Clinical trials of medicinal products in Estonia
Clinical trials in their modern meaning have been carried out in Estonia since many years. Both the variety of medical specialities and the annual number of submitted clinical trial applications have steadily grown. The number of study centres per protocol, being 1-2 in the early years, has also 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
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 60 days before the planned commencement of the trial at latest. 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, immunological medicinal products 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. After that the import certificate for the study medications can be applied for.
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:
- The application is to be submitted in the EU format, acceptable in English.
- The additional documents required in Estonia are listed in the Attachment 1 of the Detailed Guidance for the Request for Authorisation of a Clinical Trial on a Medicinal Product for Human Use.
- The signed declaration by the head of the health-care institution (study centre).
- State fee for evaluation of the application has to be paid in the amount of 6000 kroons, and in the amount of 250 kroons for each additional research centre (see details of the payment). The state fee has to be paid prior to the submission of the application and the proof of payment should be enclosed.
- Assessment fee has to be paid in the amount of 6000 kroons. An invoice will be sent upon receipt of the application. No payment of assessment fee should be made in advance. Please make sure that the whole amount will be credited to our account net of any charges from the issuing or receiving bank. (NEW!)
Legislation changes became into force since 1.01.2009
Ongoing clinical trials 01.03.2010
Further information about clinical trials can be obtained from:
Dr Ülle Toomiste
Phone: + 372 7 374 140
E-mail: clinical.trials@ravimiamet.ee
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