Frequently asked questions (FAQ) - Clinical investigations of medical devices
1. How do I demonstrate a medical device's compliance with regulatory requirements regarding clinical evaluation?
In general, demonstrating compliance with general safety and performance requirements should include a clinical evaluation based on the assessment of clinical data (Article 5, Regulation (EU) 2017/745 - hereinafter MDR).
Clinical evaluation is a systematic and planned process to generate, collect, analyze, and evaluate clinical data regarding a device, with a view to verifying its safety and performance, including clinical benefit, when used as intended by its manufacturer.
2. What is clinical data?
Clinical data is understood to be information relating to the safety and/or performance obtained from the use of a device.
This information may come from clinical investigations, clinically relevant information from post-marketing clinical follow-up, or other studies contained in the scientific literature of a similar device, provided that its equivalence to the device in question can be demonstrated. It may also originate from published or unpublished reports on other clinical experiences, either with the device in question or with a similar device whose equivalence to the device in question can be demonstrated.
3. What is the legislation applicable to clinical investigation of medical devices?
Essentially, the rights and duties of investigators, sponsors, and the National Competent Authority are covered in Regulation (EU) 2017/745, as currently amended, which is supplemented by Law Nº. 71/2025 of 22 December, which implemented Regulations (EU) 2017/745 and 2017/746 in the part relating to clinical investigations and performance studies of medical devices in the national legal order.
4. What is a medical device for clinical investigation?
A medical device subject to evaluation within the scope of a clinical investigation that must meet the applicable general safety and performance requirements referred to in Annex I, except for aspects that are the subject of the clinical investigation. However, with regard to the aspects under investigation, it must be demonstrated that all necessary precautions have been taken to protect the health and safety of the participants.
5. Can I conduct clinical investigation of medical devices with retrospective data?
In retrospective studies, the involvement of human beings and their exposure to the device precedes the study itself, as the data has already been generated. This implies that the retrospective analysis of such data has no impact on patient management and the study does not introduce additional risks to the patient. Therefore, they are outside the scope of application of the MDR. However, they will remain subject to compliance with applicable requirements under the national legal framework, Law No. 21/2014.
6. Where can be conducted clinical investigation of medical devices?
Clinical investigations of medical devices should be carried out in health facilities (public and private), laboratories or other entities having the appropriate materials and human resources.
7. How to submit a clinical investigation of medical devices to Infarmed?
Regarding clinical investigations of experimental devices, conducted for conformity assessment purposes, the sponsor must plan and prepare the documentation referred to in Annex XV, Chapter II. Complete the Application Form / Clinical investigation - application form under Medical Device Regulation MDCG_2021-8, available on the European Commission website.
If applicable, pay the fee according to the national legal framework, and attach proof of payment and the corresponding payment slip to the documentation to be submitted.
Submit the application to conduct the clinical investigation of devices to INFARMED, I.P., as established in the Regulation, accompanying it with the necessary documentation (preferably organized according to the defined folder structure).
8. Is it necessary to submit the application to conduct the clinical research to an Ethics Committee as well?
In clinical investigations of medical devices, the competent Ethics Committee is the National Ethics Committee for Clinical Research (CEIC). In Portugal, one of the major changes brought about by the application of the Regulation relates to the internal organization into Member State that ensures coordination with the ethics committee, guaranteeing the evaluation of applications, in accordance with the Regulation, in all their aspects, within the established deadlines, with a single decision on a single process.
The application should be addressed only to Infarmed, which is subsequently responsible for the necessary coordination with CEIC for ethical evaluation.
9. How to submit an application for authorization/notification of a clinical investigation of medical devices to Infarmed?
Until EUDAMED is available in its fully functional version, applications and notifications relating to clinical investigations in Portugal must be submitted through RNEC. The application must be addressed to Infarmed.
10. What documents must be submitted to Infarmed?
The application for conducting an investigation must follow the guide DOCUMENTAÇÃO PARA SUBMISSÃO - Investigações clínicas de dispositivos ao abrigo do Regulamento (UE) 2017/745 - INFARMED, I.P.-CEIC, which must be correctly completed and submitted together with the documentation indicated therein, and provided for in Annex XV, Chapter II. (see Information for the Sponsor)
11. What is the "clinical investigation plan/protocol" for clinical studies with medical devices?
In Annex XV, the RDM defines "clinical investigation protocol or plan" (CIP) as the document that must establish the rationale, objectives, methodology of design, monitoring, execution, record keeping, and method of analysis of the clinical investigation. It must contain the information indicated in the aforementioned annex. If part of this information is presented in a separate document, the CIP must refer to it.
12. Can medical devices without CE marking be subjected to clinical investigation?
Yes. Even if they do not bear the CE marking, devices intended for clinical investigation may be made available to physicians or other professionals authorized for this purpose, provided they meet the conditions established in Chapter VI and Annexes I, XIV and XV, of MDR.
13. clinical investigations of medical devices with CE marking must be submitted to Infarmed?
Yes. The RDM (Medical Device Regulation) stipulates that post-marketing clinical follow-up investigations must be notified to the Member States where they are intended to be conducted.
14. What safety information should I collect and report as part of clinical investigations of medical devices?
Any adverse events identified as critical to the investigation in the CIP, all serious adverse events and device defects that could have led to serious adverse events if no measures had been taken to prevent them, must be fully collected and recorded by the sponsor.
From this information, the sponsor must immediately communicate to all Member States where the clinical investigation is being conducted any serious adverse events with a causal relationship to the experimental device, the procedure or the comparator, or where such a causal relationship is reasonably possible; any device defects that could have led to a serious adverse event if adequate measures had not been taken, if an intervention had not been performed, or if circumstances had been less favorable; and any new data relating to these events.
In Portugal, notification is made, through the RNEC (National Register of Clinical Follow-ups), to Infarmed (National Authority of Medicines and Health Products), until EUDAMED is fully available.
15. An authorization to conduct an interventional clinical study of medical devices may be suspended or revoked?
Infarmed may order the suspension, revocation, or modification of a clinical investigation of medical devices, under the terms of Article 76 of the MDR, whenever the requirements of the regulation cease to be met and/or if the existence of an anomalous situation is proven, the seriousness of which calls into question the basis of the clinical investigation itself, namely for reasons of patient and/or device user safety.
16. The sponsor of a clinical investigation of medical devices may be someone other than the manufacturer of the devices (eg.: a hospital, a centre for biomedical research, the investigator, etc.)?
A "sponsor" is understood to be a person, company, institute, or body responsible for initiating, managing, and creating financing mechanisms for clinical investigation Thus, the sponsor may be the manufacturer, if the studies are for commercial purposes, or another entity, including the investigator himself, in studies with non-commercial purposes. When the sponsor is not established in the Union, they must ensure that a person established in the Union is their legal representative, essentially ensuring that all the sponsor's obligations are known and fulfilled by them. The responsibilities expected of this legal representative can be found in MDCG 2021-6.
17. Clinical investigations of medical devices are required to pay fees?
Yes. According to Article 38 of national Law Nº. 71/2025 of December 22, with the exception of non-commercial clinical trials, as well as in cases where the sponsor is the investigator, fees are payable when submitting an application/ notification of clinical investigation of medical devices. Additional information can be found here.
18. Is the refunding of fees possible?
Article 4 of Ordinance No. 63/2015 of March 5 provides that, in the case of a non aproval decision of the clinical study, it should be returned 90% of the paid fees to the sponsor, retaining 10% of this value for administrative costs.
19. The submission of a clinical investigation of medical devices to CEIC requires the authorization of the managment board of the investigation site?
The authorization of the board may be waived by the existence of the final version, or a draft, of the financial contract, since the submission of this document assumes that there have been negotiations with the site as well as acceptance by the board for conducting the study.
20. Is the existence of a "coordinating investigator" mandatory?
No. The existence of a coordinating investigator is not mandatory, even in multicentre studies.
21. The epidemiological studies with medical devices on oral health/diseases, or the retrospective studies whose purpose is to assess the partial or total prosthetic rehabilitation of patients, require approval by the CEIC?
Clinical studies always require a favorable opinion from a competent ethics committee, which will be the health ethics committee (CES) of the study center or, if this center does not have a CES, the ECI or the CES designated by it, in the case of non-intervention studies.
According to the type of study, the competent ethics committee will be the ethics committee for health of the institution. If the ethics committee of the investigation site is not an ethics committee for health, as set by Law Nº. 97/95 of May 10, then the study should be evaluated by the CEIC.
22. What is the EUDAMED number or CIV-ID?
The RDM establish that each IC must be identified by a unique clinical investigation identification number valid throughout the Union. When EUDAMED is fully operational, this code will be automatically generated upon submission of your application. Until then, it is the responsibility of the first competent authority to which the IC application is submitted to generate this code.
If Portugal is the first Member State where you will submit your application, no prior action is required; simply inform us in the cover letter and application form that the CIV-ID (Clinical Investigation Identification Number) will be generated during the validation phase of the process.
