The European Commission (EC) published an updated Version 2.4 of the draft Questions & Answers (Q&As) relating to the Clinical Trials Regulation (EU) No 536/2014 (CTR). The Q&As have been discussed progressively since December 2014 and the final draft (Version 1) was finalized in April 2018. The Q&As enter into force on application of the CTR which depends on the notice of the full functionality of the EU Portal / database (CTIS).
1.7 What is not considered as “normal clinical practice”?
1.19 What are the language requirements for documents that constitute part I of the application dossier? (see also new Annex II)
2.10 How will missing or incomplete documents in an application for the subsequent addition of a Member State (MS) be addressed?
2.11 Can the decision on part I of a clinical trial application be changed at the moment of the addition of a MS concerned?
2.12 Can a subsequent addition of a MS concerned be submitted if another addition of a MS concerned is ongoing? In principle, this would be possible. However, it is strongly recommended to combine the addition of MS concerned in one single application.
2.13 How will missing or incomplete documents in the part II application that follows a previously submitted part I application (partial submission) be addressed?
Chapter 7 on Safety reporting: 7.19 How should reference safety information (RSI) for the development of biosimilar drug products be written? The RSI of the originator may be accepted for a biosimilar (if justified). Increased frequency of a known serious adverse reaction (SAR) has to be reported as suspected unexpected serious adverse reaction (SUSAR). The protocol shall include measures to mitigate the risks associated with the originator and the new ones associated with the biosimilar.
Annex II Language requirements for part I documents
2.8 What should be understood by conditions?
3.4 When can a sponsor submit a substantial modification concerning Part I and II?
Chapter 7 on Safety reporting: - 7.9 Which format should be chosen for the RSI? - 7.11 When are ‘suspected’ SARs considered unexpected because of specificity and / or severity, or frequency? A table with examples of SUSARs and reasons for their reporting is provided. - 7.12 What is understood by synonymous medical terms and are they allowed in the RSI? - 7.15 When is an update of the RSI considered approvable (appropriate)? - 7.28 Should SUSARs or ASRs (Annual safety reports) be submitted also to Ethics Committees?