1.关于在药品生命周期中使用人工智能(AI)的意见书（2023年7月）

        EMA Reflection Paper on the use of Artificial Intelligence (AI) in the Medicinal Product Lifecycle (Jul 2023)

        总结：

        EMA发布了关于在药品生命周期中使用人工智能(AI)的意见书。意见书的目的是考虑在药品的整个生命周期中使用人工智能（AI）/机器学习（ML），包括药品开发、许可和许可后。

        关键信息：

• 本意见书提供了关于人工智能和机器学习在药品生命周期（包括药品开发、许可和许可后）中使用的考虑。

• 鉴于该领域的快速发展，意见书的目的是反映应用这些新兴技术支持药品的安全有效开发和使用时，与监管评价相关的科学原则。

• HMA/EMA计划于2023年11月20-21日举办研讨会，讨论意见书草案。

        Summary:

        The EMA has released a Reflection paper on the use of Artificial Intelligence (AI) in the medicinal product lifecycle. The purpose of the paper is to consider the use of AI/Machine Learning (ML) throughout the lifecycle of drugs including during product development, authorization, and post-authorization.  

        Key Takeaways:

• This reflection paper provides considerations on the use of AI and ML in the lifecycle of medicinal products, including medicinal products development, authorisation, and post-authorisation.

• Given the rapid development in this field, the aim of this reflection paper is to reflect on the scientific principles that are relevant for regulatory evaluation when these emerging technologies are applied to support safe and effective development and use of medicines.

• HMA/EMA plan to hold a workshop 20-21 November 2023 to discuss the draft reflection paper.

     2.EMA针对2023年7月31日集中程序用户发布了一份EMA许可后程序建议的更新文件

        EMA Updates EMA Post-Authorisation Procedural Advice for Users of the Centralised Procedure dated 31Jul2023

        总结：

        EMA发布了一份关于2023年7月31日集中程序用户的EMA许可后程序建议的更新文件。文件可在EMA网站上找到，该文件旨在为集中许可药品的上市许可持有人，就上市后风险管理计划（RMP）生命周期的程序和监管方面，提供建议。

        关键信息：

• 本指南文件解决了上市许可持有人（MAH）可能对许可后阶段提出的许多问题。本文件概述了监管当局对问题的立场，这些问题通常在上市许可后与MAH的讨论或会议中解决。

• 文件将定期更新，以反映新的发展，将纳入关于进一步许可前程序的指南，并反映新欧洲立法的实施情况。

• 本指南所提供的信息以及富有成效的申报前会议，应能使申请人提交的申请符合法律和法规要求，并能快速获得确认。

        Summary:

        The EMA has posted an updated document on EMA post-authorisation procedural advice for users of the centralised procedure dated 31Jul2023. It is found on the EMA page intended to provide advice to marketing authorisation holders of centrally authorised medicinal products about procedural and regulatory aspects to the risk management plan (RMP) lifecycle during the post authorisation phase. 

        Key Takeaways:

•         This guidance document addresses a number of questions which marketing authorisation holders (MAHs) may have on post-authorisation procedures. It provides an overview of the Agency's position on issues, which are typically addressed in discussions or meetings with MAHs in the post-authorisation phase.

•         It will be updated regularly to reflect new developments, to include guidance on further preauthorisation procedures and to reflect the implementation of the new European legislation.

•         This guidance information and fruitful pre-submission meetings should enable applicants to submit applications, which are in conformity with the legal and regulatory requirements and which can be validated speedily. 

        3.EMA更新GCP问答（2023年8月）

        EMA Updates Q&A on GCP (August 2023)

        总结：

        EMA发布了修订后的GCP Q&A文件。在B部分（GCP事项）中增加了一个新问题。

        问题19：向临床研究中心/研究者分发更新的研究者手册（IB）和更新的知情同意书（ICF）的预期是什么？

        关键信息：

• EMA添加了一个新问题，阐明一旦监管机构批准，就分发IB，一旦伦理委员会批准，就分发更新的ICF给临床研究中心。

        Summary:

        The EMA has released a revised GCP Q&A document. They have added is a new question in section B (GCP Matters).

        Question 19: What are the expectations for distribution of updated Investigator's Brochures (IBs) and updated Informed Consent Forms (ICFs) to clinical sites/investigators? 

        Key Takeaways:

• The EMA has added a new question clarifying expectations for distribution of the IB as soon approved by competent authority and updated ICFs as soon as approved by the ethics committed to the clinical trial sites.

        4.EMA更新风险管理计划网站（2023年9月）

        EMA Updates Risk Management Plans Website (Sep 2023)

        EMA已更新了风险管理计划网站。从2023年10月20日起，EMA对所有集中审批产品发布RMP（正文和附件4和6）：

• 初始评价；

• RMP更新。

        EMA从同一日期起不再发布RMP摘要。

• 目的是提高所有集中授权产品的安全性审查过程的透明度。

• RMP或RMP摘要见各药物页，或者，提供所有RMP摘要的历史列表。

        关键信息：

• EMA从10月20日起开始发布所有通过集中程序授权产品的风险管理计划。

• 10月份之后将不再发布摘要。

• 结合更新，EMA还发布了 “风险管理计划(RMP)发布声明”的模板。

        The EMA has published an update to their Risk Management Plans Website. From 20 October 2023, EMA is publishing RMPs (main body and annexes 4 and 6) for all centrally authorised products:

• initial evaluations;

• RMP updates.

        EMA no longer publishes RMP summaries from the same date.

• The aim is to increase transparency of the safety review process for all centrally authorised products.

• The RMP or RMP summary is available on each medicine page. Alternatively, a historical list of all RMP summaries is available.

        Key Takeaways:

• The EMA will begin publishing Risk Management Plans from October 20 for all products authorized through the centralized procedure.

• Summaries will be no longer published after the October date.

• In conjunction with the update the EMA also released a template for the "declaration for risk management plan (RMP) publication."

        5.FDA发布上市后研究和临床试验指南草案：确定不符合联邦食品药品和化妆品法案第505（o）（3)（E）（ii）节的正当理由（2023年7月）

        FDA Issues Draft Guidance on Postmarketing Studies and Clinical Trials: Determining Good Cause for Noncompliance with Section 505(o)(3)(E)(ii) of the Federal Food, Drug, and Cosmetic Act (Jul 2023)

        总结：

        美国FDA发布了上市后研究和临床试验指南草案：确定不符合《联邦食品、药品和化妆品法案》第505（o）（3)（E） （ii）节的正当理由。上市后要求（PMR）是FDA确立的一种正在进行的研究的要求，即申办方即使在产品获批后仍继续（或开始）对其进行研究或临床试验。这些研究和试验旨在帮助生成关于产品安全性、有效性或使用的额外数据。

        关键信息：

• FDA的2018年年度报告显示，只有69%的PMR状态报告按时提交。

• 新的FDA指南草案文件阐述了该机构对什么是“正当理由”可以支持不遵守既定上市后要求（PMR）的想法。

• 该指南还规定了与FDA沟通潜在不合规情况的最佳实践，这对于难以遵循PMR而联系监管机构的研究/试验申办方来说，可能是有用的。

        Summary:

        The US FDA has released a draft guidance on Postmarketing Studies and Clinical Trials: Determining Good Cause for Noncompliance with Section 505(o)(3)(E)(ii) of the Federal Food, Drug, and Cosmetic Act. Post-marketing requirements (PMRs) are a kind of ongoing research requirement established by the FDA that a sponsor continues (or starts) studies or clinical trials on a product even after its approval. These studies and trials are intended to help generate additional data about the safety, efficacy, or use of the product.

        Key Takeaways:

• A 2018 annual report from the FDA showed only 69% of PMR status reports were submitted on time.

• A new FDA draft guidance document lays out the agency's thinking on what "good cause" could support noncompliance with an established post-market requirement (PMR).

• The guidance also lays out best practices for communicating with FDA about potential noncompliance, which could be informative for study/trial sponsors considering reaching out to the agency about PMR difficulties.

        6.美国FDA知情同意指南终稿：机构审查委员会、临床研究者和申办方指南（2023年8月）

        US FDA Final Guidance on Informed Consent: Guidance for Institutional Review Boards, Clinical Investigators, and Sponsors (Aug 2023)

        总结：

        美国FDA发布了标题为《知情同意：机构审查委员会、临床研究者和申办方指南》的指南终稿。本指南取代了1998年9月发布的《知情同意指南》，并于2014年7月15日发布的《知情同意信息表：机构审查委员会、临床研究者和申办方指南》的指南草案。

        关键信息：

• 本指南旨在协助参与FDA监管产品临床研究的机构审查委员会（IRB）、临床研究者和申办方履行其与知情同意相关的职责。

• 该指南提供了FDA关于知情同意的建议，并描述了监管要求，以帮助确保受试者的权利和福祉得到保护。

        Summary:

        The US FDA has released a final guidance titled: Informed Consent: Guidance for Institutional Review Boards, Clinical Investigators, and Sponsors. This guidance supersedes FDA's guidance entitled "A Guide to Informed Consent," issued in September 1998, and finalizes the draft guidance entitled, "Informed Consent Information Sheet: Guidance for Institutional Review Boards, Clinical Investigators, and Sponsors," issued on July 15, 2014.

        Key Takeaways:

• This guidance is intended to assist institutional review boards (IRBs), clinical investigators and sponsors involved in clinical investigations of FDA-regulated products in carrying out their responsibilities related to informed consent.

• The guidance provides the FDA's recommendations regarding informed consent and describes regulatory requirements to help assure the protection of the rights and welfare of people participating in clinical trials. 

        7.美国FDA指南终稿：使用RWD和RWE支持监管决策的考虑事项（2023年8月）

        US FDA Final Guidance: Considerations for the Use of RWD and RWE to Support Regulatory Decision Making (Aug 2023)

        美国FDA发布了《考虑使用真实世界数据和真实世界证据来支持药品和生物制品的监管决策》的指南终稿。

        关键信息：

• 美国FDA最终确定了关于使用真实世界数据（RWD）和真实世界证据（RWE)支持药品和生物制品监管决策的行业指南，提供数据访问和安全性监测的建议。

• FDA发布本指南作为其RWE计划的一部分，以在一定程度上满足FD&C法案第505F节的授权，帮助支持已根据FD&C法案第505（C）节（21 U.S.C. 355（C））批准的药物的新适应症或帮助支持批准后研究要求。

• 该指南要求申办方如果计划使用非干预性研究来支持上市申请，在药物开发过程的早期，咨询该机构。

        The US FDA has released a final guidance titled: Considerations for the Use of Real World Data and Real World Evidence to Support Regulatory Decision Making for Drug and Biological Products.

        Key Takeaways:

• The US FDA finalized its guidance for industry on the use of real-world data (RWD) and real-world evidence (RWE) in supporting regulatory decisions for drugs and biologics, offering recommendations for data access and safety monitoring.

• FDA is issuing this guidance as part of its RWE Program to satisfy, in part, the mandate under section 505F of the FD&C Act to issue guidance about the use of RWE to help support approval of a new indication for a drug already approved under section 505(c) of the FD&C Act (21 U.S.C. 355(c)) or to help support postapproval study requirements.

• The final guidance calls for sponsors to consult the agency early in the drug development process if they are planning to use a non-interventional study to support a marketing application.

        8.FDA指南终稿：IRB对试验用药品个体患者扩大供药申请的审评（2023年9月）

        FDA Final Guidance IRB Review of Individual Patient Expanded Access Submissions for Investigational Drugs (Sep 2023)

        总结：

        美国FDA发布了《机构审查委员会（IRB）对试验用药品和生物制品个体患者扩大供药申请的审查》终稿。FDA此前发布的关于扩大使用申请（包括针对个体患者的申请）的指南，曾确认在这一领域仍（有环节）需更加明确。（指南中的）扩大使用分为3种类型：个体患者、中等数量患者人群和较大数量患者人群。

        关键信息：

• 本指南仅涉及21 CFR 312.310中概述的个体患者扩大使用申请的IRB审评。目标是精简和提高这些审查的效率。

• 它向IRB和临床研究者阐明了个体患者扩大使用申请的审评过程，尤其是由单个IRB成员进行（的审评）。

• IRB、临床研究者和医疗保健专业人员应持续了解这些监管更新，以有效应对扩大使用项目的复杂情况。

        Summary:

        The US FDA has released a final guidance titled: Institutional Review Board (IRB) Review of Individual Patient Expanded Access Submissions for Investigational Drugs and Biological Products. Although the FDA previously issued guidance on expanded access requests, including those for individual patients, it acknowledges the ongoing need for greater clarity in this area. Expanded access is categorized into three types: individual patients, intermediate-size patient populations, and treatment for larger populations. 

        Key Takeaways:

• This guidance exclusively addresses IRB review of individual patient expanded access submissions, as outlined in 21 CFR 312.310. The goal is to streamline and enhance the efficiency of these reviews.

• It clarifies to IRBs and clinical investigators regarding the review process for individual patient expanded access submissions, mainly when conducted by a single IRB member.

• IRBs, clinical investigators, and healthcare professionals should stay informed about these regulatory updates to effectively navigate the complex landscape of expanded access programs.

        9.在灾害和突发公共卫生事件导致的重大中断期间开展医疗产品临床试验的考虑因素（2023年9月）

        Considerations for the Conduct of Clinical Trials of Medical Products During Major Disruptions Due to Disasters and Public Health Emergencies (Sep 2023)

        总结：

        美国FDA发布了《在因灾害和突发公共卫生事件导致重大中断期间进行医疗产品临床试验的考虑因素》指南的终稿。指南建议，当灾难或突发公共卫生事件（PHE）（包括但不限于飓风、地震、军事冲突、传染病爆发或生物恐怖袭击）对临床试验的实施和操作造成重大干扰时，医疗产品临床试验的申办方可以考虑采用何种方法。本指南的附录通过回答FDA在重大中断期间收到的有关临床试验的问题，进一步解释了这些方法。

        关键信息：

• 美国FDA发布了修订后的终稿指南，以协助申办方、研究者和机构审查委员会在灾难和PHE期间进行临床试验，重点关注患者安全、保持符合药物临床试验质量管理规范，并将试验完整性风险降至最低。

• 取代2020年3月COVID-19大流行期间发布的早期版本和2021年8月发布的更新，但保留了许多早期建议。

• 修订后的指南旨在消除遵守临床试验方案和程序方面的冗余和挑战。

• 美国FDA没有事先征求公众意见，因为灾难和PHE可能会在没有通知的情况下发生，并且根据我们在COVID–19 PHE期间的经验，可能会迅速对临床试验的实施造成重大干扰。因此，对公共卫生来说，重要的是提供有关方法的指导，以确保受试者的安全，并在此类重大干扰期间最大限度地降低试验完整性的风险。

        Summary:

        The US FDA has issued a new final guidance titled Considerations for the Conduct of Clinical Trials of Medical Products During Major Disruptions Due to Disasters and Public Health Emergencies. The guidance recommends approaches that sponsors of clinical trials of medical products can consider when there is a major disruption to clinical trial conduct and operations due to disasters or public health emergencies (PHEs), which can include but are not limited to hurricanes, earthquakes, military conflicts, infectious disease outbreaks, or bioterrorist attacks. The appendix to the guidance further explains those approaches by providing answers to questions that the Agency has received about conducting clinical trials during major disruptions.

        Key Takeaways:

• The US FDA issued revised final guidance to assist sponsors, investigators, and institutional review boards conducting clinical trials during disasters and PHEs, focusing on patient safety, maintaining compliance with good clinical practice, and minimizing risk to trial integrity.

• Supersedes an earlier version issued in March 2020 during the COVID-19 pandemic and an update issued in August 2021 but maintains many of the earlier recommendations.

• The revised guidance is intended to remove redundancies and challenges in complying with clinical trial protocols and procedures.

• The US FDA did not seek prior comment because disasters and PHEs may occur without notice and, as we have learned from experience during the COVID–19 PHE, may rapidly cause major disruptions to clinical trial conduct. It is thus important to public health to provide guidance on approaches to assure the safety of trial participants and minimize risks to trial integrity during such major disruptions.

        10.MHRA PV年度检查指标报告（2021年4月 - 2022年3月）

        MHRA Annual PV Inspections Metrics Report (Apr 2021-Mar 2022)

        总结：

        MHRA已发布其年度药物警戒检查指标。这些检查的目的是检查现行欧盟和国家药物警戒法规和指南的合规性。选择MAH，采用修订后的基于风险的方法进行检查，该方法旨在提高最高风险产品和药物警戒系统的检查覆盖率。

        在2021年4月1日至2022年3月31日期间，GPvP检查员对上市许可持有人（MAH）进行了32次检查。

        关键信息：

• 按主题领域细分检查结果，无论分级如何，与风险管理相关的发现比例最高，占32%（54/169个结果）。其次是与质量管理体系相关的发现，发生率为25%（42/169），药物不良反应（ADR）管理相关的发现，发生率为14%（23/169）。在上一个报告期间，不考虑分级，发现比例最高的领域是质量管理体系、风险管理和持续的安全性评价。

• 随着2020/21年修订后的GPvP检查模式的引入，4个检查组中的3个主要关注风险管理领域。因此，在该领域下报告了大量的检查发现。

• 风险管理仍然是总体上报告严重发现最多的领域。2021/22中报告了与该领域相关的5个严重发现；其中2个与RMP第III部分(NI-PASS)中额外药物警戒活动的管理相关，2个与安全性参考信息的维护相关，1个与RMP第V部分中额外风险最小化措施（aRMM）相关。

  o 风险管理是一个常规识别出高比例结果的领域；然而，在本报告期内的发现数量增加，可能是由于根据NI-PASS下进行的检查数量的增加和在检查组进行了额外的风险最小化活动。

• 持续进行的安全性评价是过去经常报告严重发现的另一个领域，2021/22年期间报告的严重发现之一在该领域，关于提交PSUR时的严重不依从。该领域的严重发现数量位居第二。

• 2021年4月1日至2022年3月31日期间的大多数检查是远程进行的，仅对与NI-PASS检查相关的研究中心进行现场检查。

        Summary:

        The MHRA has released its annual PV inspection metrics. The purpose of these inspections is to examine compliance with existing EU and national pharmacovigilance regulations and guidelines. MAHs are selected for inspection using a revised risk-based methodology that aims to increase inspection coverage for the highest-risk products and pharmacovigilance systems.

        During the period 01 April 2021 to 31 March 2022, the GPvP Inspectorate conducted 32 inspections of marketing authorisation holders (MAHs). 

        Key Takeaways:

• Breaking down the inspection findings by topic area, the highest proportion of findings regardless of grading were related to risk management, comprising 32% (54/169 findings). This was followed by findings relating to the quality management system with 25% (42/169 findings) and the management of adverse drug reactions (ADRs) with 14% (23/169 findings).  In the previous reporting period, the topics with the highest proportion of findings regardless of grading were the quality management system, risk management and ongoing safety evaluation.

• With the introduction of the revised GPvP inspection model in 2020/21, three of the four inspection arms have a primary focus in the risk management area. Accordingly, a large number of findings have been reported under this topic.

• Risk management remains the topic for which the largest number of critical findings has been reported overall. Five critical findings associated with this topic were reported in 2021/22; two of these related to the management of additional pharmacovigilance activities in Part III of the RMP (NI-PASS), two findings related to the maintenance of reference safety information and one finding related to additional risk minimisation measures (aRMMs) in Part V of the RMP.

  o Risk management is a topic in which a high proportion of findings are routinely identified; however, the increase in the number of findings identified during the current reporting period is likely attributable to the increased number of inspections conducted under the NI-PASS and additional risk minimisation activities inspection arms.

• Ongoing safety evaluation is another topic where critical findings have frequently been reported in the past, and one of the critical findings reported during 2021/22 was in this area, where a critical non-compliance was identified for the submission of PSURs. This topic has the second largest number of critical findings reported overall.

• The majority of inspections in the period 01 April 2021 to 31 March 2022 were conducted remotely, with only investigator site inspections associated with NI-PASS inspections being conducted onsite.