Regulatory Express_Jan. 2026

美国食品药品监督管理局（FDA）宣布发布一份名为"医疗产品临床评价中性别差异研究"的行业指南草案。医疗产品的临床试验和非干预性研究应设计为纳入足够数量的女性和男性，以反映所研究疾病或病症的患病率，从而有助于确保研究结果的普适性，并为探索不同性别间潜在的疗效差异提供便利。FDA鼓励申办者考虑本指南中概述的办法，并根据实际情况制定其他合适的方法。

分析医疗产品反应中与性别相关的差异，是评估产品安全性和有效性的重要组成部分，有助于了解产品在目标患者人群中的安全性和有效性，并可为产品标签内容的制定提供参考，从而改善患者照护质量。女性和男性在生理上的差异可能导致疾病表现，药代动力学，药效学和治疗反应等方面的不同。

本指南涉及的主题包括：

1. 改善临床试验中女性招募，入组和保留的做法，以帮助确保研究结果对目标患者人群的普适性；

2. 分析性别差异的统计学考量；

3. 基于性别差异分析的结果报告。

US FDA Draft Guidance on Study of Sex Differences in the Clinical Evaluation of Medical Products

The US FDA is announcing the availability of a draft guidance for industry entitled "Study of Sex Differences in the Clinical Evaluation of Medical Products." Clinical trials and non-interventional studies of medical products should be designed to enroll sufficient numbers of females and males to reflect the prevalence of the disease or condition for which the medical product is being investigated to help ensure the generalizability of results and facilitate exploration of potential differences in effects by sex. FDA encourages sponsors to consider the approaches outlined in this guidance and develop other approaches as appropriate.

Analyzing sex-related differences in medical product response is an important component of assessing product safety and effectiveness, to help understand safety and effectiveness across the intended patient population, and can inform what goes into product labeling to improve patient care. Differences in physiology between females and males can lead to differences in disease manifestation, pharmacokinetics, pharmacodynamics, and response to treatment, among other things.

Topics addressed in this guidance include: 

1. practices to improve the recruitment, enrollment, and retention of females in clinical trials, to help ensure the generalizability of research results to intended patient populations;

2. statistical considerations for analyzing sex differences; and

3. reporting results based on analyses of sex differences. 

美国FDA发布了最终指南：研究者职责——试验药物和器械的安全性报告。指南的核心目标是帮助研究者遵守IND（试验性新药应用）研究（§312。64（b），§312。66）和IDE（试验性器械豁免）研究（§812。150）的相关要求。其明确了研究者在报告严重不良事件（SAE），非预期器械不良效果（UADE）以及被视为涉及参与者风险的非预期问题的安全性信息方面的职责。本指南提供了相关建议，以帮助研究者识别需要向申办者和机构审查委员会报告的安全性信息。

US FDA Final Guidance: Investigator Responsibilities —— Safety Reporting for Investigational Drugs and Devices

The US FDA has released a final guidance for: Investigator Responsibilities —— Safety Reporting for Investigational Drugs and Devices. Key Objectives of the guidance are to help investigators comply with IND (investigational new drug application) studies (§ 312.64(b), § 312.66) and IDE (investigational device exemption) studies (§ 812.150). It clarifies responsibilities for reporting Serious Adverse Events (SAEs), Unanticipated Adverse Device Effects (UADEs) and Safety information considered an unanticipated problem involving risk to participants. Recommendations are provided in this guidance to help investigators identify safety information that needs to be reported to sponsors and institutional review boards.

美国FDA发布了一份最终指南，标题为：申办者职责——新药研究和生物利用率/生物等效性研究的安全性报告要求和安全性评估。

该指南为申办者和申办者-研究者提供了遵守研究性新药应用（IND）安全性报告和生物利用度（BA）和生物等效性（BE）研究安全性报告要求的建议。它对安全性报告中使用的术语进行了解释，就何时以及如何提交安全性报告提出了建议，并就申办者提出的其他安全性报告的问题提供了信息。为促进恰当的IND安全性报告实践，本指南还针对IND安全性报告条款中需要评估汇总数据的两项要求提供了相关建议。

US FDA Final Guidance: Sponsor Responsibilities —— Safety Reporting Requirements and Safety Assessment for Investigational New Drug Application and Bioavailability/Bioequivalence Studies

The US FDA has released a final guidance titled: Sponsor Responsibilities —— Safety Reporting Requirements and Safety Assessment for Investigational New Drug Application and Bioavailability/ Bioequivalence Studies.

The guidance provides recommendations for sponsors and sponsor-investigators to comply with the requirements of investigational new drug application (IND) safety reporting and safety reporting for bioavailability (BA) and bioequivalence (BE) studies. It provides interpretations of terms used for safety reporting, makes recommendations on when and how to submit a safety report, and provides information on other safety reporting issues raised by sponsors. To facilitate appropriate IND safety reporting practices, this guidance also provides recommendations related to the two IND safety reporting provisions that require assessment of aggregate data.

EMA发布了修订版最终指南，标题为《临床试验中的辅助医疗产品》。该文件提供了临床试验中受试者所服用的试验性药用产品（IMP）和辅助药用产品（AxMP）的定义和要求信息。除非有正当理由，否则应遵循《欧盟条例（EU）第536/2014号》中未具体要求的建议性指导内容。

与以前版本相比的变化包括：

1. 根据已授权辅助医疗产品、经修改的已授权辅助医疗产品和未授权辅助医疗产品的分类，更新了建议的结构；

2. 明确了上述分类、申请及安全性报告要求；

3. 明确了已授权辅助医疗产品源自欧盟/欧洲经济区以外地区的相关要求；

4. 更新附录I中的示例；

5. 附件中的背景治疗：作为背景治疗的标准治疗通常被视为辅助医疗产品（AxMP）。

EMA Auxiliary Medicinal Products in Clinical Trials (Oct 2025)

The EMA has released a revised final guidance titled: Auxiliary Medicinal Products in Clinical Trials.  The document provides information regarding the definitions and requirements of an investigational medicinal product (IMP) and an auxiliary medicinal product (AxMP) administered to subjects in clinical trials. Suggested guidance not specifically required by Regulation (EU) No 536/2014 should be followed unless justified.

Changes compared to the previous version:

1. Updated structure of the recommendations according to classification of authorised AxMP, modified authorised AxMP and unauthorized AxMP; 

2. Clarifications on the classifications mentioned above, application and safety reporting requirements; 

3. Clarification if authorised AxMP is sourced outside the EU/EEA; 

4. Update the examples in Annex I; 

5. Background treatment Annex I: Standard of care as background treatment is in general considered an AxMP. 

美国FDA发布了一份关于人用处方药和生物制品标签中QTc间期信息的最终指南。该指南旨在帮助申请人将心率校正QT（QTc）间期延长相关信息纳入非抗心律失常人用处方药和生物制品的标签中。其提供了建议，以确保根据人用处方药标签内容和格式的监管要求，将QTc间期延长的临床相关信息纳入标签并在各章节中合理分布。指南提供了涉及目标药物（例如药物-X（药物-X）片剂）的标签中与QTc间期延长相关信息的内容和格式的说明性示例。本指南不涉及QTc间期延长数据的评估或解读方法学考量。

US FDA Final Guidance on QTc Information in Human Prescription Drug and Biological Product Labeling

The US FDA has released a final guidance on QTc Information in Human Prescription Drug and Biological Product Labeling.  This guidance is intended to assist applicants with incorporating heart rate-corrected QT (QTc) interval prolongation-related information into the labeling of non-antiarrhythmic human prescription drug and biological products. It provides recommendations to help ensure that clinically relevant information on QTc interval prolongation is included in and distributed appropriately across sections of labeling, in accordance with regulatory requirements for the content and format of human prescription drug labeling. It provides illustrative examples of the content and format of QTc interval prolongation-related information in the labeling involving a fictitious subject drug (e.g., DRUG-X (drugozide) tablets). It does not address methodological considerations for evaluating or interpreting QTc interval prolongation data.

美国FDA发布了一份最终指导原则，标题为：如何准备预指定申请（Pre-RFD）。关于复杂产品和组合产品应如何监管以及由FDA的哪个医疗产品中心负责监管的判定可能较为复杂。该机构提供了非正式和正式的渠道，以获取对这些问题的反馈意见。在发布关于非强制性、非正式的预申请流程的最终指导原则近八年后，FDA发布了新的修订版本，其中包含了澄清内容和补充细节。

本指南旨在帮助申办者通过预指定申请（Pre-RFD）流程从美国食品和药物管理局（FDA或机构）获得初步评估。具体而言，该指南解释了组合产品办公室（OCP）的预指定申请流程，并帮助申办者了解在预RFD中需提供的信息类型。

Pre-RFD流程可提供关于人用医疗产品（作为药物、器械、生物制品或组合产品）的监管属性或分类的非正式、非强制性反馈。此外，该非正式流程还可提供关于非组合或组合产品分配至相应机构中心（药物评价与研究中心（CDER），器械与辐射健康中心（CDRH）或生物制品评价与研究中心（CBER））进行上市前审查和监管的信息。

本次修订旨在通过明确Pre-RFD提交文件中需包含的信息，并对Pre-RFD流程进行澄清和更新，以提高Pre-RFD的透明度，一致性和效率。指南的总体范围保持不变，既提供了流程细节，也说明了对提交内容的要求。

US FDA Updates Final Guidance on How to Prepare a Pre-Request for Designation (Pre-RFD)

The US FDA has released a final guidance titled: How to Prepare a Pre-Request for Designation (Pre-RFD).  Determinations on how complex and combination products should be regulated, and by which of the FDA's medical product centers, can be complicated. The agency offers both informal and formal opportunities to get feedback on these questions. Nearly eight years after finalizing guidance on its nonbinding, informal Pre-Request for Designation process, the agency has issued a new revision with clarifications and additional detail.

This guidance is intended to assist sponsors in obtaining a preliminary assessment from the U.S. Food and Drug Administration (FDA or Agency) through the Pre-Request for Designation (Pre-RFD) process.  Specifically, this guidance explains the Pre-RFD process at the Office of Combination Products (OCP) and helps a sponsor understand the type of information to provide in a Pre-RFD.

The Pre-RFD process is available to provide informal, non-binding feedback regarding the regulatory identity or classification of a human medical product as a drug, device, biological product, or combination product.  In addition, this informal process provides information about a non-combination or combination product's assignment to the appropriate Agency Center (Center for Drug Evaluation and Research (CDER), Center for Devices and Radiological Health(CDRH), or Center for Biologics Evaluation and Research (CBER)) for premarket review and regulation.

This replacement is intended to enhance the transparency, consistency, and efficiency of the Pre-RFD program by clarifying the information to include in a Pre-RFD submission and providing clarifications and updates to the Pre-RFD process." The overall scope of the guidance is maintained, offering both process details and submission content expectations.

美国FDA发布了一份指南草案，标题为：证明与参比产品生物相似性的科学考量：关于评估比较疗效研究必要性的更新建议。该指南草案更新了FDA关于在《公共卫生服务法》第351（k）条规定的生物制品许可申请（BLAs）中，何时需要进行比较疗效研究（CES）以证明生物相似性的建议。这一转变突显出FDA越来越依赖先进的分析方法和PK/免疫原性数据，而不是传统的疗效试验，这可能会简化生物类似药的研发流程。

指南草案提出了生物类似药研发的重大转变：如果可靠的的分析数据，PK和免疫原性数据能够证实相似性，通常可能无需进行比较疗效研究（CES）。对于局部作用产品或PK研究不可行的情况，CES仍然是必需的。指南强调申办者应尽早与FDA沟通，并充分利用先进的分析方法。

该方法可能会缩短研发周期并降低研发成本。

US FDA Draft Guidance: Scientific Considerations in Demonstrating Biosimilarity to a Reference Product: Updated Recommendations for Assessing the Need for Comparative Efficacy Studies

The US FDA has released a draft guidance titled: Scientific Considerations in Demonstrating Biosimilarity to a Reference Product: Updated Recommendations for Assessing the Need for Comparative Efficacy Studies. This draft guidance updates FDA's recommendations on when comparative efficacy studies (CES) are necessary to demonstrate biosimilarity in biologics license applications (BLAs) under section 351(k) of the Public Health Service Act.  This shift underscores the growing reliance on advanced analytical methods and PK/immunogenicity data rather than traditional efficacy trials, potentially streamlining biosimilar development.

The draft guidance proposes a significant shift in biosimilar development: Comparative Efficacy Studies (CES) may often be unnecessary if robust analytical, PK, and immunogenicity data confirm similarity. CES remains required for locally acting products or when PK studies aren't feasible. Emphasis on early FDA engagement and leveraging advanced analytical methods.

This approach could reduce development timelines and costs.

美国FDA发布了一份最终指南，标题为：以患者为中心的药物开发：选择，开发或修改适用的临床结局评估工具。

本指南区分了终点指标与临床结局评估工具（COA）以及该工具产生的得分。COA包括所有说明文件，施测材料，内容，格式和评分规则。COA评分是指通过标准化流程由COA生成的任何数值或等级值。

本指南是四项以患者为中心的药物研发（PFDD）方法学指导原则系列文件中的第三项，该系列文件描述了利益相关者（患者，研究人员，医疗产品开发人员等）如何提交来自患者和护理人员的患者体验及其他相关信息，以用于医疗产品开发和监管决策。

本指南是对2022年6月30日发布的同名指南草案的最终定稿。

US FDA Final Guidance: Patient-Focused Drug Development: Selecting, Developing, or Modifying Fit-for-Purpose Clinical Outcome Assessments

The US FDA has release a final guidance titled: Patient-Focused Drug Development: Selecting, Developing, or Modifying Fit-for-Purpose Clinical Outcome Assessments. 

This guidance distinguishes an endpoint from the COA, and the score produced by that COA. The COA includes any instructions, administration materials, content, formatting, and scoring rules. A COA score refers to any numeric or rated values generated by a COA through a standardized process.

This guidance is the third in a series of four methodological patient-focused drug development (PFDD) guidance documents that describe how stakeholders (patients, researchers, medical product developers, and others) can submit patient experience and other relevant information from patients and caregivers to be used for medical product development and regulatory decision-making. 

This guidance finalizes the draft guidance of the same title issued on June 30, 2022.

EMA药物警戒检查员工作组（PHVIWG）最近发布了2024年年度报告。

2024年发现问题最多的三个领域与上一年相同：

• 质量管理体系（5项重大问题）

• 不良反应的管理和报告（12项重大问题）：

• 3项与提交及后续跟进流程相关

• 2项涉及医学审阅和MedDRA编码

• 2项与文献筛选相关

• 2项与在欧盟境内单一收集点接收和整理来自所有来源的ICSR相关

• 药物警戒体系主文件（1项重大问题）

EMA Releases PV Inspection Metrics for 2024

The EMA's Pharmacovigilance Inspectors Working Group (PhV IWG) recently released its 2024 Annual Report. 

The three most common areas with findings in 2024 are the same as the prior year: 

• Quality Management System (5 Major)

• Management and reporting of Adverse Reactions  (12 Major)

• 3 related to submission and follow-up processes

• 2 to medical review and MedDRA coding

• 2 to literature screening

• 2 to the receipt and collation of ICSRs from all sources at a single collection point within the EU

• Pharmacovigilance System Master File (1 Major)

MHRA发布了一系列修订后的指南，这些指南将于2026年4月28日生效。在生效日期之前，本节中的指南均为草案版本，仅应用于支持申办者为执行新条例的实施做准备。

• 药物临床试验：在英国申请批准

• 药物临床试验：专家咨询

• 药物临床试验：标签

• 药物临床试验：需通报的试验

• 药物临床试验：修改临床试验批准

• 药物临床试验：终止临床试验

• 临床试验法规：过渡安排

• 药物临床试验：安全性事件的收集，核实和报告

• 临床试验：非试验性医疗产品

MHRA Updates Clinical Trial Guidances

The MHRA has released a series of revised guidances that go into effect 28 April 2026. Until that date, the guidance in this section is in draft and should only be used to support sponsors in preparing for the implementation of the new regulations .

• Clinical trials for medicines: apply for approval in the UK

• Clinical trials for medicines: expert advice

• Clinical trials for medicines: labelling

• Clinical trials for medicines: notifiable trials

• Clinical trials for medicines: modifying a clinical trial approval

• Clinical trials for medicines: ending a clinical trial

• Clinical trials regulations: transitional arrangements

• Clinical trials for medicines: collection, verification, & reporting of safety events

• Clinical trials: Non-investigational medicinal products

FDA发布了《用于严重疾病的再生医学疗法加速项目》指南草案。再生医学是医疗保健的一个前言领域，专注于修复，替代或再生人体细胞，组织或器官，以恢复正常功能。它并非仅治疗症状，而是通过激活人体自身的愈合过程或引入新的健康细胞，旨在治愈疾病或消除损伤的根源。本指南中描述的项目旨在促进再生医学疗法的开发和审查，以解决严重疾病患者未得到满足的医疗需求。

再生医学是一个快速发展的领域，具有治疗严重疾病的潜力，特别是对医疗需求未得到满足的患者。如果符合相关标准，申办者可以同时申请多个加速项目（例如再生医学先进疗法（RMAT）+优先审核+加速审批）。这可以显著缩短研发周期，并帮助患者更早地获得有前景的疗法。

US FDA Releases Draft Guidance on Expedited Programs for Regenerative Medicine Therapies for Serious Conditions

The FDA published the draft guidance "Expedited Programs for Regenerative Medicine Therapies for Serious Conditions." Regenerative medicine is a cutting-edge field of healthcare focused on repairing, replacing, or regenerating human cells, tissues, or organs to restore normal function. Instead of just treating symptoms, it aims to heal the root cause of disease or injury by activating the body's natural healing processes or introducing new, healthy cells.  The programs described in this guidance are intended to facilitate development and review of regenerative medicine therapies intended to address an unmet medical need in patients with serious conditions.

Regenerative medicine is a rapidly expanding field that has the potential to treat serious conditions, particularly in patients with unmet medical needs. Sponsors may pursue multiple expedited programs (e.g., RMAT + Priority Review + Accelerated Approval) if criteria are met. This can significantly shorten development timelines and facilitate earlier patient access to promising therapies.

FDA发布了两份新的质量管理体系法规演示文稿：

• 风险管理，基于风险的方法和基于风险的决策，以及

• 设计和开发。

FDA Releases Presentations on Quality Management System Regulation

The FDA has released two new Quality Management System Regulation presentations:

• Risk Management, Risk-Based Approach, and Risk-Based Decisions, and

• Design and Development.