REGULATORY CHALLENGES AND LANDSCAPES OF MONOCLONAL ANTIBODY REGISTRATION: GLOBAL OUTLOOK

Objective: This review aims to illuminate the unprecedented growth and versatile therapeutic landscape of monoclonal antibody (mAb) products, highlighting their significant impact on diverse medical fields such as oncology, septicemia treatment, infection management, and substance abuse disorder interventions. This review outlines the challenges associated with the development, manufacturing, and regulatory approval of monoclonal antibodies, emphasizing the need for diligent attention to overcome these complexities. The review comprehensively examines the historical evolution and therapeutic applications of monoclonal antibodies, emphasizing their potent and versatile characteristics that have enabled successful interventions in challenging regulatory approvals. It delves into the critical considerations in manufacturing, regulatory navigation, and the strategic integration of expedited approval pathways, providing a holistic understanding of the intricate terrain of innovation, clinical translation, and impactful patient care in the realm of monoclonal antibody products. Monoclonal antibodies have significantly advanced medical treatment in various domains, revolutionizing cancer therapy, offering new avenues for septicemia management, augmenting the arsenal against infections, and opening novel pathways for addressing substance abuse disorders. Their development and regulatory approval are associated with challenges of scientific innovation, manufacturing, and regulatory compliance. Despite the challenges, monoclonal antibodies have demonstrated remarkable potential in addressing complex medical conditions. The review serves as a compass, guiding researchers, clinicians, and regulatory authorities through the intricate terrain of monoclonal antibody innovation and clinical translation. It emphasizes the need for diligent attention to overcome the complexities associated with their development and regulatory approval while highlighting their significant impact on advancing patient care.

Analysis on approval and declaration of new Chinese medicines from 2016 to 2022 / 国际中医中药杂志

Objective:To discuss and analyze the current situation of the application and approval of new Chinese medicine in China; To provide a reference for the research and development of new Chinese medicines in the future.Methods:The drug registration data were retrieved from Xanda database from January 1, 2016 to December 31, 2022, and the information of new approval and application of new Chinese medicines during this periods was systematically organized from the aspects of the number of registered varieties, registration categories, therapeutic areas, prescription sources, dosage form distribution, development cycle, clinical research and control drugs.Results:From 2016 to 2022, the total number of application for new Chinese medicines was 265. The number of registration classification 1.1 of new compound drugs was the largest. The dosage forms of new drugs were mainly granules, capsules, and tablets. Indications mainly focused on respiratory, neuropsychiatric, digestion and cardio-cerebrovascular diseases, etc. From 2016 to 2022, the total number of approval for new Chinese medicines was 29, of these, 19 from 2021 to 2022. The number of registration classification 1.1 of new Chinese medicines was the largest. The treatment fields are mainly respiratory system, gynecology and neuropsychiatric diseases, etc. The dosage forms of new drugs were mainly granules, capsules, and tablets. The number of drugs in prescriptions was 6-15. High-frequency drugs included Glycyrrhizae Radix et Rhizoma, Ephedrae Herba, Scutellariae Radix, Pinelliae Rhizoma, Poria and Gypsum Fibrosum. Phase Ⅱ and phase Ⅲ of the clinical trials had the largest number. The development period was approximately between 10-20 years. The most prescription source of new drugs was clinical experienced prescriptions and hospital pharmaceutics.Conclusion:The results show that China has been gradually building-up a relatively complete ecosystem for research and development of new Chinese medicines, helping to develop more high-quality Chinese medicines.

Construction and application of the project approval evaluation system for traditional Chinese medicine prepara-tion in medical institutions / 中国药房

OBJECTIVE To establish the project approval evaluation system for traditional Chinese medicine （TCM） preparations in medical institutions guided by new drug conversion， to improve the success rate of approval for TCM preparations in medical institutions and lay the foundation for the later drug conversion. METHODS Research and development team used the literature research method and brainstorming method to list and organize relevant elements of project evaluation and determine the initial indicator system. Experts were consulted using the Delphi method to confirm the evaluation index. The weights were calculated based on the proportion of importance scores for each indicator and assigned specific scores to each item. The indicator system was used to evaluate 31 TCM preparations applied for filing by various departments of our hospital from April to July 2023. RESULTS After two rounds of 17 experts’ consultation， the final TCM preparation system included five primary indicators， i.e. theoretical basis， clinical research foundation， pharmaceutical foundation， prescription， and clinical value， as well as 17 secondary indicators including prescription source， traditional Chinese medicine theory， clinical positioning and so on. Human experience was considered as the item which would be rejected as one vote. Based on the above indicator system， our hospital further improved the filing and project approval process for TCM preparations in medical institutions. Among the 31 TCM preparations applied for filing by various departments from April to July 2023， 8 TCM preparations with a score ≥65 were selected for development. CONCLUSIONS The evaluation system is objective， comprehensive， and highly operable. It is suitable for the selection of TCM preparations in medical institutions before research and development.

A Study on Continuous Risk Management Plan Utilization after Drug Approval: / 医薬品情報学

Objective: In Japan, pharmaceutical manufacturers have been required to develop a Risk Management Plan (RMP) since April 2013. Publication of the RMP is expected to enable the wide content-sharing of post-marketing risk management and its utilization among medical professionals to further enhance and strengthen post-marketing safety measures. In this study, we examined what points should be focused on for continuous utilization of RMPs after drug approvals by investigating the numbers of safety concerns addition of antineoplastic and immunomodulating agents, and where safety concerns added after approval are listed in package inserts. Furthermore, we investigated the reasons why these safety concerns were considered as such. Methods: Antineoplastics and immunomodulating agents, which account for more than half of all drugs containing new active ingredients approved in recent years, among drugs containing new active ingredients approved from fiscal year (FY) 2013 to FY 2019 were included in the study. The safety concerns (excluding important missing information) in RMPs as of April 1, 2021 for the subject drugs were compared with those at the time of approval. Safety concerns added after approval were investigated where they were listed in package inserts as of April 1, 2021. Furthermore, risks that were added as important potential risks were investigated as to why they were considered as such. Results: There were 117 risks added after approval. Those added to the important identified risks were listed in one of the sections of the package insert, whereas 11 risks were added to the important potential risks that could not be confirmed in the package inserts. Some important potential risks added after approval are suspected to have a causal relationship with the drug, but were not listed in the package inserts. Conclusion: It is important to utilize RMPs continuously to further understand risks of taking the drug.

University students' attitudes towards people with disabilities: does type, exposure and the need for social approval matter? / Atitudes dos estudantes universitários em relação às pessoas com deficiência: o tipo, a exposição e a necessidade de aprovação social importam?

ABSTRACT This study aimed to explore the multidimensional attitudes of university students towards people with motor, intellectual, and sensory (vision and hearing) disabilities. Three variables were discussed: type of disability, exposure to people with disabilities, and the need for social approval. This study included 712 university students. The results confirmed that the most negative attitudes were held towards people with intellectual disability and the most positive attitudes towards persons with motor disability in all dimensions: cognitive, emotional, and social. The type of exposure to people with disabilities was significant, and the most positive attitudes were observed when respondents had a friend with a disability. The hypothesis on the correlation between the need for social approval and students' attitudes towards people with disabilities was only partially confirmed.

RESUMO Este estudo teve como objetivo explorar as atitudes multidimensionais de estudantes universitários em relação a pessoas com deficiência motora, intelectual e sensorial (visão e audição). Foram discutidas três variáveis: tipo de deficiência, exposição a pessoas com deficiência e necessidade de aprovação social. Este estudo incluiu 712 estudantes universitários. Os resultados confirmaram que as atitudes mais negativas foram as em relação às pessoas com deficiência intelectual e as atitudes mais positivas em relação às pessoas com deficiência motora em todas as dimensões: cognitiva, emocional e social. O tipo de exposição às pessoas com deficiência foi significativo, e as atitudes mais positivas foram observadas quando os entrevistados tinham um amigo com deficiência. A hipótese sobre a correlação entre a necessidade de aprovação social e as atitudes dos estudantes em relação às pessoas com deficiência foi apenas parcialmente confirmada.

Diagnostic Efficacy of Fecal Calprotectin in Inflammatory Bowel Disease: Systematic Literature Review

Introduction: Inflammatory bowel disease is a group of pathologies that include ulcerative colitis and Crohn's disease, which have similar manifestations. Currently, the diagnosis and monitoring of this disease rely mainly on endoscopic studies. Still, this method can hardly be applied to periodic disease monitoring as it is expensive, invasive, and not readily available. Fecal calprotectin is widely known, easy to use, and affordable, and it is currently the best-characterized biomarker for this pathology. Materials and methods: The research design is a systematic diagnostic test validation literature review. A search was conducted in different databases using the QUADAS-2 checklist to evaluate the methodological quality. Results: The initial search yielded 352,843 articles published chiefly in PubMed, followed by Scopus and Science Direct. After multiple filters, 221 papers were selected and wholly reviewed. They were evaluated with inclusion and exclusion criteria, with 18 articles being chosen. Conclusions: Fecal calprotectin is a reliable surrogate marker of endoscopic activity in IBD. However, there is a lack of consensus on delimiting a cut-off point and improving applicability and diagnostic accuracy. Colonoscopy remains the gold standard in all studies.

Introducción: La enfermedad inflamatoria intestinal es un conjunto de patologías entre las que están incluidas la colitis ulcerativa y la enfermedad de Crohn, las cuales tienen presentación similar. En la actualidad, el diagnóstico y seguimiento de dicha enfermedad se basa principalmente en estudios endoscópicos, pero este método difícilmente puede aplicarse a la monitorización periódica de la enfermedad al ser costoso, invasivo y con disponibilidad limitada. La calprotectina fecal cumple con ser ampliamente disponible, fácil de usar y de precio asequible, y actualmente es el biomarcador mejor caracterizado para el uso en esta patología. Metodología: Diseño de investigación tipo revisión sistemática de la literatura de validación de prueba diagnóstica. Se realizó una búsqueda en diferentes bases de datos y para la evaluación de la calidad metodológica se empleó la lista verificación QUADAS-2. Resultados: La búsqueda inicial para la selección de los artículos arrojó un total de 352.843 artículos publicados principalmente en PubMed seguido de Scopus y Science Direct. Después de múltiples filtros se logró elegir 221 artículos, los cuales se llevaron a revisión completa. Se valoraron con criterios de inclusión y exclusión, lo que determinó la elección final de 18 artículos. Conclusiones: La calprotectina fecal es un marcador sustituto fiable de la actividad endoscópica en la EII. Se evidencia la falta de consenso para delimitar un punto de corte y mejorar la aplicabilidad y la precisión diagnóstica. La colonoscopia sigue siendo en todos los estudios el estándar de oro.

A study of new drug approval pattern of a Southeast Asian developed country from 2017 to 2021

Background: The pattern of new drug approval is changing across the world as shown by the study using Center for Drug Evaluation and Research and European Medicines Agency data in US and UK with more drug approval for anti-cancer and immunomodulator drugs. There is a need to generate similar database for developed South East Asian countries too. Aims and Objectives: This study was conducted for one such country- Singapore for the new drug approval pattern of last 5 years (2017–2021). Materials and Methods: This was a pharmacoepidemiological study, in which government drug regulatory website data available in public domain was searched. The new drug approval data were classified according to active ingredient, drug approval date, new drug application category, indication of drugs, and World Health Organization Anatomic Thoracic Classification. Results: In this study, 418 new drug approvals were found in last 5 years in Singapore. From this maximum, drug approvals were given to anti-neoplastic and immunomodulator category drugs. In anti-neoplastic category new drugs approval few examples were Trastuzumab deruxtecan and Tucatinib for breast cancer therapy and Tepotinib and Capmatinib for non-small cell lung cancer therapy. Conclusion: This study shows that drug development in anti-cancer drug and immunomodulator is significant in Singapore. This trend is quite matching with other country such as US and UK.

Approval Status and Suggestions on Supervision of Class II Innovative Medical Device / 中国医疗器械杂志

Based on the current situation of approval and publicity of class II innovative medical devices in various provinces and cities, especially after analyzing the problems found in the review of class II innovative medical devices in Shanghai and the factors affecting the listing process of innovative medical devices, this study puts forward some thoughts on supervision for reference in establishing and perfecting systems and regulations, changing the review and approval thinking, extending services to the development of innovative medical devices and the formulation of clinical trial schemes.

Analysis and suggestions on the development trend of drug innovation in China / 中国药科大学学报

@#In order to comprehensivehy evaluate the stage of China in the global drug innovation, to further optimize the environment for drug innovation in China, and to unleash the vitality of drug innovation, this article mainly analyzes through comparison China''s situation of drug innovation in global competition from such perspectives as the current situation of the global drug R&D innovation market, R&D investment, product pipeline, policy support, and development trends, combined with the characteristics of China''s drug innovation development.It can be seen that China''s pharmaceutical innovation is faced with such practical problems as lagging behind some developed countries in terms of innovation development, companies bunching into research and development innovation, sudden research and development rush, and excessive dependence on capital markets for pharmaceutical innovation.Accordingly, this paper puts forward suggestions on continuously improving China''s new drug innovation environment, rationally selecting differentiated competition and new tracks, reasonably formulating drug innovation development strategies, guiding capital to return to innovative research and development, and constructing a "double cycle" strategy for drug innovation.

Risks and suggestions of Investigator-Initiated Clinical Trial approvals based on drug supply and security / 中华医学科研管理杂志

Objective:To improve the standard and quality of clinical trials, the possible risks of Investigator-Initiated Clinical Trial(IIT) approvals based on drug supply and security were discussed and suggestions were put forward.Methods:According to the laws and regulations and literature review, concerning experimental drug supply and security during project negotiation, the risk points of IIT approvals were comprehensively analyzed and suggestions were put forward.Results:There are four main types of risks in assessing IIT approvals in terms of drug supply and security: drug entry and sales, drug promotion, discounts of observation fees, and concept confusion. Healthcare institutions should pay attention to and coordinate the IIT approvals.Conclusions:IIT is a supplement and extension of Industry Sponsored Trial(IST), which should be actively carried out by healthcare institutions while also paying attention to the security and risk prevention of drug supply, ensuring a standardized and orderly manner.

Índice videoquimográfico da função glótica: análise da precisão diagnóstica / Videokymographic index of glottic function: an analysis of diagnostic accuracy

RESUMO Objetivo Elaborar um indicador composto denominado Índice Videoquimográfico da Função Glótica - IVFG, a partir de parâmetros da videoquimografia digital, captados pelo exame de videolaringoscopia de alta velocidade de mulheres sem e com alterações laríngeas de etiologia comportamental. Método A amostra foi composta por 92 mulheres, destas 55 apresentaram disfonia comportamental, com presença de alterações laríngeas e vocais, e 37 mulheres sem alterações laríngeas e vocais, entre 18 a 45 anos. A avaliação vocal foi realizada por consenso pela análise perceptivo-auditiva da vogal /a/ em frequência e intensidade habituais, e classificação através do grau geral da disfonia, onde G0 indicou qualidade vocal neutra e G1 a 3 qualidade vocal alterada. As imagens laríngeas foram obtidas pela gravação da emissão da vogal /i/, em frequência e intensidade habituais para análise da videoquimografia digital. A construção do IVFG se deu pela escolha do ponto médio da glote para análise e, elaboração foi realizada regressão logística pelo programa MINITAB 19. Resultados A regressão logística contou com duas etapas, sendo que a etapa 1 constou da análise de todas as variáveis, onde as variáveis abertura máxima e fechamento glótico apresentaram significância estatística (p-valor <0.05) e o modelo se encontrou bem ajustado de acordo com o teste de Hosmer-Lemeshow (p-valor=0,794); na etapa 2, as variáveis selecionadas foram novamente analisadas e o modelo também se mostrou bem ajustado (p-valor=0,198). O IVFG foi definido por IVFG=e^(8,1318-0,2941AbMax-0,0703FechGlo)/1+e^(8,1318-0,2941AbMax-0,0703FechGlo). Conclusão O IVFG apresenta valor de corte igual a 0,71. A probabilidade de acerto é de 81,5%, sensibilidade 76,4%, especificidade de 89,2%.

ABSTRACT Purpose To develop the Videokymographic Index of Glottic Function (VIGF), a composite indicator from digital videokymography parameters, captured by high-speed videolaryngoscopy exams of women with and without laryngeal alterations of behavioral etiology. Methods The sample consisted of 92 women aged between 18 and 45 years. Fifty-five (55) women with behavioral dysphonia, presenting with laryngeal and voice alterations, and thirty-seven (37) women without any laryngeal and voice alterations. Voice evaluation was performed by consensus via an auditory-perceptual analysis of the sustained vowel /a/ at a habitual pitch and loudness. Voice classification was obtained by means of a general degree of dysphonia, where G0 indicated neutral voice quality and G1 to G3 indicated altered voice quality. Laryngeal images were captured via digital videokymography analysis of a sustained vowel /i/ at a habitual pitch and loudness. The VIGF was based on the midpoint of the glottal region for analysis. Logistic regression was performed using the MINITAB 19 program. Results Logistic regression was composed of two stages: Stage 1 consisted of the analysis of all variables, where the maximum opening and closed quotient variables showed statistical significance (p-value <0.05) and the model was well adjusted according to the Hosmer-Lemeshow test (p-value=0.794). Stage 2 consisted of the re-analysis of the selected variables, also showing a well-adjusted model (p-value=0.198). The VIGF was defined as follows: VIGF=e^(8.1318-0.2941AbMax-0.0703FechGlo)/1+e^(8.1318-0.2941AbMax-0.0703FechGlo). Conclusion The VIGF demonstrated a cut-off value equal to 0.71. The probability of success was 81.5%, sensitivity 76.4%, and specificity 89.2%.

Semimonthly Table of Contents Nationwide investigation and problems analysis of pharmaceutical preparations in medical institutions / 中国药房

@#OBJECTIVE To investigate the situation of pharmaceutical pr eparations in medical institutions （hereinafter refer to hospital preparations ），and to promote the sustained and healthy development of hospital preparations. METHODS Under the organization of National Pharmacy Administration & Quality Control Center ，internet survey was adopted to statistically analyze the data of hospital preparations in 2019 that was completed and reported by the secondary general hospitals and above in provinces （cities，districts）and Xinjiang Production and Construction Corps. RESULTS Among the 4 639 hospitals，9.36％ had drug approval numbers and 8.15％ had preparation laboratories. The average ratio of the number of hospital preparations in production to the number of preparations approved was 0.72，and that of 41.52％ hospital was concentrated in 1-0.9. Self-produced by hospital was the main production mode of hospital preparations ；the higher hospital level was ，the higher the proportion of self-production combined with commissioned processing ，while the lower the proportion of commissioned processing only. In hospitals with preparation approval numbers ，the proportion of owning TCM preparations was the highest （73.66％），followed by common chemical preparations （69.93％）. From perspective of annual output value of hospital preparations ，tertiary hospitals were higher than secondary hospitals ，and private hospitals were higher than public hospitals ；it was related to the production mode ，varieties of hospital preparations and the establishment of the preparation laboratories. There was a trend that the development of hospital preparations in C entral China ，North China and South China was better than that in the Northeast China ，Northwest China and Southwest China. CONCLUSIONS At present ，hospital preparations in China are mainly made in medical institutions ， com and the types are relatively limited. The regional developmentis unbalanced and the scale of hospital preparations is reduced.It is suggested that medical institutions should pay attention to the innovation of hospital preparations ，especially to deve lopment of characteristic preparations with definite curative effect ，so as to give full play to their role of “shortage make-up ”. Great importance also should be paid to the policy support of dispensing and the establishment of regional dispensing centers.

Improvement and application of radiation work permit software in nuclear power plants / 中国辐射卫生

Objective To improve the efficiency of radiation work preparation, promote the comprehensive and whole-process control of radiation risk, strengthen the accumulation of experience feedback data, and improve the timeliness of approval. Methods According to the application of radiation work permits in Tianwan Nuclear Power Plant and other nuclear power plants, the radiation work permit software in Tianwan Nuclear Power Plant was improved in terms of work order connection, examination and approval process integration, approval of radiation work at different levels, unification of level classification standard, radiation risk database establishment and maintenance, and closed loop management and mobile approval of radiation work permit. Results A radiation work permit software for nuclear power plant was developed according to the requirement of radiation risk control. Conclusion The radiation work permit software effectively improves the radiation work regarding work preparation efficiency, risk control, experience feedback data accumulation, and timeliness of approval. Subsequently, information transmission efficiency and experience sharing can be improved through connection and communication with other software in nuclear power plants.

Adaptación al español chileno de la Evaluación Cognitiva Dinámica de Terapia Ocupacional de Loewenstein (DLOTCA) / Adaptação Transcultural para o espanhol chileno da Avaliação Cognitiva Dinâmica de Terapia Ocupacional de Loewenstein (DLOTCA) / Adaptation to Chilean Spanish of Dynamic Loewenstein Occupational Therapy Cognitive Assessment (DLOTCA)

Resumen Objetivo Adaptar la décima versión en inglés de la Dynamic Loewestein Occupational Therapy Cognitive Assessment al español chileno. Método Se realizó adaptación al español del manual de aplicación de DLOTCA. El proceso siguió las pautas generales para la traducción y adaptación de instrumentos de la Organización Mundial de la Salud (OMS), con traducción directa, panel de discusión de expertos, retrotraducción, pruebas previas y entrevistas cognitivas con usuarios. Resultados Se obtuvo una traducción directa al español por dos terapeutas ocupacionales bilingües que fue sometida a ajustes por un panel de expertos compuesto por 6 terapeutas ocupacionales, del total de 28 sub test el comité de expertos no tuvo discrepancia en 20 de ellos, de los 8 restantes se realizaron modificaciones. Se realiza una retrotraducción de la versión obtenida, donde solo hubo discrepancias con un término lo que fue resuelto por el equipo investigador. Finalmente se aplicó una prueba previa/pre test a 13 personas adultas con daño cerebral, los ajustes en esta etapa fueron ortográficos y de sustitución de algunos términos por palabras más comúnmente utilizados en la lengua chilena, verificando la consistencia en la comprensión de los ítems independientemente de los resultados obtenidos. Se produjeron tres versiones antes de la versión final, todas las etapas se desarrollaron de manera sistemática, logrando una traducción comprensible y consistente con la población chilena. Conclusiones Finalmente se ha puesto a disposición de la comunidad científica una versión en español chileno del instrumento DLOTCA.

Resumo ObjetivoAdaptar a décima versão em inglês do Dynamic Loewestein Occupational Therapy Cognitive Assessment para o espanhol chileno. MétodoO manual de aplicação DLOTCA foi adaptado para o espanhol. O processo seguiu as diretrizes gerais para tradução e adaptação de instrumentos da Organização Mundial da Saúde (OMS), com tradução direta, painel de discussão de especialistas, retrotradução, pré-testes e entrevistas cognitivas com os usuários. ResultadosA tradução direta para o espanhol foi obtida por dois terapeutas ocupacionais bilíngues que foi submetida a ajustes por um painel de especialistas composto por 6 terapeutas ocupacionais, do total de 28 subtestes, o comitê de especialistas não apresentou discrepância em 20 deles, das quais 8 modificações restantes foram feitas. Foi realizada a retrotradução da versão obtida, com apenas discrepâncias com um termo, o que foi resolvido pela equipe de pesquisa. Por fim, uma prova prévia / pré-teste foi aplicado a 13 adultos com lesão cerebral, os ajustes nesta etapa foram de grafia e substituição de alguns termos por palavras mais utilizadas na língua chilena, verificando a consistência na compreensão dos itens, independentemente dos resultados obtidos. Três versões foram produzidas antes da versão final, toda as etapas foram desenvolvidas de forma sistemática, alcançando uma tradução compreensível e consistente para a população chilena. Conclusões: Uma versão em espanhol chileno do instrumento DLOTCA foi finalmente disponibilizada para a comunidade científica.

Abstract Objective To adapt the tenth version in English of the Dynamic Loewenstein Occupational Therapy Cognitive Assessment to Chilean Spanish. Method The DLOTCA application manual was adapted into Spanish. The process followed the general guidelines for the translation and adaptation of instruments of the World Health Organization (WHO), with direct translation, a panel discussion of experts, back translation, pre-tests, and cognitive interviews with users. Results A direct translation into Spanish was obtained by two bilingual occupational therapists that were subjected to adjustments by a panel of experts composed of 6 occupational therapists, of the total of 28 sub-tests, the expert committee had no discrepancy in 20 of them, of which 8 remaining modifications were made. A back translation of the version obtained is carried out, where there were only discrepancies with one term, which was resolved by the research team. Finally, a pre-test was applied to 13 adults with brain damage, the adjustments in this stage were spelling and substitution of some terms for words more commonly used in the Chilean language, verifying the consistency in the understanding of the items independently of the results obtained. Three versions were produced before the final version, all stages were developed in a systematic way, achieving an understandable and consistent translation with the Chilean population. Conclusions A version in Chilean Spanish of the DLOTCA instrument has finally been made available to the scientific community.

Regulatory reliance pathways during health emergencies: enabling timely authorizations for COVID-19 vaccines in Latin America / Mecanismos de utilización de las decisiones de autoridades regulatorias de otras jurisdicciones en las emergencias de salud: autorización oportuna de las vacunas contra la COVID-19 en América Latina / Uso de decisões regulatórias de outras autoridades durante emergências sanitárias e a tempestividade da autorização de vacinas contra a COVID-19 na América Latina

ABSTRACT Objectives. To map the timing and nature of regulatory reliance pathways used to authorize COVID-19 vaccines in Latin America. Methods. An observational study was conducted assessing the characteristics of all COVID-19 vaccine authorizations in Latin America. For every authorization it was determined whether reliance was used in the authorization process. Subgroups of reference national regulatory authorities (NRAs) and non-reference NRAs were compared. Results. 56 authorizations of 10 different COVID-19 vaccines were identified in 18 countries, of which 25 (44.6%) used reliance and 12 (21.4%) did not. For the remaining 19 (33.0%) it was not possible to determine whether reliance was used. Reference agencies used reliance less often (40% of authorizations with a known pathway) compared to non-reference agencies (100%). The median review time was just 15 days and does not meaningfully differ between reliance and non-reliance authorizations. Conclusions. This study demonstrated that for these vaccines, despite reliance pathways being associated with numerous rapid authorizations, independent authorization review times were not considerably longer than reliance reviews; reliance pathways were not a prerequisite for rapid authorization. Nevertheless, reliance pathways provided rapid authorizations in response to the COVID-19 emergency.

RESUMEN Objetivos. Determinar dónde y cuándo se usaron las decisiones de autoridades regulatorias de otras jurisdicciones y la naturaleza de estos mecanismos para autorizar vacunas contra la COVID-19 en América Latina. Métodos. Se realizó un estudio observacional para evaluar las características de todas las autorizaciones de vacunas contra la COVID-19 en América Latina. Para cada autorización se determinó si se emplearon las decisiones de autoridades regulatorias de otras jurisdicciones en el proceso de autorización. Se compararon subgrupos de autoridades regulatorias nacionales (ARN) consideradas de referencia con otras ARN no usadas como referencia. Resultados. Se determinó dónde se otorgaron 56 autorizaciones de 10 vacunas diferentes contra la COVID-19 en 18 países; de estas 56 autorizaciones, 25 (44,6%) hicieron uso de las decisiones de autoridades regulatorias de otras jurisdicciones y 12 (21,4%), no. Para las 19 restantes (33,0%) no fue posible determinar si se hizo uso de las decisiones de autoridades regulatorias de otras jurisdicciones. Los organismos de referencia utilizaron las decisiones de autoridades regulatorias de otras jurisdicciones con menos frecuencia (40% de las autorizaciones con un mecanismo conocido) en comparación con los organismos no usados como referencia (100%). El plazo medio de revisión fue de tan solo 15 días y no difiere significativamente entre las autorizaciones que emplearon decisiones de autoridades regulatorias de otras jurisdicciones y las que no las emplearon. Conclusiones. En este estudio se demostró que, a pesar de que los mecanismos de utilización de las decisiones de autoridades regulatorias de otras jurisdicciones se asocian en muchos casos con autorizaciones rápidas, para estas vacunas los plazos de revisión independiente para la autorización no fueron considerablemente mayores que los de las revisiones que emplearon decisiones de autoridades regulatorias de otras jurisdicciones. También se demostró que para obtener una autorización rápida no se requería la utilización de las decisiones de autoridades regulatorias de otras jurisdicciones. Sin embargo, estos mecanismos proporcionaron autorizaciones rápidas en respuesta a la emergencia por la COVID-19.

RESUMO Objetivos. Mapear a tempestividade e a natureza do uso de decisões regulatórias de outras autoridades (reliance regulatório) para autorização de vacinas contra a COVID-19 na América Latina. Métodos. Em um estudo observacional, foram avaliadas as características de todas as autorizações de vacinas contra COVID-19 na América Latina. Para cada autorização, foi determinado se foram utilizadas decisões de outras autoridades regulatórias para embasar o processo de autorização. Foram comparados subgrupos de autoridades reguladoras nacionais (ARN) de referência (ARNr) e ARN não consideradas de referência. Resultados. Foram identificadas 56 autorizações de 10 vacinas diferentes contra a COVID-19 em 18 países, das quais 25 (44,6%) utilizaram decisões de outras ARN como base para o registro e 12 (21,4%) não. Para as 19 (33,0%) autorizações restantes, não foi possível determinar se decisões de outras ARN foram utilizadas. As ARNr utilizaram decisões de outras autoridades com menos frequência (40% das autorizações com via regulatória conhecida) em comparação com as ARN não consideradas de referência (100%). A mediana do tempo de tramitação foi de apenas 15 dias, sem diferença significativa entre processos nos quais foram utilizadas decisões de outras agências e processos que não as utilizaram. Conclusões. Este estudo demonstrou que, para estas vacinas, apesar de o uso do reliance regulatório estar associado a várias autorizações rápidas, os tempos de tramitação não foram consideravelmente maiores em autorizações independentes do que quando foram utilizadas decisões de outras ARN; o reliance regulatório não foi um pré-requisito para autorização rápida. No entanto, o uso de tais processos viabilizou autorizações rápidas em resposta à emergência de COVID-19.

Mulheres na gestão de tecnologias e engenharia clínica: o caso dos ventiladores pulmonares na Covid-19 / Women in technology management and clinical engineering: the case of pulmonary ventilators at Covid-19

RESUMO O risco iminente de desabastecimento de ventiladores pulmonares nos serviços de saúde acarretou diversas frentes de trabalho para disponibilizar o maior número possível desses equipamentos para o tratamento dos pacientes acometidos. O agravamento da crise sanitária colapsou serviços de saúde com busca isocrônica por leitos. Em meio ao colapso, foi detectada nova variante da linhagem Sars-CoV-2 e confirmado o primeiro caso de reinfecção. Entre os pontos críticos, foi destaque a escassez caótica de oxigênio e taxas de ocupação de leitos acima de 90%. Pretende-se relatar a participação das autoras nas iniciativas para o enfrentamento da pandemia de relevância internacional. Destacar a participação de mulheres em atividades que são cruciais para responder, em tempo oportuno, às demandas oriundas de emergências sanitárias. Por meio de método de pesquisa de abordagem descritiva e exploratória, buscou-se verificar o perfil das mulheres atuantes na gestão de tecnologias no enfrentamento da pandemia. Destaca-se a pesquisa recente da Associação Brasileira de Engenharia Clínica que verificou que apenas 19% dos associados respondentes eram mulheres, enquanto 81% eram do sexo masculino. Assim, divulgar e dar amplo conhecimento das ações de mulheres nessa área pode colaborar para o alcance da igualdade de gênero e empoderar todas as mulheres e meninas.

ABSTRACT The imminent risk of shortage of pulmonary ventilators in health services has resulted in several work fronts to maintain and make available the largest possible number of equipment available for the treatment of patients. The worsening of the health crisis has collapsed health services with an isochronic search for beds. Amid the collapse, a new variant of the Sars-CoV-2 strain was detected and the first case of reinfection was confirmed. Among the critical points was the chaotic oxygen scarcity and bed occupancy rates above 90%. We intend to report the participation of the authors in the initiatives to face the pandemic; highlight the participation of women in activities that are crucial to respond, in a timely manner, to the demands arising from health emergencies. Through a research method with a descriptive and exploratory approach, we sought to verify the profile of women working in the management of technologies in facing the pandemic. The recent survey by the Brazilian Association of Clinical Engineering stands out, which found that only 19% of the respondent associates were women. Thus, disseminating and giving broad knowledge of women´s actions in this area can collaborate in achieving gender equality and empower all women and girls.

The Policy and Practice of Medical Device Emergency Approval at the Local Level under the Circumstance of COVID-19 Disease / 中国医疗器械杂志

This research analyzed Chinese emergency approval policies and practices of medical devices at the local level under the circumstance of COVID-19 disease. The legal basis and administrative system were clarified, the implementation and characteristics of emergency approval policies were investigated, the products information including total approved number, product type and license's validity period were counted. Advices as enhancing the standardization of emergency approval system, strengthening registration guidance and optimize information disclose and management were provided.

Analysis of the Marketing Approval of Pediatric Drugs in the United States and Its Enlightenment to Pedia tric Drug Use Guarantee in China / 中国药房

OBJECTIVE：To provide sugge stions for improving the variety of pediatric drugs and ensuring the safety of pediatric drug use in China. METHODS ：The historical evolution of laws and regulations on the marketing approval of pediatric drugs in the United States and the implementation results of relevant policies were summarized. Combined with the current situation of the development of pediatric drugs in China ，some suggestions were put forward to ensure the accessibility and safety of pediatric drug use in China. RESULTS & CONCLUSIONS ：Since 1994，the United States had issued a series of laws and regulations to encourage the development of pediatric drugs. At present ，the marketing approval of pediatric drugs were mainly based on the two laws of Best Pediatric Drug Act（BPCA）and Pediatric Research Equality Act （PREA）. From 1998 to 2019，the amount of supplements of pediatric drug information in drug instructions of the United States showed a fluctuating growth. As of April 2020，854 kinds of drugs had been modified in pediatric instructions ，792 of which had been carried out post marketing pediatric clinical research ，and the problem of incomplete pediatric instructions had also been greatly improved. At present ，China’s policies on pediatric drugs mainly included encouraging R&D innovation ，giving priority to review and approval ，and strengthening R&D technical guidance. Although certain achievements had been made ，there were still some problems ，such as imperfect policies and regulations ，and great difficulties carrying out pediatric drug clinical trials. It is suggested that our country should draw lessons from the American regulations on pediatric drugs ，pediatric research and the catalogue of pediatric drugs ，and establish a system and catalogue of ped iatric drug use suitable for China ’s national conditions ，so as to improve the effectiveness ，safety and accessibilityof pediatric drugs.

New drugs registered in Brazil from 2003 to 2013: analysis from the perspective of child health

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.

Regulatory reliance to approve new medicinal products in Latin American and Caribbean countries / Utilización de decisiones de autoridades regulatorias de otras jurisdicciones para aprobar nuevos productos medicinales en países de América Latina y el Caribe / Uso de decisões regulatórias de outras jurisdições para aprovação de novas especialidades farmacêuticas em países da América Latina e Caribe

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.