Regulatory Express_Feb. 2024

1. WHO发布关于人工智能用于健康领域的监管思考（2023年10月）

1. WHO Issues Regulatory Considerations on Artificial Intelligence for Health (Oct 2023)

WHO发布该文，警告称在健康领域布局人工智能（AI）工具时需要负责任的管理，并呼吁监管机构与药物研发者就安全使用该类技术展开对话。随着AI健康技术快速攀升，各个国家监管需求也在持续增长，对此，该文提出了六大监管领域。

ž WHO提出一些关键原则供政府和监管部门在推出或修订各自区域的AI指南时遵循。

ž 根据新的指导，WHO要求政府和监管部门引入“稳健的法律与监管框架”以保障AI使用于健康领域。

ž 与EMA Reflection Paper类似，该文还提出了一些考虑要点，特别是风险管理与避免偏倚。

The World Health Organization has released a new document: Regulatory Considerations on Artificial Intelligence for Health. They warn that artificial intelligence tools require responsible management when deployed in the context of health and have called for regulators and drug developers to engage in dialog about the safe use of such technology. In response to growing country needs to responsibly manage the rapid rise of AI health technologies, the publication outlines six areas for regulation of AI for health.

• The WHO aims to outline key principles that governments and regulatory agencies can follow to develop new guidance or adapt existing guidance on AI at national or regional levels.

• Governments and regulatory authorities should introduce "robust legal and regulatory frameworks" to safeguard the use of artificial intelligence (AI) in the health sector, according to new guidance from the World Health Organization.

• In the EMA's reflection paper, similar points for consideration were raised, particularly around risk management and avoiding bias.

2. 美国FDA指南草案：使用真实世界证据支持医疗器械监管决策（2023年12月）

2. US FDA Draft Guidance: Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices (Dec 2023)

该指南阐明了FDA如何评价真实世界数据（RWD）以明确其质量是否可形成真实世界证据（RWE），用以支持FDA医疗器械监管决策。它包含了FDA认为RWD是否适用于监管决策的一些重要因素，以及FDA如何评估这些因素的建议。它是对2017年发布的《利用真实世界证据支持医疗器械监管决策》的扩展，但在本指南草案定稿前，2017年指南将继续有效。

The US FDA has issued a draft guidance entitled "Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices." FDA is issuing this draft guidance to clarify how FDA evaluates real-world data (RWD) to determine whether they are of sufficient quality for generating real-world evidence (RWE) that can be used in FDA regulatory decision-making for medical devices. It includes factors that the FDA considers to be important to demonstrate whether the RWD is fit for purpose for a particular regulatory decision relating to medical devices, as well as the FDA's recommendations on how the FDA intends to assess these factors. This draft guidance proposes expanded recommendations to the 2017 guidance entitled "Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices." The 2017 final guidance remains in effect until this draft guidance is finalized.

3. 美国FDA指南：在临床结局评估中使用项目反应理论的临床试验数据集和相关文件的提交（2023年11月）

3. US FDA Final Guidance on Submitting Clinical Trial Datasets and Documentation for Clinical Outcome Assessments Using Item Response Theory (Nov 2023)

针对使用项目反应理论（IRT）做临床结局评估（COA）的临床试验，该指南提供了数据递交的技术规范；它同时也是FDA CDER以患者为中心（PFDD）药品研发方法论指南系列的一个补充。该指南：

• 为标准化数据集的内容与结构以及支持性文件，提供指导方案。

• 列出术语及其定义，有助于申办方更好地理解FDA想法。

• 为申办方和FDA提供对话机会，就试验设计与执行过程中可能影响该类数据集内容的某些失误的问题进行探讨。

The US FDA has released a final guidance titled: Submitting Clinical Trial Datasets and Documentation for Clinical Outcome Assessments Using Item Response Theory. This document provides technical specifications for the submission of clinical outcome assessment (COA) data that use Item Response Theory (IRT) and supplements the FDA Center for Drug Evaluation and Research (CDER) Patient-Focused Drug Development (PFDD) Methodological Guidance Series.

• This document aims to provide general guidelines for standardized dataset content and structure, along with supporting documentation, to facilitate FDA review of the covered COA within the marketing application that the submitted data are intended to support.

• lists certain terms and their definitions, which may help sponsors better understand the FDA’s thinking.

• provide an opportunity for dialogue between the sponsor and the Agency on issues related to trial design or conduct that may affect the content of these datasets.

4. 美国FDA指南：肿瘤项目实时审查（2023年11月）

4. US FDA Guidance on Real-Time Oncology Review (Nov 2023)

肿瘤项目实时审查（RTOR）旨在向FDA审评人员更早开放数据访问权限，以便审评人员及早发现数据质量问题和潜在的审评问题并反馈给申请人，从而使审评全程更流畅高效。指南为申请人就适用于RTOR流程的肿瘤适应症进行NDA或BLA申请提供建议。RTOR项目早在2018年已启动，最初只用于补充申请，即在申办方锁定数据库后对原始数据做最低限度的预审查。自此，RTOR已成为肿瘤项目审查中的常见做法，也是其它疾病领域加速审查的模型。

The US FDA has released a final guidance titled: Real-Time Oncology Review (RTOR). The intent of RTOR is to provide FDA reviewers earlier access to data to identify data quality and potential review issues, and to potentially enable early feedback to the applicant, which can allow for a more streamlined and efficient review process. The purpose of this guidance is to provide recommendations to applicants on the process for submission of selected new drug applications (NDAs) and biologics license applications (BLAs) with oncology indications for review under Real-Time Oncology Review (RTOR). The program was launched in 2018 (initially for supplemental applications) as a way to pre-review bottom line raw data after a sponsor locked in a clinical database. RTOR has since become a common feature of the oncology review process and a model for expedited approaches in other review areas.

5. 美国FDA指南草案：GLP研究报告翻译之问答系列（2023年11月）

5. US FDA Publishes Draft Guidance: Translation of GLP Study Reports: Questions and Answers (Nov 2023)

当GLP研究报告从其初始语言翻译成英语时，充分记录至关重要，可以确保FDA提交文件的准确与完整。该问答文件向申办方和GLP实验室提供了FDA关于GLP研究报告翻译（从非英语至英语）的建议，以确保文件清晰、准确、完整和真实。

The FDA published the draft guidance: Translation of GLP Study Reports: Questions and Answers. When study reports of GLP studies are translated from their original language into English, adequate documentation is critical to ensure accurate and complete study data are submitted to FDA. This question-and-answer document is intended to clarify FDA's recommendations concerning the translation of study reports from a non-English language into English for studies conducted in compliance with GLP regulations. FDA expects that the recommendations for translating GLP study reports described in this guidance will increase our stakeholders' understanding of the documentation needed to ensure study reports translated from the original language into English are clear, accurate, complete, and truthful.

6. 美国FDA更新指南终稿：用于支持患者监护的远程无创监测器械的执行政策（2023年10月）

6. US FDA Updated Final Guidance: Enforcement Policy for Non-Invasive Remote Monitoring Devices Used to Support Patient Monitoring (Oct 2023)

远程无创监测器械无需门诊访视即可采集患者身体数据，帮助医护人员管理病患的同时减少占用门诊或住院服务资源。该指南将取代《COVID-19期间用于支持患者监护的远程无创监测器械的执行政策》（修订版：2020年10月），以帮助FDA与相关人士从COVID-19特定操作过渡到常规流程。FDA认为该指南符合减轻公共卫生负担原则，发布之前并未向公众征求意见。

The US FDA has issued a final guidance titled: Enforcement Policy for Non-Invasive Remote Monitoring Devices Used to Support Patient Monitoring. Non-invasive remote monitoring devices are used to acquire patient physiological data without the need for in-clinic visits and facilitate patient management by healthcare providers while reducing the need for in-office or in-hospital services. This document supersedes Guidance for Industry and Food and Drug Administration Staff: Enforcement Policy for Non-Invasive Remote Monitoring Devices Used to Support Patient Monitoring During the Coronavirus Disease 2019 (COVID-19) Public Health Emergency (Revised), Oct-2020. FDA believes the policy outlined in this guidance may help FDA and other stakeholders transition from COVID-19 operations and processes to normal operations and processes. This guidance is being implemented without prior public comment because the FDA has determined that this guidance document presents a less burdensome policy that is consistent with public health.

7. 美国FDA指南终稿：人用药品与生物制品的获益-风险评估（2023年10月）

7. US FDA Publishes Final Guidance on Benefit-Risk Assessment for Human Drug and Biological Products (Oct 2023)

患者及相关人士可以从该指南中了解FDA在评估获益与风险时的关键议题，以及这些议题在整个药品评估法规体系中的作用。申办方可以从中理解，在整个药品生命周期管理活动中，如何向FDA提供获益-风险信息并寻求交流沟通机会。

The FDA has published a final guidance: Benefit-Risk Assessment for Human Drug and Biological Products. The document provides patients and other stakeholders with further insight into the key issues that inform the FDA's assessment of benefit and risk, and a clearer understanding of how these issues fit into the regulatory framework of drug development and evaluation. The guidance discusses how sponsors, through their decisions and activities throughout the drug lifecycle, can inform FDA's benefit-risk assessment, as well as opportunities for interaction between the FDA and sponsors to discuss benefit-risk considerations.

8. EMA FAQ：伴随诊断（CDx）相关药品的开发与评估（2023年11月）

8. EMA FAQ on Medicinal Products Development and Assessment Involving Companion Diagnostic (CDx) (Nov 2023)

该指南主要针对药物研发者，包括为上市许可申请生成足够数据的建议以及欧洲体外诊断医疗器械法规（IVDR）对该类申请的影响。EMA建议申办方尽早计划CDx联合开发，且开发策略应基于现有的科学认知。

The EMA has released a guidance titled: Frequently asked questions on medicinal products development and assessment involving companion diagnostic (CDx). The guidance is aimed largely at drug developers. It includes recommendations on generating adequate data for the marketing authorization application and the impact of the European IVDR on that application. The EMA advises sponsors to plan CDx co-development as early as possible. The development strategy should be guided by available scientific knowledge.

9. EMA更新I期病房和计算机系统的GCP检查文件（2023年10月）

9. EMA Updates GCP Inspection Related Documents for Phase I Units and Computer Systems (Oct 2023)

以下检查文件已更新，申办方与研究中心工作人员可据此了解EMA检查内容。

• EMA GCP检查程序附录III：计算机系统。

• CHMP GCP检查程序附录V：I期病房。

These inspection documents have been updated and should be reviewed by sponsors and site staff to ensure they are aware of what the EMA will be reviewing during an inspection.

• Annex III to the procedure for conducting good clinical practice inspections requested by the EMA: Computer systems.  

• Annex V to procedure for conducting GCP inspections requested by the CHMP: Phase I units

10. MHRA发布2022年度严重违规数据（2023年12月）

10. MHRA 2022 Serious Breach Data (Dec 2023)

MHRA发布了2022年1月至12月期间GCP报告年度汇总（严重违规报告数据）。与前几年数据相比：

• 2022年严重违规报告数字再次上升，现已与新冠前持平。

• 申办方相关报告数量最多，与过去10年状况一致。

• 今年报告最多的违规类别是试验用药品（IMP），数量比第二高类别多出10%以上。

• 患者/受试者安全性类的违规，在2021年之前，连续8年位居第一，今年，该类别上升回报告最多类别之一。

• 去年，药物警戒类别排名靠前，今年没有在名单上。

• 过去3年中没有发生“触发”有因检查的严重违规。

The MHRA has released its Annual Review of MHRA GCP Referrals (Serious Breach reporting data) for the period of January - December 2022. Below is this year's data compared to the previous years of data.

• Serious Breach reporting numbers again rose this year 2022, and numbers are now similar to those seen pre-pandemic.

• Consistent with the past 10 years of data, Sponsor organizations continue to report the highest number of Serious Breaches.

• The overall category with the most serious breaches was Investigational Medicinal Product (IMP), with over 10% more findings than the second highest categories.

• Prior to 2021 the top category for reporting of Serious Breaches for the past 8 years had been "Patient/Subject Safety". This category has returned to one of the top spots this year.

• One of the top categories from last year Pharmacovigilance is not on the list this year.

• No Serious Breaches resulted in recommendations for "Triggered" inspections in the past 3 years.

11. MHRA更新QPPV指南（2023年11月）

11. Updated MHRA Guidance on QPPV (Nov 2023)

MHRA于2023-11-17更新QPPV包括PSMF的指南，该指南针对药物警戒系统，适用于英国上市许可持有人（MAH）。本次修订更新了“当前英国上市许可持有人向MHRA发送QPPV和PSMF详细信息的通知”章节，以替代先前要求，即在英国PSMF和英国QPPV信息更新后提交IA类（IN）变更和随附的eCTD序列。

The MHRA has updated their Guidance on qualified person responsible for pharmacovigilance (QPPV) including pharmacovigilance system master files (PSMF). This document provides guidance on pharmacovigilance system requirements. This document was revised on 17-Nov-2023 with the following change: Revised the section "Notification of QPPV and PSMF details to the MHRA by existing holders of UK marketing authorisations" to replace the previous requirement to submit a Type IA(IN) variation and an accompanying eCTD sequence following updates to the UK PSMF and UK QPPV information.