Recent Updates
Clinical Trials Information System (CTIS) - Sponsor Handbook
22 December 2022 – the EMA published version 3.01 of the CTIS sponsor handbook.
The Handbook addresses key questions on CTIS and provides a compilation and references to key guidance, technical information, recommendations, training materials, and supportive documentation to facilitate the submission and assessment of CTAs and additional information during the lifecycle of a trial.
Clinical Trials Highlights
21 December 2022 – the EMA published Issue 12 of the Clinical Trials Highlights newsletter.
Since the launch of CTIS on 31 January 2022, almost 200 clinical trial applications have been authorized and over 200 are under evaluation. During this time, EMA has collaborated with Sponsor and Member State users to identify and successfully resolve technical issues, providing proactive hands-on support to the CTIS user community and strengthening the system ahead of its compulsory use.
As of 31 January 2023, sponsors must submit all initial clinical trial applications under the CTR using CTIS and can no longer submit via the processes outlined in the Clinical Trials Directive.
EU Guideline on Orphan Applications (for Designation and Transfer) - 2022/C 440/02
19 December 2022 – the European Commission published the guideline on orphan applications.
This guideline gives supplementary advice on the information sponsors must provide when applying for designation of a medicinal product as an orphan medicinal product. It covers both the format and content of the application, and should be followed unless good reasons are given for deviating from it.
Updated IRIS Guide to Registration and RPIs
16 December 2022 – the EMA published updated preliminary requirements for all IRIS submissions, including substance and Research Product Identifier registration.
This guide has been produced to help new users of IRIS to complete the prerequisite steps before accessing the platform. Most of these steps are independent from the IRIS platform and are similar to those to obtain registration to use other European Medicines Agency (EMA) systems, such as Management Services for Substances, Products, Organization and Referentials (SPOR).
Q&A: Good Clinical Practice (GCP)
16 December 2022 – the EMA published updated GCP Q&A guidance.
This updated Q&A added B. GCP Matters, Question.17, which focuses on how sponsor oversight of such activities can be demonstrated and should be considered in combination with Q&As B.2, B.8 and B.11, which contain general considerations on how contracting should be addressed.
Clinical Pharmacology and Pharmacokinetics: Questions and Answers
16 December 2022 – the EMA published updated Q&A guidance on guideline requirements for parenteral oily solutions.
Section 3 Bioequivalence (general) - Question 3.12:
Clarification on Appendix II of the Guideline on the investigation of bioequivalence (CPMP/EWP/QWP/1401/98 Rev.1/Corr**) on whether viscosity and/or other in vitro comparative data are needed to demonstrate comparable physicochemical characteristics of oily solutions, sufficient to support a biowaiver.
eXtended EudraVigilance Medicinal Product Dictionary (XEVMPD) Data-Entry Tool (EVWEB) User Manual
15 December 2022 – the EMA published version 5.8 of the XEVMPD data-entry tool user manual.
This user manual is part of the official documentation prepared by the European Medicines Agency (EMA) to support marketing authorization holders (MAHs) and sponsors of clinical trials using the eXtended EudraVigilance Medicinal Product Dictionary data-entry tool (EVWEB) and focuses on EVWEB functionalities based on the XEVPRM format published by the Agency on 31 January 2014 and available in the EVWEB production environment as of 16 June 2014.
Following the publication of version 5.7 in June 2022, the links to the EMA Service Desk were amended through-out the document.
Functional Specifications for the European Database on Medical Devices (EUDAMED)
14 December 2022 – the European Commission published guidance on functional specifications for EUDAMED.
Article 34 of Regulation (EU) 2017/745 obliges the Commission to draw up the functional specifications for EUDAMED in collaboration with the MDCG. This document will also be a reference for the independent audit to be performed for verifying that Eudamed has achieved full functionality.
Recommendation Paper on Decentralised Elements in Clinical Trials
13 December 2022 – the European Commission published the recommendation paper on decentralized elements in clinical trials, version 01.
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 decentralized clinical trial setting. The intention of this recommendation paper is to facilitate the use of decentralized elements in clinical trials in the EU/EEA.
Guidance for Applicants/MAHs Involved in GMP, GCP and GVP Inspections Coordinated by EMA
13 December 2022 – the EMA published version 3.1 of guidance for applicants/MAHs involved in GMP, GCP and GVP inspections coordinated by EMA.
These GMP inspections are requested by the Committee for Medicinal Products for Human Use (CHMP) and/or the Committee for Medicinal Products for Veterinary Use (CVMP) in order to verify compliance with GMP of sites responsible for the manufacture of centrally authorized products.
These GCP inspections are requested by the CHMP in order to verify compliance with GCP for centrally authorized products, in accordance with Article 57 of Regulation (EC) No. 726/2004 and Article 78 of Regulation (EU) No 536/2014.
These GVP inspections are requested by the CHMP in order to verify compliance with GVP for centrally authorized products, in accordance with Article 57 of Regulation (EC) No. 726/2004 and CVMP, in accordance with Article 57 of Regulation (EC) No. 726/2004 and Articles 123 and 126 of Regulation (EU) 2019/6.
Joint Audit Programme for EEA GMP Inspectorates JAP
8 December 2022 – the EMA published revision 3 of the audit notification template for EEA GMP inspectorates (JAP).
The Joint Audit Program (JAP) forms an essential part of the quality system adopted by good manufacturing practice (GMP) inspectorates in the European Economic Area (EEA), aiming to ensure consistency of GMP standards and a harmonized approach throughout Europe.
The audit program, its procedures and templates form the complete set of documents used in the JAP.
EMA Human Regulatory Update on Medical Devices
8 December 2022 – the EMA updated guidance on medical devices.
EMA has distinct regulatory responsibilities per category of medical device, including in vitro diagnostics. They are as follows:
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Medicines used in combination with a medical device ─ EMA assesses the safety and effectiveness of medicines used in combination with a medical device. This is part of a centralized procedure application for the medicinal product.
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Medical devices with an ancillary medicinal substance ─ the notified body must seek EMA's scientific opinion on the quality, safety, and usefulness of the ancillary medicinal substance in three cases: if the ancillary substance is derived from human blood or plasma; if it has been previously evaluated by the EMA; or if it falls within the mandatory scope of the centralized.
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Companion diagnostics ('in vitro diagnostics') ─ the notified body must seek EMA's scientific opinion on the suitability of the companion diagnostic to the medicinal product if the latter falls within the scope of the centralized.
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Medical devices made of substances that are systemically absorbed ─ the notified body must seek the scientific opinion of a competent authority. The EMA provides scientific opinions on the compliance of the substance with the requirements laid down in Annex I to Directive 2001/83/EC.
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High-risk medical devices ─ EMA supports the medical device expert panels that provide opinions and views to notified bodies on the scientific assessment of certain high-risk medical devices and in vitro diagnostics.
EMA EudraVigilance Registration Documents and Manual
7 December 2022 – the EMA published the updated EudraVigilance registration related documents and manual.
To set-up a new organization in EudraVigilance (EV) Production or XCOMP (test) system, the following series of steps need to be followed:
Human Variations Electronic Application Forms (eAF) (DADI) Go-live Q&A Session
6 December 2022 – the EMA published the Q&A guidance on human variations eAF go-live Q&A session held on 27 October 2022 and 8 November 2022.
The web-based electronic application forms (eAF) will replace PDF eAFs used for regulatory submissions in the new dedicated PLM portal. These Q&A sessions attempted to address questions from industry and national competent authorities’ stakeholders concerning the release of the web-based variations eAF for Human CAPs.
Human Variations eAF go-live Q&A session (27 October 2022)
Human Variations eAF go-live Q&A session (8 November 2022)
ICH Guideline E8 (R1) on General Considerations for Clinical Studies
2 December 2022 – the EMA published step 5 of ICH Guideline E8 (R1).
This document provides guidance on the clinical development lifecycle, including designing quality into clinical studies, considering the broad range of clinical study designs and data sources used.
Manual on Borderline and Classification for Medical Devices under Regulation (EU) 2017/745 on Medical Devices and Regulation (EU) 2017/746 on in vitro Diagnostic Medical Devices
December 2022 – the European Commission published version 2 of the manual on borderline and classification for medical devices.
This document, hereafter called the Manual, records the agreements reached by the Member State members of the Borderline and Classification Working Group (BCWG) following the exchanges under the Helsinki Procedure under Regulation (EU) 2017/745 on medical devices (the MDR) and Regulation (EU) 2017/746 on in vitro diagnostic medical devices (IVDR).