EMA对草药产品申请上市许可或注册的非临床资料的要求

EMA于2017年8月发布了"公认和传统草药产品申请上市许可或注册的非临床文件的指导原则（草案）"。该指导原则指出传统和公认的草药物质或制剂,在获得人体充分而详实经验的情况下,单次给药和重复给药毒性、毒代动力学研究、免疫毒性以及局部耐受性试验是不必要的;而其生殖毒性、遗传毒性和致癌性,如果发表的文献不能用或不足,附加非临床试验是必要的。详细介绍该指导原则主要内容,以期对拟在欧盟上市的中草药产品有所帮助,也对我国草药监管有所启发。     

Guideline for the Treatment of Breakthrough and the Prevention of Refractory Chemotherapy‐Induced Nausea and Vomiting in Children With Cancer

This clinical practice guideline provides an approach to the treatment of breakthrough chemotherapy‐induced nausea and vomiting (CINV) and the prevention of refractory CINV in children. It was developed by an international, interprofessional panel and is based on systematic literature reviews. Evidence‐based interventions for the treatment of breakthrough and prophylaxis of refractory CINV are recommended. Gaps in the evidence used to support the recommendations made in this clinical practice guideline were identified. The contribution of these recommendations to breakthrough and refractory CINV control in children requires prospective evaluation.     

基于AGREEⅡ的儿童泌尿系感染临床实践指南质量现状分析

目的对全球儿童泌尿系感染(UTI)临床实践指南质量进行评价,为规范制订我国儿童UTI临床指南提供参考。方法计算机检索MEDLINE、EMbase、National Guideline Clearinghouse、Guidelines International Network、National Institute for Health and Clinical Excellence,以及万方、中国知网及中国指南协作网(从建库到2015年1月)等中英文数据库和相关网站。根据纳入、排除标准筛选公开发表的有关儿童UTI的临床指南,按照国际公认的指南评价工具(AGREE)分析纳入指南的方法学质量,使用组内相关系数(ICC)进行评价员间一致性检验。结果共纳入10篇儿童UTI指南,覆盖4个洲9个组织。指南发布时间跨度为1999—2015年,其中7篇为首版,3篇为更新版。纳入指南主题涉及诊断、管理、预防、危险因素评估和治疗等,均是基于循证证据的指南。纳入指南AGREEⅡ评分显示,6个领域的评价得分分别为88%、57%、54%、98%、26%、44%;纳入7篇指南的范围及目的、清晰性领域的评分均50%;英国国家卫生与临床优化研究所(NICE)、阿拉贡健康科学研究所(IACS)发布指南的6个领域评分均50%。结论不同国家和地区儿童UTI临床指南的质量差别较大。循证是当前临床实践指南的发展趋势,应注重指南制定方法的严谨性、报告的规范性和指南的实用性。     

Management of recurrent miscarriage: evaluating the impact of a guideline

BACKGROUND: Little is known on the actual diagnostic and therapeutic management of recurrent miscarriage and the impact of introducing guidelines on this topic. The objective of this study was to evaluate any changes in the management of recurrent miscarriage among Dutch gynaecologists after the introduction of the Dutch guideline 'Recurrent Miscarriage' in 1999. METHODS: Questionnaires were sent to all practices for obstetrics and gynaecology in the Netherlands. Data concerned definition, diagnosis and treatment of recurrent miscarriage. Results were compared with a similar study conducted before the introduction of the guideline and with the recommendations in the guideline. RESULTS: The response rate was 83%. Regarding gestational age, only 3% of the respondents used the definition as advised in the guideline. After the introduction of the guideline, thrombophilia factors were tested more frequently, anticoagulants were prescribed more frequently and more respondents reported to correct uterine malformations. Therapies not described in the guideline, e.g. donor insemination and oocyte donation, were still applied. CONCLUSIONS: The adherence to the Dutch guideline 'Recurrent Miscarriage' was rather poor, presumably due to guideline-related as well as physician-related barriers. Too many diagnostic tests and ineffective therapeutic interventions were performed. This study demonstrates the importance of appropriate implementation and revision.     

Developing a quality by design approach to model tablet dissolution testing: an industrial case study

Abstract

This study applied the concept of Quality by Design (QbD) to tablet dissolution. Its goal was to propose a quality control strategy to model dissolution testing of solid oral dose products according to International Conference on Harmonization guidelines. The methodology involved the following three steps: (1) a risk analysis to identify the material- and process-related parameters impacting the critical quality attributes of dissolution testing, (2) an experimental design to evaluate the influence of design factors (attributes and parameters selected by risk analysis) on dissolution testing, and (3) an investigation of the relationship between design factors and dissolution profiles. Results show that (a) in the case studied, the two parameters impacting dissolution kinetics are active pharmaceutical ingredient particle size distributions and tablet hardness and (b) these two parameters could be monitored with PAT tools to predict dissolution profiles. Moreover, based on the results obtained, modeling dissolution is possible. The practicality and effectiveness of the QbD approach were demonstrated through this industrial case study. Implementing such an approach systematically in industrial pharmaceutical production would reduce the need for tablet dissolution testing.