Bulgaria introduces procedure for authorisation of clinical trials per EU regulation


EU Regulation No. 536/2014 of the European Parliament and of the Council of 16 April 2014 on clinical trials on medicinal products for human use and repealing Directive 2001/20/EC (Clinical Trials Regulation or CTR) harmonises the rules for the conduct of clinical trials in the EU and replaces the previous procedures in which sponsors were required to submit separate clinical-trial applications to the national competent authorities and ethics committees in each country in order to obtain regulatory approval to run a clinical trial. These proceedings have been replaced by the submission of one application dossier to all concerned member states through a single portal: the Clinical Trial Information System EU Portal (CTIS or EU portal).

EU Regulation 536/2014, which became applicable on 31 January 2022, was implemented in Bulgaria by virtue of the 2018 amendment to the Bulgarian Medicinal Products in Human Medicine Act (MPHMA). Hence, as of 31 January 31, the amended provisions of Chapter IV Clinical Trials of the MPHMA also entered into force.

A draft proposal for a new Ordinance was published in the Bulgarian Portal for Public Consultations, namely Ordinance on the terms and conditions for provision of information through the EU portal under Article 80 and access to the EU database under Article 81 of CTR. The deadline for public consultation expired on 23 March 2022, and the Ordinance will enter into force on the day of its promulgation in the Bulgarian State Gazette.

The new Ordinance further harmonises clinical trial administrative procedures with the CTR and elaborates in more detail the coordination process with the local competent authorities: the Bulgarian Drug Agency (BDA) and the Bulgarian Central Ethics Committee to the Ministry of Health (Ethics Committee).

According to the MPHMA and the new Ordinance, the BDA and the Ethics Committee are the competent authorities to access the application dossiers submitted by the sponsors through the CTIS platform, and to supervise and assess the conduct of clinical trials when the sponsor has indicated Bulgaria as a reporting member state.

According to the MPHMA and the new Ordinance, the BDA and the Ethics Committee must conduct separate assessments for compliance with the Clinical Trials Regulation. The BDA assesses all documents in the application dossiers for initial application or for substantial modification and provides parts I and II of the assessment report to the applicant through the EU portal.

The Ethics Committee conducts the ethical review of the clinical trial, considering the relevant documents under Annex I of the CTR and issues positive or negative opinion for the respective clinical trial or a substantial modification. The Ethics Committee has limited access to the relevant documents of the application dossier (for initial application and for substantial modification). The BDA consolidates its assessment with the Ethics Committee opinion and issues its decision for authorisation of the clinical trial. The sponsor will be notified of the decision through the EU portal.

Notwithstanding the above, the previous administrative procedure for submission of application dossiers for clinical trials is also still in force, and is regulated by Bulgarian Ordinance No. 31 on the good clinical practice that transposes the repealed Directive 2001/20/EC.

Hence, there are currently two parallel procedures for obtaining authorisation for conduct of a clinical trial.

The sponsors are entitled to apply for authorisation of a clinical trial in both ways: via the CTIS platform and the CTR; or directly through the Bulgarian Drug Agency (and the Central Ethics Committee) in compliance with the Directive 2001/20/EC and Ordinance No. 31 on good clinical practice.

These two options will be available for the transition period only. According to Article 98 Transitional provision, para. 2 of the CTR, sponsors have until 31 January 2023 to choose whether to submit an initial clinical trial application in line with Directive 2001/20/EC or via the CTIS.

On 31 January 2023, submission of initial clinical trial applications via the CTIS becomes mandatory, and on 31 January 2025, all ongoing clinical trials approved under the current Directive 2001/20/EC will be governed by the new Clinical Trials Regulation and must be transitioned to the CTIS. The new Ordinance indicates that if the application for authorisation of a clinical trial is filed before 31 January 2023, the clinical trial may be conducted under the previous procedure as per Directive 2001/20/EC and Ordinance No. 31 that will in this case apply until 31 January 2025.

As stated, as of 31 January 2023, clinical trial sponsors must apply for a new clinical trial using the CTIS.

For more information on clinical trials proceedings in Bulgaria, contact your CMS client partner or our local CMS experts Anna Tanova and Margarita Ivanova.