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 MPA provides more information on its clinical trial page.

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?

No, as per our research, there isn’t any expedited review process by EC/IRB.

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

No, the EC is nationally recognized - Swedish Ethical Review Authority/Etikprövningsmyndigheten (“ERA”).

3.5 How frequently do EC/IRB meet?

The frequency of meetings is not specified, though decision times are.

The frequency of ERA’s meetings is not specified, but decisions are stated as follows:

The ERA should make a decision within 60 days after a complete application and the fees have been received. For applications relating to clinical drug trials, special deadlines apply as follows.

If the application concerns drugs for gene therapy or somatic cell therapy or drugs that contain genetically modified organisms, the deadline is 90 days. In cases where there are regulations on the obligation for the ERA to hear another authority, decisions should normally be made within 180 days after the application is complete.

If the application concerns xenogenic cell therapy, there is no time limit. For other new applications relating to clinical drug trials, the deadline is 60 days.

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

Yes, simultaneous submission of applications for clinical trials may be made to MPA and ERA.

In some cases, approval by the Regional Biobank Centre or a biobank is required, in addition to MPA and ERA approval.

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.)?

The fee for assessment of clinical trials under the EU CTR 536/2014 is SEK 16,000. The fee for an application amendment is SEK 2,000.

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?

At the time of submission, a document with invoice details must be attached to the application/uploaded under “Proof of Payment” in the Clinical Trials Information System (CTIS). When the application is deemed valid, an invoice will be sent to the applicant.

There is a single fee which will include the EC and MPA fees.

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, templates of patient information sheets and informed consent are available on the Swedish Ethical Review Authority website.

Additionally, under the FAQ - Informed Consent - page, there is additional information regarding informed consent.

It is important to highlight that according to the Swedish MPA provision HSLF-FS 2021:109, the person responsible for obtaining informed consent shall also be the person who conducts the interview referred to in Article 29(2)(c) of the CTR. The basic rule is therefore that it is the responsibility of the qualified medical doctor (physician licensed by the Swedish National Board of Health and Welfare) or qualified dental practitioner (dentist licensed by the Swedish National Board of Health and Welfare) to conduct the interview and obtain consent for participation in a clinical trial on a medicinal product.

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

Yes, the MPA states that a patient must be informed during the informed consent process of the right to compensation for any damage, As set out in Art 29, Clinical Trial Regulation (EU) 536/2014.

Additional guidance can be found in the “Guidance on Ethical Review of Research on Humans” published by the Ethical Review Authority.

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 of this guidebook.

Additionally, the MPA indicates their expectations with regard to the Reference Safety Information (RSI) which describes the safety profile of an IMP and is required to be a part of the clinical trial application for all IMPs. The RSI lists all known serious adverse reactions, to assist in determining whether an adverse reaction during a trial should be reported as a SUSAR. RSI’s can be attached in two ways:

• In the Investigator’s Brochure (IB)
• In the Summary of Product Characteristics (SmPC)

The cover letter shall detail where in the clinical trial application the RSI can be found.

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. 

See the MPA website for “Safety Reporting” which provides the safety reporting obligation in relation to clinical trials on medicinal products conducted in accordance with EU CTR 536/2014.