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. 

The EU Regulation 536/2014 specifies that the documents to be evaluated are divided into two sections:

• Part 1 (including protocol and investigator information, benefit-risk assessment; see Article 6)
• Part 2 (including requirements for consent; recruitment; suitability of the trial site as well as persons involved in the conduct; data protection; insurance; and handling of biomaterials; see Article 7)

The French Ministry of Health, under their guidance document titled “Documents expected in France for the filling of part II of the CTA (v3_17 Aug 2023)”, provides detailed requirements of what documents need to be included under Part II of the clinical trial application.

• EU templates available at the EUDRALEX Volume 10
• French Templates can be found on the “National Commission for Research Involving Humans (CNRIPH)”
• Additional clarifications to some of the documents listed above were published by the Ministry of Health “Newsletter for Sponsor_Dec 2023”.

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

The timelines are set out in the table below, based on Art 5 (Application), Art 6 (Assessment report – aspects covered by Part I) & Art 7 (Assessment report – aspects covered by Part II), of the EU CTR 536/2014:

• In red: Time for 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.

More information on CTIS Evaluation Timelines.

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

No, not that we have been able to determine.

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

Yes. The competence of the CPP is established by national legislation.

3.5 How frequently do EC/IRB meet?

Under the EU CTR 536/2014, in France, a draw is carried out to designate the CPP in charge of the evaluation of Part II of clinical trial authorization applications. The draw is carried out simultaneously with the filing of the file in CTIS.

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

No.

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

The Clinical Trial application is submitted to the EMA CTIS portal; no separate application is required to be made to the Ethics Committee. 

EMA provides detailed training modules to help use the Clinical Trial Information System (CTIS).

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.)?

There are no fees associated in France for the review of clinical trials with medicinal products.

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?

N/A

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 EMA guidance and training modules can be found here.

The Clinical Trial application is submitted to the EMA CTIS portal. This is the only application that needs to be made in terms of the EU CTR 536/2014.

Sponsors wishing to use CTIS must have an EMA account. Users who do not have an EMA account can register through the EMA Account Management facility.

Organizations may need to go through additional registration steps based on the user management approach that was used for CTIS. The organization-centered approach enables user management by an administrator at the organization level, rather than at the level of an individual trial. This is intended for organizations that run various trials through CTIS. To make use of this organization-based approach, organizations must ensure that they are registered in the EMA Organization Management System (OMS) and must register a CTIS High-Level Administrator through the EMA Account Management webpage. 

Below are some guidance and training modules made available by EMA:

1. Getting started with CTIS – Sponsor Quickguide
2. CTIS Sponsor handbook
3. Reference Materials for Clinical Trial Sponsors

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).

There is no indication of how digital participant-facing material should be submitted, but it is foreseen that screenshots or alternative means (i.e. video links/files) would be expected.

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

Yes. While there are no ICF templates available, the Ministry of Health has published a tool to write participants informed consents.

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

Articles R1121-4 to R1121-9 of the Public Health Code specify the insurance requirements to be met by trial sponsors. The full trial name and trial duration are to be specified on the policy and require cover in the amount of €1,000,000 euros per participant claim, €6,000,000 per research protocol, and €10,000,000 for all claims submitted during an insurance year under several research protocols.

Additional information on insurance requirements is specified within section 5 of the “Documents expected in France concerning part II of clinical drug trial evaluation request files Version 3 of August 17, 2023”, which indicates the following:

“The copy of the insurance certificate complies with article L. 1121-10 and articles R. 1121-4 to R.1121-9 of the French public health code.

It covers at least the period running from the date of first inclusion in France to the date of last visit of the last French patient.

The certificate can be annual and must mention the end date of the research and the contact details of the legal representative in the European Union.

NB: in the case of an annual certificate, the test may be subject to a favorable opinion under conditions on part II. The condition will seek to require that an amendment be submitted each year in order to submit a new, up-to-date annual certificate.

To remember:

- In France, article L. 1124-1 provides that clinical drug trials are prohibited on a person who is not affiliated to a social security scheme or beneficiary of such a scheme.

- The clinical trial insurer must be established in the European Union (see articles L. 310-2 and L. 310-10 of the insurance code).

Summary of language requirements: insurance certificate to be provided in French.”

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

For studies submitted in accordance with the provisions of EU CTR 536/2014 and therefore via the CTIS portal, annual patient safety reports and reports of unexpected serious adverse reactions to medicinal products must be submitted in accordance with that Regulation (i.e. Annual Participant Safety Reports (ASRs) to the ASR EudraVigilance Module on the CTIS Portal and reports of Unexpected Serious Adverse Reactions (SUSARs) directly to the EudraVigilance Clinical Trial Module).

For more information, please refer to Section 2.15.

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

No, annual safety reporting, along with other required notifications are submitted via the EMA CTIS portal. 

Please access the ANSM page entitled “Clinical trials: procedures for the constitution and processing of applications under the European regulation on clinical trials of medicinal products”, and within that, Part V: Vigilance of Clinical Drug Trials, Clause 6.