4. Regulatory Authority (RA)/ Competent Authority (CA)

4.1 Provide a list of documents needed to be submitted for RA/CA review and approval including the number of copies and/or translations as relevant. 

The following electronic documents are required to be submitted via CTIS (the EU’s Clinical Trials Information System): 

Part I (Scientific and Medicinal Product Documentation)

1. Application form
2. Protocol
3. Investigator’s brochure
4. GMP documentation
5. IMPD/AMPD
6. Scientific advice
7. Pediatric Investigation Plan
8. IMP/auxiliary labels

Part II (National and Patient Level Documentation)

1. Patient materials: informed consent, patient information leaflet
2. Compensation arrangements
3. Recruitment arrangements
4. Investigators' and facilities' suitability
5. Damage compensation
6. Data protection rules

The BfArM website provides guidance and links to information required by Sponsors in relation to clinical trial applications conducted under the EU CTR 536/2014, which must be submitted via CTIS.

Before using CTIS, users must have an EMA account. Users that already have an EMA account (e.g. to use Eudravigilance or the substances, products, organizations, and referential database (SPOR)) do not need to create a new account. Users who do not have an EMA account can register via EMA Account Management.

Organizations may need to complete additional registration steps based on the user management approach they choose for CTIS. The organization-centric approach allows for the management of users by an administrator at the organization level rather than at the level of an individual trial. It is intended for organizations that will run several trials in CTIS. To make use of the organization-centric approach, organizations must ensure they are registered in EMA’s Organization Management System (OMS), and they must register a CTIS High-Level Administrator via EMA Account Management.

4.2 Time required for RA/CA 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.

4.3 Does the regulation support electronic submission?

Yes. All documents are to be submitted electronically through the CTIS portal.

4.4 Does the regulation require the applicant to be a Principal Investigator (PI)/Chief Investigator (CI)?

No, the submission of clinical trials as per the EU CTR 536/2014 can be done by the Sponsor or authorized representative.

4.5 Please describe the process of RA/CA submission for clinical trial approval. 

From 31 January 2023, all clinical trial sponsors must submit new clinical trial applications in the EU and EEA through CTIS, in terms of the EU CTR 536/2014.

A single trial application form and supporting dossier must be submitted through CTIS. The CTIS Sponsor Handbook is helpful in this regard.

Section 40 of the German AMG - Division 6 - Protection of Humans in Clinical Trials - describes the procedure for the approval of a clinical trial.

The CTIS online training program, which is available on the EMA website, provides additional information. 

4.6 Does the RA/CA provide written acknowledgment of the submitted application? If not, describe how the application is tracked.

Yes, the reporting Member State provides a written acknowledgment (via the CTIS portal) of the submitted application within 6 days of submission of the application.

Art 5.1, Clinical Trial Regulation (EU) 536/2014. 

4.7 What is the relevant RA/CA fee in local currency/USD? Please provide as much information as possible (e.g. if the fee is different for notification/approval, initial submission, amendment, study with IMPD and study without IMPD, etc.)

Fees are charged in Euros and vary according to the nature of the clinical trial.

Section 40(6) of the German Medicinal Products Act prescribes specific fees for the performance of official duties in connection with clinical trials.

BfArM and PEI fees related to CTAs submitted under the CTR 536/2014 are indicated within Section 5 of the German Special Fee Ordinance (BMg-BMGBGebV).

4.8 Does RA/CA 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 information is expected to be received by the sponsor at the time of an invoice generated by the relevant Regulatory Authority in relation to the CTA submitted.

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

The Clinical Trial application is made by the centralized EMA CTIS portal. 

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

4.10 Does RA/CA require any screenshots/mock screens for participant-facing materials?

Not under Part I of the application.

Participant-facing material is only submitted within Part II of the application unless participant-facing material is linked to the endpoints of the clinical trial, and those shall be provided together with the protocol in Part I of the clinical trial application. However, there is no indication as to how those documents should be provided.