Updated Version of the Q&As regarding the Clinical Trials Regulation

Recommendation

5-7 November 2024
Hamburg, Germany

GMP meets Development
GMP and FDA Compliance in Pharmaceutical Development and IMP Manufacturing

The European Commission (EC) published an updated Version 4 of the draft Questions & Answers (Q&As) relating to the Clinical Trials Regulation (EU) No 536/2014 (CTR). The Q&As will enter into force together with the application of the CTR on 31 January 2022. However, certain sections of the Q&A document are still not yet complete and updated versions of the Q&A will be published progressively.

In addition, the EMA has recently published a Sponsor Handbook in order to help sponsors prepare for using the new CTIS (Clinical Trials Information System). According to the agency, the Handbook is aimed at pharmaceutical companies, contract research organizations (CROs), small and medium-sized enterprises (SMEs), academic sponsors and other organizations working on clinical trials.

New Q&As

Compared to the previous version 3 the following new Q&As have been introduced:

Chapter 11 ARRANGEMENTS FOR THE TRANSITIONAL PERIOD

• 11.14  What are the requirements to refer to clinical trial data, collected in clinical trials authorized under the Clinical Trial Directive?
  Data from a clinical trial (CT) can only be submitted in an application dossier if that CT has been registered prior to its start in a public register. For data from CTs that started before applicability of the CTR, it is acceptable as well that the results of the CT have been published in an independent peer- reviewed scientific publication. For trials submitted under the CTR that refer to clinical data generated under the Clinical Trial Directive, the registration obligation would be met for trials that have been registered in EudraCT.
  
  
• 11.15 After implementation of the CTR, will EU phase 1 trials meet the CTR transparency requirements as only very limited data will be published in the EU database?
  Trial data submission can only be accepted if the referenced trial was registered publicly (including registration in the EU Clinical Trial Register) or in case the results have been published in a peer-reviewed manner. The last possibility is only there for trials that started before the applicability of the CTR. If a referenced trial is not registered in a database or the results are not published, the data can not be used to support an application in the EU under the CTR, irrespective of whether it is a phase 1 trial or not.

In addition, the updated version contains a new ANNEX IV: CHANGES TO SOURCE COUNTRY including, for example, how to deal with:

• Regulatory requirements with regards to labelling & GMP,
• Changes to be submitted for authorization as a Substantial Modification.

Revised Q&As

The following Q&As have been revised or updated:

Chapter 3 SUBSTANTIAL MODIFICATIONS has been completely revised. 

Chapter 11 ARRANGEMENTS FOR THE TRANSITIONAL PERIOD

11.6 How shall a sponsor proceed in case of mono-national clinical trials? & 11.7 How should a sponsor proceed in case of multinational clinical trials?
In order to switch the regulatory framework applicable from the Directive to the CTR, the sponsor will need to submit the following information:

• New cover letter;
• New application form;
• Mono-national trials: The latest approved version of the protocol (as authorized by the Member State in question);
• Multinational trials: Consolidated protocol;
• IB (Investigators Brochure),
• GMP relevant documents;
• IMPD (Investigational Medicinal Product Dossier);
• The existing documents related to auxiliary medicinal products (if applicable).

More information can be found in the draft CLINICAL TRIALS REGULATION (EU) NO 536/2014 - QUESTIONS & ANSWERS VERSION 4.