Clinical evaluation requirements have been changing, with the latest impact coming from MEDDEV 2.7/1 Rev 4. Preparing for and meeting these requirements is important because the grace period offered by some notified bodies is ending and clinical evaluation reports (CERs) are being audited for compliance with the latest MEDDEV revision.
Furthermore and once the regulation comes into force, the European Medical Devices Regulation (MDR) will impact CERs as well. It is important to be proactive to ensure CERs will meet your notified body expectations. You must review your clinical strategy carefully.
R&Q recently presented the webinar, MEDDEV 2.7/1 & CERs: Know the changes and what to do. Towards the end of the session we answered several questions, a sample of which are below. To see all questions and answers from the session - along with the slides and recording - check out the on-demand webinar.
Q: What is the structure of a post-market data analysis that will avoid the need to generate new clinical data for an existing marketed device?
A: The need for additional clinical data is based on whether the current clinical evidence is sufficient to demonstrate conformity with the Essential Requirements for performance and safety. The purpose of post-market data analysis is to estimate residual risks, rare complications, long-term performance, or wide-spread use. Therefore, in order to avoid the need for new clinical investigations, we’d suggest having a robust Post-Market Surveillance plan. This can support adequate clinical evidence and will provide strong documentation in your clinical evaluation report that does not leave significant risks relative to safety or uncertainties relative to performance. Some things to consider in your PMS plan:
- Consider holding focus group data gathering sessions at trade conferences to gather feedback on device performance and safety
- Establishing or tapping into registries that have objectives that fit your targets
- Tap into your marketing department and gather information from their field evaluations
- Send out customer surveys
- Gather information from trade shows
- Continue to scan for new literature or medical guidelines that affect your device
A view of the MDR, Article 61, shows the future of clinical evaluation reports and starting to prepare and gather clinical evidence now will be key to transitioning to the EU MDR.
Q: What are the options for a company that does not have access to a competitor's tech file and does not have their own clinical data? There must be a way to demonstrate equivalence and use existing literature. Otherwise, companies will spend money generating data for the sole purpose of meeting the new requirements.
A: Independent of whether you have access to a competitor’s tech file, you will need to have sufficient data to prove biological, technical, and clinical equivalence. Often times, the non-clinical literature (e.g., bench testing reports) and the competitor’s labeling and marketing material has a large amount of information that can be used to substantiate equivalence; indications, patient population treated, design characteristics, general device specifications, surgical technique, principles of operation, and materials. Guidance documents can often be used to substantiate testing specifications, such as biocompatibility and mechanical testing. Therefore, the choice of an equivalence device should also take into account the availability of this information in the public domain.
Q: For an existing device being marketed, can the SOTA be justified with a review of only recent literature?
A: Yes, if that timeframe is sufficient to properly establish the clinical background and demonstrate an equivalent risk/benefit profile relative to current interventions available to patients. In some cases, new articles may be considered better since older articles may not represent current knowledge. Data for other devices (e.g., benchmark devices) and alternative therapies can be used to define the state of the art for safety and performance. Comparison studies that measure the subject or equivalent device against a state of the art treatment (typical of many clinical studies) and systematic reviews are particularly valuable for state of the art. Some of the comparison studies may overlap with the safety and performance literature, reducing the burden on the state of the art analysis. We recently performed a complicated Clinical Evaluation for a high risk Class III device and the state of the art analysis included data from the past two years. In this case, there was plenty of recent high quality data available in the literature.
Q: Per EU MDR, do we really need to have Quality Agreement in place with our comparative device so that we can look at the file (unless we want to do clinical trials)?
A: Based on a review of the EU MDR, we interpret this as only applying to class III devices. The paragraph that mentions the requirement for a contract references the prior paragraph pertaining to implantable and class III devices. However, it doesn’t explicitly state that it only applies to these devices. Therefore, it will ultimately be up to the notified body to determine the scope of this requirements.
We've copied Article 61 paragraphs 4 and 5 below for reference.
4. In the case of implantable devices and class III devices, clinical investigations shall be performed, except if:
- the device has been designed by modifications of a device already marketed by the same manufacturer,
- the modified device has been demonstrated by the manufacturer to be equivalent to the marketed device, in accordance with Section 3 of Annex XIV and this demonstration has been endorsed by the notified body, and
- the clinical evaluation of the marketed device is sufficient to demonstrate conformity of the modified device with the relevant safety and performance
In this case the notified body shall check that the PMCF plan is appropriate and includes post market studies to demonstrate the safety and performance of the device.
In addition, clinical investigations need not be performed in the cases referred to in paragraph 6.
5. A manufacturer of a device demonstrated to be equivalent to an already marketed device not manufactured by him, may also rely on paragraph 4 in order not to perform a clinical investigation provided that the following conditions are fulfilled in addition to what is required in that paragraph:
- the two manufacturers have a contract in place that explicitly allows the manufacturer of the second device full access to the technical documentation on an ongoing basis, and
- the original clinical evaluation has been performed in compliance with the requirements of this Regulation,
- and the manufacturer of the second device provides clear evidence thereof to the notified body.
Q: What is the definition of an “Evaluator”?
A: Evaluator isn’t specifically defined in the MEDDEV. We interpret this as the person (or persons) who is ultimately responsible to appraise and analyze the clinical data and determine whether it is sufficient to show compliance. In general, the clinical evaluation needs to be performed by “a suitably qualified individual or a team.” If any members of that team are making the final judgement about the data, we would call them evaluators.