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Clinical trials of medicinal products in Estonia

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Clinical trials in their modern meaning have been carried out in Estonia since early 1990s. The variety of medical specialities (2019) and the annual number of submitted clinical trial protocols have steadily increased over the last two decades but the growth has stalled in the recent few years. The government and the indusrty are constantly working to improve the clinical research environment in Estonia. The number of study centres per protocol, being 1-2 in the early years, has grown as the research has reached out from the tertiary care to the county hospitals and GP-s. Most of the trials are Phase III and II, but also a few pharmacokinetic and bioequivalence studies are carried out each year.

The clinical trials are regulated by the Medicinal Products Act and in more detail by the regulations of the Minister of Social Affairs:
Conditions and Procedure for Conducting Clinical Trials of Medicinal Products*
Procedure for reporting serious adverse events occurring in clinical trials
Rules of procedure of medical ethics committee for clinical trials, a list of data to be submitted for obtaining approval, procedure for adoption of resolutions and format of application for obtaining approval
Information to Sponsors of Clinical Trials - Reporting requirements of SUSARs

The regulation of clinical research is in full compliance with the respective EU legislation.
In general terms, approval by one of the two Independent Ethics Committees and informed consent by the study subject, according to the international codes and Declaration of Helsinki, is mandatory. Clinical trial medication should be manufactured according to the GMP (Good Manufacturing Practice) and the trials should be performed and the data generated in compliance with the GCP (Good Clinical Practice) to ensure the ethical and scientific integrity of the trial (GCP code close to the Nordic document by the NLN was mandatory since 1991, later the ICH GCP was adopted and is currently directly referred to by the legislation).

Notification of the clinical trial needs to be submitted to the State Agency using the EudraCT format. A formal letter of ‘no objection’ will be given within 30 days for phase II – IV studies (for phase I studies within 60 days and  for gene therapy or somatic cell therapy or medicinal products containing genetically modified organisms within 90 days after receipt of the application and required documentation). The time taken by the Agency depends directly on the quality and completeness of the documentation submitted. Please note that together with the notification, a signed declaration by the head of the health-care institution (study centre) has to be submitted.

An activity licence holder (according to the Medicinal Product Act § 18) can import medicinal products intended for clinical trials after the clinical trial has been approved by the State Agency of Medicines.

The State Agency of Medicines shall be duly notified of conveyance of medicinal products from the European Economic Area to Estonia. This notification should be done as soon as possible but no later than on the fifth working day after the consignment has arrived. The notification should include: date of import, information about the consignor and the consignee, information about the investigational medicinal products.
Please send your notifications through the Client Portal.

With regards to import from outside the European Economic Area directly to Estonia:

  • The importer (located in Estonia) should have a MIA – manufacturing/importation authorisation (activity licence).  MIAs are granted by the State Agency of Medicines.  The manufacturing/importing authorisation and the qualified person's declaration equivalence to EU GMP for Investigational Medicinal Products manufactured in third countries should be submitted with request for clinical trial authorisation to the State Agency of Medicines.
  • For each consignment to be imported, the importer should obtain a single authorisation for import/permission from State Agency of Medicines. Without this document the medicines cannot pass the necessary Customs’ procedures. Therefore it is important to obtain the single authorisation for import before the consignment arrives.

Please send your applications to: info@ravimiamet.ee

When exporting investigational medicinal products from Estonia to countries within or outside the European Economic Area, notification of export should be sent to the State Agency of Medicines. See details of notification above.

If a medicinal product is listed as a narcotic drug or psychotropic substance in the Annex I of the Regulation No. 73 of the Minister of Social Affairs of 18 May 2005 then it shall be imported and exported under the conditions and pursuant to the procedure provided for in the Medicinal Products Act (RT I 2005, 2, 4; 13, 63; 24, 180) and in legislation established on the basis thereof.


Medicines used in clinical trials and the requirement to verify safety features

According to the European Commission Delegated Regulation (EU) 2016/1612 article 25 section 4c, pharmacies are required to verify and decommission the unique identifier of medicines (whether investigational or auxiliary) with marketing authorisations used in clinical trials.  According to the European Commission Guidelines, authorised investigational medicinal product is excluded from the rules on the safety features only if it is known at the time of manufacture that the whole batch is manufactured for use in clinical trials.

What to take into account when supplying investigational products?

The Medicinal Products Act allows both: direct distribution to investigation sites and  through a wholsale distributor. The wholesale distributor is not required to verify the authenticity of authorised medicinal products used in clinical trials. Therefore, the sponsor may have various ways to arrange for the verification and decommission of safety features:

  • If at the investigational site, the hospital pharmacy is in charge of handling the medicinal products, then the pharmacy is also responsible for the verification and decommissioning of the unique identifier.
  • If the auxiliary medicinal products used in clinical trials are bought from a general pharmacy, then this general pharmacy will bear that responsibility.
  • If the medicinal products are distributed directly to the investigation site but the investigation site lacks a pharmacy, then it is possible to verify and decommission the unique identifier using The Estonian Medicines Verification Organisation’s (REKS) web-based solution. Further information regarding this option can be found on their website.


GMO requirements in clinical trials

In order to use Genetically modified organisms as IMPs in clinical trials, it is necessary to obtain permission from both the State Agency of Medicines and the Commission of Gene Technology. The applicant must submit the usual Clinical trial application dossier together with the GMO common application form. SAM will then forward all relevant documents to the Commission of Gene Technology for assessment. The decision of approval/non-approval will be made within 90 days and communicated to the sponsor by SAM.

An overview of GMO-related requirements in clinical trials in the European Union:

National regulation (No English translation available):


Estonia has endorsed the following documents regarding the use of GMOs in clinical trials:

Good Practice document (for assessment of genetically modified cells with retro/lentiviral vectors):

Common application form (for genetically modified cells with retro/lentiviral vectors):

Q&A: https://ec.europa.eu/health/sites/health/files/files/orphanmp/doc/2018_qa_atmps_en.pdf


The substantial amendments to the protocol and changes to the study conduct need to be submitted to the Agency in written format together with XML-file on disk (CD-ROM) for EudraCT. If written receipt confirmation is needed, this should be clearly stated and the respective form filled out (digital signature is accepted) and submitted together with the amendment.

International standards of safety reporting apply: all suspected unexpected serious adverse reactions from any country should be reported by the sponsor in accordance with ICH E2A, the CIOMS form is preferable.
The Agency has the right to inspect all aspects of a clinical trial as well as the performance of the Ethics Committees. The first GCP inspections were carried out in 1999, currently there is a for-cause inspection policy. Several international inspections by both the EMEA (European Medicines Agency) and the FDA (US Food and Drugs Administration) teams have been carried out in Estonia. The Agency participates in all inspections as an observer and expects to be notified of any planned foreign inspection in Estonia by the sponsor.
Documents required with clinical trial notification:

*  Guidance on clinical trial management in the context of COVID-19 pandemic (updated 07.10)

Coordinated assessment of multinational CTAs through the Voluntary Harmonisation Procedure (VHP)

Further information about clinical trials can be obtained from:
Phone: + 372 737 4140
E-mail: clinical.trials@ravimiamet.ee