CLINICAL TRIALS REGULATION (EU) NO 536/2014

1 REGULATION (EU) No 536/ 2014 Questions & Answers draft September 2021. September 2021. The rules governing medicinal products in the European Union VOLUME 10 - Guidance documents applying to CLINICAL TRIALS CLINICAL TRIALS REGULATION (EU) NO 536/ 2014 . DRAFT. QUESTIONS & ANSWERS. VERSION Submitted for discussion to the Expert Group on CLINICAL TRIALS . Note: Certain sections of this Q&A document are not yet complete. Updated versions of the Q&A will be published progressively. Document history: Q&As were discussed Date of discussion of draft by the expert group on CLINICAL progressively since December TRIALS 2014 .

2 Date of publication: On application of the CLINICAL Date of entry into force: TRIALS REGULATION (EU) No 536/ 2014 . Supersedes: Q&As added or revised: , Changes compared to superseded version: (new), , annex II. Keywords: CLINICAL TRIALS , REGULATION (EU) No 536/ 2014 , Questions and Answers 1. REGULATION (EU) No 536/ 2014 Questions & Answers draft September 2021. Important notice: The views expressed in this questions and answers document are not legally binding. Ultimately, only the European Court of Justice can give an authoritative interpretation of Community law. This document aims at informing on the technical aspects of Commission CLINICAL TRIALS REGULATION (EU) No 356/ 2014 with a view to facilitating its implementation.

3 This documents sets out frequently-asked 'questions and answers' regarding the implementation of the rules on CLINICAL TRIALS . All updates to this questions and answers document are presented and discussed within the Expert group on CLINICAL TRIALS and reflects the view of the group. This group is chaired by the Commission and is composed of representatives of all EU Member States and EEA contracting parties. Chapter 7 on Safety Reporting was drafted by the CLINICAL TRIALS Facilitation and Coordination Group of the Heads of Medicines Agency (CTFG) and endorsed by the Expert Group on CLINICAL TRIALS of the European Commission.

4 Q&A How to use conditions was endorsed also by CTFG. 2. REGULATION (EU) No 536/ 2014 Questions & Answers draft September 2021. Table of Contents 1. THE SCOPE OF CLINICAL TRIALS REGULATION IN THE EU ..12. Question: What are the new characteristics of the CLINICAL TRIALS REGULATION (EU) No 536/ 2014 as compared to the CLINICAL TRIALS Directive 2001/20/EC? ..12. Question: Till when is the CLINICAL Trial Directive 2001/20/EC. applicable? ..13. Question: What is a CLINICAL trial ? ..13. Question: What is a low-intervention CLINICAL trial ? ..14. Question: What can be considered as a non-interventional study ?

5 14. Question: Is the definition of 'medicinal product' relevant for the scope of the CLINICAL TRIALS REGULATION ?..15. Question: What is not considered as normal CLINICAL practice ? ..17. Question: A study might involve the administration of a medicinal product, while the object of the investigation is not the administered medicinal product, but exclusively the physiology of the body. Are these studies ' CLINICAL TRIALS ' as defined in REGULATION (EU) No 536/ 2014 ? ..17. Question: How does the issue set out in Question apply to PET. studies? ..18. Question: A study might involve a medical device what does this mean in terms of EU REGULATION of CLINICAL TRIALS ?

6 20. Question: Is a study addressing the time of surgery a CLINICAL trial, if patients receive otherwise standard treatment with medicines? ..22. Question: Does the CLINICAL TRIALS REGULATION apply to CLINICAL TRIALS with IMPs which fall under the 'hospital exemption' for advanced therapy medicinal products? ..22. Question: Is an authorised medicinal product used as comparator in a CLINICAL trial considered to be an investigational medicinal product? ..22. Question: What are the regulatory requirements for IMPs? ..22. Question: What is considered to be an auxiliary product? ..23. Question: Can a study be considered as CLINICAL trial within the scope of REGULATION (EU) No 536/ 2014 if it starts after administration/exposure of the investigational medicinal product has finished?

7 23. Question: Which principles of Good Laboratory Practice (GLP) need to be taken into account in CLINICAL TRIALS ? ..24. Question: Which principles of Good Laboratory Practice (GLP) need to be taken into account in relation to Advanced Therapy Medicinal Products (ATMPs)? ..25. Question: What are the languages requirements for documents that constitute part I of the application dossier ? ..25. 3. REGULATION (EU) No 536/ 2014 Questions & Answers draft September 2021. Member States have indicated in annex II which documents from the part I. ( CTR annex I, sections B to J) can be accepted in English, and what documents are (obligatory) to be submitted in other languages as well.

8 26. 2. APPLICATIONS LIMITED TO PART I (ARTICLE 11 OF REGULATION . (EU) NO 536/ 2014 ), ADDITIONAL MEMBER STATE (ARTICLE 14 OF. REGULATION (EU) NO 536/ 2014 ) AND OTHER MEASURES RELATED. TO THE APPLICATION PROCEDURE ..27. Question: Is it possible for a sponsor to submit a whole application (Part I and II) to some Member States concerned (on the basis of article 5) at the same time as an application limited to Part I only (on the basis of article 11) to other Member States concerned? ..27. Question: In cases of applications limited to Part I (article 11) how should a sponsor proceed to submit an application for Part II?

9 27. Question: When is it possible for a sponsor to submit an application for the subsequent addition of a Member State (article 14 of the CLINICAL TRIALS REGULATION )? ..28. Question: After the receipt of the decision on the CLINICAL trial, does the sponsor have the option to appeal against the decision? ..28. Question: Where an application for a CLINICAL trial is submitted in more than one Member State, does a sponsor have to await positive decisions from all Member States concerned, before commencing the trial in any of the Member States concerned?..28. Question: Chapter X and Annex VI of the CLINICAL TRIALS REGULATION refer to the content of the labelling of the investigational medicinal product (IMP).

10 Does this mean a mock-up needs to be submitted? ..28. Question: How will a request for information (RFI) during the initial assessment of a CLINICAL trial application, the assessment of an application for substantial modification and/or the assessment of application for subsequent addition of a Member State concerned be managed? ..29. Question: What should be understood by conditions? ..29. Question: Will the assessment report on part I and II be made public at the time of decision? ..30. Question: How will missing or incomplete documents in an application for the subsequent addition of a Member State (article 14) be addressed ?