1. US FDA Draft Guidance: Diversity Action Plans to Improve Enrollment of Participants from Underrepresented Populations in Clinical Studies
1. 美国FDA指南草案：多样性行动计划，以改善临床研究中代表性不足人群的参与者 入组率
美国FDA发布了一份指南草案，标题为：多样性行动计划，以改善临床研究中代表性不足人群的参与者入组率。
· 指南草案建议在临床试验中采用更多样的患者队列，旨在改善FDA收到的支持上市申请的数据。
· 它大致描述了申办方应在国会授权的多样性行动计划中包括哪些内容。
· 多样性行动计划应简洁，篇幅不超过10页。
· 豁免申请需要提前提交，以便在豁免被拒绝的情况下有时间提交多样性行动计划。
· FDA“强烈鼓励”申办方公开披露其入组目标的详细信息。
The US FDA has released a draft guidance titled: Diversity Action Plans to Improve Enrollment of Participants from Underrepresented Populations in Clinical Studies.
· The draft guidance recommends more diverse patient cohorts in clinical trials and is meant to improve the data the agency receives in support of premarket applications.
· It broadly describes what sponsors should include in their Diversity Action Plans as mandated by Congress.
· Diversity action plans should be succinct, running no more than 10 pages.
· Waiver requests need to be filed early so there is time to submit a DAP if the waiver is denied.
· The FDA 'strongly encourages' sponsors to publicly disclose details about their enrollment goals.
2. US FDA Releases 3 Draft Guidance on Clinical Trial Cancer Eligibility
2. 美国FDA发布了3份关于临床试验癌症合格性的指南草案
美国FDA发布了三项新的肿瘤学指南文件，重点关注临床试验入组资格。 文件分别关注于三个关键领域之一：实验室检查值、药物和洗脱期以及体能状态。
The US FDA has released three new oncology guidance documents focused on clinical trial eligibility. The documents each focus on one of three key areas: laboratory test values, medications and washout periods, and performance status.
· 当可以控制的所有明显变量都得到控制时，试验人群中的入组个体可能开始看起来非常相似。
· 同质研究人群引起了对数据普遍性的担忧，以及对代表性不足的人群缺乏临床研究（和获得临床试验机会）的担忧。
· 为了解决这个问题，FDA已经公布了近十几个与肿瘤学临床试验合格性相关的指南文件。
· 这些努力也是随着FDA努力提高临床研究多样性的同时做出的。
· When all of the obvious variables that can be controlled for are controlled, individual enrollees in a trial population can begin to look very similar.
· A homogeneous research population raises concerns about the generalizability of data, as well as concerns about a lack of clinical research (and access to clinical trials) in under-represented populations.
· To address this concern, the FDA has unveiled nearly a dozen guidance documents related to clinical trial eligibility in oncology.
· These efforts have also come as the FDA has worked to enhance diversity in clinical research in general.
关键信息：
· 所有三个文件都指出，“合格标准有时比必要的更严格，将合格标准扩展到更具有包容性是一个试验设计的考虑因素，可能会改善临床试验人群的多样性。”
· 新的文件草案涉及几个关键主题，包括随着时间的推移以及药物在开发过程中的进展（或收集到更多同类别中其他产品的信息），重点调整临床试验标准。
· 指南中的建议遵循相同的关键主题，包括证明特定排除标准的合理性（而不是依赖于研究项目的先例或先前阶段），并应采用比目前通常做法更精细、更科学合理的排除标准。
Key Takeaways:
· All three documents note that "eligibility criteria are sometimes more restrictive than necessary, and expanding eligibility criteria to be more inclusive is one trial design consideration that may improve the diversity of clinical trial populations."
· The new draft documents carry through several key themes, including a focus on adjusting clinical trial criteria over time and as a drug moves through the development process (or more information is gathered on other products in the same drug class).
· The recommendations in the guidance follow the same key themes, including justifying specific exclusion criteria (rather than relying on precedent or previous phases of the research program) and applying more granular, scientifically justified exclusion criteria than is typically current practice.
3. US FDA CDER OSI Annual Report for 2023
3. 美国FDA CDER OSI 2023年度报告
美国FDA药品评价和研究中心（CDER）科学研究办公室（OSI）发布了2023财年的年度报告。 本文附有与上一年度报告的比较，以及年度报告的原件。
The US FDA Center for Drug Evaluation and Research (CDER) Office of Scientific Investigations (OSI) has released its annual report for fiscal year 2023. Attached to the article is a comparison to the prior year, as well as an original copy of the annual report.
关键信息：
· 临床检查总数增加40%
o 申办方与临床研究者检查的比例保持不变
o 国内检查次数减少26%。
· 初始(65%)与补充(35%)检查的比率保持不变
· 与标准审查相比，优先审查的百分比略有下降(5%)
· 发出的不合规信函数量增加60%
· 有因检查次数增加10%
· 警告信数量增加57%。引用的违规示例包括：
o 未能提交并生效IND
o 未能确保按照研究计划进行研究
o 未能确保IRB持续审查和批准临床试验
· 上市后药物不良反应（PADE）检查次数增加15%，风险评估缓解策略（REMS）检查减少50%。
Key Takeaways:
· The total number of clinical inspections increased by 40%
o The ratio of sponsor to clinical investigator inspections remained the same
o There was a 26% decrease in the number of domestic inspections.
· The ratio of original (65%) vs supplemental (35%) inspections remained the same
· There was a slight decrease (5%) in the percentage of priority review vs standard review inspections
· The number of Pre NonCompliance Letters Issued increased by 60%
· The number of For Cause Inspections increased by 10%
· The number of warning letters increased by 57%. Examples of Violations cited include:
o Failure to submit and have in effect an IND
o Failure to ensure an investigation was conducted according to the investigational plan
o Failure to ensure that an IRB provided continuing review and approval of a clinical trial
· The number of PADE inspections increased by 15% and REMS inspections decreased by 50%.
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4. US FDA BIMO Inspectional Observations Summary for 2023 (PV)
4. 2023美国FDA BIMO检查观察总结（PV）
FDA已发布BIMO2023财年指标。美国FDA2023财年起止时间2022年10月1日-2023年9月30日。
The FDA has released BIMO Fiscal Year 2023 Metrics. The US FDA Fiscal Year 2023 runs from 01Oct2022 to 30Sep2023.
与药物警戒质量管理规范相关的指标包括上市后药物不良反应（PADE）和风险评估缓解策略（REMS）检查。
The metrics related to Good Pharmacovigilance Practice include both Postmarketing Adverse Drug Experience (PADE) and Risk Evaluation Mitigation Strategies (REMS) Inspections.
PADE关键信息：
· 17%的PADE检查生成了483，比上一年减少了12%。
· PADE检查占BIMO检查总数的3%，与前几年的3-5%相似。
· FDA的远程监管评估中只有一项与PADE相关，这与去年一致，但较疫情年份有所下降。
PADE Key Takeaways:
· 17% of PADE Inspections resulted in a 483, which is a 12% decrease from the prior year.
· PADE Inspections constituted 3% of total BIMO inspections, which was similar to prior years which range between 3-5%.
· Only one of FDA's remote regulatory assessments was related to PADE, which is consistent with last year but a decrease from the pandemic years.
REMS关键信息：
· 约90%的检查生成了483，与我们在疫情前几年（2017-2019）观察到的数量相似。
· REMS检查占BIMO检查总数的1%。
· FDA没有对REMS进行远程监管评估。
REMS Key Takeaways:
· Approximately 90% of inspections resulted in a 483, similar to the numbers we saw in pre-pandemic years (2017-2019).
· REMS Inspections constituted 1% of total BIMO inspections.
· No FDA remote regulatory assessments were focused on REMS.
5. US FDA BIMO Inspectional Observations Summary for 2023 (GLP)
5. 2023年美国FDA BIMO检查观察总结(GLP)
下文是2023财年FDA针对药物非临床研究质量管理规范（GLP）检查指标的分解。
Below you will find a breakdown of FDA Inspection Metrics for Fiscal Year 2023 specific to Good Laboratory Practice (GLP).
关键信息：
· 2023年，约45%的GLP检查生成了483或警告信，较上一年增长了15%。
· GLP检查占2023年BIMO检查总数的3%，与前几年持平。
· 64%的GLP检查由CDER发起，27%由CBER发起，2%由CDRH发起。CDER较前一年增加，CDRH较前一年减少。
Key Takeaways:
· About 45% of GLP Inspections resulted in a 483 or warning letter in 2023, a 15% increase from the prior year.
· GLP Inspections constituted 3% of total BIMO inspections in 2023 which is on par with previous years.
· 64% of GLP inspections were initiated by CDER, 27% by CBER and 2% by CDRH. This is an increase for CDER and decrease for CDRH from the prior year.
6. US FDA Guidance on Handling and Retention of Bioequivalence and Bioavailability Testing Samples
6. 美国FDA生物等效性和生物利用度试验样品处理和保存指南
美国FDA发布了关于生物等效性和生物利用度试验样品处理和保存的部分最终指南文件。本指南旨在根据21 CFR 320.38和320.63的要求，为研究申办方和/或药物生产商、合同研究组织(CRO)、研究中心管理组织(SMO)、临床研究者和独立第三方提供关于处理相关生物利用度(BA)和生物等效性(BE)研究留样程序的建议。
The US FDA a partially final guidance document focused on the Handling and Retention of Bioequivalence and Bioavailability Testing Samples. This guidance is intended to provide recommendations for study sponsors and/or drug manufacturers, contract research organizations (CROs), site management organizations (SMOs), clinical investigators, and independent third parties regarding the procedure for handling reserve samples from relevant bioavailability (BA) and bioequivalence (BE) studies, as required by 21 CFR 320.38 and 320.63.
关键信息：
· 在这部分草案，部分终稿指南中FDA最终确定了其关于保留生物等效性(BE)和生物利用度(BA)检测用留样数量的政策，以确保样品与参比药物(RLD)相当，并防止此类检测中的欺诈。
· 指导原则草案部分描述了受试药物和参比药物应如何分发给检测中心，检测中心应如何选择检测样品，哪些样品应保留，以及应如何保留留样样品。它还讨论了每个利益相关者在处理和保留留样方面的作用。
· 指南的定稿部分指出，申办方和CRO必须在所有试验中心的原始容器中分别留出30个单剂量单位或3个多剂量单位的受试品和参比品，且原始容器中至少有1个单位。
· 本指南旨在阐明FDA对处理和保留BA/BE试验样品的期望，该期望源自1990年的中期规则和1993年关于该主题的最终规则及其与最终规则相关的实施条例。
Key Takeaways:
· In a part-draft, part-final guidance FDA finalized its policy on the quantity of reserve samples to be retained for bioequivalence (BE) and bioavailability (BA) testing to ensure that samples are comparable to reference listed drugs (RLD) and to deter fraud in such testing.
· The draft portion of the guidance describes how the test and reference drug should be distributed to the testing sites, how testing sites should select samples for testing, which samples should be held in reserve, and how the reserve samples should be retained. It also discusses the roles of each stakeholder in handling and retaining reserve samples.
· The finalized portion of the guidance states that that sponsors and CROs must set aside 30 single-dose or 3 multi-dose units each of the test and reference products in the original container across all testing sites with at least 1 unit in the original container.
· The guidance is meant to provide clarification on FDA's expectations for the handling and retention of BA/BE testing samples, which stem from a 1990 interim rule and a 1993 final rule on the topic and its implementing regulations related to the final rule.
7. MHRA Software and Artificial Intelligence (AI) as a Medical Device
7. MHRA作为医疗器械的软件和人工智能(AI)
英国药品和保健产品监管署（MHRA）发布了关于软件和人工智能（AI）作为医疗器械的指南。MHRA将AI作为医疗器械（AIaMD）监管的驱动因素之一是该机构参与国际医疗器械监管机构论坛（IMDRF），同时MHRA还担任了IMDRFAI和机器学习设备工作组的联合主席。
The U.K. Medicines and Health Care Products Regulatory Agency (MHRA) has released a guidance on Software and artificial intelligence (AI) as a medical device. One of the drivers of the MHRA approach to the regulation of AI as a medical device (AIaMD) is the agency's participation in the International Medical Device Regulators Forum (IMDRF), along with MHRA's co-chairmanship of the IMDRF work group on AI and machine learning-enabled devices.
关键信息：
· 软件（包括AI）在健康和社会护理中发挥着重要作用。在英国，这些产品中的许多被作为医疗器械（或体外诊断医疗器械(IVD)）进行监管。本指南提供了对可能有帮助的重要软件组输出的访问。
Key Takeaways:
· Software (including AI) plays an essential part in health and social care. In the UK, many of these products are regulated as medical devices (or as in vitro diagnostic medical devices (IVDs). This guidance provides access to important software group outputs that might be of assistance.
MHRA是全球范围内争相跟上医疗器械人工智能（AI）步伐的监管机构之一，发布了一篇关于其方法的论文。本文中的一个关键考虑因素是，MHRA期望在其正在进行的监管改革中对某些启用AI的设备软件功能进行分类，该预测表明，在未来几年，这些产品的上市前路径将更加严格。
MHRA is among the regulators across the globe that are scrambling to keep pace with artificial intelligence (AI) in medical devices, releasing a paper on its approach. One of the key considerations in this paper is that MHRA expects to up-classify some AI-enabled device software functions in its ongoing regulatory revamp, a prediction that suggests a more stringent premarket path for these products in the years ahead.
8. MHRA Policy Paper Impact of AI on the Regulation of Medical Products
8. MHRA政策文件：AI对医疗产品监管的影响
MHRA发布了一份政策文件“AI对医疗产品监管的影响”。MHRA文件是为了响应英国政府的承诺，使AI监管更加“敏捷”，并为机构提供资金“开发前沿研究和实用工具，以监测和解决其部门的风险和机会”。
The MHRA has released a policy paper Impact of AI on the regulation of medical products. The MHRA paper comes in response to the UK government's commitment to making AI regulation more "agile" and providing agencies with money to "develop cutting-edge research and practical tools to monitor and address risks and opportunities in their sector."
关键信息：
· 本报告提供了MHRA使用AI作为AI产品监管机构、作为提供时间关键性决策的公共服务组织以及作为做出影响公共安全的循证决策的组织的最新信息。
· 报告讨论了AI提高MHRA效率的潜力。该机构正在探索使用监督下的机器学习来帮助评估人员检查申请文件的完整性、一致性和质量，并找出差距、错误或差异。机器学习工具将为每个准则或标准提供评分或建议。
Key Takeaways:
· This publication provides an update on the MHRA's use of AI as a regulator of AI products, as a public service organization delivering time-critical decisions, and as an organization making evidence-based decisions that impact public safety.
· The report discusses the potential for AI to make MHRA more efficient. The agency is exploring the use of supervised machine learning to help assessors check applications for completeness, consistency, and quality of the documents and to identify gaps, errors, or discrepancies. The machine learning tool would provide a score or recommendation for each criterion or standard.
9. EMA Guideline: Anonymisation of personal data and assessment of commercially confidential information during the preparation and redaction of risk management plans (body and Annexes 4 and 6) Version 1.2
9. EMA指南：风险管理计划（正文和附件4和6）版本1.2编制和编辑期间，个人数据的匿名化和商业机密信息的评估
EMA发布了在风险管理计划（正文和附录4和6），在制定和编辑过程中，关于个人数据匿名化和商业机密信息评估的修订指南。
The EMA has published a revised guideline on Anonymisation of personal data and assessment of commercially confidential information during the preparation and redaction of risk management plans (body and Annexes 4 and 6).
本文件为申请人/上市许可持有人（MAH）提供了关于在予批准过程中起草风险管理计划（RMP）时保留/删除个人数据（PD）和识别商业机密信息（CCI），以及对批准后编辑RMP以供发布的通用指南，
This document gives general guidance to applicants/marketing authorization holders (MAHs) on the retention/removal of personal data (PD) and identification of commercially confidential information (CCI) when drafting risk management plans (RMPs) in the pre-approval process, and for the redaction of the RMPs for publication post-approval.
已对新版本进行了实质性修改。除了对整个文件进行微小的澄清编辑外，主要变更还包括增加的以下章节：
· 程序指南
· 示例：需要与申请人/MAH互动的编辑RMP相关的最常见问题
This new revision has been substantially modified. Besides minor clarifying edits made throughout the document, the main changes include the addition of the following sections:
· Procedural guidance
· Examples: most frequent issues regarding the redacted RMP that require interaction with applicants/MAH
本文件取代先前的版本EMA/781194/2021版本1：《风险管理计划（正文和附件4和6）在制定过程中保护个人数据的匿名化和商业机密信息的评估》（2023年11月29日）。
This document supersedes the previous version EMA/781194/2021 Rev. 1: Anonymization of Protected Personal Data and Assessment of Commercially Confidential Information During the Preparation of Risk Management Plans (Main Body and Annexes 4 and 6), 29-Nov-2023.
10. EMA Reflection Paper on use of Real-World Data in Non-interventional Studies to Generate Real-World Evidence
10. EMA关于在非干预性研究中使用真实世界数据生成真实世界证据的思考文件
EMA发布了关于在非干预性研究中使用真实世界数据生成真实世界证据的思考文件。 根据欧洲药品管理局发布的思考文件，对于希望在非干预性研究(NIS)中使用真实世界数据(RWD)的欧洲申办方而言，数据的总体质量以及潜在偏倚风险应该是最重要的。
The EMA releases reflection paper on use of real-world data in non-interventional studies to generate real-world evidence. The overall quality of data and risk of potential bias in them should be top of the mind for European sponsors who want to employ real-word data (RWD) in non-interventional studies (NIS), according to a reflection paper released by the European Medicines Agency.
关键信息：
· 本文讨论了使用真实世界数据(RWD)进行非干预性研究(NIS)的方法学，以生成用于监管目的的真实世界证据(RWE)。
· 其重点关注方法学原则，这些原则被认为对使用RWD实施和评估NIS至关重要，并用于整个医学生命周期的监管决策。
Key Takeaways:
· This reflection paper discusses methodological aspects of non-interventional studies (NIS) using real-world data (RWD) in order to generate real-world evidence (RWE) for regulatory purposes.
· It focuses on methodological principles that are considered critical for the conduct and assessment of NIS using RWD and used for regulatory decision-making throughout a medicine's lifecycle.
11. EMA Guidance on Real-world Evidence provided by EMA Support for Regulatory Decision-Making
11. EMA提供真实世界证据支持监管决策的指南
EMA和HMA发布了一份标题为：EMA提供真实世界证据支持监管决策的指南文件。本文件简要描述了RWD分析得出的真实世界证据如何有助于监管决策、可开展的研究类型以及EMA如何帮助确定解决研究问题的最佳资源。真实世界数据(RWD)的使用越来越多地嵌入到人类药物的科学评价中。在欧洲药品管理局，数据分析和方法工作组的真实世界证据团队(TDA-RWE)可以直接和间接访问患者电子病历中的RWD，以便于监管评价和决策。在此基础上，EMA生成真实世界证据(RWE)并向EMA科学委员会、国家主管部门(NCA)、EMA职能机构和其他EU决策者和合作伙伴组织提供服务。
The EMA and HMA have released a guidance document titled: Real-world evidence provided by EMA Support for regulatory decision-making. This document briefly describes how Real-world evidence, derived from the analysis of RWD, can be useful in the context of regulatory decision-making, the types of studies that can be performed, and how EMA can help identify the best resources to address a research question. The use of Real-World Data (RWD) is increasingly embedded in the scientific evaluation of human medicines. At the European Medicines Agency, the Real-World Evidence Team (TDA-RWE) of the Data Analytics and Methods Task Force has direct and indirect access to RWD in the form of patient electronic medical records which can be used to facilitate regulatory evaluations and inform decision-making. On this basis, EMA provides a service to generate and deliver Real-World Evidence (RWE) to EMA's scientific committees, national competent authorities (NCAs), EMA functions, and other EU decision-makers and partner organisations.
关键信息：
· 本文件简要描述了RWD分析得出的RWE如何有助于监管决策、可执行的研究类型以及EMA如何帮助确定解决研究问题的最佳资源。
· 此外还说明了申请RWD研究的流程。
Key Takeaways:
· This document briefly describes how RWE, derived from the analysis of RWD, can be useful in the context of regulatory decision-making, the types of studies that can be performed and how EMA can help identify the best resources to address a research question.
· The process for requesting RWD studies is also explained.
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