December 2024
Medicines and Vaccines
ICH
- The EU Network is hosting a workshop on ICH E6 R3 (principles and Annex 1) on 19-20 February 2025, as part of the Accelerating Clinical Trials in the EU (ACT EU) initiativeโs activities to support the modernisation of good clinical practice. The workshop aims to provide an overview of major changes in the guideline and engage all relevant stakeholders to discuss the guidelineโs implementation.
- The EMA is inviting stakeholders to provide their feedback in the open consultation on the draft Annex 2 of the ICH E6 (R3) guidance on good clinical practice. Comments can be submitted to ICHE6_R3@ema.europa.eu through the dedicated template by 28 February 2025.
CTR and CTIS
- A reminder that all timers within the evaluation of a clinical trial application will stop on 22 December 2024 at 23:59:59 CET and resume on 8 January 2025 at 00:00:01 CET. More information is available in the CTIS evaluation timelines document.
- EMA has published the recording from the CTIS: Walk-in clinic held on 20 November 2024.
- Updated versions (V2.2 13 Dec 2024) of the Q&A on protection of Commercially Confidential Information and Personal Data while using CTIS, Annex I table I of Guidance on how to approach protection of personal data and CCI (essentially an update of Q3.2) and related quick user guide are available on the ACT EU website. The principles for identifying and disclosing commercially confidential information and personal data in marketing authorisation applications for human medicines are updated. This ensures extensive transparency when disclosing information to the public once a medicine is authorised, both in response to access-to-documents requests and in the proactive publication of data. The update aligns the guidance with the progress made by regulators in their transparency journey since it was initially released in 2012. The revised guidance also sets out how personal data will be protected if it can lead to the identification of a person.
- EMA will hold the next CTIS: Walk-in clinic on 29 January 2025, 16:00 - 17:00 Amsterdam time (CET). Please provide your questions in advance via Slido (use code: #clinic249) between 6 and 22 January 2025.
- EMA has published updated versions of the following documents:
- CTIS public portal: Trial Results, dated 10 December 2024
- CTIS public portal: Full trial information, dated 10 December 2024
- CTIS Structured data form instructions - initial application, additional MSC, substantial and non-substantial modifications, dated 11 December 2024
- FAQs How to create, submit and withdraw a CTA - CTIS Training Programme - Module 10, v 1.7, dated December 2024
- On 18 December 2024, EMA and HMA published an update on the principles for the ๐ข๐๐๐ง๐ญ๐ข๐๐ข๐๐๐ญ๐ข๐จ๐ง ๐๐ง๐ ๐๐ข๐ฌ๐๐ฅ๐จ๐ฌ๐ฎ๐ซ๐ ๐จ๐ ๐ฉ๐ซ๐จ๐ญ๐๐๐ญ๐๐ ๐ฉ๐๐ซ๐ฌ๐จ๐ง๐๐ฅ ๐๐๐ญ๐ (PPD) ๐๐ง๐ ๐๐จ๐ฆ๐ฆ๐๐ซ๐๐ข๐๐ฅ๐ฅ๐ฒ ๐๐จ๐ง๐๐ข๐๐๐ง๐ญ๐ข๐๐ฅ ๐ข๐ง๐๐จ๐ซ๐ฆ๐๐ญ๐ข๐จ๐ง (CCI), including an Annex containing information that may be considered PPD and CCI. ๐๐ฉ๐ช๐ด ๐จ๐ถ๐ช๐ฅ๐ข๐ฏ๐ค๐ฆ ๐ฅ๐ฐ๐ค๐ถ๐ฎ๐ฆ๐ฏ๐ต ๐ช๐ด ๐ช๐ฏ๐ต๐ฆ๐ฏ๐ฅ๐ฆ๐ฅ ๐ต๐ฐ ๐ข๐ฑ๐ฑ๐ญ๐บ ๐ต๐ฐ ๐ช๐ฏ๐ง๐ฐ๐ณ๐ฎ๐ข๐ต๐ช๐ฐ๐ฏ/๐ฅ๐ฐ๐ค๐ถ๐ฎ๐ฆ๐ฏ๐ต๐ด ๐ฉ๐ถ๐ฎ๐ข๐ฏ ๐ถ๐ด๐ฆ products, ๐ง๐ฐ๐ณ ๐ธ๐ฉ๐ช๐ค๐ฉ ๐ต๐ฉ๐ฆ ๐ณ๐ฆ๐จ๐ถ๐ญ๐ข๐ต๐ฐ๐ณ๐บ ๐ฑ๐ณ๐ฐ๐ค๐ฆ๐ฅ๐ถ๐ณ๐ฆ ๐ฉ๐ข๐ด ๐ฃ๐ฆ๐ฆ๐ฏ ๐ง๐ช๐ฏ๐ข๐ญ๐ช๐ด๐ฆ๐ฅ ๐ถ๐ฏ๐ฅ๐ฆ๐ณ ๐ต๐ฉ๐ฆ ๐ฏ๐ข๐ต๐ช๐ฐ๐ฏ๐ข๐ญ, ๐ฎ๐ถ๐ต๐ถ๐ข๐ญ ๐ณ๐ฆ๐ค๐ฐ๐จ๐ฏ๐ช๐ต๐ช๐ฐ๐ฏ, ๐ฅ๐ฆ๐ค๐ฆ๐ฏ๐ต๐ณ๐ข๐ญ๐ช๐ด๐ฆ๐ฅ ๐ข๐ฏ๐ฅ ๐ค๐ฆ๐ฏ๐ต๐ณ๐ข๐ญ๐ช๐ด๐ฆ๐ฅ ๐ฑ๐ณ๐ฐ๐ค๐ฆ๐ฅ๐ถ๐ณ๐ฆ๐ด. Link to 53-page the guidance document. This update isย reviewed in the Regulatory Focus news article here. The EMA announcement is here.ย
- EMA has published Annex 1 to the Guidance document on how to approach the protection of personal data and commercially confidential information while using CTIS, dated 13 December 2024. The annex details publication rules, structured data, document types and disclosure timelines to ensure compliance and transparency in clinical trials. The guidance document itself, can be found here.
- EMA has published a report outlining the next steps towards implementation of electronic product information (ePI) for medicines in the EU and the recommendations on how to get there. The product information of a medicine includes its summary of product characteristics, labelling and package leaflet. The EMA report and recommendations can be accessed here.
UK and MHRA News
- The UKโs new clinical trials regulations were laid in parliament on 12 December 24 by the NHS Health Research Authority and MHRA. The updated regulations will be debated in the new year and after a 12 month implementation period will come into force in early 2026. Read about the key changes at this link.ย Under the new regulations, for the first time it will be a legal requirement to register clinical trials in a World Health Organization (WHO) recognised public register, and to publish a summary of results within 12 months of the end of the trial.
- MHRA is holding an open Consultation on the International Council for Harmonisation ICH E6 (R3) Guideline for Good Clinical Practice Annex-2 (Step 2b). To contribute, click here.
FDA Guidance and News
- The latest ClinicalTrials.gov Hot Off the PRS! is available: users can now choose to compare two versions of a study record, plus additional fields have been added as part of the Research Information Systems download.
- FDA issued guidance titled Expedited Program for Serious Conditions โ Accelerated Approval of Drugs and Biologics which provides updated information on the agencyโs proposed policies and procedures regarding accelerated approval.ย ย
- FDA issued a final guidance on Standardized Format for Electronic Submission of NDA and BLA Content for the Planning of Bioresearch Monitoring (BIMO) Inspections for CDER Submissions. The guidance describes standardized electronic submissions of certain data and information used to plan and conduct BIMO inspections for new drug applications (NDAs), biologics license applications (BLAs) and supplemental applications containing new clinical study reports that are submitted to CDER.
- FDAโs CDERย has established the New Center for Real-World Evidence Innovation which aims to coordinate, advance, and promote the use of real-world data (RWD) and real-world evidence (RWE) in regulatory decision-making across CDER.ย For more information as it becomes available, visit the CCRI webpage.ย
- The NIH is releasing a new NIH Public Access Policy to make the results of NIH-funded research accessible as quickly as possible. Alongside the new Policy, NIH is also releasing its plan to make it easier for researchers, clinicians, students, and the public to find and make use of research results. More information on this plan and information on how to provide comments can be found here.
- On 26 Dec 2024 FDA released a 13-page draft guidance "Protocol Deviations for Clinical Investigations of Drugs, Biological Products, and Devices" which is in public consultation until 28 Feb 25. To address the current gaps in guidance on protocol deviations, this guidance includes definitions for protocol deviations and important protocol deviations; recommendations on the types of protocol deviations that sponsors should report to FDA in clinical study reports (CSRs) for drugs and devices; recommendations on the types of protocol deviations that investigators should report to sponsors and to IRBs; and recommendations for IRBs in their evaluation of protocol deviations. In this guidance, FDA is adopting ICH E3(R1) definitions of protocol deviation and important protocol deviation.
EMA Guidance and News
- In the EMAโs December issue of Clinical Trial Highlights, Sponsors are reminded that ongoing clinical trials that have not transitioned to the CTR by 30 January 2025 will be considered non-compliant with the Regulation, as highlighted in the European Commissionโs guidance on transition.
- For the first time, developers of medicinal products can request joint scientific advice on their applications for clinical trials and the evidence needed for marketing authorization application, provided by the Clinical Trials Coordination Group (CTCG) and EMAโs Scientific Advice Working Party (SAWP).
Real-World Data
- EMA opened a public consultation on applying the Data Quality Framework for EU medicines regulation to real-world data. The EMRN DQF sets out the principles, concepts, and definitions as intended to be applied widely across datasets used in medicine regulatory use cases. The aim is to enhance use of real-world evidence in regulatory decisions. Deadline for comments is 28 February 2025. Those participating in the public consultation are asked to submit comments via the EU Survey tool, by using the specific table for each section.
- The paper by Welzel et al titled A transparent and standardized performance measurement platform is needed for on-prescription digital health apps to enable ongoing performance monitoring proposes a platform-based approach to continuously monitor and evaluate the performance of "apps on prescription" (e.g. DiGA in Germany) in real-world settings. This approach ensures greater transparency, standardization, and performance-based pricing, aligning digital health innovations with measurable healthcare outcomes.
- The Integration of Heterogeneous Data and Evidence towards Regulatory and HTA Acceptance (IDERHA) has released the report D6.2 Report on Global Regulatory Best Practices Analysis: A scoping review of HTA and Regulatory RWD/RWE policy documents.
- On 12 December 2024, the US FDA announced the creation of the Center for Drug Evaluation and Research (CDER) Center for Real-World Evidence Innovation (CCRI) to coordinate and promote the use of real-world data (RWD) and real-world evidence (RWE) in regulatory decision-making. The FDA announcement can be found here and a Q&A document can be accessed here.
Transparency and Disclosure Resources and News
- Canadian Anonymization Network (CANON) and AccessPrivacy are holding a roundtable discussion on December 18; 12 -2 pm ET entitled: "Consultation Session on Draft De-Identification Guidance Issued by the Information and Privacy Commissioner of Ontario". The aim is to discuss the key features of the draft guidance and its practical impact, and to obtain comments from webinar attendees. More information available here.
- The PHUSE โData Transparency Winter Eventโ will take place from 4โ6 February 2025. Presentations from this virtual event will be delivered across the three days in bitesize chunks from 15:00-17:30 (GMT) 10:00-12:30 (EST). Register for the event here. Details of the presentations are here.
- Khaled El Emamโs paper titled โPerspectives of Canadian privacy regulators on anonymization practices and anonymized information: a qualitative studyโ shows the lack of precision and consistency across Canada in regulating anonymisation practices, in defining anonymised information, and that there is no generally accepted national guidance on how to anonymise data. The environment therefore impedes national technical and policy solutions for sharing anonymised data across jurisdictions. To understand the perspectives of privacy regulators on anonymisation practices and how to regulate anonymised data, the authors performed a qualitative interview study with 93 percent of privacy regulators in Canada. On 11 Feb 2025, there will be a webinar on this paper and the topic.
- Real Life Sciences have released a new podcast: Which Methodology Should I Choose? Qualitative & Quantitative Anonymization for Policy 0070 and PRCI Disclosure Submissions. Two methodologies for anonymizing clinical data are available to regulatory and transparency professionals today. This podcast examines the differences between qualitative and quantitative methodologies including a deep dive into some best practices for completing qualitative projects.
EMA Policy 0070 in Practice
- This blog post on EMA Clinical Data Publication Policy to Cover All New Marketing Authorization Applications, Line Extensions and Major Clinical Type II Variations Starting Q2 2025 provides a summary of the next steps in EMA Policy 0070 in the coming year.
Development Strategy News
- A new Clinical Trials Transformation Initiative (CTTI) project aims to identify challenges and solutions to facilitate implementation of diversity action plans (DAPs) for clinical trials. CTTI plans to generate a set of recommendations or best practices with key DAP implementation considerations and a document outlining roles and responsibilities of contributing partners. The full announcement can be found here.
- Koo et al published Review of the European Union Clinical Trials Regulation: Key Early Learnings from the United Kingdom Drug Information Association Medical Writing Committee. Our CORE Ref committee member, Vivien Fagan, is one of the co-authors of this paper, which is also available here. The Committee summarises early learnings on Investigator's Brochures, protocols, intermediate analysis, plain language protocol synopses, AxMPs, plain language summaries and more. For protocols, considerations include disclosure-ready approaches, TransCelerate CPT modifications (e.g., end-of-trial definition), anticipated number of modifications (amendments) that can be done in a year, and request for information (RFI) approaches.
- Thomassen et al published The role of the estimand framework in the analysis of patient-reported outcomes in single-arm trials: a case study in oncology. The authors look at a global QoL outcome in a single-arm lung cancer trial and identify a range of possible estimands. The variable of interest and ICE strategy were the main focus point.
- The recording and slide deck of the Transcelerate/CDISC webinar โDigital Data Flow (DDF) Solution Showcase: December 2024โ, which took place on 5ย December 2024, are now available. In the webinar, solution providers presented their innovative solutions in the protocol digitalization space.
Artificial Intelligence/Machine Learning
- The Lancet published new guidelines on how researchers must declare the use of AI in journal submissions. Check out Generative AI: ensuring transparency and emphasising human intelligence and accountability.
News from Asia Regulators
- From January 2025 onwards, the publication of the Japanese version of CORE Reference News Summary Email Updates on the website https://clinos.com/blog/category/core-reference/ (kindly provided by the president of Clinos, Yukie Uchiyama, MD) will be discontinued. Readers who need translation can take advantage of the free online AI translation tools to access the News Summaries on the CORE Reference website. Yukie San will continue sharing the headlines of selected articles from the News Summary Email Updates through the dedicated Japanese e-newsletter.
- The following trial registries will be unattended during the Christmas and New Year period:
- Japan Registry of Clinical Trials (JRCT): from 4pm Friday, 27 December 2024 to Sunday, 5 January 2025. Inquiries will be addressed sequentially starting Monday, 6 January 2025.ย
- Australian and New Zealand Clinical Trials Registry (ANZCTR): from Friday, 20 December 2024 to Monday, 6 January 2025. The Registry will re-open on Tuesday, 7 January 2025.
Medical Devices
This subsection covers transparency in relation to medical devices, and the emerging intersection of the regulatory medical devices and the regulatory drugs spaces. Devices information or regulations that impact the reporting of device studies are also covered. Contextualisation is provided, where possible, to help readers understand how the information could be used.ย
General Updates and News
- The European Association Medical Devices of Notified Bodies (Team-NB), in collaboration with the German Notified Bodies Alliance for Medical Devices have published a position paper on Artificial Intelligence in Medical Devices. The document, in the form of a questionnaire-checklistย for NBs, was prepared in accordance with the request of MDCG, and is to be used in the context of MDR and IVDR as well as the MDCG guidance on Medical Device Software (MDSW). This questionnaire is an excellent source of information to support demonstrating conformity for AI devices.ย
- The Team-NB has released the position paper High level position on the regulatory framework for the medical devices sector. The paper aims to โestablish a robust, transparent, predictable and sustainable regulatory framework for medical devices which ensures a high level of safety and health whilst supporting innovation.
- The SME Info Day on EMAโs activities on medical devices was held on 18 October 2024. The presentation is available here. The presentation covers combination products, consultations and scientific advice, assessments and the challenges and initiatives.
- The FDA has published the 2024 Report on Risks and Benefits to Health of Non-Device Software Functions. This report is published every 2 years, as required by law. The current report details best practices related to design, implementation, training techniques, and use of FDA regulated software.
- The FDA has released the Marketing Submission Recommendations for a Predetermined Change Control Plan (PCCPs) for Artificial Intelligence-Enabled Device Software Functions. The recommendations in this guidance are intended to support iterative improvement through modifications to AI-enabled devices while continuing to provide a reasonable assurance of device safety and effectiveness.
- Companion diagnostics (CDx) have become essential for targeted treatments in precision medicine. The paper Insights into post-marketing clinical validation of companion diagnostics with reference to the FDA, EMA, PMDA, and MFDS by Kang et al. look at the different guidelines on post-marketing safety and effectiveness of CDx and found similarities and key differences.
- The paper by Engler et al Usability Engineering for Medical Devices using Artificial Intelligence and Machine Learning Technology explores how to apply the established usability engineering process for safe and effective use of Artificial Intelligence (AI) and machine learning in medical devices.
- MHRA has updated the Clinical Investigations Guidance which provides Information on how to notify the MHRA of your intention to carry out a clinical investigation for medical devices.
- Australiaโs TGA has updated the index resource Australian Regulatory Guidelines for Medical Devices (ARGMD).ย
EUDAMED News
- Medical Device Coordination Group (MDCG) has published โMDCG 2024-15 - Guidance on the publication of the clinical investigation reports and their summaries in the absence of EUDAMED (November 2024).โ This document provides guidance on the submission and publication of clinical investigation reports and their summaries while EUDAMED is not fully functional and outlines interim processes to ensure transparency.
- MedTech Europe has released a position paper on Smooth transition to the mandatory use of EUDAMED, which provides perspectives from device manufacturers.
- A 16 Dec 24 RAPS article titled โEuropean Commission launches targeted consultation on MDR, IVDRโ describes the call for feedback aligns with the European Parliamentโs joint resolution passed in October 24 and calls upon the Commission to propose changes to the regulation and to conduct an impact assessment on the regulations by the end of Q1 2025. Announcement;ย call for evidence and link to survey.