3. Ethics Committee (EC)/ Institutional Review Board (IRB)

3.1 Provide a list of documents needed to be submitted for EC/IRB review and approval including the number of copies and/or translations as relevant. 

Under the EU CTR, the initial application for a clinical trial is divided into two parts:

• Part I contains scientific and medicinal product documentation (this part is reviewed by the Competent Authorities of the Member States taking part in the application, and in some cases by some of the National Ethics Committees).
• Part II contains the national and patient-level documentation (this part is reviewed by the ethics committees of the Member States taking part in the application).

3.2 Time required for EC/IRB review and approval process and turnaround time if any query is raised during the review process.

See the below table describing review timelines.

• In red: Time for the sponsor to respond to questions (RFIs).
• In green: Time for RMS or MSC to assess and discuss responses.
• RMS: Reporting Member State
• MSC: Member State Concerned

If the response to the RFI is not submitted within the timeframe provided, the application will lapse.

3.3 Does EC/IRB have any fast-track or expedited review process?

No; there is no fast track or expedited review process.

See response to 3.2 above, setting out assessment timelines.

3.4 Does EC/IRB need to be registered and/or accredited/approved by RA/CA?

Yes, this is a matter for the EU Member State concerned (i.e., a national matter) - please see the relevant country Guidebook.

3.5 How frequently do EC/IRB meet?

The concerned Member States, including reviewing ECs, have a limited time window under EU CTR in which to respond to a clinical trial application - see table under Section 3.2 above.

3.6 Is any additional approval required apart from the EC/IRB (e.g. scientific committee, subject matter expert committee, etc.)?

This is a matter for the EU Member State concerned (i.e., a national matter) - please see the relevant country Guidebook.

3.7 Please describe the process of the EC/IRB submission for clinical trial approval.

The Clinical Trial application is made by the centralized CTIS portal, as described in Section 3.2 above. This is the only application that needs to be made.

3.8 What is the relevant EC/IRB fee in local currency/USD? (e.g., is the fee different for notification/approval, initial submission, amendment, study with IMPD and study without IMPD, investigator site addition, etc.)?

This is a matter for the EU Member State concerned (i.e., a national matter) - please see the relevant country Guidebook.

The working assumption is that a fee to the EC is unlikely – a fee to the local RA is more probable, in line with the ambit of Art 86 and Art 87 Clinical Trial Regulation (EU) 536/2014. 

Article 86 - General principle

"This Regulation shall be without prejudice to the possibility for Member States to levy a fee for the activities set out in this Regulation, provided that the level of the fee is set in a transparent manner and on the basis of cost recovery principles. Member States may establish reduced fees for non-commercial clinical trials."

Article 87 - One payment per activity per Member State

"A Member State shall not require, for an assessment as referred to in Chapters II and III, multiple payments to different bodies involved in this assessment.”

i.e., The (national) fee should reflect the costs incurred by the Member State concerned in assessing the application.

3.9 Does EC/IRB accept checks or can payment be made electronically? Please provide details on (1) A/C number; (2) A/C Name; (3) Sort Code; (4) Swift Code; (5) Bank address, etc. Where can remittance advice notices be sent?

This is a matter for the EU Member State concerned (i.e., a national matter) - please see the relevant country Guidebook.

3.10 Is there any guidance tool available for making electronic applications? If yes, provide the link and/or step-by-step instructions.

Yes, EMA has created very comprehensive guidance, presentations, and videos to aid Sponsors and organizations in understanding the EU CTR requirements and navigation of the CTIS portal. 

Relevant guidance and training modules can be found here.

3.11 Does EC/IRB require any mock screens/screenshots of participant-facing material on the app? If yes, do these need to be submitted in the local language?

The position is that whilst patient materials such as informed consent forms, patient information leaflets, and participant-facing recruitment material are required to be submitted under the CTR, materials used post-consenting (patient cards, questionnaires, diaries) are not. See question 1.24 of the EMA EU CTR- Questions & Answers, the most up-to-date version can be found in Eudralex Volume 10.

Expectations and requirements by the reviewing MSC may differ per country. The recommendation is that screen-shots of informed consent, and patient information leaflets when provided electronically, be submitted under Part II of the application.

3.12 Does the EC/IRB have any template or specific element requirements on ICF and/or other participant-facing materials?

Yes, EUDRALEX Volume 10, Chapter I - Application and application documents provide different templates.

At the country level, each Member State may also have applicable templates or requirements. Please see the relevant country Guidebook.

3.13 Is there any guidance tool on participant compensation including clinical study-related injury per local requirements?

This is a matter for the EU Member State concerned (i.e., a national matter) - please see the relevant country Guidebook. However, subject to Art 76, Clinical Trial Regulation (EU) 536/2014:

“Damage compensation

1. Member States shall ensure that systems for compensation for any damage suffered by a subject resulting from participation in a clinical trial conducted on their territory are in place in the form of insurance, a guarantee, or a similar arrangement that is equivalent as regards its purpose and which is appropriate to the nature and the extent of the risk.
2. The sponsor and the investigator shall make use of the system referred to in paragraph 1 in the form appropriate for the Member State concerned where the clinical trial is conducted.”

3.14 Are there any specific local safety reporting requirements for clinical studies?

Safety reporting must comply with the EU CTR, in particular, Arts 40 to 46 and Annex III. The reporting of annual safety reports (ASRs) by the sponsor to the Agency in the context of the CTR is outlined in Art 43, applicable to trials registered in CTIS and managed under the CTR. The sponsor shall submit annually through CTIS a report on the safety of each investigational medicinal product (IMP) used in a clinical trial, other than placebo, for which it is the sponsor. This obligation referred to in paragraph 1 starts with the first authorization of a clinical trial in accordance with the CTR and it ends with the end of the last clinical trial conducted by the sponsor with the IMP.

See also section 9.2 - Annual Safety Report (ASR) - within the CTIS Sponsor handbook.

3.15 Does the EC/IRB require any periodic study reporting?

Yes, please refer to Section 2.16 where required notifications are indicated.