Clinical trials

INITIAL REQUEST:

From January 31, 2023, All the initial applications conduct clinical trials are submitted compulsorily in accordance with Regulation (EU) No. 536/2014 (CTR), i.e. exclusively through CTIS

According to Article 2 of Regulation (EU) No. 536/2014, the following definitions apply:

1) "clinical study": any investigation on humans which aims to
a) the determination or verification of the clinical, pharmacological or other pharmacodynamic effects of one or more medicinal products,
b) the determination of any adverse reactions to one or more medicines, or
(c) the study of the absorption, distribution, metabolism and excretion of one or more investigational medicinal products, with the aim of determining the safety and/or efficacy of such medicinal products;

(2) ‘clinical trial’ means a clinical study that meets any of the following conditions:
(a) the inclusion of the participant in a specific treatment strategy is pre-determined and does not fall within the normal clinical practice of the Member State concerned;
b) the decision to administer the investigational medicinal products is taken together with the decision to include the participant in the clinical trial, or
(c) diagnostic or monitoring procedures in addition to normal clinical practice are applied to participants;

AMENDMENT:

For clinical trials that have been approved or transitioned to the CTR [Regulation (EU) 536/2014], any action (e.g. modification, update, addition of Member State) is submitted exclusively through CTIS.

USEFUL DOCUMENTS & INFORMATION:

UPDATE:

  •  09/05/2022 New Joint Ministerial Decree amending Art. 3 of Government Gazette 4131/2016 regarding the translation of the protocol into Greek for clinical trials submitted through CTIS
  •  01/02/2023 Quick guide for sponsors: Practical issues of implementing Regulation 536/2014 (CTR) and CTIS
  • 07/02/2023 ACT EU: Public consultation on the development of a platform to improve clinical trials in the EU
  •  18/04/2024 CTIS Bitesize talk (changes to CTIS)
  •  08/05/2024 CTIS: Walk-in clinic
  • 20/05/2024 CTIS sponsor end user training program
  • 10/06/2024 CTIS Bitesize talk (new transparency rules)
  • 29/11/2024 Q&A (Questions-Answers) concerning the local implementation of Regulation (EU) No. 536/2014 (CTR) in Greece
  • 21/01/2025 Consultation on the educational needs of the Academic Community and Small and Medium Enterprises: Deadline 11/02/2025
  • 17/03/2025 CTIS Public Portal: ACT EU Trial Map launched
  • 28/01/2026 Participation of EOF in the pilot program for accelerated assessment of clinical trials FAST-EU

 

HIGHLIGHTS:

1. Searching for information from the Clinical Trials Department of the Hellenic Medical Authority after submitting a request is done by providing the EU CT number or the study code provided by the Service.
2. Fees: According to the Ministerial Decision DYG3a/G.P 139307/05 (Government Gazette, 1098 10/08/2006 Articles 18 and 19) the fees for clinical studies are defined as follows:

1. For approval of an (interventional) clinical study, per study: 3.000,00 euros.
2. For the modification of an (interventional) clinical study, per modification: 1.500,00 euros.
3. In NON-commercial interventional studies, the fees are 1.500,00 and 750,00 euros respectively.

 

GOOD CLINICAL PRACTICE (GCP) INSPECTIONS

 

Scope

The compliance with Good Clinical Practice (GCP) Guidelines and applicable legislation and the verification that a clinical trial fulfils the technical, scientific and ethical requirements of these rules. The inspection verifies the integrity of the data generated in a trial and ensures that the rights, safety and well-being of the participant are preserved. GCP inspections can be carried out:

a) before, during or after the conduct of a clinical trial (national)

b) in clinical trials included in the Marketing Authorization Application (MAA) dossier and in Applications for extensions of approval of centrally approved products (CAP) to the European Medicines Agency (EMA)

c) in the context of the assessment following the granting of a Marketing Authorization

Typically, EOF's routine national inspections follow a defined annual national inspection schedule and are part of the obligation of a National Agency to safeguard the health of the nation's citizens. According to Art. 2. of the Regulation (EU) 536/2014 (CTR), inspections can take place at clinical trial investigator sites, at the facilities of sponsors (commercial or not) and Contract Research Organizations (CROs), as well as at any other site/company involved in activities critical to the quality of the trial during its design or execution phases, such as laboratories, technical equipment units, phase I and bioequivalence clinical trial units, etc. Where appropriate, EOF performs additional inspections following a deviation (complaint) outside the scheduled framework.

 

Procedures

The assigned lead inspector, after consultation with the parties involved, sets the dates for the inspection. Before the Announcement Letter and the Inspection Program are dispatched by EOF, the Sponsor/CRO must send list of requested documents.

During inspection at a clinical investigator site, inspectors review the Investigator's Study File (ISF), the source records and medical records of the participants and their informed consent forms. They also review the data recorded and the corresponding data acquiring tools, the management and accountability of the Investigational Medicinal Products and the site facilities associated with the clinical trial.

During inspection at a Sponsor/CRO site, inspectors review their respective activities during the clinical trial under inspection, the roles and training of their personnel, the implemented quality management system (QMS) and their Standard Operating Procedures (SOPs) related to the design and execution of the trial, including those of monitoring, compliance with agreements with clinical service providers, the procedures followed for preparation and maintenance of the Trial Master File (TMF) and the critical to quality data acquiring tools used during the trial, including their validation. The implemented safety reporting and data governance procedures are also reviewed.

Inspector access to clinical trial records and data acquiring tools is maintained until the Final Inspection Report is issued.

 

Inspection report

The Initial Inspection Report includes categorization of findings that constitute deviations from GCP and the attribution of responsibility (to Sponsor/CRO/investigator) with the relevant references to the ICH GCP Guidelines E6 (R3)/National legislation.

The Initial Inspection Report is communicated to the Sponsor/CRO and investigator for any objections or comments and the required submission of Corrective and Preventive Actions (CAPA) by them per critical or major finding. The response must be co-signed by the sponsor/CRO and investigator, if there are findings for which they share responsibility, and sent within a deadline agreed with the inspectors.

After receiving the response, the Final Inspection Report is issued containing the sponsor/CRO and investigator responses, as well as a final position of the inspectors on the submitted CAPAs.