosagem na Europa e analisa os posicionamentos do Escritório Europeu de Patentes (EPO) e judiciários alemão e do Reino Unido sobre os requisitos de patenteabilidade e escopo de proteção, visando a contribuir com o debate técnico sobre o assunto.
Abstract: In the pharmaceutical field, the development of new drugs requires sophisticated understanding of pathophysiological mechanisms in order to identify and characterize potential biomolecular targets and proceed with clinical trials. In this context, protection of research and development results is a vital stage for guaranteeing financial return on the heavy investments in the area. One strategy to achieve this objective is to exploit second-use patents, usually drafted in the format "use of compound X characterized by the fact that it is used in preparing a drug for disease Y". Considering the possible social impact and lack of specific guidelines in Brazil, this article reviews the principal cases related to dosing regimens in Europe and analyzes the positions of the European Patent Office (EPO) and German and UK judiciary systems on the requirements for patentability and scope of protection, aimed at contributing to the technical debate on the topic.
Resumen: En el campo farmacéutico, el desarrollo de nuevos fármacos exige un grado de sofisticación en la comprensión de los mecanismos fisiopatológicos, con el fin de identificar y caracterizar potenciales objetivos biomoleculares y proseguir con los estudios clínicos. Dentro de este contexto, la protección de los resultados de Investigación y Desarrollo es una etapa vital para garantizar el retorno financiero de las costosas inversiones en este área. Una de las estrategias para alcanzar tal objetivo consiste en la explotación de patentes de segundo uso médico, habitualmente redactadas en el formato "uso del compuesto X, caracterizado por el hecho de ser empleado en la preparación del medicamento para la enfermedad Y". Considerando el posible impacto social, y la ausencia de directrices específicas en Brasil, el presente artículo revisa los principales casos relacionados con los regímenes de dosificación en Europa y analiza las posiciones adoptadas por la Oficina Europea de Patentes (EPO) y los sistemas judiciales alemanes y del Reino Unido sobre los requisitos de patentabilidad y alcance de la protección, con el objetivo de contribuir al debate técnico sobre este asunto.
Subject(s)
Patents as Topic/legislation & jurisprudence , Drug Approval/legislation & jurisprudence , Legislation, Drug , Brazil , Drug Industry/legislation & jurisprudence , Europe , Drug Dosage CalculationsABSTRACT
El dengue es un importante problema de salud pública global, que afecta a América Latina y México. Las medidas de prevención y control centradas en vigilancia epidemiológica y control de vectores han resultado parcialmente efectivas y costosas, por lo que el desarrollo de una vacuna contra el dengue ha creado grandes expectativas entre las autoridades sanitarias y las comunidades científicas en el mundo. Sólo la vacuna CYD-TDV, producida por Sanofi-Pasteur, ha sido evaluada en ensayos clínicos controlados fase 3. No obstante a pesar de la importante contribución que esto significa para el desarrollo de una vacuna contra el dengue, los tres estudios clínicos fase 3 de CYD-TDV y el metaanálisis de seguimiento a largo plazo derivado de los mismos proporcionan evidencia de que esta vacuna tiene una eficacia parcial para proteger contra dengue virológicamente confirmado. Al respecto, surgen cuatro consideraciones: a) eficacia adecuada contra infecciones por virus de dengue (DENV) 3 y 4, menor eficacia contra infecciones por DENV 1 y prácticamente nula protección contra infecciones por DENV 2; b) disminución de la eficacia en individuos seronegativos a dengue al inicio de la vacunación; c) 83 y 90% de protección contra hospitalizaciones y formas de dengue grave, respectivamente, a 25 meses de seguimiento, y d) incremento de hospitalización por dengue, en el grupo de vacunados, en niños menores de nueve años de edad al momento de la vacunación, detectado a partir del tercer año de seguimiento. El beneficio de la vacuna CYD-TDV se puede resumir en la protección contra infecciones por DENV 3 y 4, así como en la protección de hospitalizaciones y casos graves en individuos mayores de nueve años y en quienes han tenido infección previa por dengue, pues funciona principalmente como una vacuna de refuerzo. En esta revisión se identificaron elementos sobre eficacia y seguridad de esta vacuna que deben ser tomados en cuenta ante el potencial registro e inclusión en el programa de vacunación en la población mexicana. La evidencia científica disponible sobre la vacuna CYD-TDV demuestra méritos, pero también da lugar a preguntas relevantes que deberían ser contestadas para evaluar apropiadamente el perfil de seguridad del producto, así como las poblaciones blanco de potencial beneficio. Al respecto, consideramos que sería informativo completar el seguimiento indicado de seis años después de iniciar la vacunación, de acuerdo con el protocolo propuesto en los propios estudios del fabricante como una recomendación de la Organización Mundial de la Salud. Al igual que con cualquier nueva vacuna, el potencial registro e implementación de uso de CYD-TDV en el programa nacional de vacunación de México requiere una definición clara de cuál es el balance entre los beneficios y riesgos esperados. En particular, ante una vacuna con eficacia variable y algunas señales de riesgo, en caso de aprobar el registro, se deben desarrollar protocolos de manejo de riesgos detallados que permitan identificar de manera oportuna cualquier evento de salud asociado con la vacunación.
Dengue is a major global public health problem affecting Latin America and Mexico Prevention and control measures, focusing on epidemiological surveillance and vector control, have been partially effective and costly, thus, the development of a vaccine against dengue has created great expectations among health authorities and scientific communities worldwide. The CYD-TDV dengue vaccine produced by Sanofi-Pasteur is the only dengue vaccine evaluated in phase 3 controlled clinical trials. Notwithstanding the significant contribution to the development of a vaccine against dengue, the three phase 3 clinical studies of CYD-TDV and the meta-analysis of the long-term follow up of those studies, have provided evidence that this vaccine exhibited partial vaccine efficacy to protect against virologically confirmed dengue and lead to four considerations: a) adequate vaccine efficacy against dengue virus (DENV) infections 3 and 4, less vaccine efficacy against DENV 1 and no protection against infection by DENV 2; b) decreased vaccine efficacy in dengue seronegative individuals at the beginning of the vaccination; c) 83% and 90% protection against hospitalizations and severe forms of dengue, respectively, at 25 months follow-up; and d) increased hospitalization for dengue in the vaccinated group, in children under nine years of age at the time of vaccination, detected since the third year of follow-up. The benefit of the CYD-TDV vaccine can be summarized in the protection against infection by DENV 3 and 4, as well as protection for hospitalizations and severe cases in people over nine years, who have had previous dengue infection, working mainly as a booster. In this review we identified elements on efficacy and safety of this vaccine that must be taken into account in the licensing process and potential inclusion in the national vaccination program of Mexico. The available scientific evidence on the CYD-TDV vaccine shows merits, but also leads to relevant questions that should be answered to properly assess the safety profile of the product and the target populations of potential benefit. In this regard we consider it would be informative to complete the 6-year follow-up after starting vaccination, according to the company's own study protocol recommended by the World Health Organization. As with any new vaccine, the potential licensing and implementation of the CYD-TDV as part of Mexico's vaccination program, requires a clear definition of the balance between the expected benefits and risks. Particularly with a vaccine with variable efficacy and some signs of risk, in the probable case of licensing, the post-licensed period must involve the development of detailed protocols to immediately identify risks or any health event associated with vaccination.