药品中遗传毒性杂质的评估和控制

目的 综述药品遗传毒性杂质控制相关指南和法规,为制药企业执行国际标准和准则提供一些建议和思路。方法 通过查找数据库如Pubmed、Medline及欧洲药品管理局(European Medicines Agency,EMA)、美国食品药品监督管理局(US Food and Drug Administratio,U.S.FDA)、人用药品注册技术要求国际协调会议(ICH)等网站,比较各指南法规关于遗传毒性控制限度和控制措施的异同点,为遗传毒性杂质的控制提供一个可行性步骤。结果 通过比较发现,EMA、U.S.FDA和即将出版的ICH M7指南在关键原则的应用方面如毒理学关注阈值(threshold of toxicological concern,TTC)、风险评估步骤、杂质5分类法等基本相同,但现行EMA和U.S.FDA法规存在分歧,不利于其有效执行,而ICH M7将为遗传毒性杂质的控制提供一个可行框架。结论 目前还缺乏完善有效的遗传毒性控制指南,ICH M7将解决U.S.FDA 和EMA 指南间分歧,更好地指导制药企业遗传毒性杂质的控制。     

The regulatory landscape of biosimilars: Algeria's efforts and progress made from 2006 to 2021

Biologics are tremendously efficacious biological molecules that have enabled the treatment of many life-threatening diseases, which have previously been hard to treat. Biosimilars, also known as “follow-on biologics”, are highly similar versions of another already approved biologic, called the Reference Product. The European Union has been a pioneer in the regulation of biosimilars. WHO guideline on evaluation of biosimilars published in 2009 was an important landmark in biosimilar regulations worldwide, and several countries have adopted its principles in the development of their own regulatory pathway for the approval of biosimilars. Most countries in the Middle East North Africa (MENA) region still lack official and scientific guidelines for biosimilar approval pathways. This article explores the regulatory situation of biosimilar registration pathways in Algeria and describes the progress made and the regulatory landscape changes for biosimilars in Algeria during the past ten years. Our findings indicate that the development of biosimilar regulation in Algeria went through three major phases between 2006 and 2021, during which there has been much progress in drafting guidance documents for biosimilars. Since 2016, Algeria has used the EMA, FDA and WHO guidelines as the basis for approval of several biosimilars and no national guidelines or regulations have been adopted to date. Additionally, there has been no regulation on substitution/interchangeability. The Algerian regulatory authority has gained considerable experience with approval and use of increasingly complex biosimilars over the past 5 years and has the potential to create its own biosimilar-specific regulatory pathway in the near future.     

药品安全性监测ICH国际协调进展及启示

目的：了解和分析“人用药品注册技术要求国际协调会议”（ICH）在药品安全性监测技术原则和要求的国际协调进展。方法：回顾ICH的起源和工作程序，概述ICH中与药品安全性监测有关的工作。结果：ICH技术原则对我国该领域工作具有借鉴意义。结论：我国应在管理法规、技术程序和定期更新报告等方面逐步与国际接轨。     

建立东亚传统医药注册协调会的可行性分析

目的对建立东亚传统医药注册协调会的可行性进行分析。方法通过与国际人用药品注册协调会（简称ICH）的成立背景进行对比和可行性分析,表明现在是成立东亚传统医药协调会的最佳时机。结果东亚传统医药协调会必须在传统医药理论指导下工作,制定出药材、提取物、成品目录、标准及其他相关研究工作的指导原则。结论传统中医药是亚洲三大传统医药流派中医学理论体系最完整、在世界上传播最广和最有影响的流派。传统中医药随着国际贸易关系的日益紧密和区域性经济一体化进程的不断加快,迫切需要成立区域性的国际协调组织,以协调贸易各方在技术准入方面的一致性,减少贸易摩擦,节省费用和保证使用安全。     

ICH M4模块一中国行政管理文件制定及实施的考虑

为推动中国药品注册申报资料递交标准与国际接轨,提高药品注册和审评审批效率,本文深入探讨了中国ICH M4模块一文件制定及实施的关键考虑.通过梳理分析国外先进监管机构M4模块一文件特点,基于药品注册申报科学高效管理的考量,制定形成中国M4模块一文件的要求.与ICH M4中涉及药物质量、安全性和有效性相关技术资料的其他4个...     

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。     

ICH E14:一项新的评价新药研发中药物临床心脏安全性的国际药政法规

2005年5月，有关在临床研究中如何监督新药对心脏安全性的措施，经国际协调会议（ICH）讨论并通过了一项新的工作指南，即ICH协调性三方指南：非抗心律不齐药物的致QT／QTc间期延长和致心律失常的临床评价。本文概述并讨论了该指南要点，以期望对相关新药安全性监督起到一定指导作用。     

从定期安全性更新报告过渡到定期受益-风险评价报告：初步经验和挑战

人用药品注册技术要求国际协调会议（ICH）提供了定期安全性更新报告指南（PsuR,ICHE2C（R1））和新的定期受益-风险评价报告指南（PBRER,ICHE2C（R2））。PBRER由PSUR演变而来,实现了从比较传统的获批后药物警戒定期总结报告到现代定期受益-风险评价总结报告的转变,根据累积信息对批准上市产品做出最新的受益-风险评价。通过总结ICHE2CPSUR指南和PBRER指南的主要区别,介绍了某跨国制药公司在由编写PSUR改为编写PBRER的转变过程中所积累的初步经验及其遇到的挑战,讨论了中国在推进药物警戒系统的背景下实行PBRER的可能性。     

对EMA草药质量标准指南（第3修订版草案）的思考

草药及其产品的质量标准具有区别于化学药品或生物制品的特殊性，因此欧洲药品管理局（EMA）于2018年发布了“质量标准指南：草药物质、草药制剂和草药产品或传统草药产品的检验程序和可接受标准（第3修订版草案）”。EMA的草药及其产品的情况与我国中药有相似之处，从起始物料到成品多为活性成分未知的复杂混合物。目前我国尚未制定关于中药或中药材（饮片）质量标准相关指导原则。介绍该指南文件的主要内容，并结合中药质量监管情况进行分析，以期EMA相关质量标准制定的指导思路为制定中药质量标准提供参考。     

个例安全性报告规范(ICH E2B)简介及应用

药品不良反应监测受到越来越多的关注,我国已建立药品不良反应自发呈报系统,并在逐步完善中.本文介绍了人用药品注册技术规范国际协调会中关于个例安全性报告规范的主要特点及现状,以期该规范能帮助提高我国药品不良反应监测水平.     

EMA草药产品或传统草药产品质量指南的思考

介绍欧洲药品管理局（EMA）于2018年8月15日发布的"草药产品或传统草药产品质量指南（第3修订版草案）"主要内容。EMA的草药及其产品的情况与我国中药有相似之处，而我国目前尚未制定关于中药或中药材（饮片）的质量研究相关指导原则，该指南相关质量和稳定性研究的指导思路可为中药的质量研究提供参考。     

人用药品注册技术要求国际协调会定期安全性更新报告的基本原则及其对我国的启示

通过介绍人用药品注册技术要求国际协调会定期安全性更新报告的基本原则,建议我国要稳步推进定期安全性更新报告相关工作,对于在我国的数据锁定点与国际诞生日不一致的,应根据不同情况提交汇总桥接报告、补充报告以及补充病例列表和汇总表。药品生产企业通过定期安全性更新报告,重在发现药品安全风险,为深入开展研究并控制风险提供线索。     

Approach to design space from retrospective quality data

Context: Nowadays, the entire manufacturing process is based on the current GMPs, which emphasize the reproducibility of the process, and companies have a lot of recorded data about their processes.

Objective: The establishment of the design space (DS) from retrospective data for a wet compression process.

Materials and methods: A design of experiments (DoE) with historical data from 4 years of industrial production has been carried out using the experimental factors as the results of the previous risk analysis and eight key parameters (quality specifications) that encompassed process and quality control data.

Results: Software Statgraphics 5.0 was applied, and data were processed to obtain eight DS as well as their safe and working ranges.

Discussion and conclusion: Experience shows that it is possible to determine DS retrospectively, being the greatest difficulty in handling and processing of high amounts of data; however, the practicality of this study is very interesting as it let have the DS with minimal investment in experiments since actual production batch data are processed statistically.     

欧盟新的药物警戒法规简介与启示

目的对欧盟新药物警戒法进行介绍,为完善我国药品不良反应报告和监测体系提供参考。方法通过查阅国内外文献,应用文献研究的方法进行分析。结果欧盟药物警戒当前所关注的焦点问题主要集中在收集药品安全性信息,分析和挖掘药品数据信息,开展围绕公众健康监管活动以及与利益相关者进行有效沟通。结论我国应借鉴欧盟新药物警戒法,提高我国药品不良反应报告和监测能力。     

Tablet identification using near-infrared spectroscopy (NIRS) for pharmaceutical quality control

A need for more reliable and faster analytical methods for the identification of the active pharmaceutical ingredient (API) in finished pharmaceutical products is launched by the International Conference on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use, Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances, Q6A (1999). The use of infrared spectroscopy is suggested as a means to obtain specific identification. Near-infrared spectroscopy (NIRS) is a reliable method that offers important advantages for the large-scale production of tablets, such as high-throughput and accurate multiparametric data collection. Despite the grown number of reported NIRS identification methods, only a few methods have been approved by the regulatory authorities, which might be due to difficulties on clearly presenting the methods in official documents and audits. Motivated by the lack of clear protocols for the NIRS method's development, here we propose a process for building reliable identification NIRS methods. For illustration purposes, a method is described for the identification of API in coated tablets containing 2%, 4% and 8% of thiamazole. The method described was successfully validated according to the International Conference on Harmonisation (ICH) of Technical Requirement for Registration of Pharmaceuticals for Human Use, Validation of Analytical Procedures: Text and Methodology, Q2 (2005). The described method was subsequently approved by European national authorities and thus is suitable for use in cGMP environment.     

立体定向技术制作大鼠脑出血模型评价

目的 通过向大鼠注入自体新鲜不凝血制作脑出血模型,找出一种操作简便、重复性好的脑出血动物模型。方法 参照Yang和Xue的方法,通过立体定向技术注入自体不凝血制备大鼠尾状核出血模型,观察术后血肿形态、脑组织含水量动态变化。结果 血肿形态多为圆形或椭圆形,大小相近。脑组织含水量出血后12h升高,72h达高峰,2w时降至正常。结论 该模型是研究实验性脑出血后脑水肿较为理想的模型,重复性好、易于制备。     

Cardiac safety strategies

This meeting was organised by IIR Life Sciences. It was chaired by Brian Guth, (head of General Pharmacology at Boehringer Ingelheim Pharma) and brought together scientists and clinicians from the pharmaceutical industry, university and regulatory agencies. The meeting presented emerging trends in cardiac safety, including its regulatory context pertaining to ICH S7A, S7B and E14. ICH S7A and S7B highlight the importance of the hERG test and telemetric studies in non-rodents. ICH E14 describes the clinical ‘thorough QT study’ that is required by the FDA for any new drug. Marked physiological variability in QT interval over time can be observed, partly as a result of fluctuation in autonomic tone. Beat-to-beat QT variability and T-wave morphology should be considered as a part of an integrated estimate of proarrhythmic risk. A case study illustrated the predictivity of preclinical data for proarrhythmic risk in humans, showing the importance of evaluating QT effects in patients to establish a safety margin.     

欧盟前沿药物监管模式的介绍

目的通过介绍欧盟药品管理局对前沿药物的管理,为我国创新型药物的监管提供借鉴,促进我国创新药物的发展。方法通过文献检索和文献分析的方法,整理并分析欧盟药品管理局对前沿药物的监管模式和管理思路。结果与结论欧盟药品管理局已逐步探索并构建了前沿药物的监管模式和体系,并在实践中不断发展完善,值得我国在建立创新药物监管模式时参考和借鉴。