Introduction
The conduct of interventional clinical trials in Cyprus requires the submission of a Clinical Trial Application (CTA) and its relevant approval by the Drugs Council and the Cyprus National Bioethics Committee.
The Clinical Trials Department of the Pharmaceutical Services is responsible for the regulatory assessment of CTAs submitted for evaluation by the Drugs Council.
Regulation (EU) no. 536/2014 (Clinical Trials Regulation, CTR)
On January 31, 2022, Regulation (EU) No. 536/2014 on clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC, entered into application. The CTR harmonises the processes for assessment and supervision of clinical trials throughout the EU via the Clinical Trials Information System (CTIS), a European database managed by the European Medicines Agency (EMA).
Clinical trial sponsors who wish to obtain approval to conduct a clinical trial in the European Union (EU) and the European Economic Area (EEA) should submit a single CTA form and a single supporting dossier to the Member States Concerned (MSCs) electronically via CTIS.
The Regulation provides for harmonized application evaluation procedures by the MSCs (for multinational clinical trials) and a single decision per Member State with regard to the approval, or not, of the application.
The CTIS application dossier consists of two parts: Part I which includes the scientific aspects and Part II which includes of the ethical aspects.
The administrative decision takes into consideration the Drugs Council's conclusion with regard to Part I of the application and the Ethics Committee’s conclusion with regard to Part II.
More information on CTR is available HERE.
Transition Period
CTR foresees a 3-year transition period from the date of entry into application.
From 31 January 2023 onward, submission according to the Clinical Trials Regulation became mandatory for all new CTAs and, by 31 January 2025, all ongoing trials approved under the current Clinical Trials Directive will need to transition to the new Regulation and to CTIS.
Information on the transition process is available in Chapter 11 of the document Regulation EU 536/2014 - Questions and Answers.
Clinical Trials Information System (CTIS)
CTIS is the single point of entry for submitting clinical trial information in the EU and the EEA. CTIS includes a Sponsors workspace intended for clinical trial sponsors and their partner organizations, an Authorities workspace intended for EU Member States, EEA countries and the European Commission, and a public website.
More specific,
• The Sponsor secure workspace will assist clinical trial sponsors in preparing and compiling clinical trial data to submit for assessment by EU and EEA national health bodies.
• The Authority secure workspace will support the activities of EU and EEA national health bodies and the European Commission in overseeing clinical trials.
• Through the public website, members of the public can access detailed information on all clinical trials conducted in the EU and the EEA.
More information on CTIS is available HERE.
Training and support for the use of CTIS are available HERE.
The EMA online modular training program on CTIS is available HERE.
Clinical Trial Application (CTA) Dossier
The necessary documents to be submitted in CTIS with the initial CTA (initial application dossier) are listed in Annex I of Regulation (EU) No. 536/2014.
The necessary documents to be submitted in CTIS with a substantial amendment (SA) application are listed in Annex II of the Regulation.
National Requirements on Part I Application Dossier
Language Requirements
The language requirements of Cyprus for Part I documents are presented in Annex II of the document Regulation EU 536/2014 - Questions and Answers.
Good Manufacturing Practice (GMP)
The Drugs Council may apply certain derogations related to Brexit in accordance with Directive 2022/642/EC and Regulation (EU) no. 2022/641.
For CTAs that include an Investigational Medicinal Product (IMP) to be imported into Cyprus from parts of the United Kingdom other than Northern Ireland without a manufacturing/import license a relevant request should be submitted to the Drugs Council, in accordance with the Pharmaceutical Services’ circular dated 01/08/2022.
For more information with regard to Part I of the application dossier, interested parties may contact the Clinical Trials Department of the Pharmaceutical Services via e-mail at: clinicaltrials@phs.moh.gov.cy
National Requirements on Part II Application Dossier
The Cyprus National Bioethics Committee accepts the European Part II templates available on Eudralex 10 with the exception of the Patient Information and Informed Consent Form (ICF). The national ICF documents are available on CNBC’s website.
For more information with regard to Part II of the application dossier, interested parties may contact the Cyprus National Bioethics Committee via e-mail at: cnbc@bioethics.gov.cy
Fees
For new clinical trial applications (initial application and application for the subsequent addition of a Member State concerned), the applicable fee of 970.00 € should be paid via JCC (Category 15.1) through the Pharmaceutical Services website.
As provided by the applicable legislation, the 970.00 € fee constitutes the sum of fees required by the Pharmaceutical Services (170.00 €) and the Cyprus National Bioethics Committee (800.00 €) and it covers both the scientific assessment and ethical review of the application dossier.
The inclusion of the full amount payment receipt in CTIS is mandatory in order for the application to be valid.
No fees are applicable for substantial modification applications.
Safety reporting
All documents for clinical trials conducted in accordance with Regulation (EU) No. 536/2014, including Annual Security Reports (ASR), Urgent Security Measures (USM) and other safety notifications, must be submitted by sponsors to competent authorities via CTIS.
Suspected Unexpected Serious Adverse Reactions (SUSARs) are excluded from the above-mentioned procedure and must be submitted by sponsors to Eudravigilance.
More information is available HERE.
Non-commercial / Academic clinical trials
Clinical trials conducted by non-commercial sponsors (e.g. universities, hospital institutions, non-profit organizations) are subject to the same legislative provisions as commercial clinical trials.
Educational material aimed at non-commercial sponsors of clinical trials is available on the European Medicines Agency’s (EMA) website:
- CTIS for SMEs and Academia (EMA Training Module 19)
- Webinar for small and medium sized enterprises (SMEs) and academia on the Clinical Trials Regulation and the Clinical Trials Information System (CTIS)
- Dedicated training webinars detailing essential information on CTIS for micro, small and medium sized enterprises (SMEs) and non-commercial (academic) sponsors: Day 1 Day 2
Useful Documents
Quick guide for sponsors - Regulation 536/2014 in practice
CTIS – Sponsor Handbook
CTIS Newsletters
Useful Links
Clinical trials in the European Union
Eudralex 10 – Clinical Trials Guidelines
EMA – Clinical Trials in Human Medicines
Clinical Trials Coordination Group (CTCG)