When we talk about the European Regulation 745/2017 (MDR), we cannot not dedicate a focus to the post market phases of the medical devices and to the documents required to be drawn up.
The Directive (MDD) 93/42/EC has accustomed us to discussing Clinical Evaluation Report (CER), Post Market Surveillance (PMS) and Post Market Clinical Follow-Up (PMCF), the last one not considered mandatory with appropriate justifications by the medical device’s manufacturer.
The MDR focused on 4 documents in particular: Clinical Evaluation Plan (CEP), Post Market Clinical Follow-Up (PMCF) Plan and Report, Summary of Safety and Clinical Performance (SSCP), as well as requesting a higher level detail for the Clinical Evaluation Report (CER).
La Clinical Evaluation has been defined by the MDR 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.”
The first step to perform a clinical evaluation is to develop the Clinical Evaluation Plan (CEP), of which the required contents are defined, point-by-point, by Annex XIV (Part A) of the MDR:
“To plan, continuously conduct and document a clinical evaluation, manufacturers shall establish and update a clinical evaluation plan, which shall include at least:
- an identification of the general safety and performance requirements that require support from relevant clinical data;
- a specification of the intended purpose of the device;
- a clear specification of intended target groups with clear indications and contraindications;
- a detailed description of intended clinical benefits to patients with relevant and specified clinical outcome parameters;
- a specification of methods to be used for examination of qualitative and quantitative aspects of clinical safety with clear reference to the determination of residual risks and side-effects;
- an indicative list and specification of parameters to be used to determine, based on the state of the art in medicine, the acceptability of the benefit-risk ratio for the various indications and for the intended purpose or purposes of the device;
- an indication how benefit-risk issues relating to specific components such as the use of pharmaceutical, non- viable animal or human tissues, are to be addressed; and
- a clinical development plan indicating progression from exploratory investigations, such as first-in-man studies, feasibility and pilot studies, to confirmatory investigations, such as pivotal clinical investigations, and a PMCF with indication of milestones and a description of potential acceptance criteria.”
In addition, chapter 7 of the MEDDEV 2.7/1 Revision 4 defines the topics to be considered during the scoping stage of the clinical evaluation process. A well-compiled CEP should have elements from both the MDR and the MEDDEV guidelines.
The Clinical Evaluation Plan (CEP) is the document in which to define the way through the manufacturer of the medical device intends to perform the clinical evaluation, indicating the sources of the clinical data and the methods of collection, in order to confirm compliance with the relevant general safety and performance requirements.
The Clinical Evaluation Plan (CEP) is a living document to be updated proactively on a regular basis. The MDR and MEDDEV do not provide explicit guidance on the frequency of CEP updates, but the document should be reviewed during the CER update process to determine if any changes are needed.
The Post-Market Clinical Follow-Up (PMCF) is part of post-market surveillance and was required under the Medical Devices Directive (MDD) with guidance provided in MEDDEV 2.12/2 rev. 2.
This guidance gives guidance stating that “the requirement for PMCF studies is based on the identification of possible residual risks and/or unclarity on long term clinical performance that may impact the benefit/risk ratio” and cites examples of when a PMCF study might be justified. But the MEDDEV guidance is not legally binding, and manufacturers could decide that a PMCF study was not necessary according with a justifying rationale.
For European Regulation 745/2017 (MDR) the PMCF is a requirement, as a process of collecting clinical data on a CE marked device to confirm clinical performance and safety during the device’s expected lifetime.
The PMCF is carried out according to a documented method, established in a PMCF Plan.
In accordance with Annex XIV Part B of the MDR, the PMCF plan defines the methods and procedures for collecting and evaluating clinical data with the aims of:
- confirming the safety and performance of the device throughout its expected lifetime;
- identifying previously unknown side-effects and monitoring identified side effects and contraindications;
- identifying and analysing emergent risks;
- ensuring the continued acceptability of the benefit-risk ratio l Identifying possible systematic misuse or off-label use of the device.
The Annex also specifies the required contents of the PMCF plan:
- the general methods and procedures of the PMCF to be applied, such as the gathering of clinical experience gained, feedback from users, screening of scientific literature and other sources of clinical data;
- the specific methods and procedures of PMCF to be applied, such as evaluation of suitable registers or PMCF studies;
- a rationale for the appropriateness of the methods and procedures referred to in points (a) and (b);
- a reference to the relevant parts of the clinical evaluation report referred to in Section 4 and to the risk management referred to in Section 3 of Annex I (of the MDR);
- the specific objectives to be addressed by the PMCF;
- an evaluation of the clinical data relating to equivalent or similar devices;
- reference to any relevant common specifications, harmonised standards when used by the manufacturer, and relevant guidance on PMCF; and
- a detailed and adequately justified time schedule for PMCF activities (e.g., analysis of PMCF data and reporting) to be undertaken by the manufacturer.
The MDCG has published additional guidance in the form of templates for both the PMCF plan and the PMCF evaluation report:
- MDCG 2020-7 “Post-market clinical follow-up (PMCF) Plan Template”. A guidance for manufacturer and notified bodies – April 2020
- MDCG 2020-8 “Post-market clinical follow-up (PMCF) Evaluation Report”. A guidance for manufacturer and notified bodies – April 2020
The PMCF report summarizes the data collected as part of the clinical evaluation of the device (CER) and the technical documentation.
The PMCF report is prepared annually for class III and implantable devices, every two to five years or as required for class IIa and IIb devices, and as needed for class I medical devices.
The novelty introduced by the MDR is the Summary of Safety and Clinical Performance (SSCP). According to Article 32 of the MDR manufacturers shall prepare an SSCP for implantable devices and class III devices, other than custom-made or investigational devices, with the following contents:
“The summary of safety and clinical performance shall include at least the following aspects:
- the identification of the device and the manufacturer;
- the intended purpose of the device and any indications, contraindications and target populations;
- comprehensive description of the device;
- possible diagnostic or therapeutic alternatives;
- reference to any harmonised standards and Common Specifications applied;
- the summary of the clinical evaluation, and relevant information on post-market clinical follow-up;
- suggested profile and training for users;
- information on any residual risks and any undesirable effects, warnings and precautions”.
In addition MDCG guidance document suggests on how to prepare the SSCP:
- MDCG 2019-9 Rev.1 “Summary of safety and clinical performance”. A guide for manufacturers and notified bodies - March 2022.
The SSCP is intended to provide public access to an updated summary of clinical data and other information about the safety and clinical performance of the medical device. The SSCP will be an important source of information for intended users, both healthcare professionals and if relevant for patients. It is one of several means intended to fulfil the objectives of the Medical Device Regulation (MDR) to enhance transparency and provide adequate access to information.
The SSCP is not intended to:
- give general advice on the diagnosis or treatment of particular medical conditions, nor
- replace the instructions for use (IFU) as the main document that will be provided to ensure the safe use of a particular device, nor
- replace the mandatory information on implant cards4 or in any other mandatory documents.
The SSCP shall be validated by a notified body (NB) and made available to the public via the European database on medical devices (Eudamed).
Source:
- European Commission. Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EE. Official Journal of the European Union; 2017.
- European Commission. Clinical evaluation: A guide for manufacturers and notified bodies under directives 93/42/EEC and 90/385/EEC. MEDDEV 2.7/1 rev4. Official Journal of the European Union; 2016.
- European Commission. Directive 2007/47/EC of the European Parliament and of the Council of 5 September 2007 amending Council Directive 90/385/EEC on the approximation of the laws of the Member States relating to active implantable medical devices, Council Directive 93/42/EEC concerning medical devices and Directive 98/8/EC concerning the placing of biocidal products on the market. Official Journal of the European Union; 2007.
- European Commission. Post Market Clinical Follow-Up Studies. A guide for manufacturers and Notified Bodies. MEDDEV 2.12/2 rev2. Official Journal of the European Union; 2012.
- Medical Device Coordination Group (MDCG). MDCG 2020-7. Post-market clinical follow-up (PMCF) Plan Template: A guide for manufacturers and notified bodies. 2020 Apr.[cited 2020 Jul 3].
- Medical Device Coordination Group (MDCG). MDCG 2020-8. Post-market clinical follow-up (PMCF) Evaluation Report Template. A guide for manufacturers and notified bodies. 2020 Apr.[cited 2020 Jul 3].
- Medical Device Coordination Group (MDCG). MDCG 2019-9. Summary of safety and clinical performance: A guide for manufacturers and notified bodies. 2019 Aug.[cited 2020 Jul 3].