Clinical trial’ means a clinical study which fulfils any of the following conditions:
- the assignment of the subject to a particular therapeutic strategy is decided in advance and does not fall within normal clinical practice of the Member State concerned;
- the decision to prescribe the investigational medicinal products is taken together with the decision to include the subject in the clinical study; or
- diagnostic or monitoring procedures in addition to normal clinical practice are applied to the subjects.
The application dossier of a clinical trial conducted in Estonia is assessed by the State Agency of Medicines. SAM cooperates with various experts and the ethics committee. The ethics committee assesses the ethical aspects of the study, and SAM assesses the scientific and legal aspects.
Ongoing Clinical Trials
More information on clinical trials
As of 31.01.2023, the application process of a clinical trial for a medicinal product will take place via single European portal CTIS. More information on the directly applicable Regulation No 536/2014 on clinical trials can be found here.
In Estonian legislation clinical trials are regulated by the Medicinal Products Act (Chapter 5) and the relevant regulations. Further information on Estonian legislation can be found on SAM website in the relevant section.
Sponsor means an individual, company, institution or organisation which takes responsibility for the initiation, for the management and for setting up the financing of the clinical trial.
A clinical trial may be conducted by a doctor or a dentist registered with the Health Board within the limits of their competence. Each trial site must have a principal investigator who ensures that the trial conducted at that site fulfils the requirements and who is the contact person for communication with the Agency.
Substantial modification means any change to any aspect of the clinical trial which is likely to have a substantial impact on the safety or rights of the subjects or on the reliability and robustness of the data generated in the clinical trial.
More detailed information on substantial modifications with examples can be found in Annex IV (Classification of changes to ongoing clinical trials) of the European Commission's Eudralex vol 10 Questions and Answers Document - Regulation (EU) 536/2014.
An activity licence holder (according to the Medicinal Products 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: [email protected]
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.
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.
The Medicinal Products Act allows both: direct distribution to investigation sites and through a wholesale 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.
The Agency inspects clinical trials on a risk basis to ensure the rights, safety and well-being of trial subjects and the reliability of trial data. A clinical trial inspection assesses whether the trial is being conducted in accordance with the protocol, Good Clinical Practice and applicable legislation.
As a general rule, the Agency will give advance notice of clinical trial inspections, except in cases of presumed non-compliance, where advance notice may jeopardise the achievement of the purpose of the inspection.
An inspection consists of different parts: an opening and closing meeting, a tour of the inspected facility/centre, interviews with the inspected persons and a review of documentation.
Non-compliances identified during the inspection are divided into three categories: critical, significant or minor. In addition, the inspector may make observations in order to improve the quality of the trial or to reduce the occurrence of potential findings in the future.
Following the inspection, the inspector prepares an inspection report, which contains a description of the factual situation examined during the inspection and the nonconformities found. In the case of non-compliances, the inspector shall set a deadline for the submission of an action plan for preventive and corrective action and shall assess the suitability of the plan submitted. The end of the inspection will be notified when the report is complete and, where appropriate, a suitable action plan has been submitted.
The inspector has the power to issue an injunction to remedy the non-compliance (including the imposition of a penalty payment in case of non-compliance), to initiate misconduct proceedings, to carry out a follow-up inspection or to propose the suspension/termination of the clinical trial.
The Agency may appoint inspectors to accompany colleagues from the Agency and, where necessary, involve suitably qualified external experts.
Where the Agency participates in inspections of clinical trials related to the centralised marketing authorisation procedure coordinated by the EMA, the inspection will be conducted in accordance with the guidance of the European Commission and the EMA, the Good Clinical Practice, the Declaration of Helsinki and the applicable local and international legislation.
An academic clinical trial is a clinical trial that is not funded for commercial purposes by a pharmaceutical or biotechnology company, but by public bodies or institutions (usually universities or medical foundations). Academic clinical trials often focus on optimising and complementing existing treatments: for example, assessing how combining authorised medicines could improve treatment outcomes, or investigating whether an authorised medicine could be used for a different indication. Academic studies are usually initiated by medical researchers or academic research organisations.
Academic drug trials are generally subject to exactly the same requirements as any study initiator. However, there are certain exceptions for academic studies concerning the payment of specialised assessment fees and insurance.
Information on how to apply for a clinical trial can be found under the heading "Clinical trial application procedure".
EXEMPTION FROM THE SPECIALISED ASSESSMENT FEE:
Medicinal Products Act § 997 (3):
The State Agency of Medicines exempts the sponsor from the obligation to pay the specialised assessment fee where all of the following criteria are met:
1) the sponsor has submitted a respective application;
2) the sponsor of the clinical trial of the medicinal product is a health service provider holding a valid activity licence, an independent research institution or a professional organisation of doctors;
3) a person or institution specified in clause 2 of this subsection does not receive any financial or other remuneration from the manufacturer of the medicinal product or from a representative thereof.
For academic research, no additional (private) insurance cover is needed if the subject is already insured by the Health Insurance Fund:
Health Insurance Act § 26 (7):
The Health Insurance Fund has a right of recovery against the sponsor of a research study if the insured person's need for health insurance benefits arises in connection with participation in a research study, unless the study is a clinical trial of a medicinal product or a medical device and the sponsor of the study is exempt from the professional evaluation fee pursuant to section 997(3) of the Medicinal Products Act.
As of 20.10.2016, clinical data submitted by pharmaceutical companies to the European Medicines Agency (EMA) for marketing authorisation are accessible, including information on the methods used and the results of trials. The disclosure of the data will allow more information on the background to the marketing authorisation of the medicinal products to be obtained, and will allow researchers to use the data more easily for independent analysis.
If genetically modified organisms are used in the clinical trial, SAM will ask for an expert opinion from the Gene Technology Committee.
In terms of EU-regulation for clinical trials, a medical device can play a role in different contexts:
- The object of the study is one integral product which is a 'combination' of a medical device and a medicinal product: In these cases, firstly the regulatory status of this product (either medicinal product or medical device) needs to be determined in accordance with the definitions in the applicable legislation. If this assessment reveals that the product which is the object of the study is a medicinal product, the regulatory framework of the Clinical Trials Regulation applies. If this assessment reveals, however, that the product which is the object of the study is a medical device, the Clinical Trials Regulation does not apply. For example, in the case of a prefilled syringe, this product would usually be a medicinal product (with an integral 'delivery product'). An interventional study would be a clinical trial and thus fall within the regulatory framework of the Clinical Trials Regulation.
- The object of the study is a medicinal product - however, during the clinical trial medical devices are used (this is frequently the case in practice; sometimes the medical devices are supplied by the sponsor) without these being the object of study: In these cases, the Clinical Trials Regulation applies. The medical devices not being object of the study have to comply with the EU-rules for the placing on the market and putting into service of medical devices.
- The object of the study is two separate products: one is a medicinal product and one is a medical device. These two separate products may be administered/used on subjects in the same group ('arm'), or in different 'arms' (for example, a study might compare a warming medical device applied on the skin with a warming medicinal product applied topically). In these cases the Clinical Trials Regulation applies to the aspect of the study having the medicinal product as the object of the study.Regarding the medical device being the object of the study, the Clinical Trials Regulation does not apply, but the EU-rules applicable to medical devices would apply.
In Estonia, Health Board is the competent authority in the field of medical devices: [email protected].
Last updated: 06.03.2023