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. 

A list of all documents required to be submitted is provided by FAMHP.

Furthermore, In Belgium, the FAMPH indicates some special requirements regarding the content of the CTR dossier for clinical trials. 

Part I

• Protocol synopsis must be submitted in the three official languages, Dutch, French, and German, as a minimum requirement.
• Labels must be submitted in the three official languages: Dutch, French, and German, with exceptions as described in the law of 7 May 2017.

Part II

• Required BE template for site suitability
• The use of these templates is not mandatory, but strongly recommended:
  • Informed consent template for interventional clinical trials of drugs in adult patients;
  • Template for informed consent for clinical trials of vaccines in healthy adult volunteers;
  • Curriculum vitae of the principal investigator (developed by the European Commission with BE addendum on specific technical expertise).

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.

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

Only in the case of Phase I mono-national clinical trials, the review timeline is shorter. 

See Article 22, Law of 2017:

“Art. 22. For an application for authorization of a mono-national phase I clinical trial, the FAMHP notifies the decision relating to the clinical trial to the sponsor, via the Union portal, within twenty days of the submission of the application file.

This twenty-day period is suspended when use is made of the options referred to in Articles 5, and 6, § 7 and 8, of the [EU CTR].”

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

Yes. Each Ethics Committee needs to be approved by the State. The application for approval is reviewed by FAMHP and, if found favorable, then the State grants authorization.

Please see Articles 14-18, Decree of 2017.

3.5 How frequently do EC/IRB meet?

The frequency of meetings is not specified, though the Ethics Committees are required to attend any meetings, as and when called by the College.

See Article 10, Decree of 2017:

“Art. 10. The Ethics Committee takes part in the meetings organized by the College and in the work processes initiated by the latter in order to ensure the quality of the work of the Ethics Committees. The Ethics Committee appoints at least one of its members to represent it at these meetings.”

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

No. At a Member State level, only the Ethics Committee and FAMHP need to jointly review and approve a CTA submitted under the EU CTR 536/2014.

However, Article 8, Decree of 2017, requires an Ethics Committee to have written procedures available concerning “the use of external experts, representatives of external patients or any other external person and their designation”. This may be an internal sub-step during the assessment of CTA by the Ethics Committee.

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.)?

As of Feb 2024, the FAMHP has indicated that “No payment will be requested at the moment for the submission dossier. Therefore, no proof of payment must be provided for Belgium in the CTIS submission dossier”. This statement can be found within the FAMHP “List of documents for CTR submission” under “Additional Clarifications- Fee for Belgium”.

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. Please see the response to section 3.8 above.

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.

Additionally, the Belgium Regulatory Authority FAMHP provides additional information on requirements for submissions under the EU CTR 536/2014.

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.

The advice reflected within the “Guidance for sponsors on the use of electronic informed consent in interventional clinical trials in Belgium”_V2, 29 June 2023, indicates the following:

“All documents and materials have to be submitted in a format that allows to see how it will be provided to the participant (including logos, images, photos, colors, videos, links to the web-based presentations, etc.) in order to allow the evaluating Ethics Committee to assess the e-ICF and the method used to obtain the electronic signature. As it should always be possible to print the ICF on paper, a PDF of the ICF needs to be provided as well.”

Depending on the region where the participants are located, the ICF may need to be translated into Dutch, French, or German, if English is not the preferred language of the participant.

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

Yes, the Clinical Trial College has created a template for the Informed Consent Form (ICF) for interventional clinical trials with an investigational medicinal product on adult patient.

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

The Model ICF for Interventional Clinical Trials with IMP on adult patients, adopted by the CT College mentions compensation-related matters as mandatory information to be contained in the ICF. 

In addition, the template document for the Compensation of Trial Participants also acts as guidance on the kind of compensation that can be offered. 

Legal provisions around the sponsor’s responsibility, as contained in Article 12, Law of 2017, are already covered in section 2.18 of this guidebook.  

Reimbursement of expenses such as transportation costs (fuel, parking fees, public transport), meals, mandatory contraception, medication needed to treat side effects, sun cream, time investment/efforts, and hotel costs, are permitted and those should be listed within the informed consent form.

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

SUSARS are submitted to the EudraVigilance database.

The Belgian ethics committees bear no responsibility for the assessment of safety reporting.

A portion of Article 44, EU CTR 536/2014, states that “The responsible ethics committee shall be involved in the assessment of the information referred to in paragraphs 1 and 2 if it has been provided for in the law of the Member State concerned”. 

However, the Belgian Law of 2017 on clinical trials on medicinal products for human use does not mention a mandatory involvement of the evaluating ECs with regard to the assessment of ASRs and SUSARs.

The Board of the CT-College thus concludes that for the assessment of ASRs and SUSARs of CTR files:

• The ECs are not responsible according to Belgian law.
• The ECs are therefore not assigned a formal role in CTIS for this matter. 

Please see the advice for Belgian ECs regarding the assessment of safety reports in the CTR application adopted and issued by the CT College Board.

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

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