All devices, regardless of classification, are required by Article 5, 3. to fulfil the clinical requirements of Article 61 and Part A of Annex XIV. This is know as a clinical evaluation.
One of the most frequently asked questions is whether the clinical evaluation can be based solely on published literature or is a clinical (trial) investigation required. This question can only be answered by performing the clinical evaluation, as the answer will depend on several factors; the classification of the device, how novel the device is and the amount of clinical data on equivalent devices is already available in published literature. For devices in the higher classifications, IIb and III, manufacturers also have the possibility to consult a panel of EU experts on their clinical development strategy (See Article 61, 2).
The clinical evaluation process is described in Annex XIV, Part A. It begins with the preparation of the clinical evaluation plan; the minimum contents are listed in Annex XIV, Part A 1(a). In the evaluation; identify and appraise available relevant clinical data. If more clinical data is needed, it can be generated through clinical investigation(s). Clinical investigations must be planned, approved, conducted and reported following the procedures in Articles 62-81 and Annex XV.
Once all relevant clinical data has been analysed and conclusions reached, the entire clinical evaluation activity is documented in the clinical evaluation report.
In a final step, the post-market clinical follow-up plan is prepared (See Annex XIV, Part B 6 for the content).
Deliverables for demonstrating compliance:
(1) The Clinical Evaluation plan and report,
(2) Clinical Investigation documentation (if applicable),
(3) The Post Market Clinical Follow-up (PMCF) plan.
Guidance
Guidance is also available from the Medical Device Coordination Group;
on performing clinical evaluations, including of software;
- MDCG 2024 Clinical evaluation of orphan medical devices.
- MDCG 2020-6 Guidance on sufficient clinical evidence for legacy devices
- Background note on the relationship between MDCG 2020-6 and MEDDEV 2.7/1 rev.4 on clinical evaluation.
- MDCG 2020-5 Guidance on clinical evaluation – Equivalence
- MDCG 2020-1 Guidance on clinical evaluation (MDR) / Performance evaluation (IVDR) of medical device software.
- MDCG 2019-9 Rev.1 Summary of safety and clinical performance.
- MDCG 2019-3 rev.1 Clinical evaluation consultation procedure exemptions Interpretation of article 54(2)b.
on conducting clinical investigations;
- MDCG 2024-5 Guidance on content of the Investigator’s Brochure for clinical investigations of medical devices.
- MDCG 2024-5 Appendix A Template for providing cross-references between requirements in Annex XV chapter II of the MDR and the Clinical Investigation submission package.
- MDCG 2024-3 Guidance on content of the Clinical Investigation Plan for clinical investigations of medical devices.
- MDCG 2024-3 Appendix A Clinical Investigation Plan Synopsis Template.
- MDCG 2023-7 Guidance on exemptions from the requirement to perform clinical investigations pursuant to Article 61(4)-(6) MDR and on sufficient levels of access’ to data needed to justify claims of equivalence.
- 2023/C 163/06 Commission Guidance on the content and structure of the summary of the clinical investigation report.
- MDCG 2021-28 Substantial modification of clinical investigation under Medical Device Regulation.
- MDCG 2021-20 Instructions for generating CIV-ID for MDR Clinical Investigations.
- MDCG 2021-8 Clinical investigation application/notification documents.
- MDCG 2021-6 rev.1 Questions & Answers regarding clinical investigation.
- MDCG 2020-10/1 Rev.1 Guidance on safety reporting in clinical investigations
- MDCG 2020-10/2 Rev.1 Appendix: Clinical investigation summary safety report form.
and on post market clinical follow-up (PMCF);
- MDCG 2020-8 Guidance on PMCF evaluation report template.
- MDCG 2020-7 Guidance on PMCF plan template.
What are the rules for who can Author a CEP and CER?
There are no “rules” in the EU MDR, but the Competent Authorities certainly do have expectations. As MDCG 2020-1 says; “Clinical expertise and judgments are required at every step of the clinical evaluation…”, implying a clinician’s education and clinical experience. Also, MDCG 2020-13 says; “Authors (shall) have full range of required expertise represented (e.g. research methods, information management, regulatory requirements, device technology, diagnosis and management of conditions to be treated).”
Is there a requirement to update the CEP after it has been created and if there is what is the frequency?
Yes, according to Annex XIV, manufactures shall “establish and update a clinical evaluation plan…” And in ANNEX IX, the application to the Notified Body for the assessment of the quality management system shall include, “a description of the procedures in place to keep up to date the clinical evaluation plan, taking into account the state of the art.” The frequency of such reviews is not specified however.
Dear Sir/Madam
Regarding to MDR (EU) 2017/745:
“(67)
An electronic system should be set up at Union level to ensure that every clinical investigation is recorded and reported in a publicly accessible database. To protect the right to the protection of personal data, recognised by Article 8 of the Charter of Fundamental Rights of the European Union (‘the Charter’), no personal data of subjects participating in a clinical investigation should be recorded in the electronic system. To ensure synergies with the area of clinical trials on medicinal products, the electronic system on clinical investigations should be interoperable with the EU database to be set up for clinical trials on medicinal products for human use.”
I have a question:
Where can I find this database?
Best regards
Béla
At the time of your question the database is still under development. The status and roadmap for the activation of future modules can be found here. https://health.ec.europa.eu/medical-devices-eudamed/overview_en
Do i need to do clinical evaluation, if the same product has been on the market for past 4 years, under different brand name, and has been compliant with MDD and MDR under different brand name ?
Every device requires a clinical evaluation. Not only as a part of initially demonstrating conformity with the requirements, but the documentation is also updated as new information is obtained in the post-market phase.
That said, if the two products you mention are genuinely the same device with only different names, you might consider whether it may be appropriate simply to add the new names to the already existing declaration of conformity and associated documentation.
If there is no equivalant device in market or there is no public clinical data but the device is on marketing for a long time, how could we conduct the clinical investigation since we could not find out a similar device/clinical data as a comparsion?
Presumably you meant “how could we conduct the clinical evaluation (not investigation) since….” but this is exactly how the clinical evaluation process in Annex XIV is intended to be applied.
The authors of the EU MDR anticipated, in step 1(b), that the literature review might identify gaps in the clinical evidence needed to support the claims for the device. In which case, in step 1.(d), the manufacturer must generate any new or additional clinical data needed to fill those gaps.
I’d like to know if our product’s clinical investigation was conducted in a non-EU country-say ,like an Asian country, and it has been on the market ourside of the EU for a really long time, is there still the need to carry out another clinical trial in the EU?
Thank you for your question
This question can only be answered by performing a clinical evaluation for the device, as described in Annex XIV Part A. In step (c), the appraisal of all relevant clinical data, it must be evaluated whether the data produced by that earlier investigation is suitable for establishing the safety and performance of the device in the European market and user/patient population.