Regulatory Express_July 2025

 SUMMER 

美国FDA发布了一份最终指南，标题为：“执行远程监管评估-问答”。本文描述了远程监管评估（RRA)）的来源、法律依据以及使用方式，并解释了其在所有FDA监管产品中的使用范围。FDA讨论了自愿性和强制性RRA之间的差异。指南概述了实践中如何进行RRA的考虑因素，包括受监管实体可能期望从监管机构获得的记录和信息请求类型。

FDA指出，自2024年1月发布修订草案以来，对最终指南进行了多项变更，包括：

• 更清楚地区分强制性和自愿性RRA请求

• 阐明FDA如何告知企业参与自愿性RRA的条款，并获得同意

• 促进FDA在监管产品中使用RRAs的透明度和一致性（如适用）

• 阐明电子记录审查的机制和可能发生实时数据访问的条件

• 解决FDA审查企业的信息机密性和安全性问题

关键信息：

• 本指南描述了FDA目前关于远程监管评估使用的想法，并提供了常见问题的答案。

• FDA已使用RRA进行监督、降低风险、满足关键公共卫生需求并帮助评估FDA监管产品是否符合适用法规要求。

FDA Publishes Final Guidance: Conducting Remote Regulatory Assessments - Q&A

The US FDA has published a final guidance titled: Conducting Remote Regulatory Assessments - Question and Answers.  The document describes the origin of the remote regulatory assessment (RRA), its legal basis, and how it has been used, along with an explanation of the scope of its use for all FDA-regulated products. The FDA discusses the difference between voluntary and mandatory RRAs. The guidance outlines process considerations for how an RRA would occur in practice, including the types of records and information requests that regulated entities might expect from the agency.

The FDA notes that a number of changes were made to the final guidance since the publication of the revised draft in January 2024, including to:

• Distinguish more clearly between mandatory and voluntary RRA requests

• Clarify how FDA intends to inform establishments of the terms of participation in voluntary RRAs and obtain their consent to conduct the RRA

• Facilitate transparency and consistency in FDA's use of RRAs across regulated products, as applicable

• Clarify mechanisms for electronic records reviews and conditions under which live data access might occur

• Address concerns about confidentiality and security of establishment information reviewed by FDA

Key Takeaways:

• The guidance describes the FDA 's current thinking regarding its use of remote regulatory assessments and provides answers to frequently asked questions.

• The FDA has used RRAs to conduct oversight, mitigate risk, meet critical public health needs and help evaluate compliance of FDA -regulated products with applicable regulatory requirements.

美国FDA宣布对新的临床试验进行审查，包括将美国公民的活细胞送到中国和其他一些国家进行基因工程，并随后回输到美国患者体内。

根据FDA新闻稿：

• 这一行动的采取是基于越来越多的证据表明，其中一些试验未能告知参与者其生物材料的国际转移和操纵，可能使美国敏感的基因数据暴露于包括对手在内的外国政府的滥用之下。

• FDA正在积极审查依赖该豁免的所有相关临床试验，并将要求公司证明敏感生物材料的国内处理完全透明、伦理同意。不符合这些标准的新试验将不会被允许。

• 该机构还与美国国立卫生研究院(NIH)密切合作，确保没有联邦资助的研究受到这些做法的影响。更多的执法和政策措施可能即将出台。

关键信息：

• 美国FDA已宣布停止向某些国家的实验室出口美国公民细胞的新临床试验，特别是为了基因工程的目的。

• 请注意，新闻稿中没有列出中国以外国家的名单，但很可能指的是数据隐私规则中提到的国家，如中国、古巴、伊朗、朝鲜、俄罗斯和委内瑞拉。

• FDA局长Makary在FDA《播客》第9集上说，“把在中国的美国人的细胞进行基因编辑，然后输入这些美国患者体内，极有可能没有什么可怕的事情发生。但适当的知情同意至关重要。”

US FDA Halts New Clinical Trials That Export Americans’ Cells to Foreign Labs to Certain Countries

The U.S. FDA announced a review of new clinical trials that involve sending American citizens' living cells to China and some other countries for genetic engineering and subsequent infusion back into U.S. patients.

According to the FDA press release:

• This action follows mounting evidence that some of these trials failed to inform participants about the international transfer and manipulation of their biological material and may have exposed Americans' sensitive genetic data to misuse by foreign governments including adversaries.

• The FDA is actively reviewing all relevant clinical trials that relied on this exemption and will require companies to demonstrate full transparency, ethical consent, and domestic handling of sensitive biological materials. New trials that cannot meet these standards will not proceed.

• The agency is also working closely with the National Institutes of Health (NIH) to ensure that no federally funded research is compromised by these practices. Additional enforcement and policy measures could be forthcoming.

Key Takeaways:

• The US FDA has announced the cessation of new clinical trials involving the export of American citizens' cells to laboratories in certain countries, specifically for the purpose of genetic engineering.

• Please note that a list of the countries beyond China is not listed in the press release however are likely referring to countries mentioned in the data privacy rule as China, Cuba, Iran, North Korea, Russia and Venezuela.

• FDA Commissioner Makary said on an episode of the FDA Direct podcast Episode 9. "Chances are most likely there's nothing nefarious going on with the gene editing of the cells of Americans in China being infused back to … these American patients. But proper informed consent is critical."

EMA发布了标题为ICH E21关于将妊娠和哺乳个体纳入临床试验的指导原则草案。

关键信息：

• EMA发布了一项新的指南供公众参考，该指南提供了如何将妊娠和哺乳期女性纳入和/或保留在临床试验的建议。

• 目标是确保研发人员在这类人群中生成可靠的临床数据，以便这些个体及其医疗保健提供者在使用药物时做出明智的、基于证据的决策。

EMA Releases Draft Guidance: ICH E21 Guideline on Inclusion of Pregnant and Breastfeeding Individuals in Clinical Trials

The EMA has release a draft guideline titled: ICH E21 Guideline on inclusion of pregnant and breastfeeding individuals in clinical trials.

Key Takeaways:

• EMA has released for public consultation a new guideline providing recommendations on how to include and/or retain pregnant and breastfeeding people in clinical trials.

• The goal is to ensure developers generate robust clinical data in those populations, so that these individuals and their healthcare providers can make informed, evidence-based decisions when using medicines.

MHRA发布了一份关于根据真实世界数据使用外部控制组以支持监管决策的指南草案。

关键信息：

• 本指南适用于计划开展临床试验的申办方，临床试验将包括真实世界数据(RWD)外部对照组(ECA)，目的是利用该试验支持监管决策。

• 这是使用RWD支持监管决策的一系列指南之一，与MHRA指南一起使用真实世界数据进行随机对照试验以支持监管决策。

MHRA Draft Guideline on the Use of External Control Arms Based on Real-World Data to Support Regulatory Decisions

The MHRA has released a Draft Guideline on the Use of External Control Arms Based on Real-World Data to Support Regulatory Decisions.  

Key Takeaways:

• This guideline is for sponsors planning a clinical trial which will include a real-world data (RWD) external control arm (ECA), with the intention of using the trial to support a regulatory decision.

• This is one of a series of guidelines on the use of RWD for supporting regulatory decisions and alongside the  MHRA  guideline  on  randomized  controlled  trials  using  real-world  data  to support regulatory decisions.

英国开展临床试验的新法规现已签署生效，称为《人用药品（临床试验）（修正案）法规2024》。为期12个月的推出——为20多年来英国临床试验监管提供最重要的更新——目的是加强患者安全、加速批准、促进创新，并帮助更多的人从参与重要研究中获益。 新的临床试验法规将于2026年4月28日生效。

注：

目前，英国监管框架主要基于EU CTD，已以EU CTR的形式在EU层面进行了替换和升级。然而，由于英国脱欧在CTR生效日期之前生效，英国没有实施欧盟CTR，因此，英国政权与欧盟框架有些不同步，根据共识，需要更新以反映医学和技术方面的进步。

关键信息：

• 英国议会最近签署了其对临床试验法规的法律修正案。这些变化旨在提高受试者在临床试验中的地位，并简化申办方的流程和时间表。

• 该立法是关于英国一系列有关审判的更广泛文件集的一部分。MHRA和HRA正在为公众参与试验的设计、实施和传播以及参与研究的人群的多样性创建指南。

• 目的是确保研究成果改善每个人的护理，并帮助解决健康不平等问题。

UK Clinical Trial Regulation Amendments

New regulations for running clinical trials in the UK have now been signed into law, called The Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2024. A 12-month roll-out begins to deliver the most significant update to UK clinical trials regulation in two decades – with the aim of strengthening patient safety, accelerating approvals, enabling innovation and helping more people benefit from taking part in vital research.  The new clinical trial regulations will come into force on 28 April 2026.

Note: 

The UK regulatory framework is, at present, based largely on the EU CTD, which has been replaced and upgraded at EU level in the form of the EU CTR. However, the UK did not implement the EU CTR due to Brexit taking effect prior to the CTR's effective date, and consequently, the UK regime has been somewhat out of sync with the EU framework and has, by common consensus, required a refresh to reflect progress in both medicine and technology.

Key Takeaways:

• The U.K. Parliament recently signed into law amendments to its clinical trials regulation. The changes intend to elevate the participant's place in clinical trials and streamline processes and timelines for sponsors.

• The legislation is part of a broader set of documents about trials in the UK. MHRA and HRA are creating guidance on public involvement in the design, conduct and dissemination of trials and the diversity of people taking part in studies.

• The aim is to ensure research findings improve everyone's care and help address health inequalities.

FDA发布了在临床前安全性研究中减少动物实验的路线图，以使用新方法学(NAM)数据，而不是动物试验方案，来确定药物的疗效和安全性。新方法旨在提高药物安全性和加速评估过程，同时降低动物实验，降低研发(R&D)成本，最终降低药价。

路线图描述了FDA如何计划在临床前安全性研究中使用新方法（NAM）减少动物实验，例如：

• 芯片上的器官系统，

• 计算建模，和

• 先进的体外试验。

关键信息：

• FDA计划减少并可能替代动物实验，以开发单克隆抗体疗法和其他药物。

• 基于AI的计算模型有望在药物开发中发挥更大的作用。

FDA Releases Roadmap to Reducing Animal Testing in Preclinical Safety Studies

The FDA released a Roadmap to Reducing Animal Testing in Preclinical Safety Studies roadmap for using New Approach Methodologies (NAMs) data as opposed to animal testing protocols to determine the efficacy and safety of medications  The new approach is designed to improve drug safety and accelerate the evaluation process, while reducing animal experimentation, lowering research and development (R&D) costs, and ultimately, drug prices.

The roadmap describes how FDA plans to reduce animal testing in preclinical safety studies with new approach methodologies (NAMs) such as:

• organ-on-a-chip systems,

• computational modeling, and

• advanced in vitro assays. 

Key Takeaways:

• The FDA plans to reduce and potentially replace animal testing for developing monoclonal antibody therapies and other medications.

• AI-based computational models are expected to play a larger role in drug development.