November 2022

Medicines and Vaccines

CTR and CTIS

The following online training modules have been updated:

• CTIS Evaluation Timelines - overview of timelines and deadlines for tasks and actions across the Clinical Trial Application process.
• Management of Roles and Permissions - step by step guide on how to request the high-level administrator role for CTIS.
• FAQs - Management of Roles and Permissions - answers to questions regarding basic principles to access CTIS for the first time, roles and permissions, CTIS user management approaches, user profile management and the main user groups.

Please find a link to the presentation document used during the CTIS bitesize talk “Notifications - Part 2” on 23 November 2022.

Key performance indicators (KPIs) to monitor the European clinical trials environment are provided in the following report: the Clinical Trials Regulation Metrics report is published on a monthly basis. The current report reflects the status of applications in CTIS and EudraCT as of 31 October 2022 for Clinical Trial applications submitted between 1-31 October 2022 as well as cumulative figures.

Reminder: There is a dedicated introductory guide for SMEs and Academia showing how clinical trial applications submitted under CTIS - which is mandatory for trials to be conducted in the EU/EEA from 31 January 2023 - will impact them. EMA are recirculating the guide, first published in May 2022, so we think it is worth mentioning this here. 

The Working Group of Medical Ethics Committees in the Federal Republic of Germany (AKEK) and the associations of applicants for drug trials from university research and the pharmaceutical industry agree that after 10 months of practice, the CTIS portal suffers from serious deficiencies and is largely unmanageable for all parties involved and have issued a Joint Press Release (use google translate) requesting that the transitional period expiring on 31 January 2023 pursuant to Article 98 of Regulation 536/2014 be extended until the functionality of the EU portal CTIS has actually been established and demonstrated.

UK and MHRA News

FDA Guidance and News

• FDA has issued recommendations to sponsors wishing to study multiple versions of a cellular or gene therapy product in an early-phase clinical trial for a single disease (also called “umbrella trials”). This new guidance includes information on how to organise and structure the INDs, submit new information, and report adverse events. This final guidance replaces  draft guidance dated September 2021.
• Updates to ClinicalTrials.gov Beta are now available, including improvements to the Search results. See the Release Notes for more information.

EMA Guidance and News

• EMA released a general guidance entitled “Anonymisation of Protected Personal Data and assessment of Commercially Confidential Information during the preparation of RMPs” which contains changes of editorial nature that should be implemented in the RMP during the scientific review process prior to the Opinion and adoption of the final RMP version.

• EMA released in October 2022 the updated (Rev. 14) “Guidance for Applicants seeking scientific advice and protocol assistance”. This update further clarifies the scope and nature of scientific advice and protocol assistance, such requests for paediatric development, structure/content of the briefing package, and the procedure for fee determination and payment. The major changes to the document are for clarity and conciseness.

• Resources from EMA’s ‘ACT EU multi-stakeholder meeting on decentralised clinical trials’ of 04 Oct 2022 are now available.

• EMA released a ‘Concept paper on platform trials’ to address complexity around handling the Type I error control, design characteristics such as non-concurrent controls and changing randomization/allocation ratios, and bias/external validity in relation to the platform design. Deadline for comments is 31 Jan 2023. The EMA is indicating that master protocol designs are gaining traction in the clinical research landscape.

Real-World Studies

Rylands et al’s review on ‘Guiding Principles for Using Clinical Outcomes Assessments in Real-World Studies: What to Do When There Is No Regulatory Guidance’ addresses the challenges in using COAs in RWE/RWD studies (as opposed to RCTs). The overview and references are helpful for protocol authors working in RW studies.

Transparency and Disclosure Resources and News

Submissions are open for ‘Cochrane Evidence Synthesis and Methods’, Cochrane’s first open-access journal. Cochrane—a global independent network of researchers, professionals, patients, carers and people interested in health—has over 100,000 members and contributors across an established global network who publish their systematic reviews in the Cochrane Database of Systematic Reviews. The new journal opens opportunities for members and researchers to publish research outputs that go beyond Cochrane systematic reviews, aiming to further develop the evidence base published by Cochrane.

Development Strategy News

• Roberts et al’s publication, ‘Regulatory Considerations Toward Orphan Drug Designation and Orphan Drug Exclusivity in the United States and European Union: Structural Similarity, Clinical Superiority/Significant Benefit, and Case Studies’ provides “A comprehensive assessment of current regulations, case studies in exclusivities, and recommendations for improvement…”.

• A review by Peters et al titled ‘Considerations for Embedding Inclusive Research Principles in the Design and Execution of Clinical Trials’ encourages the use of patient engagement tools to include patients and carers as stakeholders in protocol design.

• TransCelerate have issued ‘Quality and culture solutions for operationalizing E8(R1) and ICH E6R(3)’. TransCelerate describe the value of this asset as follows: “Providing a framework for implementation will facilitate sponsor companies’ efforts to operationalize efficiently the principles specified in the revised Guidelines. TransCelerate’s ICH E8/E6 project provides a forum for clinical study stakeholders to foster collaboration, achieve greater efficiencies and effectiveness in operationalizing the revised ICH Guidelines, and better support regulatory compliance. The project will accelerate adoption across various stakeholder groups in the clinical research ecosystem”.

• TransCelerate have released ‘Clinical Template Suite (CTS) Release Addendum’. This is a track changes clinical protocol template (CPT v009) with limited updates. The addendum (clicking this link will force a download) also explains that the next round of templates will be released in H2 of 2023, in order to allow alignment with ICH M11 and EU PEARL. 

Medical Devices

Medical devices information is kindly compiled by Raquel Billiones.

Updates from the EU Medical Device Coordinating Group (MDCG)

• NEW: MDCG 2022-16. Guidance on Authorised Representatives Regulation (EU) 2017/745 and Regulation (EU) 2017/746 was released in October. The guidance document provides clarifications on designating an authorised representative in the EU for manufacturers without an establishment in any of the member states.

• UPDATED: MDCG 2020-10/1 Rev 1. Safety reporting in clinical investigations of medical devices under the Regulation (EU) 2017/745 was revised in Oct 2022. Changes include new definitions and clarifications. The safety reporting form MDCG 2020-10/2 (in xls format) has also been updated.

• UPDATED: MDCG 2019-6 (rev.4). Questions and answers: Requirements relating to notified bodies (NB) was updated in Oct 2022. The key change was Question III.6 on the term “employed”, ie, relating to NB personnel. 

Updates from the International Standards Organisation (ISO)

The ISO Technical Committee TC 194 W4 announced that work on the new standard ISO 18969 Clinical Evaluation of Medical Devices will start immediately.

Updates from US FDA

• Definitions and Clarifications: The FDA issued this GfI ‘Referencing the Definition of "Device" in the Federal Food, Drug, and Cosmetic Act in Guidance, Regulatory Documents, Communications, and Other Public Documents’ to differentiate between the terms “device” and “counterfeit device”.

• New FDA Presentations on Medical Devices:
  • An Introduction to FDA’s Regulation of Medical Devices
  • How is My Medical Device Classified?

Artificial Intelligence-enabled Medical Devices

In 2022 alone, the FDA authorised 91 AI- or machine-learning-enabled medical devices. The article ‘5 Takeaways from the FDA’s List of AI-Enabled Medical Devices’ provides an overview.