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. 

In Germany, Ethics committees perform statutory tasks in accordance with the German Medical Products Act and Regulation (EU) No. 536/2014 of the European Parliament and of the Council of April 16, 2014, and to this extent are a public body (authority).

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)

For Germany, it was specified in 2016 that ethics committees provide an assessment for both parts (see § 40 (4) and (5) and § 41 (1) AMG new). The higher federal authority (RA) assesses all aspects to be evaluated in part 1 and makes the final decision (approval or refusal; see Section 40 (8) AMG new). In doing so, the RA is bound by the opinion of the Ethics Committee on Part 2. The opinion on Part 1 must be taken into decisive consideration by the RA; deviations from it must be documented and justified in the RA’s decision (see § 40 (8) and § 41 (3) AMG new).

Templates can be found at different sources:                                               

• AKEK provides a list of Informed Consent templates
• The German Ordinance on the Procedure for Cooperation between the Higher Federal Authorities and the Registered Ethics Committees in the evaluation of applications for approval of clinical trials with Medicinal Products for Human use (KPBV): 
  1. Appendix 1- Application-related declaration of personal and financial interest
  2. Appendix 2- Annual Declaration of Financial Interests

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?

Yes. The BfArM and the Working Group of Medical Ethics Committees have agreed on a shortened processing period for mono-national clinical trials. Accordingly, mono-national clinical trials are evaluated within 26 days after successful validation. If the application is free of defects, a decision can be made by day 31 at the latest.

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

Yes. In accordance with Section 41a of the AMG, only the public-law ethics committees of the federal states may participate in the procedure for the evaluation of clinical trials with medicinal products for human use in accordance with Regulation (EU) No. 536/2014, which are responsible for the examination and evaluation of clinical trials in humans according to the respective state law and which have previously been approved by the BfArM in agreement with the PEI in accordance with the requirements of § 41a AMG in conjunction with §§ 2 and 3 KPBV have been registered. 

In accordance with Section 41a Paragraph 6 AMG, the BfArM publishes the list of registered ethics committees in the Federal Gazette.

3.5 How frequently do EC/IRB meet?

The ethics committees registered by the BfArM or a body designated by them will issue a joint business allocation plan, which will be updated annually. The business allocation plan specifies the order in which the registered ethics committees are responsible for processing an application for approval of a human clinical trial. In particular, the business allocation plan takes into account the total number of registered ethics committees and their respective annual capacity. 

The Business Distribution Plan of registered Ethics Committees can be found on the BfArM webpage.

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

Yes. Clinical Trials, including radiological procedures that are not considered standard for care due to their type or frequency, need to be submitted to the Federal Office for Radiation Protection (Bundesamt für Strahlenschutz - BfS) in accordance with Section 185(1) of the Radiation Protection Act (StrlSchG).

Additional information on radiation protection in clinical trials can be found on the AKEK website.

Note that, for clinical trials that have been authorized according to EU CTR 536/2014 via CTIS, the obligation to notify the German Local Competent Authorities according to Section 67 of the German Drug Law does not apply anymore.

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.)?

Fees are charged in Euros and vary according to the nature of the clinical trial. Appendix 3 of the KPBV provides the list of fees of the German ethics committees.

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?

Invoices will be sent confirming the amount to be paid and the payment methods. 

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).

Participant-facing documents as well as labels must be submitted in German.

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

Yes, the German Working Party of the German Medical Ethics Committees (AKEK) provides a list of Informed Consent templates.

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

There is no specific guidance on study participant compensation, however, the model of the Informed Consent Form created by AKEK contains a section (I.8) related to costs and compensation/reimbursement of expenses incurred. This section will need to be completed according to the study.

Additionally, the ICF template contains language related to injury and insurance while participating in a clinical trial.

The German Medicinal Products Act (40a (3) sets forth the requirements and scope for insurance conditions.

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

Sponsors are required to submit SUSARS to the EudraVigilance database. The German ethics committees bear no responsibility for the assessment of safety reporting.

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

No. Annual safety reporting and other required notifications are submitted via the CTIS portal. 

Please refer to Section 2.16 of this guidebook.