1. EMA药物临床试验质量管理规范现场核查指标2021
EMA Good Clinical Practice Inspection Metrics 2021
总结：
EMA现场核查员工作组发布了2021年的年度现场核查报告。 以下是对过去3年现场核查不符合项的比较。
Summary:
The EMA Inspectors Working Group has released their annual inspection report for the year 2021. Below is a comparison of findings for the past 3 years.
关键信息：
· 与前几年一样，大多数（41%)CHMP GCP现场核查是在临床研究中心进行，其次是申办方 （19%）和CRO（22%)。
· 由于COVID，CHMP（人用药品委员会）现场核查的数量仍然很低。
· 尽管现场核查次数有所减少，但与前一年相比，严重不符合项的数量有所增加。
· 2021年，3次CHMP要求的GCP现场核查全部经远程进行，3次现场核查由混合方式进行（部分现场，部分远程）。
· 严重不符合项的类别包括整体问题、试验管理、计算机系统、实验室设施、受试者保护和知情同意。
· 今年，与计算机系统有关的不符合项有所增加（稽查轨迹、验证、物理安全系统/备份和数据的直接访问）。
Key Takeaways:
· As in previous years, the majority (41%) of CHMP GCP inspections were carried out on Clinical Investigator sites, followed by Sponsor Sites (19%) and CROs (22%).
· The number of CHMP (Committee for Medicinal Products for Human Use) inspections remained low due to COVID.
· Even though the number of inspections decreased, there was an increase in the number of critical findings from the prior year.
· In 2021, 3 CHMP requested GCP inspections were conducted entirely remotely, and 3 inspections were conducted in a hybrid setting (part on-site, part remotely).
· Categories with critical findings include General, Trial Management, Computer System, Laboratory Facilities, Subject Protection and Informed Consent.
· This year there was an increase in findings related to computer systems (audit trials, validation, physical security system/ backup and direct access to data).
2. EMA关于在RMP编写期间对受保护的个人数据匿名化和商业机密信息评估的指南
EMA Guidance on Anonymisation of Protected Personal Data and assessment of Commercially Confidential Information During the Preparation of RMPs
总结：
欧洲药品管理局(EMA)发布了一份指南，标题为：在RMP（正文和附件4和6）编制过程中，对受保护的个人数据的匿名化和对商业机密信息的评估。
本文旨在为公司提供关于保留/删除受保护的个人数据(PPD)和识别商业机密信息(CCI)的一般指南。本指南中建议的所有变更均为编辑性变更，应在RMP的最终意见和采纳之前的科学审查过程中实施。
Summary:
The European Medicines Agency (EMA) has released a guidance titled: Anonymisation of Protected Personal Data and assessment of Commercially Confidential Information during the preparation of RMPs (main body and annexes 4 and 6).
This document aims at giving general guidance to companies on the retention/removal of Protected Personal Data (PPD) and identification of Commercially Confidential Information (CCI). All the changes suggested in this guidance are of editorial nature and should be implemented in the RMP during the scientific review process prior to the Opinion and adoption of the final RMP version.
关键信息：
EMA就如何在制定风险管理计划时匿名化受保护的个人数据和删除商业机密信息提供了指导。
Key Takeaway:
The EMA has shared guidance on how to anonymize protected personal data and delete commercially confidential information when preparing risk-management plans.
3. EMA关于临床试验中去中心化元素的推荐文件
EMA Recommendation Paper on Decentralised Elements In Clinical Trials
总结：
EMA关于临床试验中去中心化元素的推荐文件。目的是促进去中心化元素在EU/EEA临床试验中的使用。但是，应确保试验受试者的安全、权利和尊严得到必要保护。此外，应保证发表和提交的用于监管决策的数据的可靠性。
Summary:
The EMA has published a Recommendation Paper On Decentralised Elements In Clinical Trials. The intention is to facilitate the use of decentralised elements in clinical trials in the EU/EEA. However, the necessary level of trial participant's safety, protection of their rights and dignity should be ensured. In addition, the reliability of data for publication and submission for regulatory decision-making should be guaranteed.
关键信息：
· 本推荐文件的目的是，考虑到目前有限的国家指南，解决在EU/EEA进行临床试验时引入去中心化元素的问题，而不考虑任何健康危机。
· 本推荐文件将阐述去中心化试验中，申办方和研究者的角色和职责、电子知情同意、IMP运送、在家进行试验的相关步骤、数据管理和监查。
Key Takeaways:
· The aim of this recommendation paper is to address the introduction of decentralised elements in the conduct of clinical trials in the EU/EEA, regardless of any health crisis, and in consideration of the currently limited national guidances.
· The recommendation paper will address the roles and responsibilities of the sponsor and investigator, electronic informed consent, IMP delivery, trial related procedures at home, data management and monitoring in a decentralised clinical trial setting.
4. FDA采用E19选择性方法收集特定的上市前后期或上市后临床试验的安全性数据
FDA Adopts E19 A Selective Approach to Safety Data Collection in Specific Late-Stage Pre-Approval or Post-Approval Clinical Trials
总结：
ICH已经定稿了指南E19：在特定的上市前后期或上市后临床试验中收集安全性数据的选择性方法。选择性安全性数据收集是指在充分考虑了可能证明该方法合理性的因素后，减少对临床试验中某些类型数据的收集。通过调整安全性数据收集的方法和简化数据收集的方法，有可能以更高的效率进行临床试验。这可能有助于对大量受试者进行长期随访的大规模有效性和安全性临床试验的执行。
Summary:
ICH has finalized Guidance E19 A Selective Approach to Safety Data Collection in Specific Late-Stage Pre-Approval or Post-Approval Clinical Trials. Selective safety data collection refers to the reduced collection of certain types of data in a clinical trial after thorough consideration of factors that would justify such an approach. By tailoring the method of safety data collection, it may be possible to carry out clinical trials with greater efficiency by streamlining the approach to data collection. This may facilitate the conduct of large-scale efficacy and safety clinical trials with large numbers of participants and long-term follow-up.
关键信息：
· 本指导原则旨在探索在何种情况下，在某些上市前后期或上市后研究中，有针对性的安全数据收集方法是合适的，以及如何实施这种方法。
· 这种方法可以减轻那些阻碍患者参与临床研究的负担，同时认识到，在药物开发过程中保护患者福利至关重要。
· 目的是使更多的提供有用信息的临床研究能够以更高的效率、更多的全球性参与，以造福公共卫生。
Key Takeaways:
· This guideline explores under what circumstances a targeted approach to safety data collection in some late-stage pre-marketing or post-marketing studies would be appropriate and how to implement such an approach.
· This approach could reduce the burden to patients which can serve as a disincentive to participation in clinical research, while recognising that protection of patient welfare during medicine development is of critical importance.
· The aim is to enable a larger number of informative clinical studies to be carried out with greater efficiency and greater global participation in studies, for the benefit of public health.
5. 涉及儿童医疗产品临床研究的伦理考虑的FDA指南草案
FDA Draft Guidance on Ethical Considerations for Clinical Investigations of Medical Products Involving Children
总结：
美国FDA发布了一份关于儿童医疗产品临床研究的伦理考虑的指南草案。
儿童临床研究对于获取药物、生物制品和医疗器械在儿童中的安全性和有效性数据以及保护儿童，避免其接触可能不安全或无效的医疗产品而遭受相关风险至关重要。儿童是弱势群体，不能自行同意，因此在参与临床研究时可获得额外的保障。作为医疗产品开发项目的一部分，此类保障措施是启动和实施儿科研究的基本要求。
Summary:
The US FDA has released a draft guidance on Ethical Considerations for Clinical Investigations of Medical Products Involving Children.
Clinical investigations in children are essential for obtaining data on the safety and effectiveness of drugs, biological products, and medical devices in children and to protect children from the risks associated with exposure to medical products that may be unsafe or ineffective. Children are a vulnerable population who cannot consent for themselves and who therefore are afforded additional safeguards when participating in a clinical investigation. Such safeguards are an essential requirement for the initiation and conduct of pediatric investigations as part of a medical product development program.
关键信息：
· 本指南描述了FDA目前关于儿童医疗产品临床研究的伦理考虑的想法。
· FDA监管而非医疗产品的临床研究可能具有与本指南中讨论的相似的伦理考虑，但不在本指南范围内。
Key Takeaways:
· This guidance describes the FDA's current thinking regarding ethical considerations for clinical investigations of medical products in children.
· Clinical investigations involving FDA-regulated products that are not medical products may have similar ethical considerations to those discussed in this guidance but are outside the scope of this guidance.
6. FDA修订了PAI合规计划(7346.832)，以增加批准前质量文化目标，其中包括从未见过的PAI核查范围！
FDA Revises PAI Compliance Program (7346.832) to add a Pre-Approval Quality Culture Objective that includes never seen before inspectional coverage during a PAI!
总结：
新修订的批准前现场核查合规计划(7346.832)建立在2019年9月版的基础上，该修订的重点是与FDA人用药物设施评估和检查计划（“ConOps”）（2017年6月）整合的操作概念保持一致。当前的2022年修订包括3项主要变化，以促进FDA 21世纪药物质量倡议的推进：
1.增加了“目标4：药品开发中的质量承诺”，以促进ICH Q12框架中上市后变更的管理，并在确定是否应将PAI作为申请的综合质量评估（IQA）的一部分时进行基于风险的决策。这个新的目标指导了在检查期间从未见过的检查覆盖范围，包括批准前质量文化、过程开发计划的整体成熟度，以及生命周期风险管理和监督。
2.增加了“附件A：远程监管评估”，以加强FDA的监管监督。附件A包括在COVID‐19突发公共卫生事件（PHE）期间开发的设施评估的其他工具和最佳实践。
3.为了推进FDA鼓励基于现代风险的药品质量体系的努力，修订了目标2“符合申报”，以纳入核查范围，以验证控制亚硝胺杂质的风险管理体系的实施。
Summary:
The newly revised Pre-Approval Inspection Compliance Program (7346.832) builds upon the September 2019 revision that focused on alignment with the Concept of Operations for Integration of FDA Facility Evaluation and Inspection Program for Human Drugs ("ConOps") (June 2017). The current 2022 revision includes 3 major changes to facilitate the advancement of FDA's Pharmaceutical Quality for the 21st Century Initiative:
1. Added "Objective 4: Commitment to Quality in Pharmaceutical Development" to facilitate the management of Post-Approval Changes in the ICH Q12 framework and the risk based decision making when determining if a PAI should be conducted as part of the Integrated Quality Assessment (IQA) of the application. This new objective directs never seen before inspectional coverage during an inspection to include pre-approval quality culture, overall maturity of the process development program, and lifecycle risk management and oversight.
2. Added "Attachment A: Remote Regulatory Assessments" to augment FDA's regulatory oversight. Attachment A includes additional tools and best practices for Facility Assessment developed during COVID‐19 Public Health Emergency (PHE).
3. To advance FDA's pursuit to encourage modern risk based pharmaceutical quality systems, Objective 2 "Conformance to Application" was revised to include inspectional coverage to verify the implementation of a risk management system to control nitrosamine impurities.
7. US FDA发布了关于肿瘤药物联合治疗方案交叉说明书的最终指南
US FDA Releases Final Guidance on Cross-Labeling Oncology Drugs in Combination Regimens
总结：
美国FDA发布了最终指南：肿瘤药物联合治疗方案交叉说明书行业指南。肿瘤学的药物批准通常建立在治疗效果的基础上，通过在当前方案中添加药物或将研究药物与联合方案联合使用，产生具有更好疗效的新方案。
传统上，申请者并没有要求更改之前批准的药物说明书，以描述如何在新方案中使用该药物（交叉说明书）。
然而，最近越来越多的应用提出了肿瘤药物联合方案的交叉说明书。交叉说明书的目的是在产品说明书中提供用于联合方案的药物的补充和一致的信息；其目的不是在联合治疗方案中的每种药物的说明书中纳入所有相同的信息。
Summary:
The US FDA has released a final guidance: Cross Labeling Oncology Drugs in Combination Regimens Guidance for Industry. Drug approvals in oncology often build on treatment effects by adding drugs to current regimens or by combining investigational drug products in a combination regimen, creating new regimens with greater efficacy.
Traditionally, applicants have not requested changes to the labeling of a previously approved drug to describe how to use that drug in a new regimen (cross labeling).
However, there has recently been an increasing number of applications that have proposed cross labeling for oncology drug combination regimens. The intent of cross labeling is to provide information in product labeling for the drugs used in a combination regimen that is complementary and consistent; the intent is not to include all of the same information in labeling for each drug in the combination regimen.
关键信息：
· 该文件描述了FDA当前关于在已批准用于联合治疗方案的肿瘤药物的说明书中纳入相关信息的建议。
· 申办方应准备在申请前会议上与FDA讨论联合肿瘤药物治疗方案的拟定说明书。
Key Takeaways:
· The document describes FDA's current recommendations on including relevant information in labeling for oncology drugs approved for use in combination regimens.
· Sponsors should be prepared to discuss proposed labeling for combination oncology drug regimens with the FDA in pre-application meetings.
8. 美国FDA关于扩大研究药物治疗用途的指南草案修订版Q&A
US FDA Revised Draft Guidance on Expanded Access to Investigational Drugs for Treatment Use Q&A
总结：
美国FDA发布了一份修订后的行业指南草案，标题为：扩大研究药物治疗用途的问题和答案
注：原始问答指南于2016年定稿，并于2017年更新。
Summary:
The US FDA has issued a revised draft guidance for industry titled: Expanded Access to Investigational Drugs for Treatment Use Questions and Answers
Note: The original Q&A guidance was finalized in 2016 and updated in 2017.
关键信息：
· FDA将以问答形式提供本修订版指南，以解决最近提出的问题并分享建议以满足新的法定要求。
· 定稿后，本指南将取代2016年6月（2017年10月更新）的最终指南《扩大研究药物治疗使用的机会——问题和答案》。
· 对问答部分的修订强调了计划中的保障措施，强调了扩大获取和不受限制地获取研究性治疗之间的区别。
· 更新后的指南阐明，如果申办方发布了试验用药品扩大使用政策，他们不会因推广超说明书使用而面临被执法的风险。
Key Takeaways:
· FDA is providing this revised guidance in a question-and-answer format, to address the most recently asked questions and sharing recommendations to fulfill new statutory requirements.
· When finalized, this guidance will replace the June 2016 (updated in October 2017) final guidance, "Expanded Access to Investigational Drugs for Treatment Use — Questions and Answers."
· The revisions to the Q&A section play up the safeguards in the program in a fashion that emphasizes the difference between Expanded Access and unfettered access to investigational treatments.
· The updated guidance clarifies that sponsors do not risk enforcement for off-label promotion if they post investigational drug expanded access policies.
9. 美国FDA更新上市后不良事件合规性计划指南手册
US FDA Updates Postmarketing Adverse Experience Compliance Program Guidance Manual
总结：
美国FDA发布了修订后的上市后不良事件核查合规计划指南手册。 根据该合规计划，FDA核查了参与已批准和未批准的处方药和非处方药上市后安全性信息强制报告的实体，以及由药品评价和研究中心(CDER)监管的治疗性生物制剂。分配给CDER的组合产品或CDER为牵头中心的组合产品的上市后安全性报告要求，也应根据本计划接受现场核查。
Summary:
The US FDA has released a revised Postmarketing Adverse Experience Inspections Compliance Program Guidance Manual. Under this compliance program, FDA inspects entities involved in the mandatory reporting of postmarketing safety information for approved and unapproved prescription and nonprescription drugs, as well as therapeutic biologics regulated by the Center for Drug Evaluation and Research (CDER). Postmarketing safety reporting requirements for combination products assigned to CDER, or combination products for which CDER is the lead center, are also subject to inspection under this program.
关键信息：
· 本文件更新了本指南，使其更加详细，以进一步协助其核查员进行这些现场核查，并包括组合产品的上市后要求。
· 另一个关键的变化是，根据该计划进行的核查现在通常会提前通知。
Key Takeaways:
· The document has updated this guidance to be more detailed to further assist its inspectors in conducting these inspection and includes postmarketing requirements for combination products.
· Another key change is that inspections under this program will now generally be preannounced.
10. MHRA对GCP核查不符合项制定CAPA回复的指南
MHRA CAPA Guidance for Formulating Responses to GCP Inspection Findings
总结：
MHRA发布了标题为“对GCP核查不符合项制定CAPA回复的指南”。本文件旨在协助对GCP核查报告中的不符合项做出回复，提高对GCP核查员期望的认识，并帮助制定可接受的回复。
本文件进行了修订，变更如下：
· 在“简介”部分增加了有助于制定可接受的回复的信息；在“示例2”一节中增加了“不符合项的评估和根本原因”一节，以及副标题“有效性验证”和“答复格式”。
· 修订“可接受回复示例”章节的格式，以表格形式呈现。
Summary:
The MHRA has released a guidance titled: CAPA guidance for formulating responses to GCP inspection findings. This document aims to give assistance in how to respond to the GCP inspection report findings, increase awareness of the GCP Inspectors' expectations, and aid formulation of an acceptable response.
This document was revised with the following changes:
· Added information that aids formulation of an acceptable response in the section "Introduction"; and new section "Evaluation and Root Cause of the Finding" and subheadings "Effectiveness Checks" and "Format of Response" under the section "Example 2."
· Revised the format of the section "Acceptable Response Example" to present it in tabular form.
关键信息：
本文件向申办者说明了如何向MHRA展示其符合药品临床试验质量管理规范标准以及核查的预期结果。
Key Takeaways:
The document describes to sponsors how to show MHRA they're meeting good clinical practice standards and what to expect from an inspection.
11. MHRA更新药物警戒程序
MHRA Updates Pharmacovigilance Procedures
总结：
MHRA发布了更新的药物警戒程序指南。药物警戒质量管理规范（GVP）模块将继续有效，但已发布了关于药物警戒质量管理规范欧盟指南的例外情况和修改的指南说明，申办方在准备提交文件时应参考这些指南。
更新了药物警戒程序指南，以纳入：
· 关于MHRA提交要求的更多详细信息，尤其是与信号、风险管理计划（RMP）和许可后安全性研究（PASS）相关的信息。
· 定期安全性更新报告（PSUR）章节更新了提交北爱尔兰许可产品PSUR的新要求。
· 其他章节包括了MHRA安全性审查和安全性通讯。
Summary:
The MHRA has released an updated guidance on Pharmacovigilance Procedures. The Good Vigilance Practices (GVP) modules will remain in force but a guidance note on the exceptions and modifications to the EU guidance on good vigilance practices has been published and sponsors should refer to these guidelines when preparing their submissions.
The guidance on Pharmacovigilance Procedures has been updated to include:
· Further details on submission requirements for the MHRA, in particular relating to signals, Risk Management Plans (RMPs) and Post Authorisation Safety Studies (PASS).
· The section on Periodic Safety Update Reports (PSURs) has been updated with new requirements for submission of PSURs for products authorised in Northern Ireland.
· Additional sections have included on MHRA Safety Reviews and Safety Communications.
关键信息：
· 本指南总结了MHRA的药物警戒方法。
· 已更新指南，以纳入MHRA申报要求的更多详细信息
Key Takeaways:
· This guidance summarizes MHRA's approach to pharmacovigilance.
· The guidance has been updated to include further details on submission requirements for the MHRA
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