Medical devices – Health, innovation and research institute

1. General information

Please be informed that as of 26 May 2021, the European Regulation (EU) 2017/745 on Medical Devices (MDR) came into force.

The MDR introduces a major update of the regulatory framework in the European Union and brings several changes to the scope of investigations that must be submitted for approval, the submission processes for clinical investigations and their substantial modifications, submission dossier contents and safety reporting.

1.1. Definitions

All definitions provided in this section are compliant with the definitions stated in the Medical Device Regulation 2017/745.

1.2. Medical Device

Any instrument, apparatus, appliance, software, implant, reagent, material or other article intended by the manufacturer to be used, alone or in combination, for human beings for one or more of the following specific medical purposes:

diagnosis, prevention, monitoring, prediction, prognosis, treatment or alleviation of disease,
diagnosis, monitoring, treatment, alleviation of, or compensation for, an injury or disability,
investigation, replacement or modification of the anatomy or of a physiological or pathological process or state,
providing information by means of in vitro examination of specimens derived from the human body, including organ, blood and tissue donations,

and which does not achieve its principal intended action by pharmacological, immunological or metabolic means, in or on the human body, but which may be assisted in its function by such means.

The following products shall also be deemed to be medical devices:

devices for the control or support of conception;
products specifically intended for the cleaning, disinfection or sterilisation of devices as referred to in MDR Article 1(4) and products listed in Annex XVI of the MDR.

Examples: bandages, sutures, wheelchair, hospital bed, dentist mouth mirror, dental filling materials, heart rate monitor, blood pressure monitor, ECG device, EEG device, scalpel, needles, hearing aid, glasses and lenses, stents, blood bags, condoms, implants, catheters, defibrillator, eHealth app,…

Please note that when a medical device is in the development phase, for example a prototype, the prototype may be tested on subjects in order to validate certain parts of the medical device. Although the prototype may not fulfill its intended medical purpose yet, the product nevertheless already qualifies as a medical device, since that is the potential aim of the product.

1.3. Custom-made devices

Any device specifically made in accordance with a written prescription of any person authorised by national law by virtue of that person’s professional qualifications which gives, under that person’s responsibility, specific design characteristics, and is intended for the sole use of a particular patient exclusively to meet their individual conditions and needs.

However, mass-produced devices which need to be adapted to meet the specific requirements of any professional user and devices which are mass-produced by means of industrial manufacturing processes in accordance with the written prescriptions of any authorised person shall not be considered to be custom-made devices.

1.4. In-house device

A medical device manufactured or modified in-house by health institutions to address, on a non-industrial scale, the specific needs of target patient groups which cannot be met at the appropriate level of performance by an equivalent device available on the market. They must comply with the rules laid out in Article 5.5 of Regulation (EU) 2017/745.

1.5. CE-marking or CE marking conformity

Belgium.be: CE label

A marking by which a manufacturer indicates that a device is in conformity with the applicable requirements set out in the Regulation and other applicable Union harmonisation legislation providing for its affixing.

1.6. Clinical investigation

Any systematic investigation involving one or more human subjects, undertaken to assess the safety or performance (including clinical benefits) of a medical device.

All clinical investigations evaluating a medical device without CE-marking or which is used outside the scope of its CE-marking, an opinion from both the Medical Ethics Committee (MEC) and/or Federal Agency for Medicines and Health Products (FAMHP) is mandatory.

Depending on the status of the investigational medical device and the reason for collecting the study data, the submission procedure can differ. For more detailed information the ‘Guideline on Submission Processes of Clinical Investigations according to MDR in Belgium’ document on the website of FAMHP can be consulted.

2. A new clinical investigation under EC only regulatory pathway

2.1. Submission package and procedure

For academic clinical investigations evaluating a CE-marked medical device and which is used within the scope of its CE-marking, the procedure and submission package for experiments can be followed.

3. A new clinical investigation under separate opinion FAMHP and EC regulatory pathway

3.1. Submission package

Cover letter
List of documents submitted
Application form MDR, including appendices
Clinical Evaluation Plan
Clinical Investigation Plan (CIP, protocol)
Synopsis of Clinical Investigation Plan (separate document, English + local language)
Patient related documents
- Informed Consent Form(s) (ICF(s))
- Recruitment material, flyers, posters
- Diaries, questionnaires, interview topic list,…
- Description of the compensation for participants (if not included in CIP)
Data/documentation of Investigational Medical Device (IMD):
- Investigator Brochure (IB): Investigator’s Brochure, contains the clinical and non-clinical information on the investigational device that is relevant for the investigation and available at the time of application (see MDR Annex XV, Chapter II, point 2).
- Manufacturer’s Instructions for Use (local language)
- List of General Safety and Performance Requirements
- Notified Body Certificates as applicable
- Example of Device Label for the clinical investigation
Other documents
- Description of the arrangements to comply with the applicable rules on the protection and confidentiality of personal data
- Data processing register (Ghent University Hospital studies | Ghent University studies)
- (Draft) intersite agreements / proof of funding (application), as applicable
- Signed CV of all participating Principal Investigator(s)
- GCP certificate of all participating Principal Investigator(s)
- Insurance certificate (only if Ghent University (Hospital) does not act as the sponsor of the study; otherwise provided by HIRUZ CTU)

3.2. Submission procedure

3.2.1. Preparation of the submission package

For academic clinical investigations for which University (Hospital) Ghent acts as a sponsor: please contact the medical device focus team to arrange a meeting to discuss your clinical investigation before setting-up your submission package.

3.2.2. Submission through the Research Portal

All studies must be submitted through the Research Portal of Ghent University (Hospital): https://onderzoeksportaal.uzgent.be/
More information can be found here.

For commercial clinical investigations:
Once the applicant submits the clinical investigation in the Research Portal, approval of the Principal Investigator (PI), Head of Department (if applicable) and Medical Manager of the biobank (if applicable) will be asked. When all approvals are given, the clinical investigation is directly submitted to the Medical Ethics Committee (MEC) of Ghent University (Hospital). All further communication with the MEC (remarks/approval MEC) will go via the Research Portal.

Please note: The clinical investigation should be submitted simultaneously to the Federal Agency for Medicines and Health Products (FAMHP) by the sponsor.

Please note: New agreements or changes to existing agreements should be submitted to hiruz.contracten@uzgent.be by email for review. In the near future, agreements will need to be submitted through the Research Portal.

For academic clinical investigations:
Once the applicant submits the clinical investigation in the Research Portal, approval of the Principal Investigator (PI), Head of Department (if applicable) and Medical Manager of the biobank (if applicable) will be asked. When all approvals are given, the clinical investigation is submitted to HIRUZ CTU for review.

After admissibility check, HIRUZ CTU will revise the information given in the Research Portal, as well as the documents that were submitted. Once the clinical investigation is reviewed, you will be informed (by email) that the review can be found in the Research Portal (in the tab ‘HIRUZ Remarks’). HIRUZ CTU aims to provide feedback within two weeks after submission of the clinical investigation to HIRUZ CTU.

Complete applications (if applicable, after the review by HIRUZ CTU was implemented) are submitted by HIRUZ CTU to the MEC of Ghent University (Hospital) (also through the Research Portal) and the FAMHP (in case Ghent University (Hospital) is sponsor of the clinical investigation). All further communication with the MEC (remarks/approval by MEC) will go via the Research Portal (if applicable). All communication with the FAMHP (remarks/approval by FAMHP) will be communicated to you by HIRUZ CTU through the Research Portal (in case Ghent University (Hospital) is sponsor of the clinical investigation).

Please note: When the clinical investigation is submitted to the EC and FAMHP, HIRUZ Contract Unit or TechTransfer will be notified to review the draft agreement proposals or to set-up an agreement if necessary.

3.2.3. MEC and/or FAMPH approval

Information on the legal periods for advice by the MEC and FAMHP can be found here.

The clinical investigation can only start when a favorable opinion from the MEC and FAMHP has been received and as soon as all agreements are finalized (if applicable). In addition, in case Ghent University (Hospital) is sponsor, HIRUZ CTU will set-up a trial initiation visit at each participating site to discuss the practical aspects of the clinical investigation and provide the necessary training (ICH-GCP, protocol, ICF procedure, Investigator Site File, safety follow-up…). This initiation visit must take place before inclusion of the first patient at each site.

3.2.4. Start clinical investigation

Please register both the date of start of recruitment and the date of first inclusion in the Research Portal.

Don’t forget that the sponsor needs to register the clinical investigation on a publicly accessible website before inclusion of the first participant. For the public database ClinicalTrials.gov, HIRUZ CTU can provide you with the login details if Ghent University (Hospital) is sponsor of the clinical investigation. For more information, see FAQ.

3.2.5. End of clinical investigation

Please register the end of the clinical investigation in the Research Portal within 15 days and upload the final study report within one year after the end of the clinical investigation. In case Ghent University (Hospital) acts as sponsor of the clinical investigation, HIRUZ CTU will notify the end of the clinical investigation and submit the final study report to FAMHP. If the investigation is monitored by HIRUZ CTU, the monitor will set-up a close out visit at each participating site.

4. A new clinical investigation under consolidated opinion FAMHP and EC regulatory pathway

4.1.1. Submission package

Cover letter (completed by HIRUZ CTU)
List of documents submitted (completed by HIRUZ CTU)
Application form MDR, including appendices (completed by HIRUZ CTU)
Planning document
Clinical Evaluation Plan
Clinical Investigation Plan (CIP, protocol)
Synopsis of Clinical Investigation Plan (separate document, English + local language)
Patient related documents
- Informed Consent Form(s) (ICF(s))
- Recruitment material, flyers, posters
- Diaries, questionnaires, interview topic list,…
- Description of the compensation for participants (if not included in CIP)
Data/documentation of Investigational Medical Device (IMD):
- Investigator Brochure (IB): Investigator’s Brochure, contains the clinical and non-clinical information on the investigational device that is relevant for the investigation and available at the time of application (see MDR Annex XV, Chapter II, point 2).
- Manufacturer’s Instructions for Use (local language)
- List of General Safety and Performance Requirements
- Notified Body Certificates as applicable
- Example of Device Label for the clinical investigation
Other documents
- Description of the arrangements to comply with the applicable rules on the protection and confidentiality of personal data
- Data processing register (Ghent University Hospital studies | Ghent University studies)
- (Draft) intersite agreements / proof of funding (application), as applicable
- Signed CV of all participating Principal Investigator(s)
- GCP-certificate of all participating Principal Investigator(s)
- Declaration of interest of all participating Principal Investigator(s)
- Signed Suitability of sites (Written Statement)
- Signed Feasibility reports
- Insurance certificate (provided by HIRUZ CTU)

4.1.2. Submission procedure

4.1.2.1. Preparation of the submission package

For academic clinical investigations for which Ghent University (Hospital) acts as a sponsor: please contact the medical device focus team to arrange a meeting to discuss your clinical investigation before setting-up your submission package.

4.1.2.2. Submission through the Research Portal

All studies must be submitted through the Research Portal of Ghent University (Hospital): https://onderzoeksportaal.uzgent.be/
More information can be found here.

Once the applicant submits the clinical investigation in the Research Portal, approval of the Principal Investigator (PI), Head of Department (if applicable) and Medical Manager of the biobank (if applicable) will be asked. When all approvals are given, the clinical investigation is submitted to HIRUZ CTU for review.

After admissibility check, HIRUZ CTU will revise the information given in the Research Portal, as well as the documents that were submitted. Once the clinical investigation is reviewed, you will be informed (by email) that the review can be found in the Research Portal (in the tab ‘HIRUZ Remarks’). HIRUZ CTU aims to provide feedback within two weeks after submission of the clinical investigation to HIRUZ CTU.

Complete applications (if applicable, after the review by HIRUZ CTU was implemented) are submitted by HIRUZ CTU to the Federal Agency for Medicines and Health Products (FAMHP). All communication with the FAMHP (remarks/approval by FAMHP) will be communicated to you by HIRUZ CTU through the Research Portal.

Please note: When the clinical investigation is submitted to the FAMHP, HIRUZ Contract Unit or TechTransfer will be notified to review the draft agreement proposals or to set-up an agreement if necessary.

Please note: Clinical investigations under consolidated opinion pathway are not evaluated by the Ethics Committee of Ghent University (Hospital) but by an independent Ethics Committee. The submission package will be provided by FAMHP to this independent Ethics Committee.

4.1.2.3. MEC and FAMHP approval

Information on the legal periods for advice by the FAMHP can be found here.

The clinical investigation can only start when a favorable consolidated opinion from the FAMHP and an independent EC has been received and as soon as all agreements are finalized (if applicable). In addition, in case Ghent University (Hospital) is sponsor, HIRUZ CTU will set-up a trial initiation visit at each participating site to discuss the practical aspects of the clinical investigation and provide the necessary training (ICH-GCP, protocol, ICF procedure, Investigator Site File, safety follow-up…). This initiation visit must take place before inclusion of the first patient at each site.

4.1.2.4. Start clinical investigation

Please register both the date of start of recruitment and the date of first inclusion in the Research Portal.

4.1.2.5. End of the clinical investigation

Please register the end of the clinical investigation in the Research Portal within 15 days and upload the final study report within one year of the end of the clinical investigation. HIRUZ CTU will notify the end of the clinical investigation and submit the final study report to the FAMHP and the independent EC. If the investigation is monitored by HIRUZ CTU, the monitor will set-up a close out visit at each participating site.

Please note that for clinical investigations under the consolidated opinion pathway for which Ghent University (Hospital) is not the sponsor, the clinical investigation must be submitted to FAMHP and not the Medical Ethics Committee (MEC) of Ghent University (Hospital). Only a written statement is required to be obtained in case Ghent University (Hospital) is a participating site.

The sponsor can request signing of the written statement by the executive director by emailing to hiruz.contracten@uzgent.be. The following documents should be provided:

The written statement, signed by the PI at Ghent University Hospital
Confirmation of the PI (statement on honour) that he/she
- has received the following documents of the sponsor:
  - Clinical Investigation Plan (CIP);
  - Investigator’s Brochure (IB) / Instructions for Use (IFU);
  - Budget proposal;
  - Feasibility report (Ghent University Hospital);
- has read the above mentioned documents;
- wishes to participate in the clinical investigation, (if applicable) together with their study team;
- believes that the Clinical Investigation Plan can be performed by their department (adequate staffing, suitable patient population, adequate material and budget available, adequate expertise …);
- understands the responsibilities as local PI at Ghent University Hospital.

Please note: Agreements should also be submitted to hiruz.contracten@uzgent.be by email for review. In the near future, agreements and requests for written statements will need to be submitted to HIRUZ Contract Unit through the Research Portal.

5. Submission procedure under validation FAMHP and opinion EC regulatory pathway

Please note that for clinical investigation under the validation FAMHP and opinion EC pathway for which Ghent University (Hospital) is a participating site, the clinical investigation must be submitted to FAMHP and not the Medical Ethics Committee (MEC) of Ghent University (Hospital). Only a written statement is required to be obtained in case Ghent University (Hospital) is a participating site

A written statement can be requested by the sponsor via mailing to hiruz.contracten@uzgent.be.

The following documents should be provided:

The written statement, signed by the PI
Confirmation of the PI that he/she agrees to participate in the clinical investigation and that he/she has read and approved the following documents (no need to submitted):
- CV and GCP of PI
- Clinical Investigation Plan (CIP)
- CIP summary
- Investigator’s Brochure (IB)
- Instructions for Use (IFU)
- Informed Consent Form (ICF)

6. Submission of an amendment to a clinical investigation

All modifications to clinical investigations under the Medical Device Regulation (MDR) and Medical Device Directive (MDD) must be submitted through the Research Portal of Ghent University (Hospital): https://onderzoeksportaal.uzgent.be/.

More information can be found here.

Please note: substantial modifications to clinical investigations approved under the MDD must follow the MDD procedure for the approval of the modification, also after 26 May 2021. See website FAMHP.