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美国食品药品监督管理局发布了一份标题为“在药物研发中使用新方法学的一般考虑因素”的指南草案。它旨在帮助药物研发人员验证药物研发中用于替代动物试验的新方法学(NAMs)，并基于以人为中心的数据将安全、有效的药物更快地推向市场。
本指南草案确立了NAM的4个核心验证原则：
使用背景：明确定义NAM的预期监管目的
人体生物学相关性：NAM如何评估毒性的证明
技术特征：通过稳健、可靠和可重现的方法建立科学的可信度
适用目的：确保NAM有助于监管决策（例如，药物审查和潜在批准）
FDA Releases Draft Guidance on Alternatives to Animal Testing in Drug Development
The U.S. Food and Drug Administration has issued a draft guidance titled: General Considerations for the Use of New Approach Methodologies in Drug Development. It is intended to help drug developers validate new approach methodologies (NAMs) to be used instead of animal testing in drug development, and to bring safe, effective drugs to market sooner based on human-centric data.
This draft guidance establishes four core validation principles for NAMs:
Context of Use: Clear definition of NAMs' intended regulatory purpose
Human Biological Relevance: Demonstration of how NAMs can assess toxicity
Technical Characterization: Establishment of scientific confidence through robust, reliable, and reproducible methods
Fit-for-Purpose: Assurance that NAMs help in regulatory decision-making (e.g., drug review and potential approval)
美国FDA发布了指南草案，对药品生产商应如何对FDA 483表检查观察项做出回应做出了明确预期。
本指南涵盖回复格式、内容、时间表、调查计划、CAPA制定和争议解决。尽管483表回复在技术上仍然是自愿的，但该指南明确声明，在15个工作日内提交的条理清晰、内容详实的回复是FDA决定是否采取监管行动的重要考量因素。在此时限之外收到的回复通常不会影响执法进程。该机构从未如此清晰地阐述过未提交回复或回复不充分所带来的严重后果。
本指南反映了FDA对回复质量的期望。指南中的大多数建议与行业公认的最佳实践一致。该指南对于FDA当前使用与已识别风险相称的CAPA进行全面、科学合理且基于风险的调查的想法尤其有益。这与ICH Q9和Q10中定义的风险管理方法一致。
本指南草案并不代表FDA的最终政策。但是，它反映了FDA目前的想法，应被视为预期标准。我们现在必须开始调整内部做法，同时也要参与意见征询过程，以形成最终版本。
FDA Publishes Draft Guidance on Responding to Drug Facility 483 Observations
The U.S. FDA has issued draft guidance establishing clear expectations for how drug manufacturers should respond to FDA Form 483 Inspectional Observations.
The guidance covers response format, content, timelines, investigation planning, CAPA development, and dispute resolution. While 483 responses remain technically voluntary, the guidance unambiguously states that a well-structured, substantive response submitted within 15 business days is a material factor in FDA's decision on whether to pursue a regulatory action. Responses received outside this window will generally not delay enforcement. The stakes of an inadequate or no response have never been more clearly articulated by the Agency.
This guidance reflects the FDA's expectations for response quality. Most of the recommendations in the guidance are consistent with established industry best practice. The guidance is especially informative in the Agency's current thinking for a thorough, scientifically justified, and risk-based investigation with CAPAs commensurate with identified risks. This is aligned with risk management approaches defined in ICH Q9 and Q10.
This is a draft guidance and does not yet represent final FDA policy. However, it reflects the Agency's current thinking and should be treated as the expected standard. We must begin aligning internal practices now, while also engaging in the comment process to shape the final version.
人用药品注册技术要求国际协调会（ICH）宣布通过其M15指导原则，该指导原则旨在统一药物开发中采用基于模型的方法（MIDD）的一般原则和最佳实践，以助力药物开发。
什么是MIDD？在本指南中，MIDD定义为使用计算机建模和模拟（M&S）方法生成证据，这些方法可以包括并整合非临床数据、临床数据、既往信息和知识（例如，药物和疾病特征）。
MIDD的目标是通过整合数学和统计模型的数据来预测药物的作用，并尽量减少不必要的患者暴露，从而提高药物开发的效率。
在 M15 指南出台之前，由于缺乏统一的标准，不同监管机构之间以及同一监管机构内部对于基于模型的药物开发（MIDD）的整合方式各不相同。
M15指导原则“涵盖了使用MIDD的一般原则和良好实践，并就文档标准、模型开发、分析中使用的数据以及模型评估及其应用统一了预期。
接下来的步骤将是由各卫生监管机构采用该指南。
ICH Adopts M15 Guideline to Harmonize Model-Informed Drug Development General Principles
The International Council on Harmonization (ICH) announced the adoption of its M15 guideline, which aims to harmonize general principles and best practices for utilizing model-informed drug development (MIDD) to aid in drug development.
What is MIDD? For the purposes of this Guideline, MIDD is defined as the use of computational modeling and simulation (M&S) methods that can include and integrate non-clinical data, clinical data, prior information, and knowledge (e.g., drug and disease characteristics) to generate evidence.
The goal of MIDD is to improve the efficiency of drug development by integrating data from mathematical and statistical models to predict a drug's effects and minimize unnecessary patient exposure.
Prior to the development of the M15 Guideline, a lack of common standards meant that the integration of model-informed drug development (MIDD) varied between regulatory authorities and even within a given authority.
M15 guideline "covers general principles and good practices for the use of MIDD and harmonizes expectations regarding documentation standards, model development, data used in the analysis, and model assessment and its applications.
Next steps will be for individual Health Authorities to adopt the guideline.
EMA检查员工作组已发布2024年的年度检查报告。以下是过去5年的结果比较：
检查总数与上一年保持一致。
与前几年一样，大多数（63%）CHMP（欧盟药品管理局）GCP检查在临床研究中心进行，其次是申办方（27%）、CRO（7.5%）和其他（分析实验室和BE机构）。
任何级别（主要、次要和关键）中，发现项总数排名前3位主要类别为：试验管理、一般情况、研究中心。
MA Good Clinical Practice Inspection Metrics 2024
The EMA Inspectors Working Group has released its annual inspection report for the year 2024. Below is a comparison of findings for the past 5 years:
The total number of inspections remained the same as the prior year.
As in previous years, the majority (63%) of CHMP GCP inspections were carried out on Clinical Investigator sites, followed by Sponsor Sites (27%), CROs (7.5%) and Other (Analytical Labs & BE Facility).
The top 3 Main categories with overall number of findings in any grade (major, minor, and critical) were: Trial Management, General, Investigational Site.
EMA发布了关于第I部分（科学和技术试验方面）和第II部分（伦理和参与者相关文件）评估期间发现的常见问题的建议文件。
本文件提供了指导原则，以帮助临床试验申办方提高在欧盟提交的CTA的质量、效率和一致性。它汇编了国家主管部门（NCA）和伦理委员会（EC）在第I部分和第II部分评估期间报告的常见问题。
本文件旨在作为申办方准备CTA的实用工具，帮助前瞻性地预测和解决共同的问题。基于此，将有助于使评估过程更精简和可预测，从而及时启动临床试验。
EMA Recommendation paper on frequent issues identified during assessment of Part I and Part II
The EMA has released a Recommendation paper on frequent issues identified during assessment of Part I (scientific and technical trial aspects) and Part II (ethics and participant-related documents).
This document provides guidance to help clinical trial sponsors improve the quality, efficiency, and consistency of CTAs submitted in the EU. It compiles common issues reported by National Competent Authorities (NCAs) and Ethics Committees (ECs) during assessments of Part I and Part II.
This document is intended to serve as a practical tool for sponsors when preparing their CTA, helping to anticipate and address common concerns proactively. By doing so, it contributes to a more streamlined and predictable assessment process, ultimately supporting the timely initiation of clinical trials.
美国FDA发布了最终指南，标题为：适用于生物研究监测检查的流程和规范。该项目用以评估非临床研究、临床研究以及适用的上市后活动是否符合法定要求和FDA管理的规定。
本最终指南反映了公众对指南草案的意见。具体而言，除其他内容外，包含以下变更：
明确该机构访问和获取电子记录副本方面的做法。
提供有关该机构检查预告通知和沟通有关的其他细节；
提供检查后沟通的更多信息。
US FDA Final Guidance on Processes and Practices to BIMO Inspections
The US FDA has released final guidance titled: Processes and Practices Applicable to Bioresearch Monitoring Inspections. The program assesses compliance with statutory requirements and FDA's regulations governing the conduct of nonclinical and clinical studies, and applicable postmarketing activities.
This final guidance reflects consideration of the public comments on the draft guidance. Specifically, the final guidance, among other things, contains changes to:
clarify the Agency's practices for accessing and obtaining copies of electronic records.
provide additional details with respect to the Agency's inspection pre-announcement notices and communications; and
offer additional information on post-inspection communications.
EMA发布了指南草案：ICH E22关于患者偏好研究一般考虑的指南。该草案概述了用于指导药物开发的患者偏好研究的使用、设计、实施、分析和提交的一般考虑。
什么是患者偏好研究（PPS）？患者偏好研究是询问患者对他们而言，药物和其他健康干预措施最重要的是什么，如有效性、副作用、安全性、便利性和其他因素。这些研究有助于药物研发者和监管机构从患者的角度理解和考虑医疗需求。目前，患者偏好研究但并不是在每个地方都进行，且执行也不一致。
E22指南草案涵盖了一般原则、不同类型患者偏好研究的信息，以及设计和实施这些研究的建议和实际考虑因素。
本文件概述了关于PPS使用、设计、实施、分析和提交的一般考虑因素，旨在为药物开发、监管提交和评价、药物批准及其更新提供指导。
其目的是进一步协调不同国家监管机构和制药行业对这些研究的方法，并支持在决策中常规纳入患者偏好。
ICH E22 Draft Guideline on General Considerations for Patient Preference Studies
The EMA has released a draft guidance: ICH E22 Guideline on general considerations for patient preference studies. The draft guideline outlines general considerations about the use, design, conduct, analysis, and submission of patient preference studies aimed at informing drug development.
What are patient preference studies? Patient preference studies ask patients what matters most to them about drugs and other health interventions, such as effectiveness, side effects, safety outcomes, convenience and other factors. These studies help drug developers and regulatory authorities to understand and consider medical needs from the perspective of patients. Patient preference studies are used today but not everywhere and not consistently.
The E22 draft Guideline covers general principles, information on different types of patient preference studies, and recommendations and practical considerations for designing and conducting these studies.
It outlines general considerations about the use, design, conduct, analysis, and submission of PPS aimed at informing drug development, regulatory submission and evaluation, drug approvals and maintenance of such approvals.
It aims to further harmonies approaches to these studies for regulatory authorities and the pharmaceutical industry in different countries and support the routine inclusion of patient preferences in decision-making.
审阅｜刘海涛、施媛媛、张淼、宋婷婷
编辑｜李茜然、乐园
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