Clinical evaluation between EU Directives (MDD, AIMDD) and EU Regulation (MDR)
The German Medical Devices Act and the still valid EU directives for medical devices (93/42/EEC and 90/385/EEC) require clinical evaluations for medical devices in all risk classes. On 29 June 2016 the new Revision 4 of the current MEDDEV 2.7/1 ‘Clinical Evaluation: A Guide for Manufacturers and Notified Bodies under Directives 93/42/EEC and 90/385/EEC’ was published. The changes in the new revision have greatly increased the requirements for the clinical evaluation.
Clinical evaluations are based on the principles of evidence-based medicine. They no longer focus solely on safety and performance of a medical device but also on the benefits and the user friendliness (usability) for patients, users and third parties. As a result, there are considerably higher requirements for the evidence of equivalence of comparator products. In this sense, comparator products should have European CE certification or the literature search should include Europe-oriented databases. The requirements for the qualification of authors have also increased. If internal clinical data have to be generated, compliance with ISO 14155 is of central importance.
Since 25 May 2017 the new regulations for medical devices (MDR 2017/745/EU) and in-vitro diagnostic devices (IVDR 2017/746/EU) are valid (see our article under EU Medical Devices Act MDR/IVDR). In addition to the MEDDEV changes referred to above, the MDR also tightens the provisions for the equivalence principle. Equivalence is, for example, limited to products from the same manufacturer and the comparator products must be part of the same product family. Other control mechanisms by the notified bodies, authorities and the Commission have also been created. The contents of the MEDDEV guideline have been transposed to the MDR (Chapter VI and Annex XIV) and therefore have become directly applicable law. Requirements from EN ISO 14155 have also been incorporated into the MDR, Chapter VI, Article 62ff and Annex XV. For in-vitro diagnostic devices Chapter VI and Annex XIV of IVDR 2017/746/EU apply for the provision of evidence of clinical performance or performance studies.
The subject of post-market clinical follow-up studies is also given greater importance in MDR and IVDR and the testing activities of the notified bodies were also specified. For example, manufacturers of medical devices and IVD are obliged to establish a system appropriate for the risk profile of the medical device or in-vitro diagnostic device for post-market surveillance (PMS) as part of the quality management system.
According to Chapter VII of the MDR and IVDR, the surveillance system must be planned, established, documented and subject to ongoing updates. The plan for the follow-up of the performance after placing a product on the market must describe the methods and procedures used for the proactive collection and evaluation of safety, performance data and scientific data. The gathering of market surveillance data is used to confirm and check the benefit/risk profile of the device/IVD and must be submitted to the notified body as part of a regularly updated report (key word ‘safety report’ in accordance with MDR Article 86 and Annex XIV and analogously IVDR Article 81 and Annex XIII – also known as Periodic Safety Update Report). The results of the safety report and the clinical follow-up after placing the medical device on the market must then be incorporated in the regular update of the clinical evaluation throughout the entire life cycle of a medical device. The same also applies for IVD devices in accordance with IVDR, Article 56, paragraph 6.
For class III medical devices, implantable devices and class C and D in-vitro diagnostic devices the evaluation report about the clinical follow-up after placing the devices on the market must be updated as needed but at least once a year using these data. For other devices this should be done at least every two to five years. Manufacturers must justify these periods. The brief report on safety and clinical performance indicated in Article 32 (MDR 2017/745/EU) or Article 29 (IVDR 2017/746/EU) must also be regularly updated.
The new MEDDEV guideline on clinical evaluations came into effect in June 2016 with no transition period. There is no deadline for implementation either. Notified bodies are still able to accept a clinical evaluation report based on Version 3 but soon they will be expecting reports based on Version 4. For this reason, the new version should definitely be used as soon as possible. It is now best practice in science and technology that not only is an analysis of the clinical data required but also that the methods used, and the steps carried out are described. Appendices with the search strategies, complete search results, testing strategy and results, the analysis of the data and a clear and functional reference list should therefore also be included. All articles and reports should also be sent to the investigator.
Because of the introduction of the MDR in May 2017, the MEDDEV 2.7/1 guideline and DIN EN ISO 14155 are not repealed. They remain valid and indeed provide additional instructions for carrying out and documenting the clinical evaluation and testing. There are now inconsistencies in terms of the validity, however. The manufacturer of medical devices that already have marketing authorisation have a transition period of three years, that is, until 26 May 2020 in order to adapt their devices to the new specifications of the MDR.
We believe that in this transition period it is best to comply with the MEDDEV guideline. Although the largest, by its own estimation, German notified body TÜV SÜD has notified that for these reasons the time line for implementation of MEDDEV 2.7/1 Rev. 4 is extended, it is nevertheless useful to deal with the future requirements well in advance to accomplish timely implementation. The possibility of extension by TÜV SÜD is, however, only available if the requirements for clinical evaluations in accordance with best practice in technology and science are met and the PMS is implemented in accordance with the corresponding medical device directive. The marketing authorisation/extension application shall also include a plan in which the implementation and the time of the MEDDEV 2.7/1 Rev. 4 are stated. orangeglobal is your partner for devising the planning and its implementation.
MDR requires high-quality clinical evaluations. MEDDEV 2.7/1 Revision 4 takes a big step in this direction. Compliance with the updated MEDDEV therefore helps manufacturers in their preparation for the new regulation. With an extension to a marketing authorisation in accordance with the Medical Devices Act in Germany, compliance with the MEDDEV guideline is also required. orangeglobal prepares these high-quality clinical evaluations for your medical devices.
Pushing the new requirements for clinical evaluations onto the back burner and sitting back and relaxing is meanwhile not a good option because the new requirements are enormous. The workload for those manufacturers who have large numbers of medical devices in circulation is particularly onerous. The clinical evaluation also forms the centrepiece of the technical documentation and marketing authorisation/extension application. If the clinical evaluation meets the requirements of the new MEDDEV guideline and MDR, there is a good chance that the application will be approved.
Do it properly: Act now! Plan with us and make sure you are well prepared for this new challenge.
orangeglobal guides you throughout the process of planning to market surveillance of your medical device.
You can download an online presentation about our procedure for the preparation of a clinical evaluation here (note: the presentation is only sent as a PPSX screen presentation after providing name and company as well as an email address).
THE SERVICE PACKAGE FOR CLINICAL EVALUATIONS IN DETAIL:
• Consultation on the feasibility and needs analysis for initial preparation of a clinical evaluation
• Gap/fit analysis for the revision of the clinical evaluation incl. consultation and clarification of the
requirements from local authorities and notified bodies
• Draft and analysis of the evaluation methods
• Database research, query and evaluation of the literature
• Initiation and monitoring of safety studies (product safety studies)
• Biological evaluation in accordance with EN ISO 10993 (biocompatibility)
• Creation and updating of the clinical evaluation report in accordance with MEDDEV 2.7/1 Rev. 4
• Preparation and compilation of the technical documentation in accordance with IMDRF guideline and
• Fit/gap analysis and updating of existing technical documentation or product files in accordance with
the new Medical Device Regulation (MDR) or In-Vitro Diagnostic Regulation (IVDR)
• Establishment of an appropriate post-marketing surveillance and device-vigilance system
• Scientific and strategic consultation
• Support in selecting the notified body and local authorities
• You benefit from the experience and competent expertise of the orangeglobal group as your
• We achieve quality enhancement for you and increase the safety of product, documentation
• You obtain a flawless clinical evaluation that is at the state-of-the-art level in
your product area
• You have the security of knowing that legal specifications are met
• You obtain a document ready for submission with robust argumentation
for your notified body that takes into account
the requirements for the contents, structure, layout and language quality
YOUR CONTACT PERSON:
Dr. Philip Welbergen MBA
Head of Global Regulatory Affairs & Vigilance
Tel. +49 (0) 731 954 95 - 513