Clinical evaluation is defined as a systematic and planned process to continuously generate, collect, analyse and assess the clinical data pertaining to a device in order to verify the safety and performance, including clinical benefits, of the device when used as intended by the manufacturer.
Before placing a medical device on the market, the manufacturer of the device must provide a clinical evaluation as part of the device’s technical documention. Clinical evaluation is based on the clinical data available and demonstrates that clinical benefits of the device outweigh the potential risks for the user. The evaluation is usually done by proving equivalence with a similar device already placed on the market. Clinical evaluation must be thorough and objective, and take into account both favourable and unfavourable data.
Additional details regarding the clinical evaluation can be found in Regulation (EU) 2017/745 also known as MDR (Medical Device Regulation) Article 61 and Annex XIV.
In case available clinical data is insufficient to demonstrate the safety, efficacy, and appropriate benefit-risk ratio of the device, a clinical investigation must be performed with the device.
Clinical investigation is defined as a systematic investigation involving one or more human subjects, undertaken to assess the safety or performance of a device.
Several modifications regarding clinical investigations were introduced since the MDR entered into force. Various types of clincal investigations have been defined for which different regulatory requirements have been established. The procedure for conducting clinical investigations has been determined in Chapter VI and Annex XV of the MDR.
In addition to the requirements set in the MDR, additonal national provisions for conducting clinical investigations can be found in the § 211 - 222 of the Medical Devices Act. To aid in the interpretation of the MDR, the European Commission and the Medical Device Coordination Group have published several guidances.
You can learn more about the principles of regulation in the field of medical devices on the Regulation in the field of medical devices in Estonia subpage.
CLINICAL INVESTIGATIONS WHICH REQUIRE AN APPLICATION:
- Pre-market clinical investigation (without CE-marking) or CE-marked device used outside their intended purpose
- Introducing substantial modifications to an already ongoing clinical investigation
NB! Fees are applied for the application submission of a clinical investigation or a substantial modification. Fee rates and payment procedures can be found on the Fees page. Be aware that there are two types of fees to be paid, the State fee and a fee payable directly to the State Agency of Medicines.
CLINICAL INVESTIGATIONS which require a notification:
- Post-market clinical investigation with a CE-marked device within the scope of its purpose, where the investigation would involve submitting subjects to additional procedures considered invasive or burdensome.
For other clinical investigations not performed pursuant to any of the purposes listed in the Article 62 (1) of the MDR, additional national provisions can be found in the Medical Devices Act § 222.
Sponsors of a clinical investigation are obliged to submit a clinical investigation report to the State Agency of Medicines within one year from the end of the clinical investigation or within three months from the early termination or temporary halt of the clinical investigations conducted in Estonia. The clinical investigation report is accompanied by a summary presented in terms that are easily understandable to the intended user. Clinical investigation reports and their summaries can be found here.
Before placing an in vitro diagnostic medical device (IVD) on the market, the manufacturer of the device must specify and justify the level of the clinical evidence to demonstrate conformity with the relevant general safety and performance requirement. For this, the manufacturer plans, conducts and documents a performance evaluation.
Additional details regarding the performance evaluation can be found in Regulation (EU) 2017/746 also known as IVDR (In Vitro Diagnostic Medical Device Regulation) Article 56 and Annex XII part A.
In case available clinical data is insufficient to demonstrate the conformity with the relevant general safety and performance requirements, a performance study must be performed with the device.
A performance study is defined as a study undertaken to establish or confirm the analytical or clinical performance of a device. The procedure for conducting performance studies has been determined in Chapter VI, Annex XIII part A, and Annex XIV of the IVDR.
In addition to the requirements set in the IVDR, additonal national provisions for conducting performance studies can be found in the § 211 - 222 of the Medical Devices Act (MDA). To aid in the interpretation of the MDR, the European Commission and the Medical Device Coordination Group have published several guidances.
You can learn more about the principles of regulation in the field of medical devices on the Regulation in the field of medical devices in Estonia subpage.
Performance studieS WHICH REQUIRE AN APPLICATION:
- Performance study in which surgically invasive sample-taking is done only for the purpose of the performance study
- An interventional clinical performance study where the test results may influence patient management decisions and/or may be used to guide treatment
- Performance study where the conduct of the study involves additional invasive procedures or other risks for the subjects of the studies
- Performance studies involving companion diagnostics (excluding studies where only left-over samples are used)
- Introducing substantial modifications to an already ongoing performance study
NB! Fees are applied for the application submission of a clinical investigation or a substantial modification. Fee rates and payment procedures can be found on the Fees page. Be aware that there are two types of fees to be paid, the State fee and a fee payable directly to State Agency of Medicines.
performance studieS WHICH REQUIRE A notification:
- Performance study involving companion diagnostics where only left-over samples are used
- Post-market performance study with a CE-marked device within the scope of its purpose, where the investigation would involve submitting subjects to additional procedures considered invasive or burdensome
- Other performance studies as defined in the MDA § 222
Sponsors of a performance study are obliged to submit a performance study report to the State Agency of Medicines within one year from the end of the performance study or within three months from the early termination or temporary halt of the performance study conducted in Estonia. The performance study report is accompanied by a summary presented in terms that are easily understandable to the intended user.
Ethics Committee Assessment
As of 1st of October 2025, a new version of the Medical Devices Act has entered into force, under which the ethical evaluation of clinical investigations of medical devices and performance studies of in vitro diagnostic medical devices has been brought under the Ethics Committee operating at the State Agency of Medicines. The new procedure is also specified in the regulation “Ethics Committee for Clinical Investigations”, which entered into force on 1st of October 2025, and the related fees are laid down in the regulation “Chargeable Services Related to the Conformity Assessment Bodies and Studies of Medical Devices”.
The new system reduces the administrative burden of the procedure, and a clear and efficient organizational framework ensures that all ethical assessments of clinical investigations and performance studies are carried out transparently and in a coordinated manner through the State Agency of Medicines.
Under the previous system, the sponsor had to take into account longer processing times and a greater administrative burden, as it was necessary to obtain a positive opinion from the ethics committee before submitting an application to the State Agency of Medicines. With the implementation of the new act, the ethical evaluation of medical device studies will be conducted by the Ethics Committee for Clinical Investigations of Medicinal Products at the State Agency of Medicines, which allows:
submission of a single application to the State Agency of Medicines, which coordinates both the scientific and ethical evaluation processes;
a single payment, with remuneration distributed internally (including through contracts with members of the ethics committee);
shorter processing times and less need to manage parallel processes;
clearer administrative capacity for the State Agency of Medicines, as both areas (medicinal products and medical devices) fall under the competence of one authority.
Q&A
In the European Union, two regulations apply to medical devices — (EU) 2017/745 (MDR) and, for in vitro diagnostic medical devices, (EU) 2017/746 (IVDR). In Estonia, clinical investigations and performance studies are additionally regulated by the Medical Devices Act (MDA).
For medical devices, the MDR applies and the study is referred to as a clinical investigation. Based on the MDR, the applicable type of clinical investigation can be defined as follows:
Article 62 investigations
Article 74 investigations
Article 82 investigations: all other clinical investigations not covered above. Additional requirements for conducting other medical device clinical investigations are described in §221 of the Medical Devices Act.
For in vitro diagnostic devices, the IVDR applies and the study is referred to as a performance study. The IVDR also defines several types of performance studies:
Article 58(1) studies
Article 58(2) studies
Article 70(1) studies
Article 70(2) studies
Requirements for studies not falling under the above categories are described in §222 of the Medical Devices Act.
An authorisation from the State Agency of Medicines is required for:
MDR Article 62 investigations
MDR Article 82 investigations
IVDR Article 58(1) studies
IVDR Article 58(2) studies, except studies using only residual samples
IVDR Article 70(2) studies
A notification must to The State Agency of Medicines must be submitted for:
MDR Article 74 investigations
IVDR Article 58(2) studies investigating a companion diagnostic device using only residual samples
IVDR Article 70(1) studies
All other IVDR studies not falling under Article 58 or 70 that interfere with the integrity of a human, human embryo, or fetus
NB. The Agency must be notified of the intention to conduct studies requiring notification at least 10 days before the study begins. Notification must be sent to the Medical Devices Department's general email: [email protected]. No state fees or charges apply for notification.
The application process for a clinical investigation or performance study licence consists of the following steps:
Preparation of the relevant documents
Payment of the state fee and the State Agency of Medicines' expert assessment fee
Submission of documentation to the State Agency of Medicines and obtaining a positive opinion from the ethics committee
1. Preparation of the relevant documents
Before starting the application process, the sponsor must prepare the application and all required documentation. The study documentation and its content are described in both the MDR and IVDR according to the study type. The following guidelines are helpful:
For medical devices within the scope of the MDR: MDCG guidance "MDCG 2021-8 Clinical investigation application/notification documents";
For in vitro diagnostic devices: MDCG guidance "MDCG 2022-19 Performance study application/notification documents under Regulation (EU) 2017/746".
2. Payment of fees
To submit an application, the sponsor must pay two types of fees:
State fee of €210 — stipulated in §2853(1) of the State Fees Act.
This payment is made to the State Agency of Medicines. No invoice is issued for this payment and the sponsor may pay at their convenience.
State Agency of Medicines fee according to the type of study being conducted.
Fees are set out in §3 and §4(1) and (2) of the regulation "Fee-based services related to medical device conformity assessment bodies and studies." An invoice will be issued for this fee. To issue the invoice, the Agency requires the following information from the sponsor:
Company name;
Registration code;
Legal address;
Contact details (email address, phone number, and name of contact person);
The type of fee the sponsor is applying for.
The invoice is issued to the contact person within 10 days of submitting the application and must be paid within 40 days of the invoice date.
Submission of application and documents to the State Agency of Medicines
The application, together with all relevant documents, is submitted to the Medical Devices Department's general email: [email protected]. The Medical Devices Department also forwards the documents to the ethics committee, which reviews the application and provides its opinion on the conduct of the study. A positive opinion from the ethics committee is a prerequisite for starting the study.
As of 1 October 2025, a new version of the Medical Devices Act came into force, bringing the ethical review of medical device clinical investigations and in vitro diagnostic medical device performance studies under the ethics committee operating at the State Agency of Medicines.
The application, together with all relevant documents, is submitted to the Medical Devices Department's general email: [email protected]. The Medical Devices Department forwards the documents to the ethics committee, which reviews the application and provides its opinion — meaning all documents submitted by the sponsor to the Medical Devices Department are forwarded to the ethics committee and no separate forms need to be submitted to the ethics committee. If the ethics committee requests additional documents, the sponsor will be notified.
The application and accompanying documents may be prepared in either Estonian or English, with the exception of documents used to obtain informed consent, which must be prepared in the study participant's native language.
When planning changes, it should first be established whether the change(s) constitute a substantial or non-substantial modification. Substantial modifications are those likely to have a significant impact on the safety, health, or rights of study participants, or on the reliability or robustness of the data collected during the study. Anything that does not qualify as a substantial modification may be considered a non-substantial modification.
A non-exhaustive list of examples of substantial modifications can be found in Annex II of the guidance documents "MDCG 2021-6 Regulation (EU) 2017/745 – Questions & Answers regarding clinical investigation" and "MDCG 2025-5 Questions & Answers regarding performance studies of in vitro diagnostic medical devices under Regulation (EU) 2017/746".
For substantial modification(s), the sponsor must submit an application to the State Agency of Medicines and all relevant documents regarding the substantial modification to the Department of Medical Devices at [email protected]. The application form for substantial modifications to clinical investigations can be found in the guidance "MDCG 2021-28 Substantial modification of clinical investigation under Medical Device Regulation," and the equivalent form for performance studies can be found in "MDCG 2022-20 Substantial modification of performance study under Regulation (EU) 2017/746".
The Department of Medical Devices forwards the documents to the ethics committee, which reviews the application and provides its opinion — meaning all documents submitted by the sponsor to the Department of Medical Devices are forwarded to the ethics committee and no separate forms need to be submitted to the ethics committee. If the ethics committee requests additional documents, the sponsor will be notified. In addition, the sponsor must pay the fee for the professional assessment of a significant change to a clinical trial or performance study, as set out in §5 of the “Paid services related to medical device conformity assessment bodies and studies”. To issue an invoice, the sponsor must submit the following information to the State Agency of Medicines:
Name of the clinical investigation or performance study in which the substantial modification is being made;
Number of modifications;
Name of the legal entity;
Registration code;
Legal address;
Contact person's name, email, and phone number.
Last updated: 23.04.2026
