Below is a list of the most important new developments and changes relating to clinical trials with in-vitro diagnostic products (IVDs) which from 26 May 2022 are regulated by the Ordinance on Clinical Trials with Medical Devices (ClinO-MD):
*Categorisation
- Clinical trials with in-vitro diagnostic products (IVDs) will in principle continue to be split into categories A to C, but now further into the sub-categories A1, A2 and C1, C2, C3.
- As with other clinical trials (involving medical devices, medicinal products, etc.), applications for category A clinical trials with IVDs must only be submitted to the ethics committee responsible, while applications for category C trials must additionally be submitted to Swissmedic.
- If a substantial modification to a clinical trial with IVDs authorised before 26 May 2022 is submitted to the authorities, the sponsor must simultaneously apply for recategorisation under ClinO-MD.
- You will find here links to the categorisation scheme and the categorisation case studies.
- With the transfer of clinical trials with IVDs from ClinO to ClinO-MD, the concept of “clinical trial” in ClinO-MD will now contain two new sub-concepts:
1. Clinical investigation = clinical trial with a medical device in accordance with the Medical Devices Ordinance (MedDO)
2. Performance study = clinical trial with an IVD in accordance with the Ordinance on In-Vitro Diagnostics (IVDO) - A performance study is designed to ascertain or confirm the analytical or clinical performance of an IVD.
- Performance studies are subdivided into interventional and non-interventional performance studies:
o Interventional performance studies are performance studies where it cannot be ruled out that the result of a diagnostic test that is performed may influence decisions relating to the treatment or the management of the participant being tested.
o This is not the case for non-interventional studies.
o The submission and performance of certain non-interventional performance studies are subject to Chapter 2 or 3 of the Human Research Ordinance (HRO) rather than to ClinO-MD
- The application documents to be submitted for the approval procedures have been broadly harmonised with the documents to be submitted under the EU-IVDR.
- The approval procedure at Swissmedic and the ethics committees now requires formal irregularities in the application to be corrected by the sponsor within a given timeframe. If the irregularities are not corrected in due time, the authorising body will not process the application.
- In addition to the existing obligation to prospectively register clinical trials with IVDs, the results of trials with IVDs must now also be published in a trial registry.
- This also applies to clinical trials with IVDs already under way when the ClinO-MD enters into force on 26 May 2022.
The following points remain the same as under the previous ClinO regulations:
*Nothing changes as far as the mechanism for submitting applications to the ethics committees and Swissmedic is concerned
- As before, applications are submitted via the ethics committees’ electronic system (BASEC) and, in the case of category C trials, additionally via the Swissmedic medical devices information system.
- Authorised clinical trials with IVDs (performance studies) must be registered before the trial commences.
- As explained above, however, the results of the trial must also be entered in a primary register.
Previous updates on ClinO-MD:
Update from 12.05.2022
Information on the transition to the new regulations on clinical trials with in-vitro diagnostic products
From 26 May 2022, clinical trials with in-vitro diagnostic products (IVDs) will be regulated by the Ordinance on Clinical Trials with Medical Devices (ClinO-MD) and no longer by the Clinical Trials Ordinance (ClinO).
During the transition to the new regulations, when applying for authorisation and conducting trials you should pay attention to the following:
- Clinical trials with what products now fall under the ClinO-MD?
Now, from 26 May 2022 onwards, the amended ClinO-MD also regulates clinical trials with IVDs and the associated equipment as per Article 1 para 1 of the Ordinance on In-Vitro Diagnostics, which likewise comes into force on 26 May 2022. Otherwise, nothing changes with regard to the existing allocation of clinical trials between the ClinO and the ClinO-MD.
- From 26 May 2022 how and where must I submit my application for a clinical trial with an IVD?
Nothing changes as far as the mechanism for submitting applications is concerned. As before, applications must be submitted via the ethics committees’ electronic system (BASEC) and where applicable via the Swissmedic medical devices information system.
- What happens with clinical trials with IVDs that were authorised before 26 May 2022 and have not yet been completed?
Authorisation granted under the previous regulations (ClinO) by Swissmedic and the ethics commission for clinical trials with IVDs remain valid (Art. 67 para. 1 HRA and Art. 48 para. 1 ClinO-MD); for these trials no authorisation under the new regulations (ClinO-MD) must be obtained.
However, the new regulations apply when it comes to notifications, changes and reporting in the course of conducting the trial.
The findings of all clinical trials with IVDs completed after 26 May 2022 must now be published in a register (c.f. Art. 48 para. 2 ClinO-MD).
- Further information will shortly be published on the following topics:
Categorizer
Casestudies
- Further resources:
New regulations for clinical trials of medical devices
Ordinance text: Ordinance on Clinical Trials with Medical Devices (German)
Update from 04.05.2022
In-vitro diagnostic products (IVDs) are a special sub-group of medical devices. In the course of adapting Swiss legislation to the new EU Medical Device Regulation (MDR) and the new EU regulation on IVDs (In Vitro Diagnostics Regulation, EU-IVDR), clinical research with IVDs in Switzerland will now also be regulated in the Ordinance on clinical trials with medical devices (ClinO-MD). The changes will enter into force on 26 May 2022 at the same time as the EU-IVDR.
Until the amended ClinO-MD comes into force, further practical information for applicants will follow on this website.
Further information on the ClinO-MD legislative project and on the adaptation of Swiss legislation to the EU’s new legislation on medical devices (EU-MDR and EU-IVDR) can be found on the FOPH's website.
Update from 26.05.2021
Not updated MRA EU-Switzerland on medical devices.
- Switzerland's negotiations with the European Union on the Framework Agreement have stalled. Therefore, the EU has announced that it will not update existing agreements with Switzerland. This directly affects the update of the Mutual Recognition Agreement (MRA) in the area of medical devices, which Switzerland had concluded with the EU.
Impact
- Even without an updated MRA, the ClinO-MD will come into force.
- Most provisions of the ClinO-MD are not dependent on the update of the MRA.
- The main consequences are:
- Eudamed is not accessible to Swiss enforcement authorities and sponsors of clinical trials in Switzerland. However, Eudamed is not yet fully functional anyway. Due to this, the transitional provisions according to Art. 49 ClinO-MD will be applied. Applications and notifications of trials as well as information for the public must be entered via the portals of the ethics committees (BASEC) and Swissmedic (eMessage) as before.
- In the case of clinical trials that take place both in Switzerland and in the EU/EEA, certain reporting obligations to the Swiss authorities will not become applicable for the sponsor of the trial abroad. This information gap is to be compensated.
Mitigation of the information gap: Adjustment of the ClinO-MD by means of amending decree as of 26 May 2021.
- The inflow of safety-relevant information regarding clinical trials that take place both in Switzerland and in EU/EEA countries is important for the safety assessment of the clinical trial in Switzerland.
- To ensure that this flow of information to the Swiss enforcement authorities continues, additional reporting obligations are imposed on the sponsor of the clinical trial in Switzerland (see also Art. 20 and Art. 33 - 36 ClinO-MD). Should the MRA be updated at a later date, it is intended to remove these additional reporting obligations again.
Further information on measures decided by the Federal Council due to the missing update of the MRA on medical devices can be found in the media release of 19 May 2021.
Update from 11.05.2021
Error corrections in the amended ClinO with effect from 26 May 2021
The entry into force of the new ClinO-MD will result in changes to the existing ClinO. The following errors and gaps in the approved version of the amended ClinO will still be corrected with effect as of 26 May 2021:
- Clinical trials with inseparable combination products between medicinal products and medical devices in which the medicinal product has the main function (combinations according to Art. 2 para. 1 let. f and g MedDO) are treated as clinical trials with medicinal products. This means that they fall under Art. 19 ClinO and not under Art. 20 ClinO.
- Clinical trials with products consisting of human devitalised cells or tissues or combination products whose function is mainly achieved by a component made of human devitalised cells or tissues (products according to Art. 2a para. 2 TPA, incl. combinations according to Art. 2 para. 1 let. h MedDO) fall, as before, under Art. 20 ClinO. However, products consisting of derivatives of human devitalised tissues or cells fall under the MedDO (and the MDR), therefore the ClinO-MD applies to them.
- Clinical trials with transplant products continue to fall under the ClinO and are treated analogously to clinical trials with medicinal products under Art. 19 ClinO.
Update from 20.04.2021
Preliminary remark on Eudamed:
The European database on medical devices (Eudamed) is not yet fully operational. The clinical investigations module will not be available until 2022 at the earliest. The rights and obligations set out in the ClinO-MD that require Eudamed have therefore not yet entered into force (e.g. the coordinated assessment procedure in accordance with chapter 3 ClinO-MD), or are subject to transitional regulations (e.g. submission of applications, see below). See also Arts. 49 and 50 para. 2 ClinO-MD.
The most important changes regarding clinical trials with medical devices under the ClinO-MD are:
Updated categorisation
- Clinical trials with medical devices will in principle continue to be split into categories A to C, but now further into the sub-categories A1, A2 and C1, C2, C3 (Art. 6 ClinO-MD).
- You’ll find a diagram illustrating this here.
- The kofam categoriser can be used for (legally non-binding) categorisation.
Differentiating conformity-related and non-conformity-related
- Clinical trials are described as ‘conformity-related’ if they are conducted to verify the conformity of the investigated devices (Art. 2 let. B ClinO-MD). See also Art. 62 para.1 EU-MDR.
- The distinction between conformity-related or non-conformity-related is only made for clinical trials in sub-categories C1 and C2.
- For conformity-related clinical trials, additional duties to provide information and to report to foreign authorities may be applicable.
Adaptation of application documents to be submitted
- The application documents to be submitted for the approval procedures under Annex 1 ClinO-MD have been broadly harmonised with the documents to be submitted under the EU-MDR.
Reply deadline for sponsors
- The approval procedure at Swissmedic and the ethics committees now requires formal irregularities in the application to be corrected by the sponsor within a given timeframe. If the irregularities are not corrected in due time, the authorising body will not process the application (Arts. 12, 13, 15, 19 and 20 ClinO-MD).
Obligation to publish results
- In addition to the existing obligation to prospectively register the clinical trial (see below), the results of the trial must now also be published in a trial registry (Art. 42 ClinO-MD).
- This also applies to clinical trials that are still under way when the ClinO-MD enters into force on 26 May 2021 (Art. 48 para. 2 ClinO-MD).
- Eudamed cannot currently be used for this purpose. The registration and publication of results must therefore be carried out in an international trial registry, such as clinicaltrials.gov (Art. 49 para. 3 ClinO-MD).
The following points will remain the same as under the current regulations under ClinO:
There are not likely to be any changes to the mechanism for submitting applications to the EC and Swissmedic until 2022 at the earliest
- Applications will continue to be submitted via the ethics committees’ electronic portal (BASEC), and for category C trials, also via Swissmedic’s information system for medical devices, as before.
- Submission via Eudamed is not yet possible. See also the transitional regulations under Art. 49 para. 1 ClinO-MD.
- The coordinated assessment procedure as set out under chapter 3 ClinO-MD is not yet available.
The distinction between clinical trials with medical devices under ClinO-MD and (non-clinical) research projects using medical devices under the Human Research Ordinance (HRO) will remain as before under the ClinO
The obligation to register results in a primary registry and to record supplementary information in BASEC will remain unchanged for now
- Until applications can be submitted via Eudamed, approved clinical trials with medical devices must continue to be registered in accordance with Arts. 64, 65 paras. 1 and 3, and Art. 66 ClinO (Art. 49 para. 3 ClinO-MD).
- However, as stated above, the results of the trial must now additionally be registered in a primary registry (Art. 49 para. 3 ClinO-MD).
Update from 16.03.2021
The new regulation on clinical trials with medical devices (ClinO-MD) will come into force on 26 May 2021 and will thus replace the previous regulation on clinical trials with medical devices according to ClinO from 2013.
This is what you, as an applicant and investigator, must bear in mind during the transition to the new regulation:
How should I handle my application for a clinical trial with a medical device before the ClinO-MD comes into force on 26 May 2021?
- Submit missing documentation for pending applications promptly so that they can be concluded as soon as possible and before ClinO-MD goes into effect on 26 May 2021.
- From 1 April 2021: If possible, wait until 1 May 2021 before submitting new applications for clinical trials with medical devices, as there is no guarantee that the application can be concluded before the law changes.
- From 1 May 2021: For reasons of procedural economy, it is strongly recommended to use the new documents and templates provided by the licensing enforcement authorities for the submission of applications according to ClinO-MD. It is recommended to take into account the requirements of the specifications regarding the product requirements of the MDR (GSPR) and safety notifications that will be valid from 26 May 2021. It is expected that a decision on the application will be made after the ClinO-MD comes into force on 26 May 2021.
- More information on how to handle applications during the transition to the new regulation can be found on the Swissmedic and swissethics websites. If you have any questions, please contact Swissmedic, swissethics or your local ethics committee directly.
Which products are covered by the new ClinO-MD?
- The new ClinO-MD regulates clinical trials with medical devices and other products according to Article 1 paragraph 1 of the Medical Devices Ordinance of 1 July 2020 (e.g. also those without medical purpose such as cosmetic contact lenses). Clinical trials with in-vitro-diagnostic devices are still regulated unchanged in the ClinO until presumably 26 May 2022.
How and where do I have to submit my application for a clinical trial with a medical device from 26 May 2021?
- The mechanism for submitting applications is not expected to change until at least 2022. Submission will continue to take place via the electronic system of the ethics committees (BASEC) or Swissmedic (information system for medical devices). Submission via the European database for medical devices EUDAMED is not yet possible. See also the transitional regulation in Art. 49 para. 1 ClinO-MD.
What happens to clinical trials with medical devices that were approved before 26 May 2021 and have not yet been completed?
- Authorizations granted by Swissmedic and the Ethics Committee for clinical trials with medical devices under the previous law (ClinO) remain valid (Art. 67 para. 1 HRA and Art. 48 para. 1 ClinO-MD); no authorizations under the new law (ClinO-MD) need to be obtained for these trials.
- However, as far as events or circumstances during the conduct of the trial are concerned, the new law applies. This therefore concerns the obligations to report adverse events within a certain period of time, to report according to certain specifications and deadlines, etc.
- The results of all clinical trials with medical devices that are completed after 26 May 2021 must now be published in a register (see also Art. 48 para. 2 ClinO-MD).
Further resources:
- New regulations for clinical trials of medical devices
- Ordinance text: Ordinance on Clinical Trials with Medical Devices (German)
Further information on the ClinO-MD legislative project and on the adaptation of Swiss legislation to MDR can be found on the FOPH's website.
The "Factsheet containing general information on the HRA and the ethics committees" from 2016 is no longer valid with the inception of the ClinO-MD and will be removed from the website.